breast cancer - hanys

Breast Cancer

Treatment Guidelines for Patients

Version IV / September 2002

The mutual goal of the National Comprehensive Cancer Network (NCCN) and the AmericanCancer Society (ACS) partnership is to provide patients and the general public with state-of-the-art cancer treatment information in understandable language. This information, based on theNCCN’s Clinical Practice Guidelines, is intended to assist you in the dialogue with your doctor.These guidelines do not replace the expertise and clinical judgment of your doctor. Each patient’ssituation must be evaluated individually. It is important to discuss the guidelines and all infor-mation regarding treatment options with your doctor. To ensure that you have the most up-to-date version of the guidelines, consult the Web sites of the ACS (www.cancer.org) or NCCN(www.nccn.org). You may also call the NCCN at 1-888-909-NCCN or the ACS at 1-800-ACS-2345for the most recent information.

Breast Cancer


Version IV / September 2002

NCCN Clinical Practice Guidelines were developed by a diverse panel of experts. The guidelinesare a statement of consensus of its authors regarding the scientific evidence and their views ofcurrently accepted approaches to treatment. The NCCN guidelines are updated as new significantdata become available. The Patient Information version will be updated accordingly and will beavailable on-line through the NCCN and the ACS Web sites. To ensure you have the most recentversion, you may contact the ACS or the NCCN.

©2002 by the National Comprehensive Cancer Network (NCCN) and the American CancerSociety (ACS). All rights reserved. The information herein may not be reprinted in any form forcommercial purposes without the expressed written permission of the NCCN and the ACS. Singlecopies of each page may be reproduced for personal and non-commercial uses by the reader.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Making Decisions About Breast Cancer Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Normal Breast Tissue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Types of Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Benign Breast Lumps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Breast Cancer Work-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Breast Cancer Stages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Types of Breast Cancer Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Choosing Between Lumpectomy and Mastectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Reconstructive Breast Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Other Things to Consider During and After Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

Work-Up (Evaluation) and Treatment Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Decision Trees

Stage 0 (LCIS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Stage 0 (DCIS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Stages I, II, and Some IIIA Breast Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Axillary Lymph Node Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Adjuvant (Additional) Treatment for Stages I, II, and Some IIIA . . . . . . . . . . . . . . . . . . . . . 38

Preoperative Treatment for Stage II and Some Stage IIIA Large Breast Cancers . . . . . . . . 42

Treatment for Stages III and IV Invasive Breast Cancers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Follow-up of Women with Stages I, II, or III Breast Cancer and Work-Up and Treatment of Recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Stage IV or Systemic Recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

Glossary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University

City of Hope Cancer Center

Dana-Farber Cancer Institute

Duke Comprehensive Cancer Center

Fox Chase Cancer Center

Fred Hutchinson Cancer Research Center

H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida

Huntsman Cancer Institute at the University of Utah

Memorial Sloan-Kettering Cancer Center

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Roswell Park Cancer Institute

St. Jude Children’s Research Hospital

Stanford Hospital and Clinics

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

UCSF Comprehensive Cancer Center

University of Alabama at Birmingham Comprehensive Cancer Center

University of Michigan Comprehensive Cancer Center

University of Texas M. D. Anderson Cancer Center

UNMC/Eppley Cancer Center at the University of Nebraska Medical Center

IntroductionWith this report, patients have their firstaccess to information on the way breast canceris treated at the nation's leading cancer cen-ters. Originally devised for cancer specialistsby the National Comprehensive CancerNetwork (NCCN), these treatment guidelineshave now been translated for the general pub-lic by the American Cancer Society (ACS). Toobtain another copy of these guidelines, as wellas more information, call the American CancerSociety at 1-800-ACS-2345 or the NCCN at 1-888-909-NCCN, or visit these organizations'Web sites at www.cancer.org (ACS) andwww.nccn.org (NCCN).

Since 1995, doctors have looked to the NCCNfor advice on treating cancer. NCCN ClinicalPractice Guidelines were developed by adiverse panel of experts from 19 of the nation'sleading cancer centers. The guidelines repre-sent the authors' consensus regarding the sci-entific evidence and their views of currentlyaccepted approaches to treatment. The NCCNguidelines are updated as new significant databecome available. The Patient Information ver-sion will be updated accordingly and will beavailable on-line through the NCCN and theAmerican Cancer Society Web sites. To ensurethat you have the most recent version, you maycontact the American Cancer Society or theNCCN.

For more than 85 years, the public has relied onthe American Cancer Society for informationabout cancer. The Society’s books andbrochures provide comprehensive, current,and understandable information to hundredsof thousands of patients, their families, andfriends. This collaboration between the NCCN

and ACS provides an authoritative and under-standable source of cancer treatment informa-tion for the general public.

These patient guidelines will help you betterunderstand your cancer treatment and yourdoctor’s counsel. We urge you to discuss themwith your doctor. Here are some questions youmight want to ask.

• How many tumors do I have? How large arethey?

• What is my cancer’s grade (how abnormalthe cells appear) and histology (type andarrangement of tumor cells), as seen under amicroscope?

• Do I have any lymph nodes with cancer (pos-itive lymph nodes)? If yes, how many?

• What is the stage of my cancer?

• Is my cancer estrogen receptor-positive orprogesterone receptor-positive?

• Is breast-conserving therapy an option forme?

• In addition to surgery, what other treatmentsdo you recommend? Radiation? Chemo-therapy? Hormonal therapy?

• What are their side effects?

Making Decisions AboutBreast Cancer Treatment On the following pages you’ll find flow chartsthat doctors call “algorithms” or “decisiontrees.” The charts represent different stages ofbreast cancer. Each one shows you step-by-stephow you and your doctor can arrive at thechoices you need to make about yourtreatment.

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Lobular cells

Lobules

Lobule

Ductcells

Duct

Ducts

Nipple

Areola

Fatty connective tissue

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To reach an informed decision you need tounderstand some of the medical terms yourdoctor uses. You may feel you’re on familiarground already, or perhaps you need to refer tothe various sections listed in the table of con-tents. Not only will you find background infor-mation on breast cancer, but also explanationsof cancer stage, work-up, and treatment – allcategories used in the flow charts. We’ve alsoprovided a glossary at the end of the booklet.

Although breast cancer is a very seriousdisease, it can be treated by a multidisciplinaryteam of health care professionals. This teammay include a surgeon, radiation oncologist,medical oncologist, radiologist, pathologist,oncology nurse, social worker, and others. Butnot all women with breast cancer shouldreceive the same treatment. Doctors must con-sider a woman’s specific medical situation.This booklet can help you and your doctordecide which choices best meet your medicaland personal needs.

Normal Breast TissueThe main parts of the femalebreast are lobules (milk-producingglands), ducts (milk passages thatconnect the lobules and the nip-ple), and stroma (fatty tissue andligaments surrounding the ductsand lobules, blood vessels, andlymphatic vessels). Lymphaticvessels are similar to veins butcarry lymph instead of blood.

Lymph is a clear fluid that contains tissuewaste products and immune system cells.Most lymphatic vessels of the breast lead toaxillary (underarm) lymph nodes. Cancer cellsmay enter lymph vessels and spread out alongthese vessels to reach lymph nodes. Cancercells may also enter blood vessels and spreadthrough the bloodstream to other parts of thebody.

Lymph nodes are small, bean-shaped collec-tions of immune system cells important infighting infections. When breast cancer cellsreach the axillary lymph nodes, they can con-tinue to grow, often causing swelling of thelymph nodes in the armpit.

If breast cancer cells have multiplied in theaxillary lymph nodes, they are more likely tohave spread to other organs of the body as well.

Types of Breast CancerBreast cancer is an abnormal growth of cellsthat line the ducts and the lobules. The classi-fication of types of breast cancer is based onwhether the cancer started in the ducts or thelobules, whether the cells have “invaded”through the duct or lobule, and the appearanceof the cancer under a microscope.

Carcinoma In SituIn situ means that the cancer stays confined toducts or lobules and has not invaded sur-rounding fatty tissues in the breast or spread toother organs in the body. There are two types ofbreast carcinoma in situ:

• Lobular carcinoma in situ (LCIS): Also calledlobular neoplasia. It begins in the lobules butdoes not penetrate through the lobule walls.Most breast cancer specialists think thatLCIS, itself, does not usually become an inva-sive cancer, but women with this conditiondo run a higher risk of developing an invasivecancer in either breast.

• Ductal carcinoma in situ (DCIS): The mostcommon type of noninvasive breast cancer.Cancer cells inside the ducts do not spreadthrough the walls of the ducts into the fattytissue of the breast.

Infiltrating (or Invasive) DuctalCarcinoma (IDC)Starting in a milk passage, or duct, of thebreast, the cancer cells break through the wallof the duct and invade the breast’s fatty tissue.They can then invade lymphatic channels orblood vessels of the breast and spread to otherparts of the body (metastasis). Infiltrating orinvasive ductal carcinoma accounts for about80% of all breast cancers.

Infiltrating (or Invasive) LobularCarcinoma (ILC)This type of cancer starts in the milk-producing glands. Like IDC, this cancer canspread beyond the breast to other parts of thebody. About 10% to 15% of invasive breastcancers are invasive lobular carcinomas.

Medullary CarcinomaThis special type of infiltrating ductal cancerhas a relatively well-defined, distinct boundarybetween tumor tissue and normal breasttissue. It also has a number of other specialfeatures, including the large size of the cancercells and the presence of immune system cellsat the edges of the tumor. It accounts for about5% of all breast cancers. Medullary carcinomahas a slightly better prognosis (outlook forchances of survival) and a slightly lower chanceof metastasis than invasive lobular or invasiveductal cancers of the same size.

Colloid CarcinomaThis rare type of invasive ductal breast cancer,also called mucinous carcinoma, is formed bymucus-producing cancer cells. Colloid carci-noma has a slightly better prognosis and aslightly lower chance of metastasis than inva-sive lobular or invasive ductal cancers of thesame size.

Tubular CarcinomaTubular carcinoma is a special type of infiltrat-ing ductal breast carcinoma. About 2% of allbreast cancers are tubular carcinomas. Theyhave a slightly better prognosis and a slightlylower chance of metastasis than invasivelobular or invasive ductal cancers of the samesize.

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Inflammatory Breast CancerInflammatory breast cancer accounts forabout 1% of invasive breast cancers. The skinof the affected breast is red, feels warm, andhas the appearance of an orange peel.

The name for this type of breast cancer waschosen many years ago because the tissueappeared inflamed. Doctors now know thatthese changes are not due to inflammation butrather to spread of cancer cells within lym-phatic channels of the skin.

Inflammatory breast cancer has a higherchance of spreading and a worse prognosisthan typical invasive ductal or lobular cancers.Inflammatory breast cancer is automaticallystaged as stage IIIB unless it has already spreadto other organs at the time of diagnosis. Suchspread is more common with inflammatorybreast cancer and makes it stage IV (see dis-cussion of stages below).

Benign Breast LumpsMost breast lumps are benign (not cancerous).Fibrocystic changes usually cause these lumps.Fibrosis refers to excessive formation of scar-like connective tissue; cysts are fluid-filledsacs. Women with fibrocystic changes oftenexperience breast swelling and pain. Thebreasts may feel lumpy, and the nipple maydischarge a clear or slightly cloudy liquid.

Benign breast lumps such as fibroadenomas orintraductal papillomas are quite common.They cannot spread outside of the breast toother organs. Talk to your doctor aboutwhether it is necessary to remove these lumps.This booklet only refers to treating breastcancer, not benign breast conditions.

Breast Cancer Work-Up An evaluation of a breast lump or mammo-gram finding includes a thorough medicalhistory, a physical examination, and breastimaging (such as x-rays) including a diagnosticmammogram. A biopsy is needed for a worri-some finding, though many of these suspiciousareas prove to be benign (not cancer). If canceris found, other imaging and laboratory testsare needed. Exactly which tests are helpfuldepends on the type of cancer and the extentof the cancer. This section provides a summaryof the steps, tests, and types of biopsy that maybe suggested.

Doctor Visit and ExaminationA woman’s first step in having a new breastlump, symptom, or a change on a mammogramevaluated, is to meet with her doctor. He or shewill take a medical history which includes aseries of questions about your symptoms andabout factors that may be related to breastcancer risk (such as family history of cancer).Your physical examination should include ageneral examination of your body as well ascareful examination of your breasts. Yourdoctor will look for:

• Any breast change, including its texture, size,relationship to skin and chest muscles

• Any changes in the nipple or skin of thebreast

• Any evidence of lumps or masses in thebreast

• Lymph nodes under the armpit or above thecollarbone (enlargement or firmness of theselymph nodes might mean spread of breastcancer)

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• General examination of other organs tocheck for obvious spread of breast cancerand to help evaluate the general condition ofyour health.

Breast Imaging TestsAfter completing your physical examinationand taking your medical history, your doctorwill recommend that you have breast imagingstudies, including a mammogram unless thishas already been done.

Women who have no breast lumps or symp-toms will have a screening mammogram. Thisincludes two pictures of each breast, a top-to-bottom and a side-to-side view.

Women with a lump in the breast, other suspi-cious symptoms, or with a change found on ascreening mammogram will have a procedurecalled diagnostic breast imaging. A diagnosticmammogram includes more mammogramimages of the area of concern to give moreinformation about the size and character of thearea. A breast ultrasound or sonogram alsomay be done. Ultrasound examination useshigh-frequency sound waves to further evalu-ate a lump or mammogram finding. Mostimportantly, ultrasound helps determine if thearea of concern is a fluid-filled cyst or solidtissue that may be cancer.

To get a high-quality mammogram picture, it isnecessary to compress the breast slightly. Atechnician places the breast on the mammo-gram machine’s lower plate, which is made ofmetal and has a drawer to hold the x-ray film.The upper plate, made of clear plastic, is low-ered to compress the breast for a few secondswhile the technician takes a picture. Althoughcompression may be uncomfortable, mostwomen do not say it is painful.

Some women may have breast magnetic reso-nance imaging (MRI) in addition to a diagnos-tic mammogram and ultrasound. In somecases, breast MRI may help define the size andextent of cancer within the breast tissue. Itmay especially be useful in women whose“dense” breast tissue makes it more difficult tofind tumors with a mammogram. Breast MRIis not proven as a screening test and is not areplacement for a screening mammogram.

Breast BiopsyIf a woman or her doctor finds a suspiciousbreast lump, or if imaging studies show aworrisome area, the woman must have abiopsy. This is a procedure to provide a tissuesample to be examined under the microscope.This examination is what actually determinesif cancer is present.

There are several different types of breast biop-sies. Biopsy may be done by a needle, or it mayrequire a surgical procedure. Each type ofbiopsy has advantages and disadvantages. Thebest type of biopsy for each situation dependson the patient.

In most cases, if it is possible, a needle biopsy ispreferred instead of a surgical biopsy as thefirst step in making a cancer diagnosis. Aneedle biopsy provides a diagnosis more rap-idly and with less discomfort. In addition, itgives the woman an opportunity to discusstreatment options with her doctor before anysurgery is performed. There is no danger thatneedle biopsy itself will spread the breastcancer. However, in some cases, a surgicalbiopsy may still be needed to remove all or partof a lump for microscopic examination after aneedle biopsy has been performed, or it may benecessary to do a surgical biopsy instead ofneedle biopsy.

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Two types of needle biopsies are used to diag-nose breast cancer. The most common is coreneedle biopsy that removes a small cylinder oftissue. A less commonly used biopsy is fineneedle aspiration (FNA) biopsy. FNA uses asmaller needle than a core biopsy but onlyremoves a small amount of cells. FNA can alsobe used to remove fluid from a suspicious cyst.

Your doctor can do a core needle biopsy orFNA biopsy if he/she can feel the lump. If alump cannot be felt easily or is not felt at alland only seen on mammogram or ultrasound,the doctor can use the ultrasound or mammo-gram to guide the needle during the biopsy.The mammogram-directed technique is calledstereotactic needle biopsy. In this procedure,computerized mammogram breast imageshelp the doctor map the exact location of thebreast lump and guide the tip of the needle tothe right spot. Ultrasound images can be usedin the same way to guide the needle. Thechoice between a mammogram-directedstereotactic needle biopsy and ultrasound-guided biopsy depends on the type of breastchange and the experience and preference ofthe doctor.

In patients who need a surgical (excisional)biopsy, the surgeon generally removes theentire area with the breast change with a zoneof surrounding normal-appearing breast tissuecalled a margin. If the breast change cannot befelt, then the mammogram is used to guide thesurgeon through a technique called wire local-ization. After numbing the area with a localanesthetic, x-ray pictures are used to guide asmall hollow needle to the abnormal spot inthe breast. A thin wire is inserted through thecenter of the needle, the needle removed, and

the wire used to guide the surgeon to the rightspot.

Most breast biopsies cause little discomfort.Only local anesthesia (numbing of the skin) isnecessary for needle biopsies. For surgicalbiopsies, most surgeons use a local anestheticplus some intravenous medicines to make thepatient drowsy. A general anesthetic is notneeded for most breast biopsies.

Examination of tissue: After the breast tissueis removed by either needle biopsy or surgicalbiopsy, it is sent to a pathology laboratory todetermine if it is cancer. This process may takeseveral days and cannot be rushed in mostcases. This examination of the breast tissuedetermines if the lump is cancer.

Your doctor should give you your pathologyresults. Or, you can ask for a copy of yourpathology report and to have it explained care-fully to you. If you want, you can get a secondopinion on the pathology of your tissue byhaving the microscope slides from your tissuesent to a consulting breast pathologist at anNCCN cancer center or other laboratorysuggested by your doctor.

Other Tests After Cancer Has BeenDiagnosedIf your breast biopsy results show that you havebreast cancer, your doctor will order someother tests to find out if your cancer has spreadand to help determine your treatment. Formost women with breast cancer, extensivetesting provides no benefit and is not neces-sary. Unfortunately, there is no test that cancompletely reassure you that the cancer hasnot spread. The NCCN Guidelines describewhich tests are needed based on the extent of

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the cancer and on the results of the history andphysical examination. Tests that may be doneinclude:

Chest x-ray: All women with breast cancershould have a chest x-ray before surgery tomake sure that the breast cancer has notspread to the lungs.

Bone scan: This may provide informationabout spread of breast cancer to the bones.However, all changes that show up on a bonescan are not cancer. Unless there are symptomsof spread to the bone, including new pains orchanges on blood tests, a bone scan is notnecessary except in patients with advancedcancer. To scan bones, a small dose of aradioactive substance is injected into yourvein. This radioactive substance collects inareas of abnormal bone. These areas show upon x-rays. Other than the needle stick, a bonescan is painless.

Computed tomography (CT) scans: CT scansare done when there are symptoms or otherfindings to suggest the cancer has spread toother organs. For most women with an earlystage breast cancer, a CT scan is not needed.CT scans take multiple x-rays of the same partof the body from different angles to providedetailed pictures of internal organs. Except forthe injection of intravenous dye, necessary formost patients, this is a painless procedure.

Magnetic resonance imaging (MRI): MRIscans use radio waves and magnets to producedetailed images of internal organs without anyx-rays. MRI is useful in looking at the brain andspinal cord and in examining any specific areain the bone. Routine MRI for all patients withbreast cancer is not helpful and is not needed.

Blood tests: Some blood tests are needed toplan surgery, to screen for evidence of cancerspread, and to plan treatment after surgery.

These blood tests include:

• Complete blood count (CBC): This deter-mines whether the blood has the correct typeand number of blood cells. Abnormal testresults could reveal other health problems,including anemia, and could suggest thecancer has spread to the bone marrow. Also,if you receive chemotherapy, doctors repeatthis test because chemotherapy affects theblood-forming cells of the bone marrow.

• Blood chemical and enzyme tests: Thesetests are done in patients with invasivebreast cancer (not needed with in situcancer) and may show the cancer has spreadto the bone or liver. If these test results arehigher than normal, your doctor will orderimaging tests such as bone scans or CTscans.

Tumor marker testing (estrogen receptor,progesterone receptor, HER-2/neu): Testingthe tumor itself for certain chemicals helpsdetermine the chances the cancer will spreadand helps your doctor determine the besttreatment. The pathology laboratory tests thecancer tissue that is removed, either from thefirst biopsy or the final surgery.

Tumor hormone receptor testing helps deter-mine the best treatment. Two hormones inwomen – estrogen and progesterone – maystimulate the growth of normal breast cellsand play a role in some breast cancers. Cancercells respond to these hormones through theestrogen receptors (ER) and progesteronereceptors (PR). These receptors are the cell’s

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“welcome mat” for these hormones circulatingin the blood. If a cancer does not have thesereceptors, it is referred to as estrogen-receptornegative and/or progesterone-receptor nega-tive. If the cancer has these receptors, it isreferred to as estrogen-receptor positiveand/or progesterone-receptor positive or justhormone-receptor positive (ER-positive, PR-positive).

These hormone receptors are importantbecause cancer cells that are ER- or PR-positive will stop growing if the woman takeshormone drugs that block the effect ofestrogen and progesterone. These drugsincrease the chance that the cancer will nevercome back (recur) in other body organs andimprove the chances of long-term survival.Most women whose breast cancer is ER- or PR-positive should take hormone drugs as part oftheir treatment. However, these hormonedrugs are not effective if the cancer is ER- orPR-negative.

All women with invasive breast cancer (notnecessary with in situ cancer) should be testedfor hormone receptors. You should ask yourdoctor for these results and whether youshould consider hormone drugs as part of yourtreatment.

Women with invasive breast cancer shouldalso be tested for a cancer gene that helpscancer cells grow. This gene is called HER-2/neu. Breast cancer cells with too much HER-2/neu tend to grow faster and may respondbetter to combinations of chemotherapy drugsthat include drugs of the anthracycline class(such as doxorubicin or epirubicin).

In addition to helping choose the type ofchemotherapy, women with cancers that are

positive for HER-2/neu may be treated with anew drug that directly attacks HER-2/neu.This drug is an antibody called trastuzumab(Herceptin®). Trastuzumab, along with othertreatments, is used in women whose breastcancer has spread to other organs and who areHER-2/neu-positive. Trastuzumab is not rou-tinely used unless it is known that the cancerhas spread, but studies are being done to deter-mine if it helps when combined with standardchemotherapy in women whose cancer has notspread.

Breast Cancer StagesCancers are classified by stage. Staging acancer is the process of finding out how muchcancer there is in the body and where it islocated. Doctors determine the stage of acancer by gathering information from exami-nations and tests on the tumor, lymph nodes,and distant organs.

• Clinical stage is determined by informationfrom the doctor’s examination and imagingtests (x-rays, mammograms, etc).

• Pathologic stage includes information fromthe surgical removal of the cancer and lymphnodes.

A breast cancer’s stage is one of the mostimportant factors that may predict prognosis(outlook), or the chance of cancer coming backor spreading to other organs. A cancer’s stagetherefore is one of the important factors inchoosing the best treatment.

Each woman’s prognosis with breast cancerdiffers, depending on the cancer’s stage andother cancer factors such as hormone recep-tors, her general state of health, and her treat-

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ment. You should feel you are able to talkfrankly with your doctors about your cancerstage and prognosis, and how they affect treat-ment options.

The system most often used to describe thegrowth and spread of breast cancer is the TNMstaging system, also known as the AmericanJoint Committee on Cancer (AJCC) system. InTNM staging, information about the tumor,nearby lymph nodes, and distant organ metas-tases is combined and a stage is assigned tospecific TNM groupings. The grouped stagesare described using the number 0 and Romannumerals from I to IV.

T stands for the size of the cancer (measured incentimeters). N stands for spread to lymphnodes in the area of the breast, and M is formetastasis (spread to distant organs of thebody).

T categories: T categories are based on thebreast cancer’s size, its location within thebreast, and spread to nearby tissue.

• T0: No evidence of primary tumor.

• Tis: Carcinoma in situ or noninvasive breastcancer.

Ductal carcinoma in situ (DCIS): Cancercells are located within the breast duct andhave not invaded the duct wall and into sur-rounding tissue.

Lobular carcinoma in situ (LCIS): Alsocalled lobular neoplasia. The abnormal cellsgrow within the breast lobule (milk-producingglands), but do not penetrate or invadethrough the wall of the lobule. LCIS is not trulya cancer, but women with LCIS are at higherrisk of developing invasive breast cancer laterin life.

• T1: The cancer is 2 cm in diameter (about3/4 inch) or smaller.

• T2: The cancer is more than 2 cm but notmore than 5 cm in diameter.

• T3: The cancer is more than 5 cm indiameter.

• T4: The cancer is any size and has spread tothe chest wall or the skin.

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5 cm

2.5 centimeters (cm) = 1 inch1 cm = 10 mm

Tumor Sizes

1 cm 2 cm 3 cm

N categories: The N category is based onwhich of the lymph nodes near the breast, ifany, are affected by the cancer.

• N0: The cancer has not spread to lymphnodes.

• N1: The cancer has spread to lymph nodesunder the arm on the same side as the breastcancer. Lymph nodes have not yet attachedto one another or to the surrounding tissue.

• N2: The cancer has spread to lymph nodesunder the arm on the same side as the breastcancer. Lymph nodes are attached to oneanother or to the surrounding tissue.

• N3: The cancer has spread to internal mam-mary lymph nodes (located beneath thebreast and inside the chest).

M categories: The M category depends onwhether the cancer has spread to any distanttissues and organs.

• M0: No distant cancer spread.

• M1: Cancer may have spread to distantorgans or to the supraclavicular (above thecollarbone) lymph nodes.

Stage grouping for breast cancer: Once theT, N, and M categories have been assigned, thisinformation is combined to assign an overallstage of 0, I, II, III, or IV.

Types of Breast CancerTreatmentTwo separate issues need to be addressed forall women treated for breast cancer: the treat-ment of the breast itself, and the treatment forcancer cells that may have spread to otherparts of the body. Doctors use the term “localtherapy” to refer to treatment of the breast andsurrounding lymph nodes (usually a combina-tion of surgery and radiation therapy), and the

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Overall Stage T category N category M category

Stage 0 Tis N0 M0

Stage I T1 N0 M0

Stage IIA T0 N1 M0T1 N1 M0T2 N0 M0

Stage IIB T2 N1 M0T3 N0 M0

Stage IIIA T0 N2 M0T1 N2 M0T2 N2 M0T3 N1 M0T3 N2 M0

Stage IIIB T4 Any N M0Any T N3 M0

Stage IV Any T Any N M1

term “systemic therapy” to refer to chemother-apy or hormone therapy to control cancer cellsthat may have spread elsewhere.

Breast-Conserving SurgeryNearly all women with breast cancer will havesome type of surgery. Lumpectomy removesonly the breast lump and the surrounding area,or margin, of normal tissue. If cancer cells arepresent at the margin (the edge of the exci-sional biopsy or lumpectomy tissue), an exci-sion can usually be done again to remove theremaining cancer.

In almost all cases of invasive breast cancer, 6to 7 weeks of radiation therapy follow lump-ectomy. Doctors call this combination (oflumpectomy and radiation) breast-conservingtherapy. It’s an option for most, but not all,women with breast cancer. Those who proba-bly should not have lumpectomy, or breast-conserving therapy, include:

• Women who have already had radiation ther-apy to the affected breast or chest

• Women with two or more areas of cancer, inthe same breast, too far apart to be removedin one incision

• Women whose first excisional biopsy – or,when needed, their re-excision – has notcompletely removed their cancers

• Women with certain connective tissuediseases that make body tissues especiallysensitive to the side effects of radiation

• Pregnant women who would require radia-tion while still pregnant

• Women whose tumor is larger than 5 cm (2inches) and can’t be shrunk by treatmentbefore surgery.

MastectomyIn a simple (total) mastectomy procedure, sur-geons remove the entire breast but do not cutaway any lymph nodes from under the arm ormuscle tissue from beneath the breast. Thisprocedure is used to treat noninvasive breastcancer. In a modified radical mastectomy, sur-geons remove the entire breast and someaxillary (underarm) lymph nodes.

Doctors rarely perform the radical mastec-tomy, which removes not only the entire breastand lymph nodes under the arm, but also thechest wall muscles under the breast as well. Atone time this surgery was quite common, but it left women disfigured and caused sideeffects. The modified radical mastectomy hasproven as effective as the radical mastectomy.

The possible short-term side effects of bothmastectomy and lumpectomy include woundinfection, hematoma (accumulation of bloodin the wound), and seroma (accumulation ofclear fluid in the wound).

Lymph Node SurgeryWhether a woman has a mastectomy or alumpectomy for invasive cancer, she and herdoctor usually need to know if the cancer hasspread to the lymph nodes. If the lymph nodesare affected, that increases the likelihood thatcancer cells have spread through the blood-stream to other parts of the body. Women withductal carcinoma in situ or lobular carcinomain situ do not need lymph node testing.

Doctors once believed that removing as manylymph nodes as possible would reduce the riskof developing distant metastasis and improve awoman’s chances for long-term survival. Wenow know that the lymph node surgery itself

15

probably does not improve the chance for long-term survival, and that systemic treatmentoffers the best chance of killing cancer cellsthat have spread beyond the breast.

Surgery is the only way to accurately determineif the cancer has spread to the lymph nodes.This usually means removing some or all of thelymph nodes in the armpit. Usually 10 to 20lymph nodes in the armpit are removed. Thisoperation is called an axillary lymph nodedissection.

For some women, removing the underarmlymph nodes can be considered optional. Thisincludes:

• Women with tumors so small and with sucha favorable outlook that lymph node spreadis unlikely

• Instances where it would not affect whetheradjuvant treatment is given

• Elderly women

• Women with other serious medical conditions.

Although lymph node dissection is a safe oper-ation and has low rates of serious side effects,doctors have tried to develop new ways of find-ing out if cancer has spread to lymph nodeswithout removing all of them first.

Over the past 5 years, a new procedure calledthe sentinel lymph node biopsy has been intro-duced. In this procedure the surgeon finds andremoves the “sentinel node” – the first lymphnode into which a tumor drains and the onemost likely to contain cancer cells. The surgeoninjects a radioactive substance and/or a bluedye into the area around the tumor. Lymphaticvessels carry these substances into the sentinelnode and provide the doctor with a “lymphnode map.” The doctor can either see the bluedye or detect the radioactivity with a Geigercounter. He or she then removes the node forexamination by the pathologist, and the inci-sion is closed. If the sentinel node containscancer, the surgeon will perform an axillarydissection – removal of more lymph nodes inthe armpit. This may be done at the same timeor several days after the original sentinel nodebiopsy.

If the sentinel node is cancer-free, the patientwill not need more lymph node surgery andcan avoid the side effects of full lymph nodesurgery, discussed further on.

This limited sampling of lymph nodes is notappropriate for some women. The guidelinesrecommend sentinel lymph node biopsy bedone only if there is a team with documentedexperience with this technique. In addition, itis only done if there is a single tumor less than5 cm in the breast, no prior chemotherapy or

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Normal Lymph Drainage

Lymph nodes

Axillary lymphnodes

Internalmammarylymphnode

Lymphvessels

hormone therapy has been given, no more thana 6 cm biopsy has been performed, and thelymph nodes feel normal.

Whenever a patient has axillary lymph nodesurgery, she may have temporary or permanentnumbness in her skin on the inside of herupper arm; the procedure can also limit armand shoulder movements. Without normallymph drainage, fluids can collect and lead toarm and hand swelling known as lymphedema.No one can predict which patients will developthis condition or when. Lymphedema can

develop just after surgery, or even months oryears later. Most women, however, do not haveserious lymphedema.

With care, patients can take steps to help avoidlymphedema or at least keep it under control.Talk to your doctor for more details.

Among the steps to take to help avoidlymphedema:

• Avoid having blood drawn from or IVsinserted into the arm on the side of thelymph node surgery.

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Choosing Between Lumpectomyand MastectomyThe advantage of lumpectomy is that it savesthe appearance of the breast. A disadvantageis the need for several weeks of radiationtherapy after surgery. However, some womenwho have a mastectomy will still need radia-tion therapy.

Women who choose lumpectomy and radia-tion can expect the same chance of survivalas those who choose mastectomy.

Although most women and their doctorsprefer lumpectomy and radiation therapy,your choice will depend on a number offactors, such as:

• How you feel about losing your breast

• How far you have to travel for radiationtherapy

• Whether you are willing to have moresurgery to reconstruct your breast afterhaving a mastectomy

• Your preference for mastectomy as a wayto “get rid of all your cancer as quickly aspossible”

Lumpectomy and radiation are not appro-priate if:

• The patient has had radiation to the breastor chest wall

• The patient is pregnant

• The disease is in several areas of the breast

• There are suspicious areas of calciumspread out in the breast

Lumpectomy and radiation may not beappropriate if:

• Two separate incisions are needed toremove the disease

• The patient has a connective tissue diseasesuch as scleroderma

• The tumor is larger than 5 cm (about 2inches)

• Do not allow a blood pressure cuff to beplaced on the arm on the side of the lymphnode surgery. If you are in the hospital, tell allhealth care workers about your arm.

• Tell your doctor immediately if your arm orhand feels tight or swollen. Don’t ignore it.

• Wear a well-fitted compression sleeve ifneeded.

• Wear gloves when gardening or doing otherthings that are likely to lead to cuts.

Radiation TherapyRadiation is used to destroy cancer cells leftbehind in the breast, chest wall, or lymphnodes after surgery. Radiation treatments areusually given 5 days a week for 6 to 8 weeks.

Side effects most likely to occur includeswelling and heaviness in the breast, sunburn-like skin changes in the treated area, andfatigue. Changes to the breast tissue and skinusually go away in 6 to 12 months. In somewomen, the breast becomes smaller and firmerafter radiation therapy. If the lymph nodesunder the arm are treated with radiation, itcan also cause lymphedema.

Systemic TherapyTo reach cancer cells that may have spreadbeyond the breast and nearby tissues, doctorsgive cancer drugs by mouth or into a vein. Thistype of treatment is called systemic therapy.Examples of systemic therapy include chemo-therapy and hormone therapy.

Systemic therapy given to patients after sur-gery is called adjuvant therapy. The goal ofadjuvant therapy is to kill undetected cells.Even in the early stages of the disease, cancercells can break away from the primary breast

tumor and spread through the bloodstream.These cells usually don’t cause symptoms youcan feel, and they don’t show up on an x-rayand can’t be felt during a physical examination.But they can establish new tumors in otherplaces in the body.

Systemic therapy given to patients before sur-gery is called neo-adjuvant therapy. Sometimesoncologists give patients neo-adjuvant therapyto try to shrink the tumor enough to make sur-gical removal possible. This may allow womenwho would otherwise need mastectomy tohave breast-conserving surgery. Systemic ther-apy is the main treatment for women diag-nosed with metastatic breast cancer.

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Reconstructive SurgeryThese procedures create the shape andappearance of a breast after mastectomy.For most women, the breast can be recon-structed at the same time as mastectomy(immediate breast reconstruction) or later(delayed reconstruction). Surgeons mayuse silicone or saline-filled implants, ortissue from other parts of your body. Ifthey use your own body tissues, this iscalled autologous tissue reconstruction.How do a woman and her doctor decideon the type of reconstruction and whenshe should have the procedure? Theanswer depends on the woman’s personalpreferences, the size and shape of herbreasts, the size and shape of her body, herlevel of physical exercise and details of hermedical situation, such as how much skinis removed and if she needs chemotherapyor radiation.

Chemotherapy: Patients take anti-cancerdrugs intravenously (injected into a vein) or bymouth. Either way, the drugs travel in thebloodstream and move throughout the entirebody. Doctors who prescribe these drugs(medical oncologists) generally use a combi-nation of medicines proven more effectivethan a single drug.

• The chemotherapy options for women withnode-negative breast cancer are CMF, CAF,or AC. (See box on page 19 for specificchemotherapy regimens.)

• Women with node-positive breast cancerreceive CAF, CEF, AC with or without pacli-taxel, A-CMF, or CMF. (See box for specificchemotherapy regimens.)

• Women with recurrent or metastatic breastcancer may receive:

Preferred first-line chemotherapy (given first):

• Anthracycline-based, taxane or CMF

Preferred second-line chemotherapy (givenafter first-line):

• If anthracycline is given first, then CMF or taxane

• If taxane is given first, thenanthracycline-based or CMF

• Other possible drugs include capecita-bine, vinorelbine, gemcitabine, mitox-antrone, and platinum compounds

If the cancer has high amounts of HER-2/neu,or the cancer has spread to the lymph nodes, aregimen containing an anthracyline (doxoru-bicin or epirubicin) is usually given.

Doctors give chemotherapy in cycles, witheach period of treatment followed by a rest

period. The total course of chemotherapyusually lasts 3 to 6 months, depending on thedrugs used. The side effects of chemotherapydepend on the type of drugs used, the amounttaken, and the length of treatment.

Doxorubicin and epirubicin may cause heartdamage, but this is very uncommon in peoplewho do not have preexisting heart disease. Ifyou know you have heart disease or there isconcern you have heart disease, your doctor

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Drugs Commonly Used to Treat Breast Cancer

Generic Brand

Cyclophosphamide Cytoxan

Docetaxel Taxotere

Doxorubicin Adriamycin

Epirubicin Ellence

Paclitaxel Taxol

Tamoxifen Nolvadex

Toremifen Fareston

Trastuzumab Herceptin

Chemotherapy regimens containing two ormore drugs

CMF: Cyclophosphamide, methotrexate, andfluorouracil

CAF: Cyclophosphamide, doxorubicin, andfluorouracil

AC: Doxorubicin and cyclophosphamide

AC+ Paclitaxel: Doxorubicin, cyclophospha-mide, and paclitaxel

A➔CMF: Doxorubicin followed by CMF

CEF: Cyclophosphamide, epirubicin, andfluorouracil

may suggest special heart tests before you usethese drugs and may suggest other chemother-apy drugs if your heart function is impaired.

Temporary side effects might include loss ofappetite, nausea and vomiting, mouth sores,hair loss, and changes in the menstrual cycle.Chemotherapy can damage the blood-producing cells of the bone marrow. A drop inwhite blood cells can raise a patient’s risk ofinfection; a shortage of blood platelets cancause bleeding or bruising after minor cuts orinjuries; and a decline in red blood cells canlead to fatigue.

There are treatments for these side effects. Forexample, several drugs can prevent or reducenausea and vomiting. A new group of drugscalled growth factors can help bone marrowrecover after chemotherapy and can treatproblems resulting from low blood counts.These drugs are often not necessary. Talk withyour doctor about which treatment will beright for you.

Women can also have permanent effects suchas early menopause and infertility from anti-cancer drugs. The older a women is when shereceives chemotherapy, the more likely it is shewill stop menstruating or lose her ability tobecome pregnant.

Ask your doctor for a copy of NCCN’s specificguidelines for treating many of the side effectsassociated with chemotherapy, such as Feverand Neutropenia Treatment Guidelines forPatients with Cancer.

Monoclonal antibody therapy: Trastuzumabis a drug that is an antibody directed againstthe HER-2/neu receptor on the surface of thebreast cancer cells of some patients. It works

alone or when combined with chemotherapyfor patients whose cancer has spread. Becauseheart muscle cells also have the HER-2/neureceptor, Trastuzumab can cause heart dam-age when combined with doxorubicin andcyclophosphamide. It should be used cau-tiously when combined with other heart-damaging drugs such as anthracyclines(doxorubicin and epirubicin). Currently,trastuzumab is only used for women withproven spread of breast cancer whose tumorsare positive with HER-2 neu or who are takingpart in a clinical trial.

Hormone TherapyEstrogen, a hormone produced by the ovariesand the adrenal glands, causes some breastcancers to grow. Doctors use severalapproaches to block the effect of estrogen or tolower estrogen levels. In the past, removing theovaries in premenopausal women and theadrenal glands in postmenopausal womenwere often effective treatments. Today, themost commonly used drug to block the effectof estrogen is the antiestrogen drug tamoxifen.Another antiestrogen drug called toremifene isavailable and works like tamoxifen.

Studies show that tamoxifen can reduce thechances of cancer coming back after surgery ifthe breast cancer cells contain receptors forestrogen or progesterone. Doctors also use thedrug to treat metastatic breast cancer.

In postmenopausal women, the adrenal glandsproduce male hormones that are released intothe blood. In fat, bones, and some breast can-cer, this male hormone is changed into estro-gen. Drugs called aromatase inhibitors whichprevent the change to estrogen, have proven as

20

effective as tamoxifen in treating metastaticbreast cancer in women in this age group.

Some studies have shown a slight increase ofearly-stage endometrial cancer (which occursin the lining of the uterus) among post-menopausal women taking tamoxifen. If youtake tamoxifen and have any unusual vaginalbleeding – a possible symptom of endometrialcancer – tell your doctor right away.

Another uncommon side effect of tamoxifen isdeep-vein thrombosis, a condition in whichblood clots form in the deep blood vessels ofthe legs and groin. The blood clots sometimesbreak off and spread to the lungs. The risk ofstroke is also slightly increased.

Other side effects may include hot flashes,mood swings, and cataracts. But for mostwomen the benefits of taking tamoxifen faroutweigh the risks. One of the advantages ofthe aromatase inhibitors in postmenopausalwomen is that they don’t cause these sideeffects except for the hot flashes, but thinningof the bones may be increased.

Other hormonal treatments are megestrolacetate (a progesterone-like drug), fluoxymes-terone (a male hormone like testosterone), andethinyl estradiol (an estrogen drug that is effec-tive if it is given in high doses).

Premenopausal women can take another typeof drug, called luteinizing hormone-releasinghormone (LHRH) agonist. It is given by injec-tion and prevents estrogen production.

Bisphosphonates: These drugs are used tostrengthen bones that have been weakened byinvading breast cancer cells. The most com-monly used drug, is pamidronate.

Treatment of Pain and OtherSymptomsMost of this booklet discusses ways to removeor destroy breast cancer cells or to slow theirgrowth. But maintaining your quality of life isan important goal. Don’t hesitate to discussyour symptoms or how you feel with yourcancer care team. There are effective and safeways to treat pain, most other symptoms ofbreast cancer, and most of the side effectscaused by breast cancer treatment. If you don’ttell your health care team, they may have noway of knowing about your problems.

Complementary or AlternativeTherapiesIf you are considering any unproven alternativeor complementary treatments, it is best todiscuss this openly with your cancer care teamand request information from the ACS or theNational Cancer Institute. Some unproventreatments can interfere with standard med-ical treatments or may cause serious sideeffects.

Other Things to ConsiderDuring and After TreatmentDuring and after your treatment for breastcancer you may be able to speed up your recov-ery and improve your quality of life by takingan active role. Learn about the benefits andrisks of each of your treatment options, andask questions of your cancer care team if thereis anything you do not understand. Learnabout and look out for side effects of treat-ment, and report these right away to membersof your cancer care team so they can take stepsto ease them and shorten their duration.

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Remember that your body is as unique as yourpersonality and your fingerprints. Althoughunderstanding your cancer’s stage and learn-ing about your treatment options can helppredict what health problems you may face, noone can say for sure how you will respond tocancer or its treatment.

You may have special strengths such as a his-tory of excellent nutrition and physical activity,a strong family support system, or a deep faith,and these strengths may make a difference inhow you respond to cancer. There are alsoexperienced professionals in mental healthservices, social work services, and pastoralservices who may assist you in coping withyour illness.

You can also help in your own recovery fromcancer by making healthy lifestyle choices. Ifyou use tobacco, stop now. Quitting willimprove your overall health and the full returnof the sense of smell may help you enjoy ahealthy diet during recovery. If you use alcohol,limit how much you drink. Have no more than1 or 2 drinks per day. Good nutrition can helpyou get better after treatment. Eat a nutritiousand balanced diet, with plenty of fruits, vegeta-bles, and whole grain foods.

If you are being treated for cancer, be aware ofthe battle that is going on in your body. Radia-tion therapy and chemotherapy add to thefatigue caused by the disease itself. Give yourbody the rest it needs so that you will feelbetter as time goes on. Exercise once you feelrested enough. Ask your cancer care teamwhether your cancer or its treatments mightlimit your exercise program or other activities.

It is important that you consider your emo-tional, psychological, and spiritual health

along with the physical aspects of your recov-ery from cancer.

A woman’s choice of treatment will likely beinfluenced by her age, the image she has of her-self and her body, her hopes and fears, and herstage in life. For example, many women selectbreast-conserving surgery with radiation ther-apy over a mastectomy for body image reasons.On the other hand, some women who choosemastectomy may want the affected arearemoved, regardless of the effect on their bodyimage, and others may be more concernedabout the side effects of radiation therapy thanbody image.

Other issues that concern women include lossof hair from chemotherapy and skin changes ofthe breast from radiation therapy. In additionto these body changes, women may also beconcerned about the outcome of their treat-ment. These are all factors that affect how awoman will make decisions about her treat-ment, how she views herself, and how she feelsabout her treatment.

Concerns about sexuality are often very worri-some to a woman with breast cancer. Sometreatments for breast cancer can change awoman’s hormone levels and may have a nega-tive impact on sexual interest and/or response.A diagnosis of breast cancer when a woman isin her 20s or 30s is especially difficult becausechoosing a partner and childbearing are oftenvery important during this period.Relationship issues are also important becausethe diagnosis can be very distressing for thepartner, as well as the patient. Partners areusually concerned about how to express theirlove physically and emotionally during andafter treatment.

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Suggestions that may help a woman adjust tochanges in her body image include looking atand touching her body; seeking the support ofothers, preferably before surgery; involving herpartner as soon as possible after surgery; andopenly talking about the feelings, needs, andwants created by her changed image.

A cancer diagnosis and its treatment is a majorlife challenge, with an impact on you andeveryone who cares for you. Before you get tothe point where you feel overwhelmed, con-sider attending a meeting of a local supportgroup or contacting other patient advocacygroups. If you need individual assistance inother ways, contact your hospital’s social serv-ice department or the ACS for help in contact-ing counselors or other services.

Clinical TrialsThe purpose of clinical trials: Studies ofpromising new or experimental treatments inpatients are known as clinical trials. A clinicaltrial is only done when there is some reason tobelieve that the treatment being studied maybe valuable to the patient. Treatments used inclinical trials are often found to have realbenefits. Researchers conduct studies of newtreatments to answer the following questions:

• Is the treatment helpful?

• How does this new type of treatment work?

• Does it work better than other treatmentsalready available?

• What side effects does the treatment cause?

• Are the side effects greater or less than thestandard treatment?

• Do the benefits outweigh the side effects?

• In which patients is the treatment mostlikely to be helpful?

Types of clinical trials: A new treatment isnormally studied in three phases of clinicaltrials before it can be approved by the FDA(Food and Drug Administration).

Phase I clinical trials: The purpose of a phaseI study is to find the best way to give a newtreatment and find out how much of it can begiven safely. Doctors watch patients carefullyfor any harmful side effects. The treatment hasbeen well tested in laboratory and animalstudies, but the side effects in patients are notcompletely known. Doctors conducting theclinical trial will start by giving very low dosesof the drug to the first patients and increasingthe dose for later groups of patients until sideeffects appear. Although doctors are hoping tohelp patients, the main purpose of a phase Istudy is to test the safety of the drug.

Phase II clinical trials: These are designed tosee if the drug works. Patients are usually giventhe highest dose that doesn’t cause severe sideeffects (determined from the phase I study)and closely observed for an effect on thecancer. The doctors will also look for sideeffects.

Phase III clinical trials: Phase III studiesinvolve large numbers of patients. Some phaseIII clinical trials may enroll thousands ofpatients. One group (the control group) willreceive the standard (most accepted) treat-ment. The other group will receive the newtreatment. Usually doctors study only 1 newtreatment to see if it works better than thestandard treatment, but sometimes they will

23

test 2 or 3. All patients in phase III studies areclosely watched. The study will be stopped ifthe side effects of the new treatment are toosevere or if one group has had much betterresults than the others.

If you are in a well-designed clinical trial, youwill receive excellent care. You will have a teamof experts looking at you and monitoring yourprogress very carefully. The study is especiallydesigned to pay close attention to you.

However, there are some risks. No one involvedin the study knows in advance whether thetreatment will work or exactly what sideeffects will occur. That is what the study isdesigned to discover. While most side effectswill disappear in time, some can be permanentor even life threatening. Keep in mind, though,that even standard treatments have sideeffects. Depending on many factors, you maydecide to enroll in a clinical trial.

Deciding to enter a clinical trial: Enrollmentin any clinical trial is completely up to you.Your doctors and nurses will explain the risksand possible benefits of the study to you indetail and will give you a form to read and signindicating your understanding of the studyand your desire to take part. This process isknown as giving your informed consent. Evenafter signing the form and after the clinicaltrial begins, you are free to leave the study atany time, for any reason. Taking part in thestudy will not prevent you from getting othermedical care you may need.

To find out more about clinical trials, ask yourcancer care team. Among the questions youshould ask are:

• What is the purpose of the study?

• What kinds of tests and treatments does thestudy involve?

• What does this treatment do?

• What is likely to happen in my case with, orwithout, this new research treatment?

• What are my other choices and their advan-tages and disadvantages?

• How could the study affect my daily life?

• What side effects can I expect from thestudy? Can the side effects be controlled?

• Will I have to be hospitalized? If so, howoften and for how long?

• Will the study cost me anything? Will any ofthe treatment be free?

• If I am harmed as a result of the research,what treatment would I be entitled to?

• What type of long-term follow-up care is partof the study?

• Has the treatment been used to treat othertypes of cancers?

You can get a list of current clinical trials bycalling the National Cancer Institute’s CancerInformation Service toll free at 1-800-4-CANCER or visiting the NCI clinical trials Websites for patients or health care professionals(cancer.gov).

Participating in a clinical trial may help youdirectly, and it may help other women withbreast cancer in the future. For these reasons,the NCCN and the ACS are committed to help-ing people with cancer learn more about thesestudies.

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25

Work-Up (Evaluation) and Treatment Guidelines

Decision TreesThe “decision trees”, or algorithms, on the following pages represent different stages of breast cancer. Each one shows you step-by-step how you and your doctor can arrive at the choices youneed to make about your treatment.

Keep in mind, this information is not meant to be used without the expertise of your own doctorwho is familiar with your situation, medical history, and personal preferences.

Participating in a clinical trial is an option for women at any stage of breast cancer. Taking partin a study does not prevent you from getting other medical care you may need.

The NCCN guidelines are updated as new significant data become available. To ensure you have the most recent version, consult the web sites of the ACS (www.cancer.org) or NCCN(www.nccn.org). You may also call the NCCN at 1-888-909-NCCN or the ACS at 1-800-ACS-2345for the most recent information on these guidelines or on cancer in general.

Stage 0 Lobular Carcinoma In SituThe work-up for lobular carcinoma in situ(LCIS) includes a complete medical historyand physical examination and diagnosticmammograms of both breasts to see whetherthere are any other abnormal areas in eitherbreast. Pathology review (a second opinion onexamination of the biopsy sample) is suggestedby NCCN to be certain you have LCIS and notan invasive cancer or a benign condition.

Generally, no treatment is given. Observation(careful follow-up without surgery) is the pre-ferred option for most women who are diag-

nosed with LCIS because their risk of develop-ing invasive cancer is low. Invasive cancers thatdo develop during observation of LCIS areusually not aggressive and tend to be easilytreated.

A preventive mastectomy of both breasts maybe an option for some women with LCIS whomay have a greater risk of developing invasivebreast cancer–for example, women with anextensive family history of breast cancer. Yourdoctor can help you decide whether to con-sider this treatment. You should also considergenetic counseling before deciding to have apreventive (prophylactic) mastectomy. After

26


Keep in mind that this information is not meant to be used without the expertise of your owndoctor, who is familiar with your situation, medical history, and personal preferences.

Participating in a clinical trial is an appropriate option for women at any stage of breast cancer.Taking part in a clinical trial does not prevent you from getting other medical care you may need.

Stage 0 Lobular car-cinoma in situ (LCIS) Observation

Stage Work-Up Treatment

• Medical history and physical exam

• Diagnostic mammograms (both breasts)

• Pathology review of biopsy sample

mastectomy, you can have breast reconstruc-tion right after surgery or later on.

Strategies for reducing your risk of breastcancer have become as important as methodsof detecting and treating the disease. There isevidence that tamoxifen, an antiestrogen drugthat has been used as hormone therapy forbreast cancer, can also lower your risk of devel-oping an invasive breast cancer after LCIS hasbeen diagnosed. When used in this situation,tamoxifen is taken daily by mouth for 5 years.Tamoxifen is not used if the woman has hadboth breasts removed.

If your doctor decides to just watch you as theprimary treatment, the follow-up for womenwith LCIS includes a medical history andphysical exam every 6–12 months for 5 years,and once a year thereafter. You should have amammogram every year. Because tamoxifenincreases endometrial cancer risk in post-menopausal women, women taking this drugshould have a pelvic exam each year andshould promptly report any abnormal uterinebleeding. These precautions are not needed ifthe uterus has been removed.

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Stage 0 Noninvasive Lobular Carcinoma In Situ (LCIS)

©2002 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society(ACS). All rights reserved. The information herein may not be reprinted in any form for commercialpurposes without the expressed written permission of the NCCN and the ACS. Single copies ofeach page may be reproduced for personal and non-commercial uses by the reader.

Risk Reduction Follow-Up

• Medical history and physical examevery 6–12 months for 5 years, thenonce every year

• Yearly mammogram unless there wasa double mastectomy

• Yearly pelvic exam for women takingtamoxifen

Counseling about taking tamox-ifen for 5 years

In special circumstances:Mastectomy of both breasts,with or without breastreconstruction

Widespread DCIS intwo or more areas

Excisional biopsy

Stage 0 Ductal Carcinoma In SituAs in LCIS, the work-up for ductal carcinomain situ (DCIS) involves a complete medical his-tory and physical examination. Diagnosticmammograms of both breasts should be per-formed to help estimate how far DCIS hasspread within the ducts of the breast and to

check whether the opposite breast containsany abnormal areas. The NCCN recommendsthat you get a second opinion by a pathologistto be certain that the cancer is DCIS ratherthan an invasive cancer or a benign condition.

If the mammogram, physical examination, orbiopsy results show that two or more areas of

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• Medical history and physical exam

• Diagnostic mammograms (bothbreasts)

• Second-opinion pathology reviewof biopsy sample

Stage 0 Ductal car-cinoma in situ(DCIS)

Stage Work-Up

the breast contain DCIS, mastectomy is thetreatment of choice.

If DCIS is present in only one area and nocancer is found at the edges of the first surgicalexcision (or, if necessary, after re-excision) –either a total mastectomy or a lumpectomyplus radiation therapy is suggested. Mastec-

tomy is recommended if the DCIS cannot becompletely removed by breast-conservingsurgery.

Mastectomy provides the most certain localcontrol of DCIS. But studies have shown thatwomen with DCIS who are treated with radia-tion after their lumpectomy live as long as

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Stage 0 Ductal Carcinoma In Situ (DCIS)


Lumpectomy followed byradiation

or

Total mastectomy withoutlymph node removal with orwithout breast reconstruction

Lumpectomy followed byradiation

or

Total mastectomy withlymph node removal withor without breast recon-struction

or

Lumpectomy alone

Margins*positive

Margins*negative

Treatment

*Margin means the normal tissuearound the tumor. Negative meansthere is no cancer in the margin.Positive means there is cancer.

If there is only one low-grade tumor smaller than0.5 cm (1/5 inch)

Total mastectomy withoutlymph node removal with orwithout breast reconstruction

those who have a mastectomy. After lumpec-tomy, a mammogram is suggested to ensurethat the entire tumor has been removed.

If a DCIS tumor is very small (less than a halfcm, or 1/5 inch), and is low-grade and lumpec-tomy is chosen, radiation may not always beneeded.

Women with DCIS who are treated with mas-tectomy do not need lymph nodes removed.

Also, these women have options for eitherimmediate or delayed breast reconstruction.The value of tamoxifen in women with DCISwho have had a mastectomy is less clear.Therefore they should discuss the risks andbenefits with their health care team.

Women with DCIS treated with breast-conserving therapy should strongly considertaking tamoxifen after their initial treatment.

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Risk reduction:

Counseling about taking tamoxifenfor 5 years to reduce cancer risk inother breast

Adjuvant treatment:

Consider tamoxifen for 5 years

Postoperative TreatmentPrimary Treatment

Lumpectomy with orwithout radiation

Mastectomy

This drug can lower the risk of developing aninvasive breast cancer after DCIS has beenremoved. It may also lower the risk of cancer inthe other breast.

Standard follow-up for women with DCISincludes a history and physical exam every 6months for 5 years, then every year thereafter.

They should have yearly mammograms.Because tamoxifen increases endometrialcancer risk, women taking this drug shouldhave a pelvic exam every year and shouldpromptly report any abnormal uterine bleed-ing. These precautions are not needed if theuterus was removed.

31

Stage 0 Ductal Carcinoma In Situ (DCIS) (continued)


Follow-Up

Medical history and physical examevery 6 months for 5 years, thenevery year

Mammogram every year

Pelvic exam every year for womentaking tamoxifen

Stage I, II, and Some Stage IIIABreast Cancers (T3, N1, M0)The guidelines for stages I and II and thosestage III tumors that are larger than 5 cm (2inches) with lymph nodes affected but notattached to each other recommend thefollowing:

• Complete medical history and physicalexamination

• Complete blood count, platelet count, andliver function tests

• Chest x-ray

• Diagnostic mammograms of both breasts

• Breast ultrasound and MRI if needed

• Pathology review

32




Primary (Local and Regional)Treatment

Stages I, II

and

only Stage IIIAwith tumorlarger than 5cm, withlymph nodeinvolvementbut the lymphnodes are notattached toeach other

• Medical history and physicalexam

• Blood counts and liver func-tion tests

• Chest x-ray

• Diagnostic mammograms(both breasts)

• Breast ultrasound and breastMRI if needed

• Pathology review of biopsysample

• Estrogen/progesteronereceptor and HER-2/neu testof tissue

• Bone scan (only if symptomsor tests suggest cancer hasspread to bones)

• HER-2/neu test

• Bone scan (optional forStage II)

• CT, MRI, or ultrasound ofabdomen for Stage III

Clinical Stage Work-Up

If tumor is larger than 2 cm, andbreast-conserving therapy is anoption, consider preoperativetherapy (see page 42)

Lumpectomy and removal ofunderarm lymph nodes followedby radiation therapy*

Mastectomy and removal ofunderarm nodes with or withoutbreast reconstruction

OR

OR

• Estrogen/progesterone-receptor tests tocheck whether the tumor is hormone-responsive

• HER-2/neu test.

If the patient is having bone pain or if certainblood test results are abnormal, a bone scanshould be done.

The treatment of breast cancer involves surgi-cal removal of the cancer. In most cases thismeans a lumpectomy, removing only the can-cer and some surrounding normal tissue (mar-gin). Lumpectomy is possible in most womenwith stage I or II breast cancer. Radiation to thebreast should follow lumpectomy.

33

Invasive Breast Cancer: Primary Treatment (Stages I, II, and Some IIIA)


Primary (Local and Regional) Treatment(Stage I, II, and Some IIIA)

After surgery and chemotherapy, radiation therapy given to the chest wall and above the collarbone area(supraclavicular lymph nodes); consider radiation therapyto lymph nodes next to the breastbone (internalmammary lymph nodes)

After surgery and chemotherapy, radiation therapy tothe chest wall. Consider radiation to collarbone area

After surgery and chemotherapy, consider radiationtherapy to the chest wall, collarbone area, and lymphnodes next to the breastbone

No radiation therapy

Cancer spread to 4 or morelymph nodes

Tumor that is larger than 5cm or positive margins

Cancer spread to 1, 2, or 3lymph nodes

Tumor smaller than 5 cmand no cancer spread tonodes

•Radiation after surgery should usually be given after any adjuvantchemotherapy except if chemo is CMF (see box, page 19) therapythen it may be given at the same time.

In some cases, a mastectomy is needed. Inchoosing lumpectomy versus mastectomy,women must understand that as long aslumpectomy can be done (based on the factorsthat follow), the chances of successful treat-ment and survival are the same with bothtreatments.

What factors would prevent a woman fromchoosing breast-conserving surgery?

• The patient has had radiation to the breastor chest wall

• The patient is pregnant

• The disease is in several areas of the breast

• There are suspicious areas of calcium spreadout in the breast

• Two separate incisions are needed to removethe disease

• The patient has a connective tissue diseasesuch as scleroderma

• The tumor is larger than 5 cm (about 2inches)

If a woman and her doctor choose a modifiedradical mastectomy as her primary treatment,the guidelines recommend postoperative

34


NOTES

radiation in certain instances. Post-surgeryradiation and chemotherapy should be usedwhen the cancer has spread to 4 or more lymphnodes, or if the tumor is larger than 5 cm orshows positive margins (that is, cancer cells atthe boundary around the tumor). Women withcancer metastasis in up to 3 lymph nodesshould consider radiation therapy given aftersurgery and chemotherapy.

Women who have not had a modified radicalmastectomy do not need radiation if:

• Their tumors are smaller than 5 cm

• The margins are not involved by cancer, and

• No cancer has spread to lymph nodes

In the past, women with stage I or II breastcancer received chemotherapy (based onlymph node involvement, tumor type, andtumor size) after surgery. Doctors now offersome women with larger tumors chemother-apy before surgery. Sometimes chemotherapycan shrink the tumor so that a lumpectomy ispossible when it otherwise would not havebeen.

35

Invasive Breast Cancer: Primary Treatment (Stages I, II, and Some IIIA) (continued)

NOTES

Axillary Lymph Node SurgeryIn addition to the surgery for the cancer in thebreast, surgery to remove lymph nodes underthe arm is sometimes done to provide staginginformation to guide further treatment.Lymph node surgery is usually done at thesame time as the breast surgery.

The standard surgery is to remove the fattytissue containing all the lymph nodes underthe armpit, and under the muscle. In a mastec-tomy, the lymph nodes are removed through

the same incision (cut in the skin). In alumpectomy, it is done through an incisionseparate from the lumpectomy incision.

A new procedure called sentinel lymph nodebiopsy may be substituted for removing all theunderarm lymph nodes in certain circum-stances. In this procedure, only the few lymphnodes most likely to contain cancer areremoved and checked for cancer. An average of3 lymph nodes are removed with sentinellymph node biopsy. If these lymph nodes do

36




Stages I and II

Stage Treatment

Sentinel node procedure can be doneif:

• There is only a single cancer

• The tumor is smaller than 5 cm (2inches)

• There has been no large previoussurgery on the breast

• There has been no previouschemotherapy or hormonal therapy

AND

There is a team of doctors experiencedin the sentinel node procedure*

No

Yes

*Team includes surgeon, radiologist, nuclearmedicine doctor, and pathologist. The teammust discuss the use of this procedure fortreatment decisions with the medical andradiation oncologist.

not contain cancer, then no further lymphnode surgery is performed. If these lymphnodes contain cancer, then the standard lymphnode surgery is done to determine how manyhave cancer, and to remove them.

The advantage of sentinel lymph node biopsy isthat there is less pain and discomfort with thesurgery, and less chance of developing armswelling called lymphedema than with fulllymph node removal. Sentinel lymph node

biopsy is not appropriate for all women. Itshould only be used if the team of doctors hasproven experience with the technique. In addi-tion, it is only appropriate for women withbreast tumors smaller than 5 cm, who have hadno previous chemotherapy or hormonal ther-apy. It is not appropriate when the lymphnodes are enlarged and hard on physical exam-ination and in women who have more than onecancer in the breast.

37

Axillary Lymph Node Surgery – Stages I and II


Sentinel nodemapping andexcision

Sentinel nodecontains nocancer

Sentinel nodecontains cancer

Sentinel nodenot identified

Lymph nodes areenlarged and canbe felt

Lymph nodes arenot felt to beenlarged

No further surgery

Removal of underarmlymph nodes

Removal of underarmlymph nodes

OR

Adjuvant (Additional) Treatment forStages I, II and Some IIIADecisions about adjuvant chemotherapy orhormonal therapy are based on the status ofthe lymph nodes in the armpit, the size of thecancer, and its appearance under a micro-

scope. If the nodes are negative (do not containany cancer cells) and the tumor measures ahalf centimeter or smaller, the woman needsno adjuvant (post-surgery) therapy. Womenwith lymph node-negative tubular, colloid,medullary, or adenoid cystic types of tumorsthat measure smaller than 1 cm (about 2/5

38




Adjuvant (Additional)Therapy

Stages I, II, andStage IIIA withtumor largerthan 5 cm (2 inches), but limited (unattached)lymph nodeinvolvement(after work-upand primarytreatment)

Stages I and II, nodenegative

All node positive

Stage Node Status

Adjuvant chemotherapy

Tumor smaller than 0.5 cm

Hormone receptor-negative

Hormone receptor-positive

Cancer type is: • tubular• colloid• typical medullary

Cancer type is:• invasive • ductal• invasive lobular• mixed

Tumor smaller than 1 cm

Tumor 1 cm or larger but smaller than 3 cm

Tumor 3 cm or larger

Tumor smaller than 1 cm with no unfavorable features*

Tumor 0.6 to 1 cm with 1 ormore unfavorable features*

Tumor larger than 1 cm

Tamoxifen for 5 years plusadjuvant chemotherapy

inch) also need no additional treatment. But ifsuch a tumor measures 1 to 2.9 cm in diameter,the guidelines state that patients and theirdoctors should consider adjuvant therapy; andif this type of tumor has grown to 3 cm orlarger, then the guidelines recommend adju-vant therapy.

In women without lymph node metastasis,NCCN recommends that when the tumor is

smaller than 1 cm and cancer is not present inthe blood and/or lymph vessels, no adjuvanttherapy be given. When the tumor measures0.6 to 1 cm and has one or more unfavorablefeatures, the doctor may recommend that thepatient consider adjuvant chemotherapy orhormonal therapy.

If the tumor has grown larger than 1 cm andhormone-receptor test results are negative, the

39

Invasive Breast Cancer: Adjuvant Treatment (Stages I, II, and Some IIIA)


No adjuvant therapy

No adjuvant therapy

Consider adjuvant therapy

Adjuvant therapy

No adjuvant therapy

Consider adjuvant therapy

Adjuvant chemotherapy

Tamoxifen for 5 years pluschemotherapy

Adjuvant (Additional) Therapy (Stages I, II, and Some IIIA)

Hormone receptor-negative

Hormone receptor-positive

*This means the cancer looks aggressive underthe microscope, has high HER-2/neu levels, oris hormone receptor-negative.

NCCN guidelines recommend adjuvant chemo-therapy. If the tumor is hormone receptor-positive, tamoxifen is given for 5 years inaddition to chemotherapy.

The guidelines recommend that patients withhormone receptor-negative tumors whosecancer has spread to their lymph nodes receiveadjuvant chemotherapy. Those with hormonereceptor-positive tumors should receive adju-vant chemotherapy plus tamoxifen for 5 years.(Follow-up care guidelines appear on page 48.)

The early results of a clinical trial have shownthat the aromatase inhibitor anastrozole pro-

vides better control of breast cancer and hasfewer side effects than tamoxifen in post-menopausal women with hormone-receptorpositive breast cancer. The follow-up of thisclinical trial is short, and so definitive conclu-sions cannot yet be made. Currently, anastro-zole may be an alternative option to tamoxifen.If you have been through menopause, youmight wish to discuss this with your healthcare team. Anastrozole is not effective in pre-menopausal woman, and tamoxifen remainsthe preferred hormone treatment for thesewomen.

40


NOTES

Adjuvant Chemotherapy OptionsLymph Node Negative Lymph Node Positive

CMF FAC, CAF, CEF

FAC, CAF AC with or without paclitaxel

AC A followed by CMFCMFEC

(refer to page 19 for specific names of drugs)

41

Invasive Breast Cancer: Adjuvant Treatment (Stages I, II, and Some IIIA) (continued)

NOTES

Preoperative Treatment for Stage IIand Stage IIIA Large Breast CancersPreoperative chemotherapy is an option thatallows some women who would otherwiseneed a mastectomy because of large tumors tohave breast-conserving treatment. Tumorsmay shrink enough during chemotherapy topermit a lumpectomy that completely removesthe main tumor and still keeps the size andshape of the breast.

The work-up recommended before startingpreoperative chemotherapy includes:


• Blood counts and blood chemistry tests

• Chest x-ray


• Breast ultrasound and MRI if needed

• Pathology review

• Estrogen/progesterone receptor tests

• HER-2/neu test.

42


Preoperative TreatmentWork-Up

Breast tumor largerthan 2 cm and breast-conserving treatmentis an option

Wants to preservebreast

Doesn’t want topreserve breast

Preoperative chemotherapy (3-4cycles of treatment that includesan anthracycline)

Treat as stage II with mastectomy option(See page 32-33)



See page 32

A bone scan is recommended for all stage IIIApatients and for stage II patients with symp-toms or blood test results suggesting distantmetastasis. It is optional for other women withstage II cancers. A CT, MRI, or ultrasoundexam of the abdomen is recommended forstage IIIA patients but not for stage II patients.

Preoperative chemotherapy for these womenshould include an anthracycline drug such asdoxorubicin or epirubicin. If this treatment issuccessful, lumpectomy and removal of under-

arm lymph nodes is the next step; otherwise, amastectomy is done along with removal ofunderarm lymph nodes. After mastectomy orlumpectomy, more chemotherapy may begiven. Chemotherapy given after lumpectomymay include a taxane, such as paclitaxel ordocetaxel. Tamoxifen is given for hormonereceptor positive tumors. Radiation therapy issuggested after this chemotherapy, with theexact areas treated depending on the type offirst surgery.

43

Preoperative Treatment for Stage II and Stage IIIA Large Breast Cancers

• Consider more chemotherapy

OR

• Tamoxifen if hormone receptor-positive

AND

• Radiation therapy to the breast and thearea above the collarbone and considerradiation to internal mammary lymphnodes (alongside sternum or breastbone)

Primary (Local) Treatment Adjuvant (Additional) Treatment

Tumor still toolarge forlumpectomy

Tumor shrinksenough forlumpectomy

Lumpectomy and removal ofunderarm lymph nodes

Mastectomy and removal ofunderarm nodes with orwithout reconstruction

• Consider more chemotherapy

OR

• Tamoxifen if hormone receptor-positive

AND

• Radiation therapy to the breast and thearea above the collarbone and considerradiation to internal mammary lymphnodes (alongside sternum or breastbone)


Treatment for Stages III and IVInvasive Breast CancerThe recommended work-up for all stage IIIbreast cancers includes:


• Blood counts and complete blood count,platelet count, chemical liver function tests

• Chest x-ray (to check for spread to the lungs)


• Breast ultrasound test (if necessary to fur-ther clarify findings)

44


All stage III(except stageIIIA with tumorlarger than 5 cmand spread tolymph nodesthat aren’tattached toeach other orsurrounding tissue)

• Medical history and physicalexamination

• Blood counts and chemistry tests

• Chest x-ray

• Diagnostic mammograms (bothbreasts)

• Breast ultrasound, if needed

• Pathology review of biopsy sample

• Pre-chemotherapy estrogen/progesterone receptor tests, HER-2/neu test

• Bone scan*

• CT, MRI, or ultrasound ofabdomen*

Clinical Stage Work-Up Preoperative Chemotherapy

Only lymph nodes above the collarboneinvolved on the same side as breast cancer

Cancer has spread elsewhere

Chemotherapy that includes ananthracycline with or withouttamoxifen



Stage IV

*Doctors do not agree on whether thesetests should be done. Your doctor may ormay not suggest these tests.

• Pathology review (second opinion on thebiopsy sample)

• Hormone-receptor tests of the biopsy sample

• HER-2/neu test (to help predict the responseto certain drugs).

In addition, the guidelines recommend a bonescan and CT, MRI, or ultrasound scan of theabdomen.

Women with stage IIIA tumors larger than 5cm that have spread to lymph nodes that arenot attached to one another or surroundingtissues have three options that have beendescribed in the previous algorithms.

Women with stage IV tumors have alreadygone through a work-up. Stage IV cancer canmean distant metastasis of the cancer. But italso can mean the only metastasis away from

45

Treatment for Stage III and Stage IVInvasive Breast Cancer

Follow decision tree for recurrence/Stage IV(See page 52)

Primary Treatment Adjuvant Treatment

Response

No response

Consider additionalchemotherapy and/orpreoperative radiation

Response

No response

Additional chemotherapyand tamoxifen for 5 years ifhormone-receptor positiveor hormone-receptor statusis unknown

Treatment to be discussed with doctor

• Mastectomy and removal of under-arm lymphnodes, radiation to chest wall, area abovecollarbone and internal mammary nodes (nextto breastbone) if they are enlarged with orwithout delayed breast reconstruction

OR

• Consider lumpectomy and removal of under-arm lymph nodes, radiation to chest wall, areaabove collarbone and internal mammary nodes(next to breastbone) if they are enlarged

OR

• Radiation only to the breast and lymph nodes


the breast and underarm lymph nodes is in thelymph nodes above the collarbone on the sameside as the breast cancer.

The treatment for stage III and stage IV withmetastasis only to lymph nodes above the col-larbone (supraclavicular lymph nodes) startswith chemotherapy, with or without tamoxifendepending on the hormone-receptor status ofthe cancer. Patients whose tumors shrinkenough to be surgically removed have threeoptions:

• Modified radical mastectomy (with or with-out reconstruction) and removal of under-arm lymph nodes, followed by radiationtherapy to the chest wall, supraclavicularlymph nodes, and, if they are enlarged, inter-nal mammary (inside the chest, where theribs meet the sternum or breastbone) lymphnodes

• Lumpectomy with lymph node removal,followed by radiation therapy to the breastand other areas

46


NOTES

• Radiation to the breast and lymph nodes.Among breast cancer specialists, this optionremains controversial.

For these patients the guidelines recommendadding more chemotherapy after surgery. If thehormone-receptor status is positive orunknown, the guidelines recommend tamox-ifen for 5 years.

Women with stage IIIA or IIIB breast cancerwho do not respond to one chemotherapy reg-imen may be given another chemotherapyregimen with or without radiation. If theyrespond, they can be treated as outlined withstandard breast cancer surgery. If they do notrespond, they should discuss treatment withtheir doctor.

47

Treatment for Stage III and Stage IVInvasive Breast Cancer (continued)

NOTES

Follow-up of Women with Stages I,II, or III Breast Cancer and Work-Upand Treatment of RecurrenceRoutine follow-up for all patients who havehad invasive breast cancer includes the follow-ing: a medical history and physical exam every4–6 months for 5 years, then once a year.

Women who have had a lumpectomy shouldhave a mammogram of the treated breast 6months after radiation therapy, and thenmammograms of both breasts every year.

Women who have had a mastectomy shouldhave an annual mammogram of the remainingbreast after the surgery. Because tamoxifenincreases a woman’s risk of developing cancerof the endometrium (lining of the upper part ofthe uterus), women taking this drug shouldhave an annual pelvic exam and shouldpromptly report any abnormal uterine bleed-ing to their doctor.

48


Local disease(cancer returned tobreast, underarmlymph nodes, ornearby tissues)

Systemic disease(cancer spread to distant organs)

• Medical history andphysical examevery 4–6 monthsfor 5 years, thenevery year

• Mammogram ofboth or remainingbreast every year.For lumpectomypatients, the firstone should be 6months after radia-tion is completed

• Women takingtamoxifen: pelvicexam every year ifthe uterus ispresent

• Medical history andphysical examination

• Blood counts and liverfunction tests

• Chest x-ray

• Bone scan

• Consider x-rays ofbones

• Consider CT or MRI ofchest and abdomen

• Biopsy of suspectedrecurrence, if possible

• HER-2/neu testing ifnot done before

Follow-Up Work-Up for Stage IV or SuspectedRecurrence

Stages I, IIand III



Recurrent Breast CancerWork-up for a suspected recurrence of breastcancer includes:


• Complete blood counts

• Liver function tests

• Chest x-ray

• Bone scan

Weight-bearing bones that are painful orshowed abnormalities on the bone scan shouldalso be x-rayed, and CT or MRI scans of the

49

Follow-up of Women with Stages I, II, and III Breast Cancer,and Work-up and Treatment of Recurrence

If possible, remove cancer and followwith radiation therapy if none givenbefore

Treatment of Recurrence

Same treatment as for Stage IVcancer (see page 52)

For patients first treatedwith mastectomy

For patients first treatedwith lumpectomy andradiation therapy

Consider systemic therapy

Mastectomy


abdomen, chest, or head should be done ifthere are symptoms affecting these areas.

• A biopsy should be done to confirm the firstrecurrence whenever possible.

• If HER-2/neu testing was not done on theoriginal cancer, it should be done if possible.

A recurrence may be local, meaning thatcancer has returned to the breast, underarm

lymph nodes, or nearby tissues, or it may besystemic, which means that cancer has spreadto distant organs. If the recurrence is local, andthe woman was first treated with mastectomy,the cancer should be removed by surgery (ifpossible with limited surgery). The area of therecurrence and surrounding tissues shouldreceive radiation therapy if it has not beengiven before. If the cancer cannot be removed

50


NOTES

by surgery, the woman should have radiationtherapy if it was not given before. In either case,the NCCN recommends considering chemo-therapy and/or hormonal therapy after theradiation treatment.

If the woman was first treated with lumpec-tomy and radiation, a local recurrence shouldbe treated with a mastectomy, and then con-

sideration of chemotherapy and/or hormonaltherapy.

If the recurrence is systemic, then the treat-ment should be the same as for patients withstage IV breast cancer.

51

Follow-up of Women with Stages I, II, and III Breast Cancer,and Work-up and Treatment of Recurrence (continued)

NOTES

Stage IV or Systemic RecurrenceVery few women with newly diagnosed breastcancer have distant metastases (stage IV).With one exception, those who do are treatedthe same as patients with systemic recurrenceof breast cancer. Women with stage IV diseasewhose cancer has spread no further than supr-

aclavicular (above the collarbone on the sameside as the cancer) lymph nodes should receivethe same treatment as women with stage IIIbreast cancer (see page 44).

The work-up for patients with stage IV breastcancer is the same as that listed on page 48.

52


Cancer is hormonereceptor-positive and no vital organsinvolved

Cancer is hormonereceptor-negative orhas spread to internalorgans causingsymptoms

Antiestrogen therapy within the last year

No antiestrogen therapy within last year

HER-2/neu presentin large amounts

HER-2/neu not present in largeamounts

Stage IV

or

Systemic recurrence of breast cancer

Stage

Postmenopausal

Premenopausal



For patients whose cancers are estrogen/prog-esterone receptor-positive and no vital organis heavily involved with cancer, hormone ther-apy is recommended. If a woman has notreceived an antiestrogen (such as tamoxifen ortoremifene) within the last year, and she is pre-menopausal, an antiestrogen with or without

luteinizing hormone-releasing hormone(LHRH) agonist is recommended. If she ispost- menopausal, antiestrogens or an aroma-tase inhibitor such as anastrozole or letrozolecan be given. If the woman has received anantiestrogen in the last year, the NCCN recom-mends the use of other hormonal therapies,

53

Stage IV (Metastatic) or Systemic Recurrence of Breast Cancer


No response after 2 differenthormone regimens

• Supportive care, focused onrelieving symptoms or

• Clinical trials

Treatment

Try different hormonal therapy

No response after 2 different chemotherapy regimens (given in a row)or patient is very weak and spending most time in bed

Anastrozole or letro-zole or an antiestrogen

Antiestrogen with orwithout LHRH agonist

Trastuzumab with or without chemotherapy

Chemotherapy

Chemotherapy

such as progestins, aromatase inhibitors (inpostmenopausal women) androgens, high-dose estrogens, or (in premenopausal women)removal or radiation treatment of the ovaries.

Women whose tumors shrink or stop growingshould continue to receive hormonal therapy.If the disease progresses again, a different hor-monal therapy should be tried.

If the cancer leads to a vital organ or is hormone receptor-negative or a patientbecomes unresponsive to hormonal therapy,chemotherapy is recommended. When the pri-mary chemotherapy regimen no longer works,another chemotherapy protocol should betried. If tests of the tumor tissue show highlevels of HER-2/neu, giving trastuzumab alone

or along with chemotherapy is an option.Eventually, the tumor will develop resistanceto each chemotherapy drug. In that case, achemotherapy regimen may be given followedby a different regimen. If two or more differentchemotherapy regimens have no effect on thetumor, supportive care focused on relievingsymptoms or a clinical trial may be a betteroption than more chemotherapy.

If there are signs that the cancer has spread tothe bones and are weakened, a bisphosphonate(pamidronate or zoledronate ) should be given.These help strengthen the bones.

Treatment may also depend on the site of dis-tant recurrence or metastasis. For example,when there is spread to the brain, spinal cord,

54


NOTES

or membranes covering the brain and spinalcord, methotrexate may be given directly intothe spinal fluid, or the metastasis can betreated with radiation therapy. Painful bone

metastases can be treated with radiation ther-apy. Fluid buildup around the lungs or heartcan be treated by draining the fluid and put-ting chemotherapy drugs into the space.

55

Stage IV (Metastatic) or Systemic Recurrence of Breast Cancer (continued)

Preferred Chemotherapy for Recurrent or Metastatic Breast Cancer

Preferred first-line chemotherapy

• Anthracycline-based, taxane or CMF

Preferred second-line chemotherapy

• If anthracycline is given first, then CMF or taxane

• If taxane is given first, then anthracycline-based or CMF

• Other possible agents include capecitabine, vinorelbine, gemcitabine, mitoxantrone, and

platinum compounds

NOTES

56

Adjuvant therapyTreatment that is added to increase the effec-tiveness of a primary therapy. It usually refersto hormonal therapy, chemotherapy, or radia-tion added after surgery to kill any cancer cellsstill remaining and increase the chances ofcuring the disease or keeping it in check.

AntiestrogenA substance (for example, the drug tamoxifen)that blocks the effects of estrogen on tumors.Antiestrogens are used to treat breast cancersthat depend on estrogen for growth.

Aromatase inhibitorsDrugs that block production of estrogens by the adrenal gland. They are used to treathormone-sensitive breast cancer in post-menopausal women. These include anastro-zole, letrozole, and exemestane.

Axillary dissectionA surgical procedure in which the lymph nodesin the armpit (axillary nodes) are removed andexamined to find out if breast cancer hasspread to those nodes and to remove any can-cerous lymph nodes.

BiopsyRemoval of a piece of tissue for examinationunder a microscope to see whether cancer cells are present.

BisphosphonatesDrugs that help strengthen bones weakened bycancer by encouraging the deposition of cal-cium. These include pamidronate and zole-dronate.

Breast-conserving therapySurgery to remove a breast cancer and a smallamount of benign tissue around the cancer,without removing any other part of the breast.This procedure is also called lumpectomy, seg-mental excision, or limited breast surgery. Themethod may require an axillary dissection andusually requires radiation therapy in additionto the breast conservation surgery.

Breast reconstructionSurgery that rebuilds the breast contour aftermastectomy. A breast implant or the woman’sown tissue provides the contour. If desired, thenipple and areola may also be re-created.Reconstruction can be done at the time ofmastectomy or any time later.

Carcinoma in situAn early stage of cancer, in which the tumor isstill only in the structures of the organ where itfirst developed, and the disease does notinvade other parts of the organ or spread todistant sites. Most in situ carcinomas arehighly curable.

Glossary

ChemotherapyTreatment with drugs to destroy cancer cells.Chemotherapy is often used in addition to sur-gery or radiation to treat cancer when metas-tasis is proven or suspected, when the cancerhas come back (recurred), or when there is astrong likelihood that the cancer could recur.

Clinical stageDescribes the extent of cancer present basedon results of diagnostic tests and the physicalexamination.

CystA fluid-filled mass that is usually benign. Thefluid can be removed for analysis.

Diagnostic mammogramA screening mammogram is performed onwomen with no evidence of lumps or othersymptoms. This includes two x-ray views ofeach breast (top to bottom; side-to-side). Adiagnostic mammogram includes additional x-ray views of areas of concern found on physicalexamination or on the screening mammogramto provide more information about the sizeand character of the abnormality.

DuctA hollow passage for gland secretions. In thebreast, a passage through which milk passesfrom the lobule (which makes the milk) to thenipple. These ducts are the starting point formost breast cancers.

Ductal carcinoma in situThe most common type of noninvasive breastcancer. Cancer cells have not spread beyondthe ducts.

EstrogenA female sex hormone produced primarily bythe ovaries, and in smaller amounts by theadrenal gland. In breast cancer, estrogen maypromote the growth of cancer cells.

FibroadenomaA type of benign breast tumor composed offibrous tissue and glandular tissue. On clinicalexamination or breast self-examination, it usu-ally feels like a firm, round, smooth lump.These usually occur in young women.

Fibrocystic changesA term that describes certain benign changesin the breast; also called fibrocystic disease.Symptoms of this condition are breast swellingor pain. The breast often feel lumpy or nodular.Because these signs sometimes mimic breastcancer, diagnostic mammography or ultra-sound or even a biopsy may be needed to showthat there is no cancer.

FibrosisFormation of fibrous (scar-like) tissue. Thiscan occur anywhere in the body.

GradeCancer cells are graded using numbers 1 to 3by how much they look like normal cells. Grade1 (also called well-differentiated) means thecancer cells look like the normal cells, grade 3(poorly differentiated) cancer cells do not looklike normal cells at all. Grade 1 cancers aren’tconsidered aggressive; in other words, theygrow more slowly and metastasize slower.Grade 3 cancers are more likely to grow fasterand metastasize. A cancer’s grade along withits stage is used to determine treatment.

57

HER-2/neuA gene that produces a type of receptor thathelps cells grow. Breast cancer cells with toomany HER-2/neu receptors tend to be fastgrowing and may respond to treatment withan antibody called trastuzumab.

HormoneA chemical substance released into the body bythe glands, such as the thyroid, adrenal, orovaries. The substance travels through thebloodstream and sets in motion various bodyfunctions. For example, prolactin, which isproduced in the pituitary gland, begins andsustains the production of milk in the breastafter childbirth.

Hormone receptor assayA test to see whether a breast tumor is likely tobe affected by hormones or if it can be treatedwith hormones.

Hormone therapyTreatment with hormones, drugs that interferewith hormone production or hormone action,or surgical removal of hormone-producingglands to kill cancer cells or slow their growth.The most common hormonal therapy forbreast cancer is the drug tamoxifen. Other hor-monal therapies include megestrol, aromataseinhibitors, androgens and surgical removal ofthe ovaries (oophorectomy).

Internal mammary lymph nodesLymph nodes located inside the chest, next tothe junction of the sternum (breastbone) andthe ribs.

Intraductal papillomasSmall, finger-like, polyp-like, noncancerousgrowths in the breast ducts that may cause abloody nipple discharge. These are most oftenfound in women 45 to 50 years of age. Whenmany papillomas exist, breast cancer risk isslightly increased.

Luteinizing hormone-releasinghormone (LHRH agonist)LHRH is a hormone produced by the hypothal-amus, a tiny gland in the brain. The LHRHagonist is a man-made hormone that blocksthe action of other hormones in the body.

Lobular carcinoma in situAlso called lobular neoplasia. Cancer that hasnot spread beyond the lobules. The lobules arethe milk-producing parts of the breast at thedistant end of the ducts.

LumpectomySurgery to remove the breast tumor and asmall amount of surrounding normal tissue.

Lymph nodesSmall bean-shaped collections of immune sys-tem tissue such as lymphocytes, located alonglymphatic vessels. They remove waste and flu-ids from lymph and help fight infections. Alsocalled lymph glands.

LymphedemaAn infrequent complication after breast cancertreatment. Swelling in the arm caused byexcess fluid that collects after lymph nodesand vessels are removed by surgery or treatedby radiation.

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MastectomyRemoval of the entire breast. In a simple ortotal mastectomy surgeons do not cut awayany lymph nodes or muscle tissue; in a modi-fied radical mastectomy, surgeons remove thebreast and some armpit lymph nodes; in a rad-ical mastectomy (now rarely performed) sur-geons remove the breast, armpit lymph nodes,and chest wall muscles under the breast.

MenopauseThe time in a woman’s life when monthlycycles of menstruation cease forever and thelevel of hormones produced by the ovariesdecreases. Menopause usually occurs in thelate 40s or early 50s, but it can also be causedby surgical removal of both ovaries (oophorec-tomy) or by chemotherapy, which oftendestroys ovarian function.

MetastasisThe spread of cancer cells to distant areas ofthe body by way of the lymph system or blood-stream.

Preoperative therapySystemic therapy, such as chemotherapy orhormone therapy, given before surgery.Preoperative therapy can shrink some breastcancers, so that surgical removal can beaccomplished with a less extensive operationthat would otherwise be needed.

Node statusIndicates whether a breast cancer has spread(node positive) or has not spread (node nega-tive) to lymph nodes in the armpit (axillarynodes). The number and site of positive axil-lary nodes can help predict the risk of cancerrecurrence.

OophorectomySurgery to remove the ovaries.

OvaryReproductive organ in the female pelvis.Normally a woman has two ovaries. They con-tain the eggs (ova) that, when joined withsperm, result in pregnancy. Ovaries also pro-duce estrogen.

Pathologic stageDescribes the extent of cancer present basedon surgical removal and examination of tissue.

ProgesteroneA female sex hormone released by the ovariesduring every menstrual cycle to prepare theuterus for pregnancy and the breasts for milkproduction (lactation).

PrognosisA prediction of the course of disease; the out-look for the cure of the patient. For example,women with breast cancer that was detectedearly and received prompt treatment have agood prognosis.

Sentinel node biopsyIn a sentinel lymph node biopsy, the surgeoninjects a radioactive substance and/or blue dyeinto the area around the tumor. Lymphatic ves-sels carry these materials to the sentinel lymphnode (also called the sentinel node). The doc-tor can see the blue dye or detect the radioac-tivity (with a Geiger counter) in the sentinelnode, which is cut out and examined. If thesentinel node contains cancer, more axillarylymph nodes are removed. But if it is free ofcancer, the patient can avoid additional axil-lary surgery and its potential side effects.

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StageIndicates how far a cancer has spread.

Stereotactic needle biopsyA method of needle biopsy that is useful insome cases in which calcifications or a masscan be seen on mammogram but cannot belocated by touch. Computerized equipmentmaps the location of the mass, and this is usedas a guide for the placement of the needle.

Supportive careMeasures taken to relieve symptoms andimprove quality of life, but not expected todestroy the cancer. Pain medication is anexample of supportive care.

Supraclavicular lymph nodesLymph nodes located in the area above theclavicle (collarbone).

Systemic therapyTreatment that reaches and affects cellsthroughout the body; for example, chemo-therapy.

TamoxifenThis drug blocks the effects of estrogen onmany organs, such as the breast. Blockingestrogen is desirable in some cases of breastcancer because estrogen promotes theirgrowth. Recent research suggests that tamox-ifen may lower the risk of developing breastcancer in women with certain risk factors.

ToremifeneAnother anti-estrogen.

UltrasoundHigh-frequency sound waves used to produceimages of the breast.

For a more comprehensive glossary, you mayaccess the ACS Web site at www.cancer.org.

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Current ACS-NCCN Treatment Guidelines for PatientsBreast Cancer Treatment Guidelines for Patients

Breast Cancer Treatment Guidelines for Patients (Spanish)

Cancer Pain Treatment Guidelines for Patients

Cancer Pain Treatment Guidelines for Patients (Spanish)

Cancer-Related Fatigue Treatment Guidelines for Patients

Cancer-Related Fatigue Treatment Guidelines for Patients (Spanish)

Colon and Rectal Cancer Treatment Guidelines for Patients

Colon and Rectal Cancer Treatment Guidelines for Patients (Spanish)

Fever and Neutropenia Treatment Guidelines for Patients with Cancer

Lung Cancer Treatment Guidelines for Patients

Lung Cancer Treatment Guidelines for Patients (Spanish)

Melanoma Treatment Guidelines for Patients

Nausea and Vomiting Treatment Guidelines for Patients with Cancer

Nausea and Vomiting Treatment Guidelines for Patients with Cancer (Spanish)

Ovarian Cancer Treatment Guidelines for Patients

Prostate Cancer Treatment Guidelines for Patients

Prostate Cancer Treatment Guidelines for Patients (Spanish)

Terri Ades, MS, APRN-BC, AOCNAmerican Cancer SocietyHealth Content Products

Robert W. Carlson, MDStanford Hospital and Clinics

Stephen B. Edge, MDRoswell Park Cancer Institute

Herman Kattlove, MDAmerican Cancer SocietyHealth Content Products

Joan McClure, MSNational Comprehensive CancerNetwork

Eric P. Winer, MDDana Farber Cancer Institute

Mary-Lou SmithY-ME National Breast CancerOrganization

Dia TaylorPatient Information SpecialistNational Comprehensive Cancer Network

Rodger Winn, MDUniversity of Texas M.D. Anderson Cancer Center

The Breast Cancer Treatment Guidelines for Patients were developed by a diverse group of expertsand were based on the NCCN clinical practice guidelines. These patient guidelines were trans-lated, reviewed, and published with help from the following individuals:

The original NCCN Breast Cancer Clinical Practice Guidelines were developed by the followingNCCN Panel Members:

Benjamin O. Anderson, MDUniversity of Washington MedicalCenter

William Bensinger, MDFred Hutchinson CancerResearch Center

Robert W. Carlson, MDStanford Hospital and Clinics

Charles Cox, MDH. Lee Moffitt Cancer Center andResearch Institute at theUniversity of South Florida

Stephen B. Edge, MDRoswell Park Cancer Institute

William B. Farrar, MDArthur G. James Cancer Hospital& Richard J. Solove ResearchInstitute at Ohio State University

Lori J. Goldstein, MDFox Chase Cancer Center

William Gradishar, MDRobert H. Lurie ComprehensiveCancer Center of NorthwesternUniversity

Beryl McCormick, MDMemorial Sloan-Kettering Cancer Center

Lisle M. Nabell, MDUniversity of Alabama atBirmingham ComprehensiveCancer Center

Lori J. Pierce, MDUniversity of MichiganComprehensive Cancer Center

Elizabeth Reed, MDUNMC Eppley Cancer Center at the University of NebraskaMedical Center

Samuel M. Silver, MDUniversity of MichiganComprehensive Cancer Center

Mary Lou SmithY-ME National Breast CancerOrganization

George Somlo, MDCity of Hope National MedicalCenter

Richard Theriault, DO, MBAUniversity of Texas M.D. Anderson Cancer Center

John Ward, MDHuntsman Cancer Institute at theUniversity of Utah

Eric Winer, MDDana-Farber Cancer Institute

Rodger Winn, MDNCCN Guidelines SteeringCommittee

Antonioi C. Wolff, MDThe Sidney KimmelComprehensive Cancer Center of Johns Hopkins

©2002, American Cancer Society, Inc. 99-(Rev. 08/02)-80M-No.9405.00-HCP

1.800.ACS.2345 www.cancer.org

Hope.Progress.Answers.®

1.888.909.NCCNwww.nccn.org

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