Breast Cancer Treatment: Breast Cancer Treatment: An Evidence-based ReviewAn Evidence-based Review

Judith Luce, M.D.Judith Luce, M.D.

Patient OnePatient One

Your 45 yo patient had her first screening Your 45 yo patient had her first screening mammogram and was found to have mammogram and was found to have abnormal calcificationsabnormal calcifications

An ultrasound guided core biopsy was An ultrasound guided core biopsy was performed and show DCIS (ductal performed and show DCIS (ductal carcinoma in situ). carcinoma in situ).

What do you tell her about treatment?What do you tell her about treatment? What about life expectancy?What about life expectancy?

Ductal Carcinoma In Situ: What is the Risk?Ductal Carcinoma In Situ: What is the Risk?

DCIS is not invasive cancerDCIS is not invasive cancer: however it : however it can recur in the breast as invasive cancer can recur in the breast as invasive cancer about half the timeabout half the time

Recurrence riskRecurrence risk is dependent on is dependent on Age of the patient at diagnosis Age of the patient at diagnosis Histology of the DCIS:Histology of the DCIS:

• Comedonecrosis, high grade are risk factorsComedonecrosis, high grade are risk factors Extent of disease: larger=higher riskExtent of disease: larger=higher risk Extent of resection: negative marginsExtent of resection: negative margins

Age Affects DCIS RecurrenceAge Affects DCIS Recurrence

Silverman, Buchanan Breast, 2003

Treatment Options for DCISTreatment Options for DCIS Do nothing. Lifetime risk of Do nothing. Lifetime risk of invasiveinvasive cancer ranges from cancer ranges from

<10 to >50%. May be a choice for small low grade DCIS <10 to >50%. May be a choice for small low grade DCIS in older ptsin older pts

Remove all of the DCISRemove all of the DCIS Lumpectomy if feasibleLumpectomy if feasible Mastectomy if not: lowest odds of recurrenceMastectomy if not: lowest odds of recurrence

Add radiation to the breastAdd radiation to the breast Reduces recurrence risk by at least 50%Reduces recurrence risk by at least 50% No real risk of lymphedema; other risk sameNo real risk of lymphedema; other risk same

Add hormone therapyAdd hormone therapy Check for ER positivityCheck for ER positivity Reduces risk by about 20%Reduces risk by about 20% ““Usual” duration five yearsUsual” duration five years

Patient TwoPatient Two

A 55 yo diabetic woman presents with a A 55 yo diabetic woman presents with a small mass in her LUOQ. The FNA is small mass in her LUOQ. The FNA is “ductal carcinoma”. You can’t feel any “ductal carcinoma”. You can’t feel any axillary masses, and the mass itself is axillary masses, and the mass itself is about 4 cm. She’s frantic.about 4 cm. She’s frantic.

Should you do a staging workup?Should you do a staging workup? What do you tell her about the initial What do you tell her about the initial

treatment?treatment? What do you tell her about prognosis?What do you tell her about prognosis?

Assessing the Risk of Invasive Assessing the Risk of Invasive Breast Cancer: StagingBreast Cancer: Staging

Spread of breast cancer to adjacent lymph Spread of breast cancer to adjacent lymph nodes indicates high risk of distant spread of nodes indicates high risk of distant spread of cancercancer If no further therapy, 50% or more will recur with If no further therapy, 50% or more will recur with

metastatic cancermetastatic cancer

Size of tumor indicates risk of relapse: higher Size of tumor indicates risk of relapse: higher “T” stage indicates higher risk“T” stage indicates higher risk

Certain subtypes are higher risk:Certain subtypes are higher risk: Inflammatory breast cancer very highInflammatory breast cancer very high Tubular, medullary carcinomas very lowTubular, medullary carcinomas very low

Assessing the Risk of Diagnosed Assessing the Risk of Diagnosed Breast Cancer: StagingBreast Cancer: Staging

Staging is performed surgically:Staging is performed surgically: Removal of entire massRemoval of entire mass Sampling of lymph nodes—sentinel nodeSampling of lymph nodes—sentinel node

Higher risk patients staged withHigher risk patients staged with CT scans of abdomen and chestCT scans of abdomen and chest Bone scanBone scan Little role: brain scan, PET scanLittle role: brain scan, PET scan

Selection of Adjuvant Therapy for Invasive Selection of Adjuvant Therapy for Invasive Breast Cancer: a Risk-Benefit EquationBreast Cancer: a Risk-Benefit Equation

Prognostic factors: what is the risk of relapse?Prognostic factors: what is the risk of relapse? Patient characteristics: age, menopause, racePatient characteristics: age, menopause, race Disease characteristics: size, histology, nodesDisease characteristics: size, histology, nodes Biomarkers: ER/PR, growth fraction, Her2/neu, OncotypeBiomarkers: ER/PR, growth fraction, Her2/neu, Oncotype

Predictive factors: what will affect the choice of therapy?Predictive factors: what will affect the choice of therapy? Patient characteristics: age, comorbid illness, performance Patient characteristics: age, comorbid illness, performance

statusstatus Biomarkers: ER/PR, Her2/neu, Oncotype, possibly growth Biomarkers: ER/PR, Her2/neu, Oncotype, possibly growth

fractionfraction

Risk/benefit: will the absolute magnitude of the benefit Risk/benefit: will the absolute magnitude of the benefit exceed the long term risks?exceed the long term risks?

Surgery for Invasive Breast CancerSurgery for Invasive Breast Cancer

Lumpectomy +radiation therapy = mastectomyLumpectomy +radiation therapy = mastectomy Slight difference in local recurrence rate, esp younger womenSlight difference in local recurrence rate, esp younger women Who is a lumpectomy candidate?Who is a lumpectomy candidate?

• Woman wishes to preserve breast, willing to get radiationWoman wishes to preserve breast, willing to get radiation

• Lump less than 5 cm diameter, mobile, not in centerLump less than 5 cm diameter, mobile, not in center

• Breast would look acceptable after resectionBreast would look acceptable after resection

• Margins must be clear of both invasive and in situ cancerMargins must be clear of both invasive and in situ cancer

• No other suspicious masses in breastNo other suspicious masses in breast

• No inflammatory breast cancerNo inflammatory breast cancer

New developments: core biopsies, laser removalNew developments: core biopsies, laser removal• need to demonstrate completeness of excisionneed to demonstrate completeness of excision

Breast Surgery: Sentinel Node BiopsyBreast Surgery: Sentinel Node Biopsyfor Staging of the Axillary Nodesfor Staging of the Axillary Nodes

What is it? Radionuclide and dye-assisted What is it? Radionuclide and dye-assisted identification of the first node area, local bxidentification of the first node area, local bx

If nodes negative and sampler proficient, then If nodes negative and sampler proficient, then predicts negative axillary dissectionpredicts negative axillary dissection

No need for axillary dissection if negative—spares No need for axillary dissection if negative—spares patient the risk of lymphedemapatient the risk of lymphedema

No need to do this if mastectomy planned, if high No need to do this if mastectomy planned, if high likelihood of positive nodes, if tail of breast involved, if likelihood of positive nodes, if tail of breast involved, if going to treat an older woman with adjuvant going to treat an older woman with adjuvant Tamoxifen anywayTamoxifen anyway

Costlier, more time- and labor-intensiveCostlier, more time- and labor-intensive

Patient Two….Patient Two….

She comes back to ask your advice about She comes back to ask your advice about her surgical choices—mastectomy and her surgical choices—mastectomy and reconstruction versus lumpectomy. She reconstruction versus lumpectomy. She says she’s “scared” of radiation.says she’s “scared” of radiation.

What are the pros and cons of the two What are the pros and cons of the two approaches?approaches?

What are her patient risk factors for one or What are her patient risk factors for one or the other?the other?

Breast ReconstructionBreast Reconstruction for Women with Mastectomy for Women with Mastectomy

Tissue reconstruction: use of autologous flaps for Tissue reconstruction: use of autologous flaps for reconstructionreconstruction

Abdominal flaps “TRAM” flap—rectus abdominisAbdominal flaps “TRAM” flap—rectus abdominis Latissimus dorsi flaps Latissimus dorsi flaps Free flaps: DIEP flap—require vascular anastomosisFree flaps: DIEP flap—require vascular anastomosis Can be done any time; Calif law requires insurance to cover Can be done any time; Calif law requires insurance to cover

cost including contralateral reductions, mastopexycost including contralateral reductions, mastopexy

Implants: best evidence suggests that silicone is Implants: best evidence suggests that silicone is actually safe; still are problems with any implantactually safe; still are problems with any implant

Puncture—forms intense inflammatory reaction and more Puncture—forms intense inflammatory reaction and more lumps if silicone, collapses if saline. Usually retropectoral, lumps if silicone, collapses if saline. Usually retropectoral, so problems less vs augmentationso problems less vs augmentation

““Capsule” formation—alters shape, consistencyCapsule” formation—alters shape, consistency

Radiation Therapy for Radiation Therapy for Primary Invasive Breast CancerPrimary Invasive Breast Cancer

As consolidation for lumpectomy patientsAs consolidation for lumpectomy patients Small effect on survival —1-2%?Small effect on survival —1-2%? Affects breast outcome: 30+% risk of local failure Affects breast outcome: 30+% risk of local failure

in younger women without XRTin younger women without XRT May not be necessary in oldest women: risk of May not be necessary in oldest women: risk of

local failure with Tamoxifen, over 70, less than 5% local failure with Tamoxifen, over 70, less than 5% in studiesin studies

After mastectomy for high risk patientsAfter mastectomy for high risk patients Large tumor, inflammatory, bulky nodesLarge tumor, inflammatory, bulky nodes Controversial impact on survival (see figure)Controversial impact on survival (see figure)

Long Term Hormone Therapy EffectsLong Term Hormone Therapy Effects

Tamoxifen effects better researchedTamoxifen effects better researched Tamoxifen does not cause menopause, but it Tamoxifen does not cause menopause, but it

definitely increases the symptoms of menopause—definitely increases the symptoms of menopause—most common reason women stopmost common reason women stop

Serious risks due to agonist effects: Serious risks due to agonist effects: thrombosis (strongly age-related, includes stroke, MI, PE, thrombosis (strongly age-related, includes stroke, MI, PE,

DVT) DVT) endometrial Ca for postmenopausal women (2-3X increase endometrial Ca for postmenopausal women (2-3X increase

in risk)in risk) Both risks disappear when drug is stopped—aromatase Both risks disappear when drug is stopped—aromatase

inhibitors do not have these effects at allinhibitors do not have these effects at all

Tamoxifen Tamoxifen doesdoes protect bones: castration and protect bones: castration and aromatase inhibitors do notaromatase inhibitors do not

Patient Perspectives on Adjuvant Patient Perspectives on Adjuvant Therapy for Breast CancerTherapy for Breast Cancer

Women need help with decision-makingWomen need help with decision-making Often find differing opinions among physiciansOften find differing opinions among physicians Are usually more satisfied if they have participatedAre usually more satisfied if they have participated Reliable sources of information are increasingReliable sources of information are increasing ““Utility” is highly personal, variable, and persons being Utility” is highly personal, variable, and persons being

asked in current studies are not representativeasked in current studies are not representative Diagnosis of breast cancer induces stressDiagnosis of breast cancer induces stress

Women recover with timeWomen recover with time Women with premorbid problems are most likely to Women with premorbid problems are most likely to

need and benefit from supportneed and benefit from support

Long Term Follow-up After Breast CancerLong Term Follow-up After Breast Cancer

Women who have had breast cancer are at lower risk Women who have had breast cancer are at lower risk for new breast cancer event if treated systemicallyfor new breast cancer event if treated systemically

Women who have been treated with 5 years of Women who have been treated with 5 years of Tamoxifen have a reduced new opposite breast Tamoxifen have a reduced new opposite breast cancer risk of about 40%; AI similar.cancer risk of about 40%; AI similar.

Mammography annually, breast exam every 6-12 Mammography annually, breast exam every 6-12 months is recommended by all expertsmonths is recommended by all experts

Routine CT or bone scanning is NOT recommendedRoutine CT or bone scanning is NOT recommended—no survival benefit—no survival benefit

Most experts use routine laboratory tests and Most experts use routine laboratory tests and occasional chest x-rays as screening testsoccasional chest x-rays as screening tests

Most important aspect is careful history and physical Most important aspect is careful history and physical examexam

Summing UpSumming Up

Evidence-based therapies for DCIS and Evidence-based therapies for DCIS and invasive breast cancer:invasive breast cancer:

Surgical excision—less is moreSurgical excision—less is more

Radiation therapy—preserves breastsRadiation therapy—preserves breasts

Chemotherapy—younger, higher riskChemotherapy—younger, higher risk

Hormone therapy—ER+ all agesHormone therapy—ER+ all ages

Patient care includes education, support, Patient care includes education, support, long term follow-uplong term follow-up