breast care / breast cancer - kaiser permanente • breast cancer is the most frequently diagnosed...

BREAST CARE / BREAST CANCER

Overview

The Kaiser Permanente Breast Care Management Algorithm provided on this site was developed by the Inter-Regional Breast Cancer leaders group (IRBC). This multidisciplinary group includes physicians from Primary Care, Surgery, Oncology, Obstetrics and Gynecology, Radiology, Mammography, Genetics and Womens Services and representatives from various regional Breast Cancer Task force groups, Clinical Nursing, Quality Resource & Risk Management, Public Relations & Issues Management, Prevention Services, and the Permanente Federation.

The algorithm was developed to:

Improve the quality of care for our members with breast complaints, Improve the timeliness of the identification of breast abnormalities and diagnosis of breast

cancer, Improve the satisfaction of members with breast complaints, and Respond to the increase in malpractice allegations of failure to diagnose breast cancer.

In 2002, the IRBC group held periodic conference calls to develop information to assist primary care clinicians in improving the quality of care for patients with breast complaints. A multidisciplinary consensus-based method was used to develop the content of the algorithm. The group also identified additional information and resources available internally and externally which would support implementation.The Breast Care Leaders in each Region have been encouraged to review and modify the algorithm to reflect local operations. Therefore, prior to use, PCPs are advised to contact a Regional member of the Inter-Regional Breast Care leaders group about revisions for your Region

This site is for use within Kaiser Permanente only.

What is Available on this Site?

The IRBC group and the project management staff from the Permanente Federation worked together to define the project scope and develop the following products and information:

I. Rationale II. Breast Care Management Algorithm: The Algorithm provides suggestions to help primary care providers along a care path for evaluating a patients breast complaint (e.g., Clinical Breast Exam, abnormal screening mammogram follow-up suggestions, inflammation, breast mass/lumps, spontaneous nipple discharge, and breast pain) to the point where cancer is ruled in or out. III. Information Related to Clinical Practice Guidelines for Breast Cancer Screening: Contact information regarding regional Clinical Practice Guidelines for Breast Cancer Screening. IV. New Technology Report: This section provides information regarding new technologies used to diagnose breast cancer. V. Breast Cancer Tracking System : Information regarding various computer tracking systems for breast cancer is provided in this section.

Version 2.0 October, 2003 - 1 -

VI. Sample Presentations, Additional Resources and Regional Continuing Medical Education(CME) Contact information : Sample presentations describing Issues in Breast Cancer and Risk Management information and other available resources to support Breast Care are listed in this section. Contacts for regional CME are provided. VII. Bibliography : This section contains the list of references utilized for development of the algorithm VII. Inter-Regional Breast Cancer leaders group (IRBC): Contact information for the IRBC.


I. Rationale

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in women.

205,000 new cases of breast cancer will be diagnosed in the U.S. in 2002 An average women has a 2.5% chance of developing breast cancer between the ages of 35 and

55. Approximately 70-75% of breast cancers are diagnosed in women over the age of 50. There are 127 cases per 100,000 women age 40-44 years compared to 450 per 100,000 cases in

women age 70-74 years. Although a woman, between 25 and 34 years of age, has a relatively low risk of developing breast

cancer compared to older women, nationally, KP can expect 100 women in this age group to be diagnosed with breast cancer in 2002.1,2, Therefore, complete follow-up and documentation of care to the point of normal findings, is essential for all breast complaints, regardless of a womans age.

Family history of breast cancer predicts approximately 15% of all cases. A positive family history of breast cancer is defined as having a first-degree relative who developed breast cancer before the age of 50. Those with relatives whose onset of breast cancer was after age 50 are not considered at higher risk. The risk for women with a first-degree relative with early breast cancer is increased fourfold. Other risk factors include history of previous breast cancer, women with atypical hyperplasia on breast biopsy, late age of first pregnancy, nulliparity, and high socioeconomic status.

1. Actual membership from third quarter 2002 per Performance Analysis, Program Offices. 2. Surveillance, Epidemiology and End Results Program, National Cancer Institute, SEER Incidence Crude Rates, 11 Registries, Years

of Diagnosis 1992 -1999, All Races, Females.


II. Breast Care Management Algorithm

The Kaiser Permanente Breast Care Management Algorithm provides suggestions to help primary care providers along a care path for evaluating a patients breast complaint (e.g., Clinical Breast Exam, Abnormal Screening Mammogram Follow-up Suggestions, Breast Mass/Lumps, Inflammation, Spontaneous Nipple Discharge, and Breast Pain) to the point where cancer is ruled in or out.

This algorithm is not an evidence based clinical practice guideline. A multidisciplinary consensus-based method was used to develop the algorithm. The suggestions provided in the algorithm do not replace the reasonable exercise of independent clinical judgment in any particular set of circumstances for each patient encounter.

The Breast Care Leaders in each Region have been encouraged to review and modify the algorithm to reflect local operations. Therefore, prior to use, PCPs are advised to contact a Regional member of the Inter-Regional Breast Care leaders group about revisions for your Region.

The algorithm may be viewed and navigated on this sight or viewed and printed using Adobe Acrobat:

Algorithm: Introduction/ Clinical Visit for Breast Complaint Abnormal Screening Mammogram Follow-up Suggestions, Breast Mass/Lumps Inflammation Spontaneous Nipple Discharge Breast Pain

Please direct any questions about the algorithm to Robin Cisneros, Director of Medical Technology Assessment, Quality and Performance Improvement, The Permanente Federation at 510-271-5863.


Breast Care Management Algorithm

Evaluation of the Breast Complaint

Obtain historyincluding previous mammogram(s) (plus other imaging) findings, and follow-up; medication history including hormone and birth control; and onset and duration of symptoms of current complaint. If prior mammogram was abnormal determine if there is documented completion of follow-up. If not, proceed to page 3 for abnormal mammogram follow-up algorithm.

Identify risk factorspersonal or family (first-degree relative) history of breast cancer including age of diagnosis, atypia on previous breast biopsies,age of menarche, age at first completed pregnancy, and breastfeeding history.

Conduct a Clinical Breast Exam (CBE)Inspect both breasts (unaffected breast first) for ulceration or contour change, nipple skin changes, or nipple discharge. Palpate breast in both the upright and supine positions to determine the presence of a palpable mass/lump. Evaluate nodes (axillary,supraclavicular).

Assess risk Consider history and physical findings, risk factors and patient concernsLink to NCI Risk Calculator: http://bcra.nci.nih.gov/brc/q1.htm

Document all characteristics of the history and physical findingsDocument symptom characteristics such as size, location, texture, mobility and character for reference in follow-up examinations. A breast clinic record template is available for use.

Order breast imagingif indicated or per regional screening/diagnostic guidelines.

CLINIC VISIT

Signs of Inflammation(Redness, Warmth, Swelling, Purulent Discharge,

Draining Wound)

Inflammation

See page 4

No Signs of Inflammation

Characterize Primary Complaint

Breast Mass/Lump

If not palpable, Educate on risk and screening intervals Re-examine in one month.

If palpable, See page 5

Spontaneous Nipple

Discharge (without mass)

See page 6

Breast Pain (without mass)

See page 7

Version: January 28, 2003 2003 Kaiser Permanente Medical Care Program Next review: January 2004 For use within Kaiser Permanente only

http://bcra.nci.nih.gov/brc/q1.htm

AdditionalConsiderations

If the patient ispregnant or lactating,consult the appropriatespecialist prior tofollowing this care

h.


Abnormal Screening Mammogram Follow-up

Abnormal Screening Mammogram

Full Diagnostic Mammogram and/or Ultrasound

Short-term follow-up per appropriate

specialists recommendations

Suspicious of Malignancy

Highly Suggestive of

Malignancy

Malignant OR

Any type of atypia

Indeterminate Insufficient sample Lack of imaging/

pathology correlation

Second biopsy OR

Surgical Follow-up

Surgical Follow-up

Benign

BI RADS Assessment

Categories 1,2

Benign

BI RADS Assessment Category 4

BI RADS Assessment Category 5

Clinical breast exam (f not previously completed)

Biopsy

Probably Benign

BI RADS Assessment Categories 3

pat

Additional Considerations

If the patient is pregnant or lactating, consult the appropriate specialist prior to following this care path.

SCPMG Breast Cancer Member Satisfaction Survey findings suggests that the time frame from suspicion to diagnosis should not exceed 14 days.

Document mammogram and pathology findings

Document surgical outcomes and other treatment, if applicable

Inform all providers and patient of findings and treatment results

Inform all of appropriate follow-up including next screening date (mammogram and CBE)


Annotations to Algorithm

(1) Antibiotics

Cephalexin 500 mg po QID x 10 days

Dicloxacillin 500 mg po QID x 10 days

E mycin 333 mg. TIC x 10 days if allergicto penicillin (if not breastfeeding)

(2) If implants, consider longer course ofantibiotics or referral to Plastic Surgery.


Inflammation (Inflammatory carcinoma should always be considered)

Treat with Warm Packs, NSAIDS, Antibiotics1,2

Continue treatment 5-7 days or less

Signs and Symptoms Alleviated

Not-Breastfeeding Breastfeeding

Advise to continue breastfeeding Consider Ob/Gyn consultation

SCPMG Breast Cancer Member Satisfaction Survey findings suggest that the time frame from suspicion to diagnosis should not exceed 14 days.

Continue treatment 7-10 days or less

Evaluate signs and symptoms

Signs and Symptoms Unchanged or Increased

Consider biopsy and additional imaging

If breastfeeding, consider discontinuing

Follow-up to resolution of symptoms

Documentation of care to the point of normal physical findings

Inform patient of next screening date (mammogram and CBE)

Inform all involved providers of resolution

-


(1) Antibiotics

Cephalexin 500 mg po QID x 10 days

Dicloxacillin 500 mg po QID x 10 days

E-mycin 333 mg. TIC x 10 days if allergic to penicillin (if not breastfeeding)

(2) If implants, consider longer course of antibiotics or referral to Plastic Surgery.


Annotations to Algorithm (1) If patient is under 35,

consider referring the patientto the appropriate specialistbefore ordering any breastim


EVALUATION OF BREAST MASS/LUMP

Pre-menopausal Post-menopausal

Cyclical Non-Cyclical Re-examine after next cycle

(or 4 weeks)

Resolved Unresolved aging.

Annotations to Algorithm (1) If patient is under 35, consider referring the patient to the appropriate specialist before ordering any breast imaging.

SCPMG Breast Cancer MemberOrder a diagnostic mammogram if none in last 6 months1

Follow all radiological recommendations Satisfaction Consider additional imaging Survey findings

Obtain consultations and/or additional tests

Suspected Cyst (Fluid)

Aspirate to total resolution

Not Bloody Bloody And OR

No Residual Indeterminate Mass exists cytology

OR

Suspected Solid

(No fluid)

suggest that the time frame from suspicion

Not a suspected Cyst or Solid to diagnosis should not Re-examine in 1 month exceed 14 days.

Persistent Mass Residual Resolves

Mass

Biopsy (regardless of mammogram results) Examine at Residual Mass 4-8 weeks Exists

Mass Mass Benign Malignant or Does Reoccurs Consider complete Indeterminate NOT excision Pathology

Reoccur

Surgical Follow-up







If the patient is under 35,consider consultationwith the appropriatespecialist before orderingany breast imaging.

(2) Medications that maycause discharge include:Phenothiazine,Reserpine, Estrogen, andOpiates.


Spontaneous Nipple Discharge (other than lactating state) (without mass, if mass see page 5)

Evaluate and document the characteristics of discharge Single Duct may be cancer. Multiple Duct is not as worrisome.

Order diagnostic bilateral mammogram if none in the last 6 months and patient is 35 years or older. Follow all radiological recommendations1


Unilateral Bilateral

Consider additional imaging Non-Bloody Discharge

Clear, yellow, green, gray or milky.

Bloody Discharge

Rule Out Mechanical stimulation

Rule Out medication2 Surgical

Follow-up


If the patient is under 35, consider consultation with the appropriate specialist before ordering any breast imaging.

(2) Medications that may cause discharge include: Phenothiazine, Reserpine, Estrogen, and Opiates.

Endocrine Evaluation (prolactin/TSH)

Normal Prolactin/

TSH

Abnormal Prolactin/

TSH

Endocrine Follow-up






Annotations to Algorithm(1) 2 cycles if pre-menopausal or 2 months ifpost-menopausal(2) If the patient is under35, consider consultationwith the appropriatespecialist before orderingany breast imaging.(3) Symptommanagement andtreatment may include:For mild to moderatecyclical pain there are noevidence-basedtreatments available.Non-evidence based, non-hormonal therapyrecommended for 4-6months includes:reassurance, caffeinereduction, supportive wellfitting bra, vitamin E, B6,Evening Primrose oil, orover-the-counteranalgesics.Moderate to severecyclical pain: Possible


Breast Pain (without mass, if mass see page 5)

Non- Cyclical Evaluate medication (e.g., hormones, birth control) R/O pregnancy Differential diagnosis (Breast disorder, chest wall pain (bone, muscle, joint), pleural disease, cardiac disease, GI disease) Order a diagnostic bilateral mammogram if none in last 6 months and patient is 35 or older. Follow all radiological recommendations 2

Unilateral Bilateral

Cyclical

Focal Symptom Management3 Follow-up after 2 cycles1

Global

Negative Bilateral Mammogram

Symptom Management3

Follow-up after 2 cycles1

Consider additional tests and consultations

Abnormal Bilateral Mammogram

Follow all radiologic recommendations

Immediate referral to appropriate specialists

Resolves Persistent Pain

Pain Resolves

Persistent Pain

-

hormone therapy.

Annotations to Algorithm (1) 2 cycles if pre-menopausal or 2 months if post-menopausal (2) If the patient is under 35, consider consultation with the appropriate specialist before ordering any breast imaging. (3) Symptom management and treatment may include: For mild to moderate cyclical pain there are no evidence-based treatments available. Non-evidence based, non-hormonal therapy recommended for 4-6 months includes: reassurance, caffeine reduction, supportive well-fitting bra, vitamin E, B6, Evening Primrose oil, or over-the-counter analgesics. Moderate to severe cyclical pain: Possible hormone therapy.





Resolved Not resolved

Re-examination

after 2 cycles1

Symptom Management3 and follow-up PRN Consider additional imaging studies, biopsy,

and consultations

Bilateral mammogram if none in last 6 months

> 35< 352

Ob/Gyn

Consult



http://pkc.kp.org/pkc/national/cpg/ebsummaries/summaries/000069.html?subjectName=Fibrocystic+Breast+Disease&subShortName=fibrocystic-breasthttp://pkc.kp.org/pkc/national/cpg/ebsummaries/summaries/000069.html?subjectName=Fibrocystic+Breast+Disease&subShortName=fibrocystic-breastszetote

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III. Information Related to Clinical Practice Guidelines for Breast Cancer Screening

This section provides contact information for your regional representative who can give you specific information regarding your regions Clinical Practice Guidelines for Breast Cancer Screening.

Contact for Breast Cancer Screening

ADDRESS Internal Web SitePhone/Fax/E-mail (if available)Information

Sue Jane Fox Prevention Specialist II Kaiser Permanente, Colorado

Department of Prevention 10350 East Dakota Avenue Denver, CO 80231 303-344-7256 303-344-7721 Fax [email protected]

Breast Cancer Screening

Adrienne Mims, MD, Chief of Prevention and Health Promotion Or John Zetzsche Director of Population Based Care Kaiser Permanente, Georgia

9 Piedmont Center 3495 Piedmont Road NE Atlanta, GA 30305-1736 404-364-7289 404-364-4798 [email protected]

404-364-7297 404-364-4798 [email protected]

Clinical Practice and Prevention Guidelines Use Bookmarks under Adult Medicine to locate Breast Cancer Screening Guidelines

Charles Sakamoto, MD Chief of Family Practice

Or

Jean Kumamoto, Director of Health Education Kaiser Permanente Hawaii

KP Mililani Clinic 95-660 Lanikuhana Avenue Mililani, HI 96789 808-432-4254 808-625-4242 [email protected]

KP Honolulu Clinic 1010 Pensacola Street Honolulu, HI 96814 808-432-2260 808-432-2249 [email protected]

Preventive Care Services for Adults

Hanadi Shamkhani, MD Director for Practitioner Performance Review and Oversite Kaiser Permanente, Mid-Atlantic

KPMG, 2101 E. Jefferson Street, 2 West, Rockville, MD 20852 301-816-6624 [email protected]

Preventive Care of Asymptomatic Adults

Susan Kutner, MD Department of Surgery Breast Cancer Care Committee Permanente Medical Group, Northern California

KP, 280 Hospital Parkway San Jose, CA 95119 408-972-6017 Tie-line: 8-440-6017 [email protected]

Screening Neoplastic Diseases, Breast Cancer


mailto:[email protected]://pkc.kp.org/co/cpg/cpg/breast_cancer_screening_2002.htmmailto:[email protected]:[email protected]://kpnetz.kp.org/ga/healthcare/docs/guidelines.pdfmailto:[email protected]:[email protected]://web.hi.kp.org/cpg/Guideline%20Files/PCSFAworksheet12-09-2003.dochttps://www.mapmgonline.com/portal/documents/264638019/May2002PrevCareofAsympAdults.docmailto:[email protected]://clinical-library.ca.kp.org/clib/guidelines/cpg/prevention/cpg_prevention_screen_neop_breast.htm

Contact for Breast ADDRESS Internal Web SiteCancer Screening Phone/Fax/E-mail (if available)Information

Nancy Stevens, PhD Prevention Systems Manager Kaiser Permanente, Northwest

500 NE Multnomah Suite 100 Portland Oregon 97232 503-813-3828 503- 813-2669 Fax [email protected]


Group Health Breast Cancer Screening Guideline

Wendy Dahar Health Outcomes Coordinator Kaiser Permanente, Ohio

Division of Clinical Innovation 5410 Lancaster Street Brooklyn Heights, OH 44131 216- 778-6088 216-778-6090 [email protected]

Preventive Health Recommendations for Screening

Susan Chen, RN, MSN Clinical Services Kaiser Permanente, Southern California

KP, 393 E. Walnut Street, 7th Floor Pasadena, CA 91101 626-405-2554 Tie-line:8- 335-2554 626-405-6991 Fax [email protected]



mailto:[email protected]://internal.kpnw.org/cpg/guideline/G10904.HTMLhttp://incontext.ghc.org/clinical/cg/breast/bcstoc.htmlmailto:[email protected]://bhnetsrvr1.oh.kp.org:81/corelibrary/guide/preventivecareage11andolder.pdfmailto:[email protected]://pkc.kp.org/scal/cpg/cpg/html/BreastCaScreen.html

IV. New Technology Report

This section provides information regarding new technologies used to diagnose breast cancer.

Full field digital mammography (3-2002, 12-2002)

Computer-assisted detection mammography (3-2002, 12-2002)

Random epithelial cell cytology evaluation (3-2002, 12-2002)

MRI

PET Scan


New Technology Breast Cancer Screening

Summary of Technology Assessments March 18, 2002

Full-Field Digital Mammography (FFDM) FFDM is proposed as an alternative to screen-film mammography (SFM). SFM, the conventional form of mammography, uses film as the medium for image acquisition, storage and viewing. SFM is neither perfectly sensitive nor highly specific. Dense breast tissue and diffuse involvement of the breast with tumor tends to reduce the sensitivity of screening mammography. Approximately 1020% of breast cancers that are detected by self-breast examination or physical examination are not visible by screen-film mammography. (Baker 1982) In addition, when lesions are detected by mammography and biopsy is recommended by experienced radiologists, only 540% of lesions prove to be malignant. (Sickles 1991).

A major limitation of screen-film mammography is the film itself. The film serves as the medium of image acquisition, storage and display. Once a screen-film mammogram is obtained, it cannot be significantly altered. Contrast loss due to film underexposure, especially of dense glandular tissues, cannot be regained through film display. Radiologists cannot manipulate the image directly. Improvements in image display involve acquiring more images with magnification or focal compression (and thus exposing the patient to more radiation), or looking at the images with a hot light or magnifying glass. Breast cancer is often quite similar in X-ray absorption to surrounding normal dense breast tissue.

Digital mammography uses solid state digital detectors and has the potential to improve breast cancer detection and breast lesion characterization . The distinguishing characteristic of FFDM is digital image acquisition, without the need for film. The processes of acquisition, storageand display can be separated and individually optimized. The digital images can be processed by a computer and displayed in multiple formats, on film or on a monitor. Since the steps of image acquisition and display are separated, each can be optimized. In addition, image storage, transmission and retrieval can be improved. Computer-aided diagnosis (CAD) software to assist the radiologist in interpreting the images can also be utilized to provide a second opinion and improve diagnostic accuracy. Furthermore, digital mammograms may provide the best estimate of mammographic density, a predictor of breast cancer risk. (Boyd et al. 1998).

Two FDA systems have received PMA approval by the FDA: GE Senorgraphe 2000 system (1/28/00) and Fischer Imaging Corportation Senoscan System (9/25/01).

This BCBSA TEC assessment (March 2002) reviews the evidence comparing FFDM and SFM for use in two settings: the screening population and the population of patients referred for diagnostic mammography based on initial suspicious findings. Recall rates, biopsy rates and cancer detection are of primary importance in this review.

The assessment compared the results of screen-film mammography (SFM) and full-field digital mammography (FFDM), performed on either the same group or two groups of patients. Additionally, studies had to report on cancer detection based on histologic results for at least some of the patients in the sample. For the screening population, the assessment concluded that there is insufficient evidence to permit conclusions about the effects of full-field digital mammography (FFDM) relative to screen-film mammography (SFM) in screening for breast cancer. Two main studies comprise the currently available data, both of which used the GE system. The first study, performed in two U.S. centers, was reported in a journal article and a conference slide presentation. Target enrollment in this study is 15,000 patients, but the most recent update is for 4,521 patients. The recall rate for FFDM (11.8%) is significantly lower than that for SFM (15.0%). The biopsy rate is also significantly lower for FFDM compared with SFM (11.8% versus 14.3%). FFDM detected 27


of 51 cancers while SFM detected 34 cancers. The positive predictive values for both modalities was 3.4%. The sensitivities, 52.9% for FFDM and 66.7% for SFM, were not significantly different in this interim analysis. If the magnitude of this difference in sensitivity remains at this level through subject accrual increases, FFDM could be shown to significantly inferior to SFM in cancer detection. This underscores the need to reserve conclusions until final reporting of the study.

The second study, conducted in Oslo, Norway, has been reported in a proceedings paper and two conference abstracts. Statistical test results are lacking for all comparisons between FFDM and SFM. Unlike the findings of the U.S. study, recall rates in the Norwegian study were higher for FFDM than for SFM. However, recall rates varied from in all three data sources, although 2 of them were based on the same number of patients (3,683 in the largest update). The number of cancers detected by FFDM was 23, compared with 27 for SFM, a nonsignificant difference. Sensitivities was 74.2% for FFDM and 87.1% for SFM. It is uncertain whether this study was powered to detect a difference in sensitivities as large as 13 percentage points.

A third study using the GE system, presented only as a conference abstract, does not clearly state whether patients presented for screening or diagnostic mammography, or both. Separate groups of patients underwent FFDM (n=1,849) and SFM (n=5,415). It is also unclear whether the cancer detection rates for FFDM and SFM differed significantly. A fourth study using the GE system is being conducted by the American College of Radiology Investigative Network (ACRIN), with a target of 49,500 patients. No reports on this large study are available yet.

A single journal article, presenting interim results for less than half of study target enrollment, has been published on use of FFDM in screening. All other sources of data come from a proceedings paper or conference abstracts. Additional detailed publications for large numbers of patients are needed before conclusions can be reached about the detection of breast cancer by FFDM relative to SFM in a screening population.

Diagnostic Population. Patients with findings suspicious for breast cancer based on initial SFM or breast physical examination are referred for additional work-up and comprise the diagnostic mammography population. Four studies are available on the GE system in this population: one journal article on 692 patients, a proceedings paper on 625 patients, one conference abstract on 55 patients and another abstract on 100 patients. The published article reported relatively low inter-test agreement between FFDM and SFM (a kappa value as low as 0.20). A total of 16 cancers were detected by SFM and 13 were detected by FFDM. Sensitivities were 72.7% for FFDM and 88.9% for SFM. The study appeared to lack sufficient power to detect a difference in sensitivities as large as 16 percentage points. The proceedings paper reported sensitivities of 68.2% for FFDM and 69.5% for SFM, indicating that FFDM was not inferior to SFM, however the number of cancers detected was not specified. This paper, reported in a low degree of detail does not resolve concerns raised in the only published paper about what may be a substantially lower sensitivity for FFDM. The two other GE studies have only been reported as conference abstracts and do not provide sufficient detail to permit meaningful analysis of methods and results. Thus, conclusions about the performance of FFDM relative to SFM in a diagnostic mammography population await additional published reports for large patient samples.

Evidence on the Fischer FFDM system is limited to a single conference abstract of 247 patients. This source did not mention results of statistical tests comparing FFDM and SFM. Sensitivities were reported to be 66% for FFDM and 74% for SFM, while specificities were 67% for FFDM and 60% for SFM. The area under the ROC curve was 0.715 for FFDM and 0.765 for SFM. A journal article described results for 22 patients imaged with the Fuji digital luminescence mammography (DLM) device. Area under the ROC curve was 0.781 for DLM, compared with 0.732 for SFM. These results are clearly inadequate to permit conclusions about relative performance of these digital mammography systems versus SFM.


Computer-Assisted Detection (CAD) , also called computer-aided detection, CAD systems for mammography digitize mammogram films, analyze them for patterns that may represent microcalcifications or masses, and provide a marked image (either printed copy or on a display monitor) that is compared to the original mammogram. CAD systems are not designed to replace the original mammograms or the radiologist(s) reading the film but has been proposed as an alternative to double reading. Designed as a tool for the screening environment, the value of this technology depends on the ability to diagnose and treat early disease.

You did not receive an assessment prior to today on this technology. However, SCPMGs TAG unit has addressed this technology. We will forward the final assessment to you as soon as it is available but I was told that I could discuss the draft assessment with you today.

Several types of computer-assisted detection devices are FDA-approved for marketing in the United States. , the ImageChecker M1000 System produced by R2 Technologies, Inc. (Los Altos, CA), the CADx Medical Systems Second Look system, and ISSIs MammoReader are FDA-approved for marketing in the United States. The MAMMEX TR system is being tested at the University of Southern California, and study results were recently reported in abstract form. This system has been installed in Switzerland.

The assessment didnt results in a a precise determination of the sensitivity or specificity of CAD mammography because the available evidence is lacking. The NTAT recommends that the NTDST carefully review the estimates of the marginal increase in sensitivity along with the associated number of expected call backs and incorporate operational considerations in the evaluation of CAD mammography. The NTDST, with the support of the NTAT and the key technology clinical committees, should determine if CAD technology is appropriate for deployment in Kaiser Permanente, Southern California.

The available published evidence does not permit definitive conclusions regarding the sensitivity and specificity of CAD. In addition, the evidence does not permit a determination of the effect of CAD screening mammography on intermediate or long-term health outcomes. However, because CAD is used as a second read and identifies locations of suspected mammographic abnormalities, the sensitivity is expected to be the same or higher compared to a single reading. The false positive rate is also expected to be higher. The literature demonstrates that the effect of CAD on sensitivity and specificity is dependent on the experience and skill of the radiologist with most benefit accruing to radiologists less experienced in reading mammograms. In addition, sensitivity and specificity are likely to be related to the size of the tumor, type of tumor and age of the patient. Moreover, the ratio of extra workups to extra cancers is sensitive to small changes in sensitivity and specificity and these are quite variable from radiologist to radiologist and from study to study.

As calculated from the average increase in sensitivity reported in the literature (5 retrospective studies with an enriched case selection and variability in radiologist experience), the marginal increase in sensitivity for CAD plus radiologist compared to radiologist alone is 6.5%. A large prospective study (Freer and Ulissey, 2001) found a 19.5% increase in cancers detected when using CAD. A decrease in specificity of 1.1% can be calculated from two of the small retrospective studies (Brem and Schoonjans, 2001; Thurfjell et al., 1998). Freer and Ulissey found a 1.2% increase in recall rate. This could result in an estimated 12/1000 women being called back for further medical and/or surgical follow up to determine whether or not the highlighted abnormalities identified on CAD and warranted as actionable by the radiologist are undetected breast cancers.

These numbers may not be applicable to all SCPMG radiologists and/or may vary among departments or among radiologists within a department. In Kaiser Permanente Southern California, it is estimated that CAD mammography would generate in the range of 100-125 callbacks per 10,000 mammograms. Of these 100-125 callbacks, it is estimated that 2-5 additional breast cancers would be detected.


PMG expert opinion is divided. All of the experts contacted agree that CAD mammography is an emerging technology, and several physicians see it as a useful adjunct to radiologist-read mammography because of its demonstrated ability to pick up missed cancers. Others have concerns about the specificity and the cost of the device, and question whether it would be worth the investment.

SCPMG Thomas Mahon, MD (Diagnostic Imaging, LAMC, 8-363-2374) Ideally we would all perform double reading of mammograms, however, few if any of the S.C. Kaiser Radiology Departments have sufficient Radiologists to do this. Double reading increases cancer detection rates by 4 to 15%. Therefore, is CAD a useful and viable alternative to double reading? As you point out there are no studies comparing these two techniques. I agree the studies published so far often have potential bias and have an "enriched" case selection, however, they do seem to suggest that CAD increases detection rate and in the study by Freer of 12,860 patients the patient recall rate did not significantly increase. I think the paper by Jiang in Radiology, September 2001, is important because he states that with CAD there was a two-thirds decrease in substantial disagreements between different radiologists assessing the same group of mammograms. The author thus suggests CAD may result in an improvement in both accuracy and consistency in image interpretation.

The main potential disadvantages of CAD would be if the recall rate was to significantly increase and this is not suggested by the studies, nor by the users I talked to in KP in Northern California. Another potential problem would be if use of CAD were to increase the time spent by Radiologists reading each mammogram, and again the users I talked to did not report this. The false positive rate is inconvenient, but if it does not affect either the recall rate or the time spent interpreting a mammogram, then it is not a significant issue. A false negative rate would only be significant if the radiologist using CAD were to miss a cancer that he or she without CAD would diagnose. By that I mean, were CAD to miss a large spiculated mass, then this lesion should be easily seen by the Radiologist. Whereas it is more important that CAD should detect a subtle group of calcifications in a dense breast that could be easily missed by the Radiologist interpreting without CAD. I think it is important that CAD detect clinically relevant cancers, and this is suggested by the paper by Burhenne et all, where of the 8 cancers seen by CAD, 3 were invasive cancers. As you know missed breast cancers is a very important source of litigation and the average award in this area settled by Kaiser, I understand has now reached $700,000. It would be of interest to know if CAD could successfully decrease successful litigation. There are a number of ways it could potentially do this. Firstly, it may decrease the rate of missed cancers, particularly in the important demographic of younger women with dense breasts that can obscure calcifications. Secondly, that by using CAD we can say that the mammograms are in effect second read. Thirdly, that lesion detectability by CAD might establish a reasonable standard of detectability.

The current status of CAD appears similar to that in the early 1990's when Stereotactic breast biopsy was introduced. Stereotactic biopsy has proven to be a great success and has literally revolutionized the way we manage breast lesions and yet to this day the studies in the literature remain relatively small, with potential bias. To this day the only Radiology modality that I am aware of that has been tested with large randomized studies is Mammography, and the interpretation of the results of these studies remains probably the single most controversial issues in all of Medicine. CAD will be standardly available when we go over to Digital Mammography, but this is still several years down the road and I think we need to consider CAD before then. The expense of CAD is an issue. If CAD were to decrease medical malpractice claims then that could go towards paying for it.

TPMG KM Tan, MD, Chair, KPNC Imaging Clinical Technology Committee. (as of March, 2001) A FEW YEARS AGO, KPNC HAD THREE BETA SITES FOR R2 IMAGECHECKER: REDWOOD CITY, SOUTH SAN FRANCISCO, AND SAN FRANCISCO. FOLLOWING THE TRIAL, THE VENDOR OFFERED THE EQUIPMENT TO EACH SITE FOR APPROXIMATELY $75,000, DISCOUNTED FROM THE RETAIL PRICE OF APPROXIMATELY $170,000. DR. TANS IMAGING COMMITTEE WOULD NOT APPROVE REGIONAL FUNDING. REDWOOD CITY AND SAN FRANCISCO CHOSE TO FUND THE EQUIPMENT OUT OF MEDICAL CENTER FUNDS; SOUTH SAN FRANCISCO DID NOT BUY THE R2 IMAGECHECKER. TPMG RADIOLOGY CONSIDERS THE R2 IMAGECHECKER A TECHNOLOGY


THAT MAY BE NICE TO HAVE, BUT A LUXURY. EVEN THE TWO TPMG RADIOLOGISTS, SHERRY BUTLER, MD, SAN FRANCISCO, AND DEBORAH KASS, MD, REDWOOD CITY, WHO EMPLOY THIS TECHNOLOGY WITH THE GREATEST FREQUENCY, HAVE STATED TO DR. KAM THAT R2 IMAGECHECKER IS NOT COMMUNITY STANDARD. DR. TAN ESTIMATES THAT, GIVEN THAT THE UNITED STATES HAS MORE THAN 10,000 BREAST IMAGING PRACTICES, A NATIONWIDE TOTAL OF 140 TO 180 R2 IMAGECHECKER SYSTEMS IN USE MEANS THAT PERHAPS 1% OF MAMMOGRAMS IN THE UNITED STATES ARE NOW READ WITH THE ASSISTANCE OF R2 IMAGECHECKER. DR. KASS HAS INFORMED DR. TAN THAT, IN HER SEVERAL YEARS OF EXPERIENCE WITH THE R2 IMAGE CHECKER, NONE OF THE CASES SHE SENT TO BIOPSY ON THE BASIS OF R2 IMAGECHECKERS FLAGGING AREAS OF INTEREST TURNED OUT TO BE CANCER. ON PATIENTS WHO HAVE BEEN DIAGNOSED WITH BREAST CANCER AFTER A MAMMOGRAM USING THE R2 IMAGECHECKER, DR. KASS HAS PROCESSED THOSE PATIENTS PRIOR MAMMOGRAMS READ WITHOUT R2 IMAGECHECKER. IN A FEW CASES, R2 IMAGECHECKER HAS FLAGGED POTENTIAL AREAS OF CONCERN ON THE PRIOR MAMMOGRAMS, SO THERE IS SOME VALUE TO THE TECHNOLOGY. DR. KASS TOLD DR. TAN THAT SHE DOES FEEL THAT R2 IMAGECHECKER TECHNOLOGY WILL EVENTUALLY BE INCORPORATED INTO MAMMOGRAPHY MACHINES AND BECOME PART OF THE COMMUNITY STANDARD IN THE FUTURE. DR. TANS IMAGING COMMITTEE HAS NO CURRENT PLANS TO PURCHASE R2 IMAGECHECKER SYSTEMS FOR THE REGION. Deborah A. Kass, MD (Radiology, Redwood City Medical Center, 8-424-2315) (December 2001) THE VALUE OF CAD MAMMOGRAPHY HAS BEEN DOCUMENTED WITH A VERY LARGE NUMBER OF CASES OBTAINED FROM MULTIPLE MEDICAL CENTERS AND MULTIPLE DIFFERENT MQSA-CERTIFIED RADIOLOGISTS. EXTENSIVE DATA WAS PROVIDED TO THE FDA, LEADING TO APPROVAL OF THE IMAGECHECKER. STATISTICALLY, IN A HOSPITAL WITH 14,000 SCREENING MAMMOGRAMS PER YEAR, THE DATA PREDICT THAT 4-5 OVERSIGHT ERRORS MIGHT BE PREVENTED. THIS COULD POTENTIALLY RESULT IN DETECTION OF BREAST CANCER IN ITS MORE EASILY TREATABLE EARLY STAGE POTENTIALLY LEADING TO SIGNIFICANT COST SAVINGS. THERE IS A VERY RAPID LEARNING CURE AND IMAGECHECKER HAS NOT SLOWED DOWN THE WORKFLOW. IT BECOMES VERY AUTOMATIC, AND IS VALUED AS A SAFETY NET BY THE RADIOLOGISTS WHO USE IT. THEY FIND THAT IF THEY ARE GETTING TIRED, IMAGECHECKER PROMPTS THEM SO THAT THEY BECOME MORE ALERT. FORMAL DATA COLLECTION SHOWS THAT THE ADDITIONAL PATIENTS IDENTIFIED AND CALLED BACK DO NOT RESULT IN A STATISTICALLY SIGNIFICANT INCREASE IN WORK UPS WHEN COMPARED WITH THE BASELINE VARIATION. IN THE BAY AREA, IMAGECHECKER IS USED ONLY AT SAN FRANCISCO AND REDWOOD CITY. THEY RECENTLY HAD A NEAR MISS WITH DMHC, WHEN A MEMBER WHO HAD HAD A NEGATIVE MAMMOGRAM AT ANOTHER FACILITY ATTEMPTED TO HAVE HER NEGATIVE FILMS SENT TO REDWOOD CITY TO HAVE THEM PUT THROUGH IMAGECHECKER. WHEN THIS WAS DENIED, THE MEMBER CONTACTED DMHC. DR. KASS WAS ABLE TO INTERVENE AND READ THE FILMS IN THIS INSTANCE, AVOIDING A POTENTIAL VIOLATION FOR DENIAL OF CARE. LATELY HER FACILITY HAS HAD 100 REQUESTS FROM OTHER NCAL FACILITIES. ONE PHYSICIAN EVEN CIRCUMVENTED THE SYSTEM BY GIVING A PATIENT A NEW MAMMOGRAPHY REFERRAL SO SHE COULD HAVE A SECOND MAMMOGRAM DONE AT REDWOOD CITY. THESE ISSUES HAVE LED NCAL TO THE CONCLUSION THAT THEY NEED A REGION-WIDE POLICY, WHICH THEY ARE IN THE PROCESS OF DEVELOPING.

JOHN REGO, MD, CHAIR (SAN FRANCISCO-BASED), CHIEFS OF RADIOLOGY. (MARCH, 2001) WE HAVE FOUND THE R2 IMAGE CHECKER A VALUABLE ADJUNCT TO OUR PRACTICE. IT IS MY FEELING THAT IT ADDS CONSISTENCY TO ALL OF OUR READINGS. ITS MAJOR STRENGTH IS THAT IT ACT AS A SECOND PAIR OF EYES OR A DOUBLE READ WHICH IS SOMETHING WE ARE NOT RESOURCED TO DO. IT IS MY FEELING THAT ALL WOULD BENEFIT FROM THIS TECHNOLOGY BUT ESPECIALLY THOSE WHO HAVE AVERAGE ABILITY. THE EXPERT MAMMOGRAPHER BENEFITS LESS FROM THE TECHNOLOGY. SINCE MOST OF US ARE IN THE FORMER CLASS, I THINK OVERALL WE WOULD ALL BENEFIT. I THINK FROM A FINANCIAL OR MEDICAL LEGAL ASPECT OR EVEN FROM A HEALTH BENEFIT ASPECT IT IS VERY TOUGH TO PROVE THE BENEFIT OF THE TECHNOLOGY SINCE YIELD OF CANCER ON MAMMOGRAPHY IS LESS THAN ONE PERCENT ANYWAY. I THINK AS AN ORGANIZATION THERE ARE MANY OTHER PRIORITIES WE SHOULD BE ADDRESSING WITH OUR MONEY THAN TO INVEST IN THIS TECHNOLOGY FOR ALL OTHER FACILITIES. I WOULD DEFINITELY


FEEL DIFFERENT IF DOUBLE READING WERE MANDATED AND THIS TECHNOLOGY WOULD SUBSTITUTE FOR THAT.

Random Epithelial Cell Cytology Evaluation. IN BREAST CANCER RISK ASSESSMENT AND HIGH-RISK PATIENT MANAGEMENT This discussion will include three ductal cytology techniques: random periareolar fine-need aspiration (FNA), nipple aspiration, and ductal lavage. The assessment will review the value of these techniques in the evaluation of risk and high-risk patient management. The BCBSA TEC assessment (March 2002) will be the basis of this discussion.

random breast epithelial cell cytology for breast cancer risk assessment and patient management in women who are already at increased risk of breast cancer does not meet the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.

[Direction to Staff: Because the concept of increasing detection of breast cancer is compelling, the Assessment needs to clearly and carefully spell out the reasons why this technology doesnt meet criteria. Specifically discussed were the unknowns of whether the technology would increase unnecessary biopsies, potential adverse effects of the procedure, impact on future monitoring/diagnostic procedures, and the unknown implications of a negative cytology result. Also, the data in the cited studies do not derive from a patient population in whom the test would be used; and there are concerns as to the reproducibility of the test.

use of epithelial cell cytology in breast cancer risk assessment and high-risk patient management Random breast epithelial cell cytology for breast cancer risk assessment and patient management does NOT meet criteria.

Women identified as being at a higher risk of breast cancer than the general population, whether by Gail risk assessment, family history, genetic analysis, or a history of breast cancer, must make choices regarding prevention or frequency of surveillance. The high-risk population represents a continuum of risk, and women at the upper end of the continuum may make different choices than those at the lower end. Thus, additional information derived from intermediate biomarkers associated with later cancer development could revise risk estimates and influence management choices. Women originally at a lower risk who are positive for an additional risk factor and at a higher risk level as a result may be more likely to select beneficial preventive treatment. Conversely, women negative for an additional risk factor who may still benefit from preventive treatment may be more likely to avoid such treatment. Potential biomarkers are hyperplasia and hyperplasia with atypia identified by cytologic analysis of random epithelial cell specimens.

Case-control and prospective cohort studies of benign breast disease have shown an increased risk of breast cancer in women with a history of ductal hyperplasia by surgical biopsy, particularly in those with atypical ductal hyperplasia. Family history of breast cancer combined with atypical hyperplasia results in a higher risk than either factor alone. There is no indication for biopsy in asymptomatic high-risk women with no evidence of a mammographic lesion or a palpable mass. However, various techniques are available for obtaining random samples of ductal epithelial cells. These include:


Random periareolar fine-needle aspiration (FNA): the needle is positioned near the areolar margin and breast tissue is probed deeply in several locations to sample the terminal lobular duct unit.

Nipple aspiration: Aspiration of ductal fluid from the nipple using a nonpowered breast pump similar to those used to express milk in lactating women. The procedure may be assisted by breast compression.

Ductal lavage: A microcatheter is inserted into the natural nipple opening of the individual mammary ducts that have been identified by nipple aspiration as yielding fluid. Saline is then infused and diluted ductal fluid withdrawn.

This Assessment evaluates whether random epithelial cell cytology evaluation on samples obtained by nipple aspiration, ductal lavage, or random periareolar FNA can assist in risk assessment and patient management and improve outcomes for women at high risk of breast cancer. Outcomes of interest are incidence of breast cancer, and morbidity and mortality from breast cancer in high-risk women whose management is influenced by ductal epithelial cell cytology results.

The female adult, non-pregnant, non-lactating breast secretes fluid into the breast ductal system; this fluid also contains shed ductal epithelial cells. Such fluid can be obtained via nipple aspiration. Ductal lavage enhances ductal fluid collection by first infusing saline solution to increase the fluid and cellular volume. Either technique can be performed during an office visit by non-physician, trained health care personnel. Both are limited in that not all women yield fluid, and in successful procedures, only fluid-yielding ducts are sampled. Random periareolar FNA is a more invasive procedure, performed by a physician, that attempts to randomly sample ductal epithelial cells from all quadrants of the breast.

Nipple Aspiration. Ductal fluid can be aspirated from the nipple using a syringe or a pump connected to a small cup that fits over the nipple; the procedure may be assisted by breast compression. Only those ducts that yield fluid can be studied. The nipple aspirate fluid can be used for cytologic and biochemical studies. Patient factors that are associated with increased ability to obtain nipple aspirate fluid include an age of 3050 years, early onset of menarche, non-Asian ethnicity, and prior parity and/or lactation (Petrakis 1993).

Random Periareolar Fine Needle Aspiration. In the absence of a mammographic lesion or palpable mass, the needle is positioned near the areolar margin. Tissue is probed deeply to sample the terminal lobular duct unit. Typically, 810 aspirations are performed per breast, sampling from all 4 quadrants of the breast, and aspirates are pooled for each breast for cytologic and biochemical studies.

Ductal Lavage. The technique of ductal lavage involves several steps. First, fluid-yielding mammary ducts are identified using nipple aspiration. Next a microcatheter is inserted into the natural nipple opening of the individual mammary ducts. Only ducts that initially yielded nipple fluid are studied. Saline is then infused and ductal fluid withdrawn. The fluid is then analyzed for cytologic or biochemical abnormalities. In women with a history of breast cancer who received mastectomy or lumpectomy plus radiation, only the contralateral breast is examined. In cancer patients who received lumpectomy alone, and in all other high-risk patients without evidence of disease, both breasts are examined.

Ductal endoscopy or ductoscopy. Fiberoptic ductoscopy is an emerging technique that allows direct visual access of the ductal system of the breast through nipple orifice cannulation and exploration. Saline can also be injected and extracted for examination of ductal lavage cytology. To date, this technique has been used in pilot studies of women with spontaneous nipple discharge. The technology was developed in Japan and has been studied primarily in Asia. As no studies of ductoscopy have focused on random examinations of high-risk women, ductoscopy will not be evaluated in this Assessment.

Breast duct fluid aspirators are similar to nonpowered breast pumps used to express milk in lactating women. They include the InDuctTM Breast Aspirator manufactured by Cytyc Health Corporation (originally Windy Hill Technology, renamed Pro-Duct Health, now a wholly owned subsidiary of Cytyc Corporation) and the Mammary Aspiration Specimen Cytology Test (MASCT) manufactured by Nastech Pharmaceutical Company, Inc.


The InDuctTM Breast MicroCatheter is manufactured by Cytyc Health Corporation for performing ductal lavage and is similar to catheters originally designed for galactography.

Each of these devices has received U.S. Food and Drug Administration (FDA) approval as substantially equivalent to devices previously cleared for marketing (i.e., 510(k) approval).

Fine-needle aspiration is a surgical procedure and, as such, is not subject to regulation by the FDA. ALTHOUGH NOT EXTENSIVE, THE EXISTING EVIDENCE SUGGESTS THAT CYTOLOGIC ATYPIA IS ASSOCIATED WITH SIGNIFICANTLY INCREASED RISK OF BREAST CANCER, AND IS INDEPENDENT OF OTHER RISK FACTORS SUCH AS FAMILY HISTORY. THIS IS TRUE WHETHER SAMPLING IS BY NIPPLE ASPIRATION OR BY RANDOM FNA AND IS LIKELY TO BE TRUE WHEN SAMPLES ARE OBTAINED BY DUCTAL LAVAGE, ALTHOUGH DIRECT EVIDENCE IS NOT YET AVAILABLE. HOWEVER, THE PREDICTIVE SIGNIFICANCE OF A NEGATIVE CYTOLOGY RESULT BY ANY SAMPLING METHOD IS UNKNOWN. NO STUDIES ADDRESS THE CONSISTENCY OF CYTOLOGIC ANALYSIS AND THE EFFECT ON RISK ESTIMATES. NOR HAVE ANY QUANTITATIVE METHODS OF EVALUATING CYTOLOGY BEEN APPLIED IN THE STUDIES OF RISK ESTIMATION.

FINALLY, THERE IS INSUFFICIENT EVIDENCE TO SHOW THAT CYTOLOGIC HYPERPLASIA WITH ATYPIA IS REVERSIBLE WITH PREVENTION INTERVENTIONS KNOWN TO DECREASE CANCER INCIDENCE; NOR DO ANY STUDIES DIRECTLY ADDRESS A POSSIBLE ASSOCIATION OF REDUCED CANCER INCIDENCE WITH PREVENTIVE TREATMENT OF HIGH-RISK WOMEN WITH CYTOLOGIC ATYPIA. ALTHOUGH THE BREAST CANCER PREVENTION TRIAL P-1 INDICATES A GREATER BENEFIT FROM TAMOXIFEN TREATMENT IN WOMEN WITH A HISTORY OF ATYPICAL HYPERPLASIA THAN IN WOMEN WITHOUT THIS BIOPSY RESULT, IT IS NOT CLEAR THAT WOMEN WITH A CURRENT CYTOLOGIC RESULT OF ATYPIA REPRESENT A SUFFICIENTLY SIMILAR POPULATION SUCH THAT THE SAME BENEFIT CAN BE PREDICTED. IT IS ALSO NOT CLEAR THAT WOMEN WITH BENIGN CYTOLOGY RESULTS WOULD NOT BENEFIT FROM TAMOXIFEN.

GIVEN THE LOW UPTAKE OF TAMOXIFEN THERAPY IN WOMEN WHO ARE AT INCREASED RISK (PORT ET AL. 2001), IT IS POSSIBLE TO SPECULATE THAT KNOWLEDGE OF ADDED RISK AS A RESULT OF CYTOLOGIC ANALYSIS MAY INFLUENCE THOSE AT GREATEST RISK AND MOST LIKELY TO BENEFIT, TO CHOOSE TAMOXIFEN THERAPY. HOWEVER, WHETHER OR NOT A CYTOLOGIC RESULT OF ATYPIA DOES INFLUENCE PATIENT MANAGEMENT AND IMPROVES PATIENT OUTCOMES IS NOT KNOWN. IT IS ALSO POSSIBLE THAT KNOWLEDGE OF A NEGATIVE CYTOLOGIC ANALYSIS RESULT WOULD INFLUENCE PATIENTS TO AVOID TAMOXIFEN WHEN THEY MIGHT OTHERWISE BENEFIT. HOWEVER, THERE IS NO EVIDENCE FOR SUCH POTENTIAL HARM.

THUS, THE EVIDENCE IS INSUFFICIENT TO SUPPORT THE USE OF CYTOLOGIC HYPERPLASIA WITH ATYPIA AS A CLINICALLY USEFUL INTERMEDIATE BIOMARKER OUTSIDE OF CLINICAL TRIALS AT THIS TIME. THE EXISTING EVIDENCE IS OF HIGH CLINICAL INTEREST BUT FURTHER FOLLOW-UP STUDIES OF RISK AND TRIALS OF INTERVENTION IN WOMEN WITH THIS MARKER WILL BE NEEDED.

Effect on risk assessment. Only a few studies evaluate the effect of cytologic hyperplasia with atypia on cancer risk in women who are already at increased of breast cancer. However, the results of these studies consistently indicate significantly increased risk whether sampling is by nipple aspiration or by random FNA. Ductal lavage has been compared to nipple aspiration and is more likely to obtain an evaluable sample with much larger numbers of epithelial cells; no prospective data evaluates risk when sampling is by ductal lavage. Presumably, risk estimates using ductal lavage cytology would be similar to those of nipple aspiration. However, the single study comparing ductal lavage to nipple aspiration cytology also indicates greater prevalence of atypia by ductal lavage; the effect of this on risk estimates is unknown. Also unknown is the predictive value of the absence of cytologic hyperplasia with atypia, regardless of sampling method.

Effect on patient outcomes. There are no studies that directly compare routine surveillance vs. routine surveillance plus epithelial cell cytology analysis in the follow-up of high-risk women for the detection of long-term clinical outcomes. No studies compared the outcomes of patients whose management was determined


by the results of routine surveillance vs. routine surveillance plus epithelial cell cytology analysis. No studies have used ductal lavage, nipple aspiration, or random periareolar FNA to influence patient management in the population of interest.

There is some indirect evidence from the NSABP Breast Cancer Prevention Trial (P-1), which enrolled women at high risk and randomly assigned them to placebo or tamoxifen for 5 years. Women with a history of atypical hyperplasia who received tamoxifen had a risk ratio for subsequent breast cancer of 0.14 (0.030.47) compared to those who received placebo over a median follow-up time of 54.6 months. Thus, high-risk women with a history of atypical hyperplasia benefited to a greater degree than the study population as a whole (RR 0.51; 95% CI, 0.390.66). It was noted, however, that the number of women in this subgroup was small, and that this was only one of five subgroups examined. Women without a history of atypical hyperplasia who received tamoxifen also benefited with a risk ratio of 0.56 (95% CI, 0.420.73). Thus, lack of a history of atypical hyperplasia does not preclude improved outcomes with tamoxifen treatment.

These trial results cannot address whether or not participants, particularly those with a negative history, had cytologic evidence of hyperplasia or atypical hyperplasia at the time of enrollment. It is possible that some of the women who were negative for a history of atypical hyperplasia would have been positive at study entry by random cytology, and may have accounted for at least part of the benefit in this subgroup. Nevertheless, it cannot be ruled out that women with no detectable atypical hyperplasia may still benefit from tamoxifen treatment.

TPMG Pascal Fuchshuber, MD, Thoracic Surgery, Walnut Creek. I believe this is an excellent review of the topic and me being a strong advocate of evidence based medicine I would agree with the conclusions. However, I believe that Kaiser is particularly well positioned to participate in developing its own trial regarding the value of breast cytology in this context. We have to have better evidence to fully support its application in the routine clinical practice.

Emerging Technology

NMP-66 Matritech, Inc. has developed a blood test for NMP-66, a protein, that may detect breast cancer. This test is being described as a a test similar to the PSA test for prostate cancer. It is recognized that even if early research shows the test has promise (current study in 1,100 women), additional research will be necessary to show it works. The test is being touted as a possible back-up to a mammogram.


http:0.420.73http:0.390.66http:0.030.47

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New Technology Breast Cancer Screening

Summary of Assessments on Select New Technologies December 2002

In March 2002, the Interregional Breast Cancer Leaders requested a review of new technologies used to screen for breast cancer. Evidence summaries for full-field digital mammography (FFDM), computer-assisted detection (CAD) mammography, and random epithelial cell cytology were provided. The purpose of this document is to update the interregional group on these technologies, based on evidence reviews created since March 2002. (See Appendix A for additional references to evidence reviews for other breast cancer technologies.)

FULL-FIELD DIGITAL MAMMOGRAPHY (FFDM)

In May 2002, KPs Interregional New Technologies Committee (INTC) discussed full-field digital mammography, using the technology assessment from the Blue Cross Blue Shield Association (BCBSA) as the primary evidence review. (This BCBSA review was summarized in the previous new technology summary, March 2002.) The INTC concluded that there was insufficient evidence to determine whether full-field digital mammography (FFDM) is a medically appropriate diagnostic option for any patient.

FFDM has not been demonstrated to be superior to screen-film mammography (SFM) applied in the screening or diagnostic setting. The evidence on use of FFDM in screening for breast cancer include interim data for 4,521 of 15,000 patients in the Lewin study. These preliminary results suggest a trend toward lower cancer detection with FFDM. A second study from Norway (Skaane) shows lower sensitivity for FFDM, but no statistical test results are available. Lewin consistently reports a lower recall rate for FFDM (11.5% and 11.8% versus 13.8 and 15% for SFM). Skaane observed higher recall rates for FFDM (reported by different investigators in the same study as 13.3%, 4.6% and 11.4% for FFDM versus 10%, 3.5% and 7.1% for SFM). The INTCnoted that the American College of Radiology Investigative Network (ACRIN) is conducting a study with a target enrollment of 49,500 subjects in the United States and Canada. The ACRIN study should have sufficient power to detect very small differences in cancer detection between SFM and FFDM, if any exist. Nineteen facilities will participate. Digital mammography systems from GE Medical Systems, Fischer Imaging, Hologic/Lorad, and Fuji Medical Systems will be tested in the study. Results will not be available until 2005 or later. In addition, the INTC noted that if FFDM is shown to be clinically equivalent to SFM, there may be operational reasons to consider FFDM including throughput, efficiency of FFDM versus SFM when used with CAD, and teleradiology advances.

Questions concerning this paper can be addressed to Robin Cisneros (Director of Medical Technology Assessment, The Permanente Federation) at (510)271-5863 or at [email protected]


mailto:[email protected]

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A technology assessment vendor, ECRI, completed a TARGET Fact Sheet on FFDM in May of 2002. No additional evidence was available for this review than for the BCBSA TEC assessment. The report noted the following: The published evidence evaluating the effectiveness of full-field digital mammography is sparse,

although there are numerous studies on performance characteristics and physics. There is a forthcoming comparative study on digital and film mammography for detecting microcalcifications (Fischer et al. 2002) and data from the abstract was reviewed in the report. Since both the BCBSA TEC and the ECRI reviews were completed, the Fischer U et al study was published in European Radiology 2002 Nov;12(11):2679-83. ( See Appendix B for the abstract for this study.)

Compared to film mammography, FFDM reduces film costs and other disadvantages associated with film storage and use, such as film degradation. It also can lower the radiation dosage to the patient and reduce the need for retakes. Additional advantages over conventional film mammography include manipulation of digital images to enhance detection of suspicious lesions and easy availability of digital data files for such applications as telemammography and computer-assisted detection. Initial studies and user reports also suggest that digital mammography offers advantages in imaging the dense breast. More clinical trials are necessary to determine whether full-field digital mammography using dedicated workstations results in improved detection of earlier-stage cancers and cancers in dense breasts and decreased false-positive biopsy rates.

Cost-effectiveness will ultimately determine whether full-field digital mammography technology is adopted, since hospitals must justify their purchase based on exam volume and patient population. The acquisition cost of digital mammography systems is significantly higher than film mammography systems, and high-resolution monitors used for soft-copy interpretation are expensive. Reimbursements for screening mammography are low and may not be sufficient to offset the increased expenditures for the new technology. Initial studies suggest that digital mammography may be able to reduce recall rates, and possibly necessary follow-up procedures, which will lower costs. Some facilities have reported substantial decreases in examination time and retakes, which will increase patient throughput and lower costs. Additional larger studies in screening populations are necessary to determine whether the cost benefits of using digital mammography relative to screening mammography outweigh the high acquisition costs.

There has also been another publication from Lewin et al which appears in the America Journal of Roentgenol 2002 Sep;179(3):631-7. (See Appendix B for abstract ). This publication updates the data available from this prospective trial to now include 6,736 of 15,000 examinations. This data is discussed in the report from CCOHTA, October 2002 (summarized below).

The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) published a Technology Report (Issue 30) in October 2002, Digital Mammography versus Film-Screen Mammography: Technical, Clinical and Economic Assessments. (This report is available upon request.) The scope of the report was digital mammography systems for breast cancer detection and the terminology used in the report is as follows:

Film-screen mammography (FSM) current standard of x-ray examination of the breast Digital mammography (DM) digital capture of images through two different technologies:

o Digital radiography mammography (DR-M) a direct system; x-ray information is directly converted into a digital image.

o Computed radiography mammography (CR-M) is an indirect system; x-ray information captured on a detector plate, from which a digital image is created.

The report offered the following overall conclusion:


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DR-M has significantly higher annualized costs than either FDSM or CR-M. Potential clinical benefits (improved diagnostic accuracy, shorter examination time, lower radiation dose) for patients, institutions and payers have not been demonstrated in a clinical setting. The ability to detect cancer is comparable for DR-M and FSM. (There is no sufficient data on clinical effectiveness of CR-M.) Assuming that DR-M and CR-M are, at best clinically equivalent to FSM, the minimum-cost system is preferred; therefore, conventional FSM is preferable to DM at this time.

An excerpt from the CCOHTA executive summary on the review of clinical effectiveness: Limited evidence indicated that DM might result in fewer women being recalled for additional workup after a screening examination. DM was not found to be superior or inferior to FSM for screening, based on receiver operating curve analysis and cancer detection rate. There was a large variability in interpretation of images. Studies also showed that DM is better for visualizing subcutaneous structures, while FSM is limited in detecting microcalcifications in dense breast tissue. Although computed radiography would be expected to have performance similar to digital radiography, there was limited direct evidence of similarities or differences.

COMPUTER-ASSISTED DETECTION (CAD) MAMMOGRAPHY

In May 2002, KPs Interregional New Technologies Committee (INTC) discussed computer-assisted detection (CAD) mammography, using an assessment from SCPMGs Medical Technology Assessment unit as the primary evidence review. The INTC concluded that CAD is a medically appropriate diagnostic option when used to supplement a radiologists initial reading of a mammogram. CAD has demonstrated that it has the potential to be equivalent in cancer detection to double reading of mammograms in some operational settings depending on the experience of the radiologists and the volume of mammograms. CAD for mammography has not been demonstrated to be superior to mammogram interpretation by two radiologists or by a single expert mammographer. CAD has also not been shown to improve health outcomes of breast cancer in any operational setting.

Excerpts from the INTCs discussion follow: There is no published evidence from controlled trials comparing the benefits and harms of CAD to

conventional mammography. Since CAD is used as a second read and identifies locations of suspected mammographic abnormalities, the sensitivity is expected to be the same or higher compared to a single reading. The recall rate is also expected to be higher. In addition, the sensitivity and specificity are likely to be related to the size of the tumor, type of tumor and age of the patient. Current data from five retrospective studies demonstrate the marginal increase in sensitivity for CAD plus radiologist compared to radiologist alone to be 4%. Dr. Adcock noted that the improvement in sensitivity will vary depending on the experience and skill of the radiologist reading the initial mammogram and the volume of mammograms the radiologists reads on a daily basis. In addition, the evidence suggests that CAD mammography is more likely to detect missed microcalcifications rather than malignant masses, calling to question to clinical significance of the discovered disease. There is no evidence that CAD screening mammography improves health outcomes.

Another external vendor of technology assessment, HAYES, Inc., updated an evidence review of CAD mammography in July 2002. This update did not yield evidence that would lead HAYES to change its rating of C from 1999. (The definition of the C Rating is: Investigational and/or experimental. The data on this procedure are promising but inconclusive regarding safety and/or efficacy. The 2002 update stated there is no clear medical consensus regarding its safety and/or efficacy.) Although HAYES rates the overall quality of the evidence as good, they found the efficacy and patient selection criteria unchanged and no long-term follow-up data available.

In October of 2002, the Blue Cross Blue Shield Association (BCBSA) completed a technology assessment on CAD mammography. Following review and discussion, the Medical Advisory Panel voted that:


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use of computer-assisted detection (CAD) devices after initial radiographic interpretation as a quality adjunct to single-reader mammography meets the Blue Cross and Blue Shield Technology Evaluation Center (TEC) criteria for patients having film-screen mammography;

use of CAD devices in patients without a prior independent interpretation of a mammogram does not meet criteria;

use of CAD devices as an adjunct to single-reader mammography does not meet the TEC criteria for patients having full-field digital mammography.

Note: Technology Evaluation Center (TEC) criteria. 1. The technology must have final approval from the appropriate government regulatory bodies. 2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes. 3. The technology must improve the net health outcome; and 4. The technology must be as beneficial as any established alternatives. 5. The improvement must be attainable outside the investigational settings.

A third party vendor, ECRI, published a Windows on Medical TechnologyTM report on CAD mammography in October of 2002. ECRI concluded there is insufficient evidence that CAD improves patient outcomes or lowers breast cancer mortality. While cancers detected with CAD are earlier in stage than cancers detected without CAD, over diagnosis, lead-time bias, and length bias all detract from the apparent benefits of mammography and other screening tests. Furthermore, the effect of earlier diagnosis is reduced by the fact that treatment is ineffective for many patients. These phenomena all contribute to the ongoing controversy about the net benefits of screening mammography after all the benefits and harms of screening and subsequent tests and treatments are accounted for. Ultimately, screening mammography and CAD are best evaluated in outcomes-oriented clinical trials. But it will be years before such trials on CAD can be completed.

Additional excerpts from the WINDOW report follow:

CAD systems are designed to reduce the number of cancers missed in diagnostic imaging examinations. Because this is a relatively new technology and clinical follow-up of screened patients takes time, clinical trials measuring both sensitivity and specificity of CAD in screening mammography have not yet been reported in the literature.

One large trial has found that CAD with the ImageChecker system increases the sensitivity of screening mammography without decreasing the PPV. Because CAD systems are intended to increase the number of examinations called positive, they will increase both the number of cancers detected and the number of women who must undergo follow-up procedures unnecessarily because of a false-positive mammogram result. But if the PPV of screening mammography without CAD is clinically acceptable (19 false positives per cancer detected), the increased false positives with CAD will be an acceptable price to pay for increased sensitivity. There is no evidence available for analysis of the effectiveness of other CAD systems, nor is there evidence directly comparing the effectiveness of CAD with the effectiveness of double reading and alternative methods of increasing the sensitivity of screening mammography.

Group Health Cooperative discussed the R2 Image Checker in October of 2002. This review found two studies of reasonable size and design and critically reviewed them. (Both of these studies were included in the BCBSA TEC assessment and ECRI Windows reports from October of 2002.)

Freer TQ, Ulissey MJ. Screening mammography with computer-aided detection: Prospective study of 12,860 patients in a community breast center. Radiol 2001; 220: 781-786.

Brem RF, Schoonjans JM. Radiologist detection of microcalcifications with and without computer-aided detection: A comparative study. Clin Radiol 2001; 56: 150-154.

This review acknowledged the following:


There is evidence from a large, prospective study (Freer) that, when radiologists interpret mammograms aided by the R2 Imagechecker, they can detect additional cancers. In the Freer study of over 12,000 mammograms, 8 out of 49 malignancies (16%) were first identified by the R2 Imagechecker. This led to the identification of an additional 0.6 cancers per 1,000 women screened (from 3.2 to 3.8 cancers per 1,000) compared to mammogram interpretation by the radiologist-only. The clinical significance of this degree of increase needs to be considered. Brem did not find a statistically significant difference in the sensitivity of mammography reading by radiologists alone versus reading by radiologists aided by the R2 Imagechecker, but the study may have been underpowered or may not have found a difference because the radiologists were highly experienced. Additional large clinical studies of the R2 Imagechecker would strengthen the evidence. There is a study on the use of R2 ImageChecker among GHC radiologists forthcoming. In summary, The R2 Image Checker passed all of GHCs Medical Technology Diagnostic Test Evaluation Criteria.

RANDOM EPITHELIAL CELL CYTOLOGY EVALUATION

In May 2002, KPs Interregional New Technologies Committee (INTC) discussed random epithelial cell cytology techniques. The INTC concluded that there is insufficient evidence to determine whether random epithelial cell cytology evaluation is a medically appropriate diagnostic option to:

evaluate breast cancer risk and contribute to high-risk patient management screen patients for breast cancer follow-up previously diagnosed breast cancer patients or monitor response to chemoprevention treatment.

The INTC used a technology assessment from BCBSA as its primary evidence review. (This assessment was summarized for the interregional breast cancer leaders in the March 2002 summary.) The BCBSA TEC assessment from March of 2002 considered the following methods of ductal cytology: ductal lavage, nipple aspiration, and random periareolar fine-needle aspiration (FNA). The assessment reviewed the value of these techniques in risk assessment and high-risk patient management. Excerpts from the INTC discussion follow:

There is some evidence that patients already at increased risk of breast cancer with cytologic hyperplasia with atypia (sampling by nipple aspiration or random FNA), are at significantly increased risk. There is no prospective data that evaluates breast cancer risk based on epithelial cytology obtained by ductal lavage. No studies have used ductal lavage, nipple aspiration, or random periareolar FNA to influence treatment decisions in high-risk women. Only a few studies evaluate the effect of cytologic hyperplasia with atypia on cancer risk in women who are already at increased of breast cancer. However, the results of these studies consistently indicate significantly increased risk whether sampling is by nipple aspiration or by random FNA. Ductal lavage has been compared to nipple aspiration and is more likely to obtain an evaluable sample with much larger numbers of epithelial cells; no prospective data evaluates risk when sampling is by ductal lavage. Presumably, risk estimates using ductal lavage cytology would be similar to those of nipple aspiration. However, the single study comparing ductal lavage to nipple aspiration cytology also indicates greater prevalence of atypia by ductal lavage; the effect of this on risk estimates is unknown. Also unknown is the predictive value of the absence of cytologic hyperplasia with atypia, regardless of sampling method.

There are no studies that directly compare routine surveillance vs. routine surveillance plus epithelial cell cytology analysis in the follow-up of high-risk women for the detection of long-term clinical outcomes. No studies compared the outcomes of patients whose management was determined by the results of routine surveillance vs. routine surveillance plus epithelial cell cytology analysis. No studies have used ductal lavage, nipple aspiration, or random periareolar FNA to influence patient management in the population of interest.

There is some indirect evidence (NSABP Breast Cancer Prevention Trial, P-1), that women with a history of atypical hyperplasia who received tamoxifen had a reduced risk ratio for subsequent breast cancer compared to those who received placebo. Thus, high-risk women with a history of atypical hyperplasia benefited to a greater degree than the study population as a whole. However, women without a history of atypical hyperplasia who received tamoxifen also benefited. Thus, lack of a history of atypical hyperplasia does not preclude


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improved outcomes with tamoxifen treatment. It is possible that some of the women who were negative for a history of atypical hyperplasia would have been positive at study entry by random cytology, and may have accounted for at least part of the benefit in this subgroup. Nevertheless, it cannot be ruled out that women with no detectable atypical hyperplasia may still benefit from tamoxifen treatment.

The net benefit of tamoxifen treatment varies with patient age and Gail risk. If the presence of atypical cytology substantially changed Gail risk, as does a history of atypical hyperplasia on surgical biopsy, then cytologic analysis of random duct fluid or FNA specimens could be used to revise Gail risk and influence patient management. However, there is insufficient evidence to show either how Gail risk would be modified, or whether the use of cytology results to change patient management influences net health outcomes.

A third party vendor, HAYES, Inc. published a report on ductal lavage in July of 2002. This review also noted a paucity of evidence on ductal lavage. All studies found in this review were included in the BCBSA TEC assessment from March of 2002. The review concluded that the limited published evidence regarding ductal lavage suggests that ductal lavage is feasible and well tolerated, yields a greater number of breast duct epithelial cells for cytological analysis than nipple aspiration, is less invasive than fine-needle aspiration, and is capable of detecting abnormal cells in nipple aspirate fluid specimens from individual breast ducts. However, there are no published data on the diagnostic sensitivity or specificity of ductal lavage, on the clinical significance of the presence of atypical cells in ductal lavage specimens, on whether the demonstration of no atypical or malignant cells correlates with a decreased risk for breast cancer, or on the use of either positive or negative test results in patient management. Although previous studies have demonstrated a relationship between the presence of atypical epithelial cells in the breast ducts and an increased risk for breast cancer, particularly in women with a strong family history of the disease or those carrying gene mutations, whether the results of ductal lavage can be used to aid in the estimation of a womans risk of breast cancer and, therefore, to guide clinical decision-making regarding preventive or therapeutic strategies has not yet been adequately determined. There is insufficient evidence from well-designed trials showing that this technique reduces breast cancer morbidity and mortality or otherwise improves health outcomes. Definitive conclusions regarding the role of ductal lavage in the diagnosis and management of breast cancers and precancers require data from well-designed clinical trials employing strict patient inclusion criteria and long-term follow-up and through the refinement of risk-assessment models incorporating ductal lavage results.

A technology assessment vendor, ECRI, completed a Windows on Medical TechnologyTM report on ductal lavage and nipple aspiration in August of 2002. No studies were discussed that were not previously discussed in the BCBSA TEC report of March 2002. The conclusions of this review follow:

Sampling ductal epithelial breast cells using ductal lavage or nipple aspiration has been suggested as a way to identify women at high risk of developing breast cancer. The relative risk of developing breast cancer after a diagnosis of atypical hyperplasia by nipple aspiration was reported by one study of more than 8,000 women to be 2.1 (95% confidence interval, 1.1 to 3.9) relative to women from whom fluid cannot be obtained by nipple aspiration. Nipple aspiration was well-tolerated and only mildly uncomfortable, with no reported side effects or morbidity.

No information about the ability of ductal lavage to predict the development of breast cancer was identified. ECRI evaluated the evidence regarding correlation between the two methods and found poor agreement. Thus, despite the apparent similarities between the two screening tests, the results of studies of nipple aspiration cannot be extended to ductal lavage. Patients reported that ductal lavage was somewhat painful (median VAS score of 2.4 on a scale of 0 to 10). The procedure carried a slight risk of breast infection. Side effects of bruising, swelling, and pain were also reported.

The available evidence suggests that nipple aspiration is not a very useful method of identifying women at high risk of developing breast cancer. Available data are insufficient to draw any conclusions about ductal lavage.


The review noted the following ongoing trials: A study sponsored by the National Cancer Institute is currently recruiting patients. This trial is enrolling patients carrying BRCA1 or BRCA2 mutations and will explore methods to screen for early breast cancer. Patients will be followed for three years and will regularly be evaluated by ductal lavage, mammography, physical examination, MRI, and positron emission tomography scanning.

Cytyc Health Corporation is sponsoring the Ductal Lavage Outcomes Tracking System (DLOTS). Cytyc states that DLOTS is a prospective, multicenter, observational outcomes database designed to collect data on the demographics, lavage procedures, cytology results, and surgical pathology results of patients at risk for developing breast cancer. The purpose is to assess the performance of ductal lavage procedures among practicing physicians and to assist physicians in patient follow-up and management. DLOTS plans to correlate ductal lavage cytology results with pathology results in patients who undergo a surgical biopsy or tumor excision and to give clinical feedback to practicing physicians using the procedure.


APPENDIX A: ADDITIONAL ASSESSMENTS ON TECHNOLOGIES RELATED TO BREAST CANCER

March 18, 2002 FULL-FIELD DIGITAL MAMMOGRAPHY (FFDM), COMPUTER-ASSISTED DETECTION (CAD) MAMMOGRAPHY, AND RANDOM EPITHELIAL CELL CYTOLOGY

BREAST BRACHYTHERAPY (INTC 10/02, BCBSA 10/02, BS of CA 10/02, HAYES 4/00 updated 9/02, CCOHTA on Mammosite 3/02)

CRYOABLATION FOR TREATMENT OF BREAST FIBROADENOMAS (HAYES 6/02)

DUCTAL LAVAGE (HAYES 7/02)

GENETIC SUSCEPTABILITY TO BREAST CANCER (HAYES 7/97 updated 3/02)

HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM CELL SUPPORT FOR THE TREATMENT OF BREAST CANCER (ICSI 4/02, HAYES 5/00 updated 9/02)

IMAGE-GUIDED, VACUUM-ASSISTED BREAST BIOPSY (ECRI TARGET, 7/02 and HAYES 11/99 updated 11/02)

LYMPHATIC MAPPING WITH SENTINAL LYMPH NODE BIPSY FOR BREAST CANCER (ICSI 7/02)

PROPHYLACTIC MEDICAL TREATMENTS FOR BREAST CANCER (HAYES 5/99 updated 7/02)

SCREENING MAMMOGRAPHY FOR WOMEN AT AVERAGE RISK FOR BREAST CANCER (HAYES 2/02)

SENTINAL NODE BIOPSY (HAYES 3/01 updated 11/02)

STEREOTACTIC BREAST BIOPSY (ECRI TARGET 8/02 and HAYES UPDATE 9/02)

TAXOL (HAYES 10/00 updated 7/02)

THERMOGRAPHY (HAYES 7/97 updated 3/02)

If you are interested in any of these reviews, please contact Robin Cisneros (Director of Medical Technology Assessment, The Permanente Federation) at (510)271-5863 or at [email protected].


mailto:[email protected]

APPENDIX B: KEY ABSTRACTS

Comparative study in patients with microcalcifications: full-field digital mammography versus screen-

film mammography. European Radiology 2002 Nov; 12(11): 2679-83. Fischer U, Baum F, Obenauer S, Luftner-Nagel S, Von Heyden D, Vosshenrich R, Grabbe E. Department of Radiology, Georg-August-University of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany, [email protected] OBJECTIVE: The goal of this prospective study was to compare a full-field digital mammography system (FFDM) to a conventional screen-film mammography system (SFM) for the detection and characterization of microcalcifications. SUBJECTS AND METHODS: Fifty-five patients with 57 isolated microcalcification clusters were examined using a FFDM system (Senographe 2000D, GE Medical Systems, Milwaukee, Wis.) and a SFM system (Senographe DMR, GE Medical Systems, Milwau

breast care / breast cancer - kaiser permanente • breast cancer is the most frequently diagnosed...

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