1 Workup of Breast Masses03/31/14

2 Objectives Review breast cancer screening and diagnostic modalitiesDiscuss causes of breast masses Describe evaluation and diagnostic strategies Most masses are benign. Breast cancer is the most common cancer in women (excluding basal and squamous cell skin cancers and in situ carcinoma except urinary bladder) and is the second leading cause of cancer deaths in women after cancers of the lung and bronchus. Twelve percent of women will be diagnosed with cancer of the breast at some time during their lifetime. The median age at diagnosis is 61: 0.0% < 20 years of age 1.9% 10.6% 22.4% 23.3% 19.8% 16.5% 5.5% 85+ An efficient and accurate workup can maximize cancer detection and minimize unnecessary procedures. Sources: American Cancer Society. Cancer facts and figures National Cancer Institute. SEER Stat Fact Sheets. SEER data Identify appropriate indications for a referral to a breast specialist 2

3 Question #1 A 42-year-old female arrives for a routine annual examination. Which of the following would you NOT include as part of your exam and discussion with her? Clinical breast exam Teaching about breast self-exam Discussion about a screening mammogram I would include all of the above I’m not sure, so I will answer after I hear the lecture! VETERANS HEALTH ADMINISTRATION 3

4 Methods to Evaluate the BreastSelf-breast exam Clinical breast exam Mammography Ultrasound MRI Fine needle aspiration Core needle biopsy

5 US Preventive Services Task Force (USPSTF) Breast Self-ExamRecommends against teaching breast self- examination Grade D recommendation There is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits USPSTF grades: A: USPSTF recommends the service. There is high certainty that net benefit is substantial B: USPSTF recommends the service. There is high certainty that net benefit is moderate to substantial C: USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patients. There is moderate or high certainty that net benefit is small. D: USPSTF recommends against the service. There is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits. I: USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Suggestions for practice A: Offer/provide this service B: Offer/provide this service C: Offer/provide this service only if other considerations support offering or providing the service in an individual patient D: Discourage use of this service I: Read the clinical considerations section of the USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms. US Preventive Services Task Force. Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009;151: USPSTF. Ann Intern Med 2009;151:

6 Breast Self-Exam USPSTF recommendation is against TEACHING women breast self-examination Harms include false-positive results, which lead to increased anxiety and unnecessary visits, imaging, and biopsies Women should contact their provider if an abnormality is found on breast self-exam Breast self-exam → breast self-awareness Data for this USPSTF recommendation included two trials in Russia and China that examined teaching BSE: St. Petersburg Russia: Community without routine mammography screening (5 yr study of BSE vs control) a. Number of breast cancer cases detected increased significantly b. However, there was no decrease in all-cause mortality (RR 1.07, 95% CI ) c. Women in BSE group had more benign biopsy results compared to controls: BSE vs Control: RR 2.05 (95%CI ) Semiglazov VF, et al. [Results of a prospective randomized investigation [Russia (St.Petersburg)/WHO] to evaluate the significance of self-examination for the early detection of breast cancer]. Vopr Onkol. 2003;49: Shanghai, China: 11 years of follow up: Women instructed in BSE Control Breast cancer rates: 6.5/ /1000 # Breast cancer deaths: 135/132, /133,085 Breast cancer deaths BSE vs control RR 1.03 (95% CI ) Breast cancer rates similar No difference in breast cancer deaths c. Women in BSE group had more benign biopsy results compared to controls: BSE vs Control: RR 1.57 (95%CI ) Thomas DB, et al. Randomized trial of breast self-examination in Shanghai. J Natl Cancer Inst. 2002;94: National Comprehensive Cancer Network recommends “Breast Awareness,” where “women should be familiar with their breasts and promptly report changes to their healthcare provider.” They note “Periodic, consistent BSE may facilitate breast self-awareness.” NCCN Clinical Practice Guidelines in Oncology. Breast Cancer Screening and Diagnosis. Version I.2011. ?

7 US Preventive Services Task Force (USPSTF) Clinical Breast Exam for ScreeningUSPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of clinical breast examination beyond screening mammography in women age 40 and older Grade I recommendation USPSTF recommendation for Clinical Breast Exam: Grade I (current evidence is insufficient to assess the balance of benefits and harms of the service). US Preventive Services Task Force. Nelson et al. Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009;151: The USPSTF noted that there are there are few trials examining the effectiveness or harms of a clinical breast exam (CBE) to decrease death from breast cancer. The trials referenced include: The Canadian National Breast Cancer Screening Study-2 - This study examined Mammography +CBE vs CBE alone - The trial found no difference in breast cancer mortality between the two groups Miller AB, et al. Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged years. J Natl Cancer Inst ;92(18): In Cairo and India, countries without mammography screening programs, there are ongoing trials to evaluate CBE as the primary screening approach vs no screening. Boulos S, et al. Breast screening in the emerging world: high prevalence of breast cancer in Cairo. Breast. 2005;14(5):340-6. One trial in the Philippines with 138,392 women comparing CBE vs no screening was discontinued due to poor community acceptance. The findings were inconclusive. Pisani P, et al. Outcome of screening by clinical examination of the breast in a trial in the Philippines. Int J Cancer. 2006;118(1): Nelson et al. Ann Intern Med 2009;151:

8 Clinical Breast Exam Technique: Vertical stripe patternDuration: 5-10 minutes 63% sensitive when 5+ minutes spent on the exam Best performed after her period Clinical breast exam sensitivity ranges from 40-69% US Preventive Services Task Force. Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009;151: Calculations suggest that 6-8 minutes would be required to examine both breasts of an average patient. McDonald S, Saslow D, Alciati MH. Performance and reporting of clinical breast examination: a review of the literature. CA Cancer J Clin. 2004;54(6): USPSTF. Ann Intern Med 2009, 151:716-27; McDonald et al. CA Cancer J Clin 2004,54:

9 Review Breast cancer is the most commonly diagnosed cancer in women*2nd leading cause of cancer death Controversy regarding initiation and interval of screening continues C recommendation recommends against routine screening for 40s USPSTF reasoned that the additional benefit gained by starting screening at age 40 years rather than at age 50 years is small, and that moderate harms from screening remain at any age. This leads to the C recommendation. The USPSTF notes that a “C” grade is a recommendation against routine screening of women aged 40 to 49 years. The Task Force encourages individualized, informed decision making about when to start mammography screening. Jemal et al. Cancer statistics, CA Cancer J Clin 2009;59: *Jemal et al. CA Cancer J Clin 2009;59:

10 RR for Breast Cancer Mortality NNI to prevent 1 Breast CA deathThe Numbers Game Age Trials included RR for Breast Cancer Mortality NNI to prevent 1 Breast CA death 39-49 8 0.85 ( ) 1904 ( ) 50-59 6 0.86 ( ) 1339 ( ) 60-69 2 0.68 ( ) 377 ( ) 70-74 1 1.12 ( ) n/a These are the numbers to consider USPSTF: Although the RRR is nearly identical (15% and 14%) for these 2 age groups, the risk for breast cancer increases steeply with age starting in the 40s. Thus, the ARR from screening is greater for women aged 50 to 59 years than for those aged 40 to 49 years. Source: Nelson et al. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med, 2009;151(10):727-37, W Nelson et al. Ann Intern Med 2009;151:727-37, W

11 US Preventive Services Task Force (USPSTF) Mammography ScreeningWomen ages 40 to 49: The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms. (Grade C) Biennial screening mammography for women aged 50 to 74. (Grade B) Current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older. (Grade I) This recommendation generated a firestorm of publicity and controversy. Concerns were that insurers would use guidelines to deny coverage of mammography screening for some patients and that the guidelines were politically motivated. USPSTF Background: “The U.S. Preventive Services Task Force (USPSTF), first convened by the U.S. Public Health Service in 1984, and since 1998 sponsored by the Agency for Healthcare Research and Quality (AHRQ), is the leading independent panel of private-sector experts in prevention and primary care. The USPSTF conducts rigorous, impartial assessments of the scientific evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling, and preventive medications. Its recommendations are considered the "gold standard" for clinical preventive services. The mission of the USPSTF is to evaluate the benefits of individual services based on age, gender, and risk factors for disease; make recommendations about which preventive services should be incorporated routinely into primary medical care and for which populations; and identify a research agenda for clinical preventive care.” (Accessed ) Data used by USPSTF included: United Kingdom Age Trial: 160, 921 women aged years of follow up. Randomly assigned to annual mammography screening until 48 years or control (usual care) Screening vs Usual Care: All cause mortality RR 0.97 (95% CI ) Breast cancer mortality RR 0.83 ( ) Number needed to invite to screening to prevent one breast cancer death over 10 years= 2512 (CI, ,544) 2. Gothenburg Trial (Sweden) Enrolled women to be randomized to mammography vs usual care with 13-yr follow up. For women aged at enrollment, RR for breast cancer mortality was 0.69 (CI ) Not significant (CI includes 1). 3. USPSTF used 8 trials for meta-analysis of women aged years. Harms of mammography examined: Radiation exposure; Pain during procedures; Anxiety, distress, and other psychological responses; False-positive and False-negative mammography results, additional imaging, and biopsies; Overdiagnosis. Source: Screening for Breast Cancer: USPSTF Recommendation Statement. Ann Intern Med 2009;151(10): JAMA had a series of articles addressing the breast cancer screening debate in the 2010; 302 (2) issue. USPSTF. Ann Intern Med 2009;151:

12 Answer to Question #1 A 42-year-old female arrives for a routine annual examination. Which of the following would you NOT include as part of your exam and discussion with her? +/- Clinical breast exam Teaching about breast self-exam Discussion about a screening mammogram I would include all of the above I’m not sure, so I will answer after I hear the lecture! VETERANS HEALTH ADMINISTRATION 12

13 Question #2a A 43-year-old Caucasian patient who has not been seen since her last child was born presents for a “check-up” because both her mother and sister were diagnosed with breast cancer in the last 2 years. You determine her Gail score to be 2.7%. You tell her this is: Lower than average risk Average risk Higher than average risk VETERANS HEALTH ADMINISTRATION 13

14 Question #2b Question #2bYou discuss with this patient that the best management at this point is: Continuing with her usual screening patterns as she is at average risk for breast cancer Referring for genetic counseling for further delineation of risks, including possible genetic evaluation, as she is at high risk for breast cancer Referring to a breast surgeon for evaluation of possible mastectomy as she is at high risk for breast cancer Managing her increased risks for breast cancer, but no need for genetic evaluation as it will not add further information to her already known high risk for breast cancer 14

15 Risk Assessment for Breast CancerAppropriately managing women with BRCA1/2 mutations decreases breast cancer incidence by 80-95% Adherence to recommendations for genetic testing and counseling for high risk women is low 41% in recent vignette-based survey Average-risk women are often mislabeled as high-risk Important barrier is lack of knowledge in genetic risk and risk reduction skills Trivers et al. Reported referral for genetic counseling or BRCA 1/2 testing among United States physicians: a vignette-based study. Cancer, 2011;117: Trivers et al. Cancer 2011;117:

16 Gail Model: Breast Cancer Risk Assessment Tool http://www. cancerAge Age at start of menarche Age at time of first live birth # of first degree relatives (mother, sister, daughter) who have had breast cancer Personal history of breast cancer or DCIS Ever had a breast biopsy Race/ethnicity The Gail model has been shown to accurately estimate the proportion of women who will develop breast cancer when used in large groups. However, it does not discriminate well at the individual level between a woman who will develop breast cancer and a woman who will not develop breast cancer. Rockhill B, et al. Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. J Natl Cancer Inst. 2001; 93(5):358–366. The Gail model significantly underestimates the risk of breast cancer in women with atypia. Pankratz VS, et al. Assessment of the accuracy of the Gail model in women with atypical hyperplasia. J Clin Oncol. 2008;26(33): Both the original and the modified version of the Gail model underestimate the risk of developing breast cancer in African-American women. More importantly, the modified Gail Model (GM-B) does a worse job at predicting the development of breast cancer for blacks than the original model (GM). Adams-Campbell LL, et al. Diagnostic accuracy of the Gail model in the Black Women’s Health Study. Breast J. 2007;13(4):332-6. Rockhill et al. J Natl Cancer Inst 2001,93:358-66; Pankratz et al. J Clin Oncol 2008,26:

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18 US Preventive Services Task Force (USPSTF) Referral for Genetic CounselingScreen women whose family history may be associated with an increased risk for potentially harmful BRCA mutations. Women with positive screening results should receive genetic counseling and, if indicated after counseling, BRCA testing. Grade B recommendation USPSTF grades: A: USPSTF recommends the service. There is high certainty that net benefit is substantial B: USPSTF recommends the service. There is high certainty that net benefit is moderate to substantial C: USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patients. There is moderate or high certainty that net benefit is small. D: USPSTF recommends against the service. There is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits. I: USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Suggestions for practice A: Offer/provide this service B: Offer/provide this service C: Offer/provide this service only if other considerations support offering or providing the service in an individual patient D: Discourage use of this service I: Read the clinical considerations section of the USPSTF Recommendation Statement. If the service is offered, patients should understand the uncertainty about the balance of benefits and harms. US Preventive Services Task Force. Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2009;151: USPSTF. Ann Intern Med 2009;151:

19 Referring for Genetic CounselingIndications for referral: Known BRCA 1/2 mutation in family Breast cancer occurring before age 50 in affected relatives Bilateral breast cancer Family history of breast and ovarian cancer ≥ 2 breast cancers from same side of family Male relatives with breast cancer Ashkenazi Jewish heritage and a family history of breast or ovarian cancer Smith et al. American Cancer Society guidelines for breast cancer screening: update CA Cancer J Clin 2003;53: Daly et al. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Canc Netw 2010;8: Smith et al. CA Cancer J Clin 2003,53:141-69; Daly et al. J Natl Compr Canc Netw 2010,8:

20 Referral for Genetic CounselingGenetic counselor may or may not say patient is appropriate for genetic testing Does not change Gail score or risk of developing breast cancer Patient may not be tested, still remain high-risk Patient tested and negative for BRCA, still remains high-risk

21 Answer to Question #2a A 43-year-old Caucasian patient who has not been seen since her last child was born presents for a “check-up” because both her mother and sister were diagnosed with breast cancer in the last 2 years. You determine her Gail score to be 2.7%. You tell her this is: Lower than average risk Average risk Higher than average risk VETERANS HEALTH ADMINISTRATION 21

22 Answer to Question #2b Question #2bYou discuss with this patient that the best management at this point is: Continuing with her usual screening patterns as she is at average risk for breast cancer Referring for genetic counseling for further delineation of risks, including possible genetic evaluation, as she is at high risk for breast cancer Referring to a breast surgeon for evaluation of possible mastectomy as she is at high risk for breast cancer Managing her increased risks for breast cancer, but no need for genetic evaluation as it will not add further information to her already known high risk for breast cancer 22

23 Question #3 Question #2b In general, all of the following tests are recommended and appropriate for breast cancer screening except: Mammography MRI Ultrasound They are all appropriate I’m not sure, but I might not be teaching BSE to my patients anymore VETERANS HEALTH ADMINISTRATION 23

24 Mammography misses 10-20% of clinically palpable breast cancersScreening Asymptomatic women 2 views (4 views if breast implants) Diagnostic Women with breast mass Spot, magnified views Decreased sensitivity in women <40 years Mammography misses 10-20% of clinically palpable breast cancers The sensitivity of diagnostic mammography is up to 87%; specificity is 88% and its positive predictive value may be as high as 22%. Source: Barlow WE, Lehman CD, Zheng Y, et al. Performance of diagnostic mammography for women with signs or symptoms of breast cancer. J Natl Cancer Inst 2002;94: Barlow et al. J Natl Cancer Inst 2002;94:

25 Magnetic Resonance Imaging (MRI)Pro: Advantageous for… Screening patients at high risk Evaluating patients with a new breast cancer diagnosis Monitoring patients undergoing neoadjuvant chemotherapy Evaluating patients with metastatic axillary adenocarcinoma and unknown primary site Evaluation of silicone breast implant patients Con: Imperfect specificity due to overlap in the features of benign and malignant lesions Higher examination cost More limited availability The key benefits of breast MRI are its high sensitivity for detection of breast carcinoma and the ability to depict cancers that are occult on mammography, ultrasound, and clinical breast examination. In the clinical setting, MRI consistently demonstrates higher sensitivity (71-100%) for detecting breast cancer than mammography (13-59%) or ultrasound (13-65%), but its specificity is low. Thus, more false positives result in excess surgery. Source: DeMartini W, LehmanC. Review of Current Evidence-Based Clinical Applications for Breast Magnetic Resonance Imaging. Topics in Magnetic Resonance Imaging. 2008; 19(3): ACS Recommendations for Annual MRI Screening in high risk patients: BRCA mutation     First-degree relative of BRCA carrier, but untested     Lifetime risk 20–25% or greater, as defined by BRCAPRO or other models that are largely dependent on family history Saslow D, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin Mar-Apr;57(2): Erratum in: CA Cancer J Clin May-Jun;57(3):185. DeMartini & Lehman. Topics in Magnetic Resonance Imaging 2008,19:143-50; Saslow et al. CA Cancer J Clin 2007;57:75-89. VETERANS HEALTH ADMINISTRATION 25

26 Ultrasound Use for diagnostic purposes:Women under age 30, pregnant or lactating women with focal breast symptoms Differentiate solid vs. cystic mass Evaluate non-palpable mass on screening mammogram Masses too small or deep for aspiration Guide core biopsies if stereotactic mammography not available If strict criteria for cyst diagnosis are followed, ultrasound has a sensitivity of 89% and a specificity of 78% for detecting abnormalities in symptomatic women. It is more sensitive than mammography for detecting lesions in dense breast tissue and is superior for diagnosing benign palpable masses (up to 97% accurate vs. 87% for mammography). Sources: Moss et al. Clin Radiol 1999;54: Kolb et al. Radiology 2002;225: Lister et al. Clin Radiol 1998;53: Bevers et al. J Natl Compr Canc Netw 2009;7: When US used as adjunct to mammography for screening, sensitivity increases but specificity decreases. In 2809 women: Diagnostic Yield Mammo /1000 screened (20 /2637) Mammo+US per 1000 (31 of 2637) Diagnostic Accuracy Mammo (95% CI, ) Mammo +US (95% CI, ) PPV Mammo %; 95% CI, 14.2%-33% Mammo +US 11.2% ( 95% CI. 7.8%-15.6%) US Alone 8.9% (95% CI, 5.6%-13.3%) PPV= The positive predictive value of biopsy recommendation after full diagnostic workup Adding a single screening US to mammography yielded 1.1 to 7.2 additional cancers/1000 high-risk women, but also substantially increased the number of false positives. Berg et al. JAMA. 2008;299(18): Ultrasound is recommended for diagnostic purposes. There is a recommendation for consideration of supplemental US use (in addition to mammography) from Society of Breast Imaging and American College of Radiology for the following women: • High-risk women for whom MRI screening may be appropriate but who cannot have MRI for any reason •Women with dense breast tissue as an adjunct to mammography Lee et al.. J Am Coll Radiol. 2010;7(1):18-27. Moss et al. Clin Radiol 1999,54:676-82; Kolb et al. Radiology 2002,225:165-75; Lister et al. Clin Radiol 1998,53:490-2; Bevers et al. J Natl Compr Canc Netw 2009,7:

27 Answer to Question #3 Question #2bAll of the following tests are recommended and appropriate for breast cancer screening except: Mammography MRI Ultrasound They are all appropriate I’m not sure, but I might not be teaching BSE to my patients anymore VETERANS HEALTH ADMINISTRATION 27

28 Causes of Breast MassesNormal structures Ribs, costochondral junction, inframammary fold, fat lobules, fibroglandular tissue Biopsy and scar tissue Cysts Fibroadenomas Fibrocystic changes Carcinomas Breast masses have a variety of etiologies. Fibroadenomas are the most common benign masses, followed by benign breast tissue and focal fibroses. Cysts account for approximately 25% of breast masses. Invasive ductal carcinoma is the most common malignant mass. Source: Schoonjans JM, Brem RF. Fourteen-gauge ultrasonographically guided large-core needle biopsy of breast masses. J Ultrasound Med 2001;20: Schoonjans & Brem. J Ultrasound Med 2001;20:

29 Breast Mass CharacteristicsBenign Soft, firm, or cystic Regular Mobile Cancerous Solitary Hard Immobile Irregular ≥2 cm in size Barton et al. The rational clinical examination. Does this patient have breast cancer? The screening clinical breast examination: should it be done? How? JAMA 1999;282: Clinical exam and characteristics are NOT reliable for definitive diagnosis: need further evaluation Barton et al. JAMA 1999;282:

30 Triple Diagnosis for Palpable MassesPhysical exam, mammography, and fine needle aspiration biopsy If all 3 tests suggest benign disease… 0.7% of women had breast cancer Follow with physical exam every 3-6 months for a year If all 3 tests suggest malignancy… 99.4% of women had breast cancer Refer for definitive therapy Clinical breast exam + mammogram has PPV of 96% The Triple Test Score (TTS) helps physicians interpret discordant triple test results. A three-point scale is used to score each component of the triple test (1 = benign, 2 = suspicious, 3 = malignant): TTS of 3 or 4 is consistent with a benign lesion TTS of 5 indicates an excisional biopsy to obtain a definitive diagnosis TTS of 6 or more indicates possible malignancy that may require surgical intervention If automated core biopsy is used rather than fine needle aspiration for the triple test, the triple test sensitivity is higher (96% with core vs. 60% with fine needle). Sources: Morris KT, Vetto JT, Petty JK, Lum SS, Schmidt WA, Toth-Fejel S, et al. A new score for the evaluation of palpable breast masses in women under age 40. Am J Surg 2002;184: Morris KT, Pommier RF, Morris A, Schmidt WA, Beagle G, Alexander PW, et al. Usefulness of the triple test score for palpable breast masses. Arch Surg 2001;136: Clarke D, Sudhakaran N, Gateley CA. Replace fine needle aspiration cytology with automated core biopsy in the triple assessment of breast cancer. Ann R Coll Surg Engl 2001;83:110-2. Morris KT et al. Arch Surg 2001 and Am J Surg 2002; Clarke D et al. Ann R Coll Surg Engl 2001.

31 Case Study 1 A 29-year-old female, G0P0, presents for an annual exam. LMP was 25 days ago. She thinks she has a right breast mass area of thickening. She has no history of previous masses. Her maternal aunt had breast cancer. She reports breast tenderness. There is an 1x1 cm area on her right breast, in the right upper outer quadrant, that is slightly tender, mobile, firm.

32 Case Study 1 Differential:Cyst, fibrocystic changes, thickening, fibroadenoma, carcinoma

33 Cysts Common in perimenopause May vary with menstrual cycleRound or oval Well circumscribed Smooth, firm, mobile Focal tenderness Recurrent or complex cysts may signal malignancy; therefore, further evaluation of these lesions is required. Source: Berg WA, Campassi CI, Ioffe OB. Cystic lesions of the breast: sonographic-pathologic correlation. Radiology 2003;227: Berg et al. Radiology, 2003;227:

34 Fibrocystic Changes Normal finding Common in women ages 20 - 40~60% of premenopausal women Rubbery, painful, diffuse, symmetric thickening Common in upper outer quadrants Spontaneous resolution in up to 20% of cases Treat symptoms: soft supportive bra, NSAIDs, acetaminophen Fibrocystic breast disease is estimated to affect over 60% of all women. It is common in women between the ages of 20 and 40. It is less common in women who take birth control pills. The cause of fibrocystic breast changes is not completely understood. The changes are thought to be associated with hormones produced by the ovaries because the condition usually subsides with menopause when ovary function changes. The changes also may vary during the menstrual cycle. Risk factors include a family history of the condition, a high fat diet, and excess caffeine intake, although these are controversial.

35 Case Study 1 Question… What would you do next ?Reassure the patient and see her back in one year Biopsy the mass Do a follow-up clinical breast exam in 4-6 months Refer her to a breast specialist Order an ultrasound

36 Case Study 1 Question… What would you do next ?Reassure the patient and see her back in one year Biopsy the mass Do a follow-up clinical breast exam in 4-6 months Refer her to a breast specialist Order an ultrasound

37 Case Study 1: Scenario #1 Ultrasound done - no abnormalitiesLikely fibrocystic changes Follow-up clinical breast exam in 4-6 weeks If residual mass, refer to breast specialist

38 Case Study 1: Scenario #2 Ultrasound done - cystFine needle aspiration if tender or suspect infection Non-bloody: do not send for cytology Bloody: send for cytology, refer to breast specialist No fluid: send tissue for cytology (no malignancy does not rule out cancer) Mass remains: refer to breast specialist No mass, no bloody aspirate: repeat CBE in 4-6 weeks, refer if mass recurs or if residual mass

39 Case Study 2 A 49-year-old female presents with a new right breast lump she noticed 1 week prior. No history of trauma to the breast. She had a normal mammogram 6 months prior. Previous breast exams showed no masses. Her last breast exam was 9 months prior to presentation. G2 P0, s/p partial abdominal hysterectomy for fibroids. Family hx: +ovarian ca, -breast ca, -colon ca.

40 Case Study 2 Question #1… All of the following increase the risk of breast cancer in women ages except: Extremely dense breasts on mammogram First degree relative with breast cancer BMI ≥ 25 kg/m2 Current use of oral contraceptives Prior benign breast biopsy result

41 Answer to Case Study 2 Question #1All of the following increase the risk of breast cancer in women ages except: Extremely dense breasts on mammogram First degree relative with breast cancer BMI ≥ 25 kg/m2 Current use of oral contraceptives Prior benign breast biopsy result Nelson HD et al. Risk Factors for Breast Cancer for Women Aged 40 to 49 Years: A Systematic Review and Meta-analysis. Ann Intern Med. 2012;156(9): Data synthesis of 66 studies. For women aged years: Risk factors associated with at least a 2-fold increase in breast cancer risk included: Extremely dense breasts on mammogram First degree relative with breast cancer Risk factors associated with at least a fold increase in breast cancer risk included: Prior breast biopsy Second degree relatives with breast cancer Heterogeneously dense breasts Risk factors associated with at least a fold increase in breast cancer risk included: Current use of oral contraceptives Nulliparity Age 30 years or older at first birth Factors associated with lower than average risk included: BMI ≥ 25 kg/m2 Low breast density Age 15 years or older at menarche Birth or 3 or more children Breastfeeding Perimenopausal or menopausal status Use of menopausal, estrogen-only hormone therapy Nelson et al. Ann Intern Med 2012;156:

42 Case Study 2 (continued)Exam shows: mobile, minimally tender, smooth 1 cm mass on right breast No axillary adenopathy bilaterally

43 Case Study 2 Question #2… What would you do next?Reassure patient that because she had a normal mammogram 6 months ago there is nothing to worry about Repeat mammogram in 6 months Have patient return in one month and recheck breast exam Repeat mammogram now, with diagnostic views and ultrasound Refer to breast surgeon

44 Answer to Case Study 2 Question #2What would you do next? Reassure patient that because she had a normal mammogram 6 months ago there is nothing to worry about Repeat mammogram in 6 months Have patient return in one month and recheck breast exam Repeat mammogram now, with diagnostic views and ultrasound Refer to breast surgeon

45 Case Study 2 Test ResultsMammogram New round 1.1 cm mass BIRADS 4 Ultrasound Irregularly marginated hypoechoic solid mass The American College of Radiologists set up standards for rating mammograms, which is called BIRADS (Breast Imaging Reporting and Data System). Category 0 -- Incomplete The mammogram or ultrasound didn't give the radiologist enough information to make a clear diagnosis. Category 1 -- Normal There are no suspicious masses or calcifications; tissue looks healthy. Category 2 -- Benign or Negative Breasts are same size and shape and tissue looks normal. Any cysts, fibroadenomas, or other masses appear benign. Category 3 -- Probably Benign There are no suspicious lesions, masses, or calcifications, but follow-up to confirm that no cancer exists is recommended. This may be needed if the radiologist does not have a baseline or previous mammogram for comparison. Category 4 -- Possibly Malignant There are some suspicious lesions, masses, or calcifications to report; a biopsy is recommended to check the suspicious area. Category 5 -- Malignant There are masses with an appearance of cancer. A biopsy is recommended to make an accurate diagnosis. Category 6 -- Malignant Tissue from a biopsy has been examined and found to be cancerous, and treatment such as surgery, chemotherapy, and/or radiation is required.

46 Case Study 2 Continued TestingDiagnostic mammogram and US: Birad 4, solid mass Core needle biopsy performed Cancer: refer for definitive therapy Negative for cancer: refer to breast specialist/surgeon For lobular neoplasia, atypical ductal hyperplasia, phylloides tumor, lobular carcinoma in situ, and papillary lesions: refer to breast specialist/surgeon for open biopsy Biopsy: Infiltrating ductal carcinoma The patient was referred to surgery, presented at tumor board. Options included: Lumpectomy with post-operation radiation Mastectomy Bilateral mastectomy (patient’s inquiry): not indicated at the time of tumor board Adjuvant hormonal therapy at minimum, possible adjuvant chemotherapy. Patient had mastectomy and subsequent lymph node dissection: +nodes. Treatment: adjuvant chemotherapy, hormonal therapy (aromatase inhibitors) and XRT after completion of chemotherapy. Review of her family hx determined that it was felt she did not have a familial syndrome, and she did not undergo genetic testing for BrCA 1 and 2.

47 Carcinoma Typically singular, unilateral, persistentTypically non-tender However, may present in a variable manner No physical exam reliably distinguishes benign vs. malignant masses Most common malpractice claim is failure to diagnose breast cancer If imaging is negative, but mass is present, refer to a breast specialist According to the Physicians Insurers Association of America (PIAA), delay in diagnosis of breast cancer is the most common reason for which physicians are sued for malpractice. The typical fact pattern involves a relatively young woman who presents with a lump in her breast. The subsequent mammogram is normal, the physician assumes that the lump is benign, and advises the patient to return in a year. The current generally accepted standard of care for new breast lumps is that the health care provider can ask the patient to watch it for no more than 3 menstrual cycles. If the lump is still there, a mammogram should be performed. Even if the mammogram is negative, the patient should be referred to a breast specialist.

48 Case Study 3 A 26-year-old G1P1 female presents to your clinic. LMP was 14 days ago. No personal or family history of breast cancer. Left breast has a 2x2 firm, non- tender mass that appears mobile.

49 Case Study 3 Question… Ultrasound shows a solid lesion, benign features, possible fibroadenoma. What would you do next? Follow-up in 3-6 months with US and breast examination Obtain a mammogram Refer for biopsy of the lesion Refer for surgical excision of the lesion Reassure the patient that no further follow-up is needed

50 Fibroadenomas Most common solid benign tumor Common in young womenMedian age at diagnosis is 30 years Firm, rubbery Well circumscribed Non-tender, very mobile Growth stimulated by: Exogenous estrogen or progestin Lactation Pregnancy Fibroadenoma is the most common benign tumor of the breast and the most common breast tumor in women under age 30. Fibroadenomas are usually found as single lumps, but about % of women have several lumps that may affect both breasts. African American women tend to develop fibroadenomas more often and at an earlier age than White women. The cause of fibroadenoma is unknown.

51 Answer to Case Study 3 QuestionAn ultrasound shows a solid lesion, benign features, possible fibroadenoma. What would you do next? Follow-up in 3-6 months with US and breast examination Obtain a mammogram Refer for biopsy of the lesion Refer for surgical excision of the lesion Reassure the patient that no further follow-up is needed

52 Case Study 4 A 32-year-old G1P1 female, three weeks post-partum, presents with a painful left breast. She is breast feeding. Her exam reveals an engorged breast, very tender, warm, erythematous. One 4x4 cm area is very hard. There is minimal milk discharge from the nipple.

53 Case Study 4 Question… What is the differential? Plugged ductsMastitis Abscess Cancer All of the above

54 Causes of Breast Masses in Pregnant or Lactating WomenLactating adenoma Plugged ducts Milk retention cyst (galactocele) Mastitis Abscess Cancer Invasive Ca seen in 1/3000-1/10,000 pregnant women Other causes noted previously Resources: Scott-Conner CEH. Diagnosing and managing breast disease during pregnancy and lactation. Medscape Womens Health, 1997; 2(5):1. Sabate JM, Clotet M, Torrubia S, et al. Radiologic evaluation of breast disorders related to pregnancy and lactation. Radiographics Oct;27 Suppl 1:S Scott-Conner. Medscape Womens Health 1997,2(5):1; Sabate et al. Radiographics 2007,27:S

55 Answer to Case Study 4 QuestionWhat is the differential? Plugged ducts Mastitis Abscess Cancer All of the above

56 Pregnant or Lactating WomenBreast ultrasound is preferred for work-up Biopsy: Fine needle aspiration biopsy is not as accurate Pregnancy: higher risk of hematoma formation Lactation: higher risk of infection or milk fistula Cessation of lactation may decrease complications Do not postpone workup because of pregnancy Do not withhold mammography in suspicious cases Ionizing radiation to fetus is minimal The incidence of pregnancy-associated breast cancer is low, but may be increasing because of the number of women who are becoming pregnant at a later age. Most pregnancy-associated breast cancer presents as a painless mass which is discovered by the patient herself in 90% of the cases. Significant delays in diagnosis have been noted, averaging 5 to 7 months, but as long as 18 months. These delays are attributable to both the patient and the physician: Difficulty in palpating masses within the engorged and enlarged breasts Tendency to attribute a mass to inflammation or mastitis Inadequate follow-up by the physician or patient Reluctance to biopsy a questionable mass

57 Case Study 4 (continued)Investigate if: Breast mass persists for >2-4 weeks Ultrasound, mammogram, biopsy if needed Mastitis recurs in same area or does not respond to antibiotics

58 Final Thoughts Guideline recommendations vary by organizationMy approach may differ from yours Work-up will depend on… Patient’s age, preferences Availability of local expertise and procedures No diagnostic test is 100% specific or sensitive

59 Final Thoughts If your patient notes a breast lump, pursue evaluation until a determination is made for benign vs. malignant Negative imaging does not necessarily rule out cancer She may need further evaluation, referral to a breast specialist False negatives from mammography are not uncommon, especially in younger women. Overall, 10% of diagnostic mammograms are false negatives, with approximately twice that rate for younger women and half that rate for women over age 65.

60 Authors Primary: Ellen Yee, MD, MPH Rachel Bonnema, MD, MSNew Mexico VA Health Care System Rachel Bonnema, MD, MS VA Nebraska-Western Iowa Health Care System Contributors: Linda Baier Manwell Division of General Internal Medicine, University of Wisconsin-Madison Molly Carnes, MD, MS University of Wisconsin-Madison Center for Women’s Health Research