Resident Ambulatory Curriculum PGY 3 Dr. Tracie Wilcox Assistant Professor of Medicine Breast Disease

1. Resident Ambulatory Curriculum PGY 3 Dr. Tracie Wilcox Assistant Professor of Medicine Breast Disease

2. Case 1: • A 41 y o female presents to clinic for her annual exam. She has no medical problems and denies a family history of breast cancer. She has had routinely normal pap smears. She is asking you about breast cancer screening. She performs self breast exams diligently every month and has not noticed any changes.

3. Screening for Breast Cancer • How would you counsel her regarding screening for breast cancer in a low risk women of her age group? • Clinical breast exam • Self breast exam • Mammogram • MRI

4. Self Breast Exams • USPTF: recommends against teaching breast self – examination – updated 11/09 • No change in breast cancer mortality • American cancer society: “ women should be educated about benefits and limitations of monthly self breast exams” • ACOG: recommends routine teaching of SBE

5. Clinical Breast Exams • American Cancer Society: • Recommends every 3 years between age of 20-39 then annually • USPTF does not recommend clinical breast exam without mammogram

6. Mammogram • ACS/ACOG/AMA • Recommend starting routine screening at age 40 with frequency of every 1-2 years • ACP/ AFP • Recommend routine screening at age 50 • Recommend shared decision making model and individual risk assessment for women age 40-49 Screening Mammography for Women 40 to 49 Years of Age: A Clinical Practice Guideline from the American College of Physicians Amir Qaseem, MD, PhD, MHA; Vincenza Snow, MD; Katherine Sherif, MD et al., For the Clinical Efficacy Assessment Subcommittee of the American College of Physicians.3 April 2007 | Volume 146 Issue 7 | Pages 511-515

7. Mammogram • New USPTF Guidelines – 11/09 • Recommends against routine screening mammogram in women of the general population age 40-49 • Recommends mammography screening every 2 years in women 50-74 • Based on data showing: • increased rate of false-positive mammograms for women in their 40’s leading to psychological harm and unnecessary tests/procedures • Higher number needed to screen to save one life

8. Mammogram • ACS response to new USPTF Guidelines: • “The ACS continues to recommend annual screening mammography and breast exam for all women beginning at age 40”. • Recommendations based on data similar to that reviewed by USPTF + “additional data the USPTF did not consider” • Based on data showing mortality benefit in women age 40-49

9. Mammogram Age 40-50 Summary • What is the argument against? • Breast cancers less common in younger women • Mortality benefit for screening smaller than seen for women 50 and over • NNTS 50-59 to save one life: 1339 • NNTS 40-49 to save one life: 1904 • Abnormal mammogram less likely to be malignant and leads to unnecessary stress and biopsies • Increased rates of detection of DCIS • Unclear how often DCIS would progress to further cancer if left untreated

10. Mammogram Age 40-50 • What is the argument for? • Screening mammograms for women 40 to 49 years of age decrease the risk for breast cancer deaths compared with women who do not get screened • A recent meta-analysis estimated the relative reduction in the breast cancer mortality rate to be 15% after 14 years of follow-up • Diagnose breast cancer at earlier stage • Breast cancers in younger patients may be more aggressive (ER negative) Humphrey LL, Helfand M, Chan BK, Woolf SH. Breast cancer screening: a summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med. 2002;137:347-60.

11. Breast MRI • American Cancer Society recommends annual MRI in the following high risk groups: • Known BRCA mutation carriers • First degree relatives of known BRCA mutation carriers • Women with increased lifetime risk of over 20-25% based upon prediction models

12. Case 2 KP is a 50 y o white female who presents with concerns about her personal risk of developing breast cancer. Her mother was diagnosed with breast cancer at age 62. She wants to know if she would be a candidate for chemoprophylaxis. How could you determine this?

13. Breast Cancer Risk Assessment Tool (Gail Model) Calculates a woman’s 5-year and lifetime risk of developing breast cancer Includes: • Current age • Number of 1st-degree female relatives with a history of breast cancer • Age at first live birth, or nulliparity • History and Number of breast biopsies • History of atypical hyperplasia • Age at menarche • Race

14. The Gail Model • Based on data from the Breast Cancer Detection Demonstration Project • involved white women undergoing annual screening examinations • Estimates the probability that a woman will develop invasive or in situ breast cancer over a defined age interval

15. Limitations of the Gail Model • Not to be used in women already with history of LCIS, DCIS, or invasive breast cancer. • May underestimate the risk in women who have 2nd-degree relatives with breast cancer or who are known BRCA carriers • May overestimate risk with women who are over age 50 with history of two or more breast biopsies or who were under age 20 at first live birth. • Updated model validated in AA women in 2007 • Not to be used in women age < 35 . Constantino JP, Gail MH, Pee D, et al. J Natl Cancer Inst. 1999;91:1541-1548

16. The CASH (Claus / Yale) Model Calculates a woman’s risk of developing breast cancer over 10-year intervals in women with family hx of breast cancer Includes: • Number of 1st- or 2nd-degree relatives with a history of breast cancer (maternal and paternal) • Age that 1st- and 2nd-degree relatives were diagnosed with breast cancer

17. Limitations of the Claus Model • Woman must have at least one 1st- or 2nd-degree relative with breast cancer • Does not take into account other risk factors associated with breast cancer • Only included 10% AA women in data collection studies • Created prior to discovery of BRCA 1 and 2 genes

18. Case 2 continued • 45 yo white female • Menarche at age 11 • Nulliparous • Mother with breast cancer at age 62; 2 healthy postmenopausal sisters • 1 previous breast biopsy with benign pathology

19. Using the Gail Model, this patient’s risk for developing breast cancer is: 5-year risk = 2.8% Lifetime risk = 23.2%

20. Chemoprevention • Would you offer this patient chemoprevention? • If so, what medication would you offer?

21. Chemoprevention • Average risk for 45 y o caucasian women is: • 5 yr: 1% • Lifetime: 11.9% • Consider chemoprevention in patients age 35-59 if 5-year GAIL model risk > 1.66%

22. Chemoprevention Options • SERM: • Tamoxifen • Shown to decrease risk of ER positive invasive breast cancer and noninvasive breast cancer • Highest benefit in younger women, women without uterus, and women with highest risk of breast cancer • Taken for 5 years • No study has shown survival benefit • Raloxifen • Reduces incidence of invasive breast cancer in high risk women • Lower risk of DVT, PE, cataract • Approved in US for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk of developing breast cancer • Aromatase inhibitors – currently being studied

23. Case 3 • 35 y o female with significant family history for breast cancer tests positive for the BRCA mutation. She opts against surgical prophylaxis. • How would you screen her for breast cancer?

24. Increased Surveillance in High Risk Women with BRCA mutations • Annual mammogram starting age 25 • Annual MRI starting age 25 • Clinical breast exam 2-4x/year starting age 20-25 • Annual self breast exam • Discuss chemoprevention options

25. Case 4 • A 45 yo AAF presents to your clinic for a routine physical. Two months prior to moving to Chicago she detected a lump on self breast examination. Follow-up mammogram and biopsy showed “fibrocystic changes”. She wants to know whether this will increase her chances of breast cancer and has brought the report for you to evaluate: • She has no family history of breast cancer.

26. Case 9 cont: • Pathology: • “Fibrocystic changes without atypia” • Her breast cancer risk is: • 1)Average • 2)Increased • 3)Decreased

27. “Fibrocystic Changes” • Non proliferative breast lesion • Most common cause of breast nodularity and pain in women age 20 to 50 • Increase in number of cysts and fibrous tissue • Exam reveals rubbery non-discrete glandular tissue. May also appreciate cysts. • May have associated nipple discharge: color can be pale green to brown

28. Fibrocystic Disease • Fibrocystic change of the breast in conjunction with severe pain (which is usually cyclical), palpable mass and occasionally nipple discharge

29. Fibrocystic Breast and Cancer Risk • Fibrocystic change denotes normal breast tissue without an appreciable increase in cancer risk • Proliferative lesions with associated atypia increase risk • Ex: Atypical hyperplasia – relative risk 3-6 fold

30. Case # 5 • A 36 y o female presents to your clinic with complaints of nipple discharge. • What questions do you ask her and how do you evaluate her?

31. Historical Questions • Is it unilateral or bilateral? • Is it spontaneous or provoked by manipulation? • What is the color and consistency of the fluid? • How long has it been going on? • Any association with physical events such as trauma? • Any new medications which might be associated? • Associated amenorrhea or symptoms of hypogonadism (hot flashes, vaginal dryness)

32. Physical Exam • Check for skin changes and asymmetry of breasts • Determine the number of ducts involved • Determine if discharge unilateral or bilateral • Check for associated breast mass and LAD • Check the color and consistency of the fluid? • Straw colored: intraductal papilloma compressing venous/lymphatic system • Grossly Bloody: • 1/3 fibrocystic breast • 1/3 intraductal papilloma • Intraductal carcinoma • Test any discharge for blood with hemoccult test • Intraductal pathology, occasionally breast CA

33. Case 5 Continued • On further questioning she reports unilateral discharge that is spontaneous and is straw colored. She denies any amenorrhea or hot flashes or vision changes. • PE reveals no breast asymmetry, no palpable mass, expressible unilateral discharge that is straw colored, from a single duct, and guiac negative. • How would you evaluate her further?

34. Diagnostic Testing • Labs for multiductal discharge: TSH, prolactin, pregnancy test • Mammogram if >30 (dedicated mammogram with magnified views of retroaerolar area) + peri-areolar u/s +/- ductal studies • Cytology – rarely helpful • If negative does not rule out malignancy • Surgical evaluation for breast lump, imaging abnormality, + guaiac test, unilateral spontaneous from one duct

35. Case 5 Continued • Mammogram shows breast nodule and breast u/s + ductogram reveal intraductal papilloma • Referred to surgeon and papilloma resected

36. Characterization of Nipple Discharge:

37. Normal Discharge • = Lactation

38. Physiologic Discharge • = galactorrhea • = nonpathologic d/c not related to pregnancy or nursing • Discharge is usually seen only with compression of ducts (usually multiple ducts are involved) • Discharge is usually bilateral • Fluid color may be clear, yellow, white or dark green • Guiac negative

39. Causes of Galactorrhea • Idiopathic • Secondary • Hyperprolactinemia – ex: pituitary adenoma • Medications: TCA’s, antipsychotics,narcotics • Menarche or Early Menopause • Nipple Stimulation • Trauma to anterior thoracic nerves • Other: stress, mastitis

40. Pathologic Causes • = suspicous causes • malignant or nonmalignant • more likely to occur spontaneously, be unilateral, and confined to one duct • Fluid more often bloody • Associated mass may be present

41. Pathologic Nipple Discharge • Ddx: • Intraducal papilloma • Most common cause ( 52-57%) • Ductal ectasia • Fibrocystic changes • Malignancy - 5-15% • Increases with increasing age • DCIS most common

42. False Nipple Discharge • Fluid does NOT originate in breast secretory unit • Eczema • Cutaneous viral infections • Nipple trauma eg. Joggers nipples • Draining sebacous cyst • Other skin infections of inflammations (e.g. moloscum contagiosum)

43. Case 6 • A 56 y o female presents with left sided nipple discharge associated with redness and skin irritation. • On PE there is no palpable lump in the breast but + erythema and skin thickening around the areola • What is your concern and what kind of work up should you order?

44. Physical Exam

45. Paget’s Disease • Clinical symptoms: • scaly, raw, vesicular, or ulcerated lesion that begins on the nipple and then spreads to the areola • Pain, burning, pruritus • yellow, clear, viscous or bloody discharge • Associated with underlying breast cancer in 97% of cases • Dx: breast exam,mammo,MRI, punch biopsy of the skin • Trx: mastectomy vs resection of nipple/areola complex + xrt