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    1. 1. Benign Breast Disease: Surveillance, Diagnosis and Treatment Helen Krontiras, M.D. Assistant Professor of Surgery Co-Director UAB Breast Health Center Co-Director Lynne Cohen Preventive Care Program for Women’s Cancers at UAB
    2. 2. Risk factors for breast cancer <ul><li>Major </li></ul><ul><ul><li>Gender </li></ul></ul><ul><ul><li>Genetic Predisposition </li></ul></ul><ul><ul><li>Histologic risk factors </li></ul></ul><ul><ul><ul><li>Personal history of breast cancer </li></ul></ul></ul><ul><ul><ul><li>Atypical hyperplasia </li></ul></ul></ul><ul><ul><ul><li>Lobular carcinoma in situ </li></ul></ul></ul><ul><ul><li>Age </li></ul></ul><ul><ul><li>Therapeutic radiation including breast tissue in the field </li></ul></ul>
    3. 3. Hereditary Breast Cancer
    4. 4. Familial Breast Cancer Syndromes <ul><li>BRCA 1 </li></ul><ul><ul><li>Familial breast and ovarian cancer </li></ul></ul><ul><li>BRCA 2 </li></ul><ul><ul><li>Familial breast and ovarian cancer, with male breast cancer and pancreatic cancers among others </li></ul></ul><ul><li>Li-Fraumeni (p53 or CHK2) </li></ul><ul><ul><li>Sarcomas, brain tumors, adrenal cortical cancers and breast cancer </li></ul></ul><ul><li>Cowden’s Disease (PTEN) </li></ul><ul><ul><li>Breast cancer, thyroid cancer and skin lesions </li></ul></ul><ul><li>Peutz-Jeghers (tumor suppressor LKB1) </li></ul><ul><ul><li>mucocutaneous melanotic pigmentation, intestinal polyposis and increased risk of breast cancer among others </li></ul></ul>
    5. 5. BRCA 1 and 2 <ul><li>Autosomal dominant </li></ul><ul><li>50% of familial breast cancer syndromes </li></ul><ul><li>The prevalence of BRCA mutations is 0.1% in the general population </li></ul><ul><li>BRCA 1 </li></ul><ul><ul><li>chromosome 17q21 </li></ul></ul><ul><ul><li>50-85% lifetime risk of breast cancer </li></ul></ul><ul><ul><li>20-40% lifetime risk of ovarian cancer </li></ul></ul><ul><li>BRCA 2 </li></ul><ul><ul><li>chromosome 13q12 </li></ul></ul><ul><ul><li>50-85% lifetime risk of breast cancer </li></ul></ul><ul><ul><ul><li>Increased risk of male breast cancer as well </li></ul></ul></ul><ul><ul><li>10-27% lifetime risk of ovarian cancer </li></ul></ul>
    6. 6. Familial Breast Cancer <ul><li>Both maternal and paternal family histories are important </li></ul><ul><li>Computational tools are available to predict the risk for clinically important BRCA mutations </li></ul><ul><li>Respect confidentiality </li></ul><ul><li>DNA testing is available for both genes </li></ul><ul><li>Genetic counseling for those whom testing is considered </li></ul>
    7. 7. General Family History Risk Factors for Carrying a BRCA1 or BCRA2 Mutation <ul><li>Known BRCA1 or BRCA2 mutation </li></ul><ul><li>Breast and ovarian cancer </li></ul><ul><li>Early onset breast cancer </li></ul><ul><li>Multiple breast primaries </li></ul><ul><li>Male breast cancer </li></ul><ul><li>Ashkenazi ancestry </li></ul>
    8. 8. Probability of developing breast cancer by age <ul><li>From age 30 to age 40 . . . . . . .1 out of 257 </li></ul><ul><li>From age 40 to age 50 . . . . . . .1 out of 67 </li></ul><ul><li>From age 50 to age 60 . . . . . . .1 out of 36 </li></ul><ul><li>From age 60 to age 70 . . . . . . .1 out of 28 </li></ul><ul><li>From age 70 to age 80 . . . . . . .1 out of 24 </li></ul><ul><li>Ever . . . . . . . . . . . . . . . . . . . . . .1 out of 8 </li></ul>Source: National Cancer Institute Surveillance, Epidemiology, and End Results Program, 1995-1997
    9. 9. Continuum of Breast Cancer Development Normal Hyperplasia Atypical hyperplasia Ductal carcinoma in situ Invasive Ductal carcinoma RR 1.5-2.0 RR 4-5 RR 8-10
    10. 10. Benign breast disease <ul><li>Proliferative breast disease </li></ul><ul><li>Relative risk 1.5-2.0 </li></ul><ul><li>Moderate or florid hyperplasia </li></ul><ul><li>Sclerosing adenosis </li></ul><ul><li>Intraductal papilloma </li></ul><ul><li>Apocrine metaplasia </li></ul><ul><li>Radial scar </li></ul><ul><li>Proliferative disease with atypia </li></ul><ul><li>Relative risk 4-5 </li></ul><ul><li>Atypical lobular or ductal hyperplasia </li></ul><ul><li>LCIS </li></ul><ul><li>Relative risk 9-11 </li></ul><ul><li>Lobular carcinoma in situ </li></ul>
    11. 11. Atypical Hyperplasia Lobular carcinoma in situ <ul><li>Markers for increased risk </li></ul><ul><li>If found on core biopsy, surgical excision necessary to rule out 30-50% incidence of coexisting cancer </li></ul><ul><li>If found on excisional biopsy, no further surgical therapy warranted </li></ul><ul><li>Management of AH and LCIS </li></ul><ul><ul><li>Surveillance or, </li></ul></ul><ul><ul><li>Chemoprevention or, </li></ul></ul><ul><ul><li>Rarely Prophylactic surgery </li></ul></ul>
    12. 12. Risk factors for breast cancer <ul><li>Minor </li></ul><ul><ul><li>Reproductive history </li></ul></ul><ul><ul><ul><li>Early menarche (<12) </li></ul></ul></ul><ul><ul><ul><li>Late childbearing (>30) </li></ul></ul></ul><ul><ul><ul><li>Nulliparity </li></ul></ul></ul><ul><ul><ul><li>Late Menopause (>55) </li></ul></ul></ul><ul><ul><li>Alcohol </li></ul></ul><ul><ul><li>Postmenopausal hormone use </li></ul></ul><ul><ul><li>Obesity </li></ul></ul>
    13. 13. Gail Model <ul><li>Developed at the National Cancer Institute by Dr. Mitchell Gail in 1989 </li></ul><ul><li>Individualized risk prediction </li></ul><ul><ul><li>Individual’s estimated 5-year and lifetime risk are calculated and compared to women the same age and race who are of average risk </li></ul></ul><ul><li>Increased risk is defined as a 5-year risk of 1.7% or greater </li></ul><ul><ul><li>Equates to the risk of an average 60 year old woman </li></ul></ul><ul><li>Gail Model </li></ul><ul><li> </li></ul>
    14. 16. Limitations of Gail Model <ul><li>Not used in those with prior history of breast cancer or LCIS </li></ul><ul><li>May underestimate risk with family history suggestive of a gene mutation </li></ul><ul><ul><li>Other models exist for this patient population </li></ul></ul><ul><li>Validity in women under 35 years of age is unknown </li></ul><ul><li>Validity in non-Caucasians is unknown </li></ul>
    15. 17. Surveillance Average Risk for Breast Cancer <ul><li>Mammography </li></ul><ul><ul><li>Annual screening beginning at age 40 </li></ul></ul><ul><li>Clinician breast examination </li></ul><ul><ul><li>Annual evaluation beginning with GYN exams </li></ul></ul><ul><li>Self breast examination </li></ul><ul><ul><li>Regular, breast self-awareness </li></ul></ul>
    16. 18. Mammography <ul><li>Screening mammogram </li></ul><ul><ul><li>Asymptomatic patients </li></ul></ul><ul><ul><li>Two view examination of each breast </li></ul></ul><ul><ul><ul><li>Craniocaudal </li></ul></ul></ul><ul><ul><ul><li>Mediolateral oblique </li></ul></ul></ul><ul><li>Compare with previous mammograms </li></ul>RCC LCC RMLO LMLO
    17. 19. Mammography <ul><li>Diagnostic mammogram </li></ul><ul><ul><li>Evaluate physical examination findings </li></ul></ul><ul><ul><li>Evaluate abnormalities on screening </li></ul></ul><ul><ul><ul><li>Spot compression </li></ul></ul></ul><ul><ul><ul><li>Magnification views </li></ul></ul></ul><ul><ul><ul><li>Additional projections </li></ul></ul></ul><ul><ul><ul><li>Sonography </li></ul></ul></ul>
    18. 20. Benefits of Screening Mammography <ul><li>Randomized trials show reduction in mortality by at least 24% </li></ul><ul><li>Cancer detected in 2-3 of every 1000 women who undergo regular screening mammography </li></ul>
    19. 21. Limitations of Screening Mammography <ul><li>Interval cancer rate 10-20% </li></ul><ul><li>Biopsy positive predictive value (PPV 2 ) 25%-40% </li></ul><ul><li>Dense breasts </li></ul><ul><li>Blind areas of the breast </li></ul><ul><li>Breast compression </li></ul><ul><li>“DCIS dilemma” </li></ul>
    20. 22. Ultrasound <ul><li>Adjunct to mammography </li></ul><ul><li>Not a screening tool </li></ul><ul><li>Used for problem solving </li></ul><ul><ul><li>Cystic vs solid </li></ul></ul><ul><ul><li>Evaluate palpable abnormalities </li></ul></ul>
    21. 23. Clinical Breast Exam <ul><li>Recommended annually for all women 20 years and older </li></ul><ul><li>Inspection of nipple and skin </li></ul><ul><li>Palpation of nodal basins </li></ul><ul><ul><li>Cervical, supraclicular, infraclavicular, and axilla </li></ul></ul><ul><li>Systematic examination of the entire breast </li></ul><ul><ul><li>Include tissue over sternum </li></ul></ul><ul><ul><li>Inframammary fold </li></ul></ul><ul><ul><li>Retroareolar area </li></ul></ul>
    22. 24. Self Breast Exam <ul><li>Inexpensive, noninvasive </li></ul><ul><li>5-7 days after the onset of menses or on the same day of the month for postmenopausal women </li></ul><ul><li>New changes should be brought to the attention of primary care provider </li></ul><ul><li>Randomized controlled trials have shown no reduction in mortality from breast cancer among women who performed monthly BSE </li></ul>
    23. 25. Options for Management of Women at Moderate Risk for Breast Cancer <ul><li>Surveillance </li></ul><ul><li>Chemoprevention </li></ul><ul><ul><li>Tamoxifen </li></ul></ul><ul><li>Lifestyle modification </li></ul>
    24. 26. Chemoprevention Tamoxifen <ul><li>Consider for women at increased risk </li></ul><ul><li>Currently only FDA approved medication for risk reduction for breast cancer </li></ul><ul><li>Selective estrogen receptor modulator </li></ul><ul><li>50% reduction in breast cancer risk </li></ul><ul><ul><li>86% with atypical hyperplasia </li></ul></ul><ul><ul><li>56% with lobular carcinoma in situ </li></ul></ul>Fisher et al, J Natl Cancer Inst 1998
    25. 27. Prevents Breast Cancer & Inhibits Recurrence Increases Thromboembolic Events Increases Incidence of Uterine Cancer Preserves Bone Density Lowers Circulating Cholesterol Tamoxifen Actions Increases incidence of hot flashes Increases incidence vaginal dryness
    26. 28. Options for Management of Women at Increased Risk for Inherited Breast Cancer <ul><li>Surveillance </li></ul><ul><ul><li>Breast self examination </li></ul></ul><ul><ul><ul><li>Monthly Beginning at age 18 </li></ul></ul></ul><ul><ul><li>Clinical breast examination </li></ul></ul><ul><ul><ul><li>Semiannually at age 25 </li></ul></ul></ul><ul><ul><li>Mammogram and MRI </li></ul></ul><ul><ul><ul><li>Annually starting at age 25 or 10 years younger than the youngest affected relative </li></ul></ul></ul><ul><li>Chemoprevention </li></ul><ul><ul><li>Tamoxifen </li></ul></ul><ul><li>Prophylactic surgery </li></ul><ul><ul><li>Bilateral Total Mastectomy </li></ul></ul><ul><ul><li>Bilateral Oopherectomy </li></ul></ul>
    27. 29. Breast MRI <ul><li>Approved for breast by FDA in 1991 </li></ul><ul><li>Contrast enhanced (Gadolinium) </li></ul><ul><li>Current data only supports its use for screening in women who are at increased risk for an inherited breast cancer </li></ul>
    28. 30. Rationale for MRI Screening of Populations at Increased Risk for Inherited Breast Cancer <ul><li>80% lifetime risk </li></ul><ul><li>Develop cancer at an early age when breasts are dense </li></ul><ul><li>Grow rapidly </li></ul><ul><ul><li>50% “interval cancers” </li></ul></ul><ul><li>Median size 1.7 cm </li></ul><ul><ul><li>50% have spread to lymph nodes </li></ul></ul>
    29. 31. Palpable Mass <ul><li>Thorough history and physical examination </li></ul><ul><ul><li>Onset, duration, change over time </li></ul></ul><ul><ul><li>Breast cancer risk factors </li></ul></ul><ul><li>Dominant mass </li></ul><ul><ul><li>Discrete or poorly defined </li></ul></ul><ul><ul><li>Cystic or solid </li></ul></ul><ul><li>Persistent through the menstrual cycle </li></ul><ul><li>Distinct from surrounding tissue </li></ul><ul><li>Asymmetric with respect to the opposite side </li></ul>
    30. 32. Palpable Masses <ul><li>Suspicious masses </li></ul><ul><ul><li>Hard or firm </li></ul></ul><ul><ul><li>Indistinct, irregular borders </li></ul></ul><ul><ul><li>Attached to the skin or deep fascia </li></ul></ul><ul><li>Benign masses </li></ul><ul><ul><li>Mobile </li></ul></ul><ul><ul><li>Well demarcated </li></ul></ul><ul><ul><li>Soft </li></ul></ul><ul><li>Accuracy of physical examination alone is limited </li></ul><ul><ul><li>Correct in 60-85% of cases </li></ul></ul><ul><ul><li>More difficult in younger women </li></ul></ul>
    31. 33. <ul><li>8 out of 10 lumps are NOT cancer </li></ul><ul><li>Most are lumps are benign conditions </li></ul><ul><ul><li>Fibroadenoma </li></ul></ul><ul><ul><li>Cyst </li></ul></ul><ul><ul><li>Fibrocystic disease </li></ul></ul>
    32. 34. Changing frequencies of discrete breast lumps with age % of total < 20 21-30 31-40 41-50 51-60 >60 10 20 30 50 40 60 70 90 80 0 Cancer Benign breast change Fibroadenoma Cyst Abscess Dixon 1995 Age
    33. 35. Algorithm to Evaluate Dominant Mass or Thickening
    34. 36. Palpable Mass <ul><li>Any discrete solid mass should prompt a surgical referral for tissue diagnosis </li></ul><ul><ul><li>Even if mammogram is negative </li></ul></ul><ul><li>If the clinical examination and mammogram are normal but the patient says she can feel a lump, follow-up clinical examination in 2-3 months </li></ul><ul><li>Diffuse nodularity without a discrete mass should be followed clinically at a different point in the menstrual cycle </li></ul>
    35. 37. Palpable Mass <ul><li>Triple test diagnosis </li></ul><ul><ul><li>Physical examination </li></ul></ul><ul><ul><li>Mammography and/or ultrasound </li></ul></ul><ul><ul><li>Cytology or histology </li></ul></ul><ul><li>There is 0.5% probability of malignancy when all three are benign </li></ul>Donnegan, NEJM 1992
    36. 38. Abnormal Mammogram <ul><li>Increased use of screening mammogram </li></ul><ul><li>has resulted in in the identification of a large </li></ul><ul><li>number of subclinical abnormalities </li></ul><ul><ul><li>Mass </li></ul></ul><ul><ul><li>Calcifications </li></ul></ul><ul><ul><ul><li>Clustered </li></ul></ul></ul><ul><ul><ul><li>Pleomorphic </li></ul></ul></ul><ul><ul><ul><li>Grouped </li></ul></ul></ul><ul><ul><ul><li>Linear </li></ul></ul></ul><ul><ul><ul><li>Branching </li></ul></ul></ul><ul><ul><li>Architectural distortion </li></ul></ul>
    37. 39. BIRADS <ul><li>Category 0: Need Additional Imaging Evaluation </li></ul><ul><li>Category 1: Negative </li></ul><ul><li>Category 2: Benign Finding </li></ul><ul><li>Category 3: Probably Benign Finding. Short Interval Follow-Up Suggested </li></ul><ul><li>Category 4: Suspicious Abnormality. Biopsy Should Be Considered </li></ul><ul><li>Category 5: Highly Suggestive of Malignancy. Appropriate Action Should Be Taken </li></ul><ul><li>Category 6: Known Malignancy </li></ul>American College of Radiology (ACR) Breast Imaging Reporting and Data System Atlas (BI-RADS® Atlas). Reston, Va: © American College of Radiology; 2003.
    38. 40. Abnormal Mammogram <ul><li>Careful physical examination </li></ul><ul><li>Diagnostic imaging often obviates the need for biopsy in patients with normal physical examination </li></ul><ul><ul><li>50% of indeterminate lesions are found to be unequivocally benign or can be followed with interval mammography </li></ul></ul><ul><li>Patients with new findings that cannot be resolved should be referred to a specialist </li></ul>
    39. 41. <ul><li>Core biopsy (preferred) or excisional biopsy for BIRADS 4 or 5 </li></ul><ul><li>Surgical excision indicated after benign core biopsy for atypical hyperplasia, LCIS, radial scar, nondiagnostic specimen, discordant result </li></ul>
    40. 42. Nipple Discharge <ul><li>Common symptom but uncommon presentation of breast cancer </li></ul><ul><li>Likelihood of discharge being associated with carcinoma increases with age </li></ul><ul><ul><li>32% of women over 60 </li></ul></ul><ul><ul><li>7% of women under 60 </li></ul></ul><ul><li>Physical examination </li></ul><ul><ul><li>Evaluate for palpable masses </li></ul></ul><ul><li>Cytology not useful in evaluating nipple discharge </li></ul><ul><li>Imaging </li></ul>
    41. 43. Nipple Discharge <ul><li>Physiologic Discharge </li></ul><ul><ul><li>With compression </li></ul></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Multiple ducts </li></ul></ul><ul><li>Pathologic Discharge </li></ul><ul><ul><li>Spontaneous </li></ul></ul><ul><ul><li>Unilateral </li></ul></ul><ul><ul><li>Single duct </li></ul></ul><ul><ul><li>Bloody </li></ul></ul><ul><li>DDx </li></ul><ul><li>Extensive nipple manipulation </li></ul><ul><li>Vigorous aerobic exercise </li></ul><ul><li>Stress </li></ul><ul><li>Pregnancy </li></ul><ul><li>DDx </li></ul><ul><li>Intraductal papilomatosis </li></ul><ul><li>Duct ectasia </li></ul><ul><li>Intraductal mastitis </li></ul><ul><li>Cancer </li></ul>
    42. 44. Nipple Discharge <ul><li>Physiologic </li></ul><ul><ul><li>Reassure </li></ul></ul><ul><ul><li>Follow-up to assure symptoms resolve and no new symptoms </li></ul></ul><ul><li>Persistent nonlactional galactorrhea </li></ul><ul><ul><li>Medical evaluation </li></ul></ul><ul><li>Pathologic </li></ul><ul><ul><li>Surgical referral </li></ul></ul><ul><ul><li>Bilateral mammogram </li></ul></ul>
    43. 45. <ul><li>The key to any breast complaint is follow-up </li></ul>