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    • 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. 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. Hereditary Breast Cancer
    • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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>http://www.cancer.gov/bcrisktool/ </li></ul>
    • 14.  
    • 15.  
    • 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>
    • 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>
    • 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
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 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
    • 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
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 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
    • 35. Algorithm to Evaluate Dominant Mass or Thickening
    • 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>
    • 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
    • 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>
    • 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.
    • 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>
    • 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>
    • 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>
    • 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>
    • 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>
    • 45. <ul><li>The key to any breast complaint is follow-up </li></ul>

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