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