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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
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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
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Hereditary Breast Cancer
90%
10%SporadicHereditary
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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
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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
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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
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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
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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
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Continuum of Breast Cancer Development
Normal HyperplasiaAtypical
hyperplasia
Ductal carcinoma
in situ
Invasive Ductal
carcinoma
RR 1.5-2.0 RR 4-5 RR 8-10
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Benign breast diseaseProliferative breast diseaseRelative risk 1.5-2.0• Moderate or florid hyperplasia• Sclerosing adenosis• Intraductal papilloma• Apocrine metaplasia• Radial scar
Proliferative disease with atypiaRelative risk 4-5• Atypical lobular or ductal hyperplasia
LCISRelative risk 9-11• Lobular carcinoma in situ
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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
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Risk factors for breast cancer
Minor– Reproductive history
• Early menarche (<12)• Late childbearing (>30)• Nulliparity• Late Menopause (>55)
– Alcohol – Postmenopausal hormone use– Obesity
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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 Modelhttp://www.cancer.gov/bcrisktool/
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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
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SurveillanceAverage 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
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Mammography
• Screening mammogram– Asymptomatic patients– Two view examination of
each breast• Craniocaudal• Mediolateral oblique
• Compare with previous mammograms
RCC LCC
RMLO LMLO
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Mammography
• Diagnostic mammogram– Evaluate physical
examination findings– Evaluate abnormalities
on screening • Spot compression• Magnification views• Additional projections• Sonography
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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
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Limitations of Screening Mammography
• Interval cancer rate 10-20%• Biopsy positive predictive value (PPV2)
25%-40%• Dense breasts• Blind areas of the breast• Breast compression• “DCIS dilemma”
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Ultrasound
• Adjunct to mammography
• Not a screening tool• Used for problem
solving– Cystic vs solid– Evaluate palpable
abnormalities
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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
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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
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Options for Management of Women at Moderate Risk for Breast Cancer
• Surveillance
• Chemoprevention– Tamoxifen
• Lifestyle modification
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ChemopreventionTamoxifen
• 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
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Prevents Breast Cancer
& Inhibits RecurrenceIncreases
Thromboembolic Events
Increases Incidence ofUterine Cancer
Preserves
Bone Density
Lowers
Circulating Cholesterol
Tamoxifen Actions
Increases incidence of hot flashes
Increases incidence vaginal dryness
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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
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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
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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
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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
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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
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• 8 out of 10 lumps are NOT cancer
• Most are lumps are benign conditions– Fibroadenoma– Cyst– Fibrocystic disease
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Changing frequencies of discrete breast lumps with age
% o
f to
tal
<20 21-30 31-40 41-50 51-60 >60
10
20
30
50
40
60
70
90
80
0
Cancer
Benign breast changeFibroadenoma
Cyst
Abscess
Dixon 1995Age
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Algorithm to Evaluate Dominant Mass or Thickening
< 30 yrs. > 30 yrs. Menopausal
Breast US,considermammo
Bilateralmammo, ± US,FNA/core
Bilateralmammograms
Cyst or classicfibroadenoma
Other Cyst thatresolves
Diagnosticbenign cytology
Non-diagnostic
Observe,biopsy if itchanges
Biopsy Observe,biopsy ifit recurs
Observe,biopsy if itchanges
Biopsy FNA,biopsy
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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
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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
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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
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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.
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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
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• 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
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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
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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
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Nipple Discharge
• Physiologic– Reassure– Follow-up to assure symptoms resolve and no
new symptoms
• Persistent nonlactional galactorrhea– Medical evaluation
• Pathologic– Surgical referral – Bilateral mammogram
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The key to any breast complaint is follow-up