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

90%

10%SporadicHereditary

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 HyperplasiaAtypical

hyperplasia

Ductal carcinoma

in situ

Invasive Ductal

carcinoma

RR 1.5-2.0 RR 4-5 RR 8-10

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

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 Modelhttp://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

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

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 (PPV2)

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

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

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

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

% 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

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

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