The Breast: an Overview

Lisa S. Dresner, MD, FACS

Associate Professor of Surgery

SUNY Downstate

Prevalence/Incidence

200,000 new cases in USA / year Incidence

– 121 / 100,000 white women– 99 / 100,000 black women

Stage– Increased numbers of early and non-invasive

cancers– Stable or slightly decreased number of advanced

Rates: vary geographically and ethnically Rates vary greatly by age

Current age

+10 yrs +20 yrs +30 yrs Eventually

0 0.00 0.00 0.05 13.22

10 0.00 0.05 0.48 13.37

20 0.05 0.48 1.92 13.40

30 0.44 1.88 4.49 13.41

40 1.46 4.11 7.56 13.14

50 2.73 6.30 9.64 12.06

60 3.82 7.40 9.52 9.99

Risk of Breast Cancer

Lifetime risk of dx: 13.22 %Lifetime risk of dying: 2.96 %

Anatomy

Anatomy

Structural Anatomy

Physiology

Cell Regulation:– Growth development and function under hormone

control– Binding of hormone to specific cell receptors trigger

effects Estrogens:

– important in development, growth and differentiation. Normal and most malignant breast cells contain ER receptors.

– E-ER complex binds with nuclear chromatin and influences protein production including progesterone receptor (PR)

History:

– Complaint, ask about SBE– Timing and nature of previous breast

surgery (atypia, cancer etc)– Family history of breast or ovarian cancer– Use of hormones– Reproductive history– Radiation exposure

Physical Exam

Best/easiest during week after menses Palpate supraclavicular, cervical and axillary

nodes Skin changes: dimpling, edema, nipple

change With patient supine with hand over head

examine breast in a systematic way against the chest wall

Evaluation of Breast Mass In women under 30 ultrasound In women over 30 mammo±ultrasound As a rule all except obviously benign masses should

have pathological diagnosis– Open biopsy– Core biopsy– FNA– Ultrasound guided core biopsy (highly sensitive and specific)

If the mass is indeterminate by your exam consider ultrasound to confirm

If mass not palpable stereotactic core biopsy

Ultrasound guided biopsy

Screening:

No controversy: all women aged 50 and older should have a mammogram every 1-2 years as well as an annual clinical breast exam (CBE)

Women 40-50: guidelines ACS mammogram every 1-2 years as well as an annual clinical breast exam (CBE)

High Risk: earlier mammography.

Mammogram: ACR Classification

Standardized way of reporting mammogram results.

BioRads Assessment

Category 0 Needs Additional Imaging Evaluation

Category 1 Negative (5/10,000 risk of breast cancer)

Category 2 Benign Finding (5/10,000 risk of breast cancer)

Category 3Probably Benign Finding: Short Interval Follow up Suggested (generally 6 months)

Category 4Suspicious Abnormality-Biopsy Should be considered (risk cancer 25-50%)

Category 5Highly suggestive of malignancy- Appropriate Action should be taken (obvious cancer: 75-100%risk)

Circumscribed

Microlobulated

Obscured

Ill-defined

Spiculated

Masses:

Round

Oval

Lobulated

Irregular

Infiltrating Carcinoma

Microcalcifications: Concerning

Microcalcs: Benign

Cluster of irregular microcalcs.

Management of Non-Palpable Mammographic abnormalities

Ultrasound: is there a mass?– Ultrasound guided core biopsy may be diagnostic

Stereotactic core biopsy– Mammographic abnormalities

Mammotome (mammo-guided very big core; may be excisional)

Needle localization biopsy– Mammo or ultrasound guided open biopsy

Cryoablation: for bx proven benign

MRI for evaluation of the breast

Highly sensative but high false postive rate

Useful for screening BRCA patients May be useful in staging known breast

cancer May become an important screening

modality

Stereotactic core biopsy

Other imaging modalities

Tc99m sestamibi scan (Miraluma) Tomosynthesis (variation of

mammogram)

MRI – Extremely sensitive (?high false positives?)

– May be useful in staging– May be useful in high risk patients with

difficult mammograms– Not yet approved for screening

Benign Breast Disorders: 1

Fibrocystic “disease”– Nodular, lumpy, tender breasts:– Mastodynia– Clear/milky nipple discharge– Within the range of normal

Confirm benign-ness, Reassurance, symptomatic relief. Encourage BSE

Fibrocystic features– Adenosis, cysts, fibrosis (not increased risk)– Ductal and lobular hyperplasia with or without atypia

(with increased risk)

Breast cysts:

A palpable mass could be a cyst– Simple cysts need no treatment

• Needle aspiration to confirm, or for pain relief• Ultrasound (conclusive)

– Complex cysts, bloody cysts deserve evaluation and biopsy (open or ultrasound guided core)

• Excision if diagnosis is in doubt after minimal invasive biopsy

Breast cyst

Fibroadenoma

May present at any age but most common women 16-24.

Rubbery, mobile, well defined Confirm by core, excision, FNA, or ultrasound,

and/or short interval observation by ultrasound Giant fibroadenomas: may be very large and

grow rapidly (late teens and perimenopause): RX: enucleation

Actual pathology may be adenoma, fibroadenoma,etc

Phylloides Tumor

Old name cystosarcoma phylloides Mesenchymal tumor: leaf like masses, cellular with

necrosis and hemorrhage May occur in adolescent (generally benign) or

premenopausal woman (may be malignant) Treated with excision with margins 25% risk of local recurrence in 10 years even with ‘benign”

path Mitotic figure count is one predictor of malignancy Metastasis even in “malignant” tumors are rare Younger: more likely benign, older women more likely

malignant

Phylloides tumor:

Other benign breast masses

Sclerosing adenosis Radial scar Fat necrosis Ductal ectasia Lactational mastitis and galactocele Mondor’s disease Intraductal papilloma Lactating adenoma

Mastodynia

– Cyclical or continuous. May be referred to axilla, upper arm, may improve with menopause

– Rarely associated with malignancy– Continuous: may be related to a large

cyst,infection or inflammation– Reassurance, NSAIDS, well fitted brassiere,

caffeine reduction, evening primrose oil, cessation of tobacco use (takes months)

– Danazol, bromocriptine and tamoxifen (side effects prohibitive)

– ?SSRI

Nipple Discharge

– Most common after lactation (as long as 2 years)– Subareolar infection (increased risk in smokers)– Galactorrhea (bilateral, milky) prolactin excess– Fibrocystic: green, yellow, brown (guiac)– Bloody: intraductal papilloma (benign), Cancer

should be ruled out. Ductogram (galactogram) may be helpful

Hyperplasias: not malignant but not really benign either

Ductal hyperplasias– Mild– Moderate– Florid– Atypical Ductal hyperplasia (ADH)– (Ductal carcinoma in-situ- DCIS*)

Lobular hyperplasias– Lobular hyperplasia– Lobular carcinoma in-situ

Lobular Carcinoma In-situ LCIS

Bystander lesion- marker of risk Commonly occurs in 4th decade of life, 2/3 are

premenopausal Lobular tumors are more likely ER/PR positive Diagnosis incidental on biopsy of other pathology Significant life time risk of breast cancer (5.9 to 12

times higher) but the risk is in both breasts Risk is greater 15-20 years after diagnosis than the

immediate post diagnostic period

Lobular Carcinoma

Clinical features, epidemiology and risk factors and treatment not different

Doesn’t form microcalcifications and is extensively infiltrative so may be mammographically occult

May present as “architectural distortion on mamography

Invasive Ductal Carcinoma

Most common tumor: from ductal elements Invasion of nerves, vessels, lymphatics in the

breast parenchyma at edge of lesions may be present and carries a poorer prognosis

May have all or partial characteristics of other types (colloid, tubular, medullary)

Breast Cancer

Breast Cancer Risk Factors

Greatly increased risk RR>4.0– Inherited genetic mutations for breast

cancer– ≥ 2 first degree relatives with breast cancer

diagnosed at early age– Personal history of breast cancer– Age >65 (increasing risk with increasing

age to 80)

Breast Cancer Risk Factors

Moderately increased risk factors RR 2.1-4.0– One first degree relative with breast cancer– Nodular densities on mammogram (>75%

of volume)– Atypical hyperplasia on breast biopsy– High dose ionizing radiation to chest

Breast Cancer Risk Factors 3

Low increased risk: RR 1.1-2High socioeconomic status, urban residence, Northern USA

Early menarche (<12), late menopause (>55)

No full term pregnancy, late (>30) first term pregnancy

Never breast fed

Postmenopausal obesity

Etoh,consumption

HRT, recent oca use

Tall

Personal history of ca endometrium, ovary or colon

Jewish heritage, mammographically dense breasts

Inherited Breast Cancer Syndromes 1. Li-Fraumeni syndrome: p53 mutation 2. Mutation on the sht arm of chromosome 2 3. BRCA-1 long arm chromosome 17 (associated

with breast and ovarian cancer) 4. BRCA-2 small region of 13q12-13 Recommendations vary from bilateral salpingo-

oophorectomy and prophylactic mastectomy to increased surveillance

Value of SERM (tamoxifen) unclear as most hereditary-linked breast cancers are ER/PR negative

Estimating Risk Gail Model

– calculates risk using 6 key risk factors• Age• Age menarche• Age first birth• Family history (1° female relative)• Number of previous breast biopsies• Number of biopsies with atypical hyperplasia

http://bcra.nci.nih.gov/brc/

Inflammatory breast cancer

Diagnosis: clinical findings of inflamed breast with underlying malignancy.

35% have obvious mets at time of diagnosis Mammogram: edema Dermal or core biopsy Treatment is neoadjuvant chemotherapy first

then mastectomy plus RT

Inflammatory Breast Cancer

Inflammatory Breast Cancer

Staging

Primary tumor– Tis: Carcinoma in-situ– T1 : 2 cm or less– T2 : >2 but not more than 5 cm– T3 : >5 cm– T4 : any size with chest wall extension,

skin involvement, skin nodules, or inflammatory breast cancer

Staging

Nodes– N0 no involved nodes– N1 mets to ipsilateral nodes (movable)– N2 mets to ipsilateral nodes matted/fixed– N3 ipsilateral internal mammary nodes

Metastasis– M0, M1

Stage Groups

Stage 0 Tis, N0, M0 Stage 1 T1, N0, M0 Stage IIA T0-1, N1,M0 T2 , N0, M0 Stage IIB T2, N1, M0 T3, N0, M0 Stage IIIA T0-2, N2, M0 T3, N1-2, M0 Stage IIIB T4, N1-2, M0 Any T, N3, M0 Stage IV Any T, Any N, M1

Tumor related prognostic factors

Size ER and PR status Margins Histologic type Pathologic prognostic features

– Nuclear grade, angiolymphatic invasion, lymphocytic response

Invasivion: DCIS vs infiltrating intraductal I– invasion of basement membrane– Often both on same specimen

Breast Cancer:Treatment Options

Local control:– Lumpectomy with irradiation– Mastectomy ± reconstruction

Regional Control– Axillary lymph node dissection– Regional RT

Neoadjuvant Chemotherapy

Recommended for Stage IV, and some III and IIb patients

May allow breast conservation therapy in women by downstaging tumor.

Unclear yet that it improves survival but good response is a good prognostic sign

Sentinal node biopsy

New standard for clinically negative axilla Avoids full axillary dissection and its

complications in patients with small tumors and negative node status

blue dye plus nuclear medicine Axillary node evaluation done to identify

node positive patients so as to guide adjuvant therapy

“Proven” benefit in women with T1 tumors (where axillary node infrequently involved)

Breast Conservation

Quality of results improved by increasing facility with autologous flaps and use of tissue expanders

Improved quality of result with advent of skin sparing mastectomy

Options include flaps (Tram, latissimus), free flaps, and implants.

Skin sparing mastectomy

Adjuvant therapy

Chemotherapy– Decreases rate of distant recurrence– Recommended for stage stage II breast cancers

Hormonal therapy– Effect in ER/PR positive breast cancers similar to

chemotherapy– New agents (aromatase inhibitors) may supplant

Tamoxifen in the next few years in post menopausal patients

Recommendations for Adjuvant therapy in stage I and II Breast CancerPremenopausal Postmenopausal

Tumor ER positive ER-Negative ER positive ER-Negative

<1 cm, negativenodes

ø ø ø ø

≥ 1 cm, negativenodes

Tam ± chemo Chemo Tam Chemo

Positive Nodes Chemo Chemo Tam Chemo

Adjuvant Therapy

On the horizon

Ductal Lavage and FNA Digital mammography Bone marrow biopsy

and staging Sentinal node biopsy ? Axillary node dissection? Aromatase therapy will supplant Tamoxifen Increasing number of women with low stage

tumors receiving chemotherapy Life long treatment with aromatase inhibitors

Prevention: Bilateral mastectomy

– Bilateral mastectomy decreases the risk of breast cancer by 90%

Salpingo-oophorectomy– Recent study demonstrated significant decrease in new

breast cancer risk in BRCA carrier women Chemoprevention

– Tamoxifen– ?Raloxifen: trials ongoing– ?Aromatase inhibitors?– Chemoprevention is less likely to be effective in BRCA1

tumors (greater # receptor negative tumors)

Internet resources:

Susan B Komen Foundation:http://www.komen.org/

National Cancer Institutehttp://www.nci.nih.gov/cancertopics/

types/breast

Mechanism of Action of Aromatase Inhibitors and Tamoxifen

Aromatase Inhibitors

Lower circulating estrogens by preventing peripheral production of estrogens

anastrazole = Arimidex letrozole = Femara exemestane = Aromasin Each has been studies in different

clinical circumstances