the breast: an overview lisa s. dresner, md, facs associate professor of surgery suny downstate
TRANSCRIPT
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