The Breast: an Overview

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The Breast an Overview

• Lisa S. Dresner, MD, FACS
• Associate Professor of Surgery
• SUNY Downstate

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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

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Risk of Breast Cancer
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
Lifetime risk of dx 13.22 Lifetime risk of
dying 2.96
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Anatomy
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Anatomy
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Structural Anatomy
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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)

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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

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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

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Evaluation of Breast Mass

• In women under 30 ultrasound
• In women over 30 mammoultrasound
• 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

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Ultrasound guided biopsy
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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.

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Mammogram ACR Classification
Standardized way of reporting mammogram results.
BioRads Assessment 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 3 Probably Benign Finding Short Interval Follow up Suggested (generally 6 months)
Category 4 Suspicious Abnormality-Biopsy Should be considered (risk cancer 25-50)
Category 5 Highly suggestive of malignancy- Appropriate Action should be taken (obvious cancer 75-100risk)
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Masses
Round
Circumscribed
Microlobulated
Oval
Obscured
Lobulated
Ill-defined
Irregular
Spiculated
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Infiltrating Carcinoma
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Microcalcifications Concerning
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Microcalcs Benign
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Cluster of irregular microcalcs.

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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

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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

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Stereotactic core biopsy
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Other imaging modalities

• Tc99m sestamibi scan (Miraluma)
• Tomosynthesis (variation of mammogram)

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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

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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)

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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

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Breast cyst
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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

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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

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Phylloides tumor
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Other benign breast masses

• Sclerosing adenosis
• Radial scar
• Fat necrosis
• Ductal ectasia
• Lactational mastitis and galactocele
• Mondors disease
• Intraductal papilloma
• Lactating adenoma

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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

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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

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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

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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

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Lobular Carcinoma

• Clinical features, epidemiology and risk factors
  and treatment not different
• Doesnt form microcalcifications and is
  extensively infiltrative so may be
  mammographically occult
• May present as architectural distortion on
  mamography

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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)

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Breast Cancer
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Breast Cancer Risk Factors

• Greatly increased risk RRgt4.0
• Inherited genetic mutations for breast cancer
• 2 first degree relatives with breast cancer
  diagnosed at early age
• Personal history of breast cancer
• Age gt65 (increasing risk with increasing age to
  80)

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Breast Cancer Risk Factors

• Moderately increased risk factors RR 2.1-4.0
• One first degree relative with breast cancer
• Nodular densities on mammogram (gt75 of volume)
• Atypical hyperplasia on breast biopsy
• High dose ionizing radiation to chest

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Breast Cancer Risk Factors 3

• Low increased risk RR 1.1-2
• High socioeconomic status, urban residence,
  Northern USA
• Early menarche (lt12), late menopause (gt55)
• No full term pregnancy, late (gt30) 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

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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

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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/

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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

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Inflammatory Breast Cancer
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Inflammatory Breast Cancer
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Staging

• Primary tumor
• Tis Carcinoma in-situ
• T1 2 cm or less
• T2 gt2 but not more than 5 cm
• T3 gt5 cm
• T4 any size with chest wall extension, skin
  involvement, skin nodules, or inflammatory breast
  cancer

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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

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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

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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

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Breast CancerTreatment Options

• Local control
• Lumpectomy with irradiation
• Mastectomy reconstruction
• Regional Control
• Axillary lymph node dissection
• Regional RT

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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

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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)

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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.

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Skin sparing mastectomy
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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

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Adjuvant Therapy
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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

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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)

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Internet resources

• Susan B Komen Foundation
• http//www.komen.org/
• National Cancer Institute
• http//www.nci.nih.gov/cancertopics/types/breast

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Mechanism of Action of Aromatase Inhibitors and
Tamoxifen
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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

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