Breast Pathology Flashcards
T/F: The breast is an essential organ
FALSE
The breast is non-essential for survival - major function = nutritional support of the infant
Describe the major changes the breast undergoes through life
-Expansion after menarche
-Remodeling during adulthood, especially during and after pregnancy
-Involution and regression
List the breast disease symptoms
-Pain
-Inflammation
-Nipple discharge
-Lumpiness
-Palpable masses
-Gynecomastia
Describe when the symptom of pain would be present in breast disease
Pain (mastalgia or mastodynia) - common to menses
-When localized usually due to a ruptured cyst of trauma to adipose (fat necrosis)
-Almost al painful masses are benign (10% of cancers cause pain)
Describe when the symptom of inflammation would be present in breast disease
Edema and Erythema
-Rare, most often caused by infection typically during lactation/breast-feeding
*one exception = inflammatory breast carcinoma
Describe when the symptom of nipple discharge would be present in breast disease
-Normal when small amount and bilateral
-Common benign lesion: Papilloma arising in large ducts below the nipple
-Spontaneous, unilateral and bloody discharge is concerning for malignancy
Describe when the symptom of lumpiness would be present in breast disease
Lumpiness (diffuse nodularity)
-Usually normal glandular tissue
-Imaging used to detect if there is a discrete mass
Describe when the symptom of palpable masses would be present in breast disease
-Arise from stromal or epithelial cell proliferation
-Generally detected when 2-3cm in size
- ~95% are benign
-Round to oval, circumscribed
-While malignancies generally have irregular borders some are circumscribed - all palpable masses require evaluation
Describe when the symptom of gynecomastia would be present in breast disease
-Breast enlargement in males (the only common breast symptom in males)
-Imbalance between estrogens and androgens causes an increase in stromal and and epithelial cells
Most symptomatic breast lesions (>90%) are _____
benign
What percentage of women with cancer have symptoms?
45%
With increasing age, symptoms are associated with increased likelihood malignancy. Describe this for both nipple discharge and for palpable mass
Nipple discharge:
- <60yrs = 7% due to cancer
- >60yrs = 30% due to cancer
Palpable mass
- <40yrs = 10% due to cancer
- >50yrs = 60% due to cancer
Describe Inflammatory Lesions
-Often benign, but because they are rare, always should rule out inflammatory carcinoma
-Symptoms: pain, erythema, edea
Mastitis
-Inflammatory lesion
-Bacterial infection in/through the nipple
-Caused by Staphyloccocus aureus most often
Traumatic fat necrosis
-Inflammatory lesions
-History of trauma to breast
-Small, localized tender lesion that over time scars with calcification, creating a palpable, firm lesion
Benign epithelial lesions
Most are incidental findings by mammography; some have risk for cancer development
Nonproliferative disease: (“fibrocystic change/disease”)
-Most common benign epithelial lesion; no increased risk of breast cancer
-Ducts keep single layer but are dilated (adenosis) forming variably sized brown/blue cysts and increased fibrous stroma
-Apocrine secretions may create microcalcifications (detected by mammography)
-Rupture induces chronic inflammation and fibrous producing palpable nodularity
Benign epithelial lesions - proliferative disease without atypia
Slightly increased risk of cancer (1.5-2x) - “ductal hyperplasia”
Benign epithelial lesions - proliferative disease with atypia
(4-5x increased risk). Can occur within the duct (atypical ductal hyperplasia) or the lobule (atypical lobular hyperplasia)
Describe the extent of breast cancer
-Most common malignancy of women (excluding nonmelanoma skin cancer)
-In US: incidence stable; 2nd leading cancer-related cause of death behind lung cancer in women
-Worldwide: incidence and mortality increasing
- 1/8 lifetime risk to get it; 25% die of disease
- >50yrs (75% of cases); <40yrs (5%)
List the risk factors for breast cancer
-Age
-Gender
-Family history
-Geographic variations
-Race/Ethnicity
-Ionizing radiation
-Reproductive history
Describe how age contributes to the risk of breast cancer
risk increases after 30, plateaus at menopause
Describe how gender contributes to the risk of breast cancer
1% incidence in men
Describe how family history contributes to the risk of breast cancer
-Greater risk = multiple affected first-degree relatives with early onset (<45yrs) breast cancer
-5-10% are related to specific inherited mutations which can lead to lifetime risk >90%
Describe how geographic variations contributes to the risk of breast cancer
high risk in western world
Describe how Race/Ethnicity contributes to the risk of breast cancer
European descent - highest rate (most often ER positive), Hispanic and AA - younger age, more aggressive tumors
Describe how Ionizing radiation contributes to the risk of breast cancer
during breast development increases risk
*mammograms do not increase risk
Describe how reproductive history contributes to the risk of breast cancer
All of these increase estrogen stimulation:
-early age of first menarche (period)
-older age at first pregnancy
-nulliparity (no pregnancies)
-absence of breastfeeding
-obesity or hormone replacement therapy (postmenopause)
What is the pathogenesis of breast cancer
Genetics, hormonal influences (estrogen excess) and environment
Describe how genetics plays role in breast cancer
Driver mutations in epithelial cells of the duct/lobular system cause differential expression of:
1. estrogen receptors (ER)
2. progesterone receptors (PR)
3. overexpression (due to amplification) of HER2
*These define the 3 major breast cancer subtypes with direct treatment implications (a tumor that is “triple negative” does not express these 3 things)
________ mutations account for 5-10% of breast cancers
Germline mutations
Genetics - Inherited Mutations
Most often in DNA repair genes
(BRCA1, BRCA2)
- 50% of inherited cases show BRCA1 mutations (often triple negative)
- ~1/3 of inherited cases show BRCA2 mutations (often ER positive)
Other mutated genes in familial breast cancer
- Li-Fraumeni syndrome (p53)
- Cowden disease (PTEN)
- Ataxia-telangiectasia
Histological Classification - Noninvasive
-Ductal carcinoma in situ (DCIS)
-Lobular carcinoma in situ (LCIS)
Histological Classification - Invasive (infiltrating)
-Invasive ductal carcinoma (most common, 70-80%)
-Invasive lobular carcinoma (10-15%)
Ductal carcinoma in situ (DCIS)
-Wide variety of histologic appearances (e.g. comedo necrosis - central necrosis within ducts)
-Calcifications commonly seen in mammograms
-With tx, 97% survival (surgery or irradiation)
-If ER positive, anti-estrogenic agents (tamoxifen) decreases risk of recurrence
-Untreated, 1/3 progress to cancer in same location
-Paget disease of the breast: extension of DCIS up lactiferous ducts onto skin of nipple
Lobular carcinoma in situ (LCIS)
-Monomorphic, bland cells in clusters in lobule
-Rarely forms calcifications - harder to detect on mammogram
-Tx w/ clinical/radiographic follow-up, tamoxifen (competitive inhibitor of the estrogen receptor) or bilateral prophylactic mastectomy
- 1/3 eventually develop invasive carcinoma (of these: 2/3 same breast, 1/3 contralateral breast)
Breast Cancer - Invasive Carcinomas.
Greater than 95% are ____________
adenocarcinomas
Breast Cancer - Invasive Carcinomas
Clinical classification (3 major groups)
-ER positive (HER2 negative; 50-65% of cancers)
-HER2 positive (ER positive or negative; 10-20% of cancers)
-Triple negative (ER, PR, and HER2 negative (10-20 percent))
Describe the clinical exam for breast cancer detection
-At detection, lesions average size = 2-3cm with 50% LN involvement
-In unscreened populations (including young women before mammograms) - most breast cancers detected as a palpable mass by the patient
Describe a mammogram
-Detects early, non-palpable (average 1cm), asymptomatic breast cancer before metastasis
-Only 15% LN involvement upon diagnosis with mammogram
-Most cancers in women >50yrs are detected by mammography
-More sensitive with age as fat replaces fibrous tissue
-Abnormal mammographic finding is more likely to be caused by malignancy with increasing age (10% at age 40, 25% at >50yrs)
Describe breast cancer screening
-Screening (exam + mammogram) guidelines vary
-Average risk:
*40-49yrs- individual choice whether to screen
*50-74yrs- every other year (biennial)
*>75yrs- optional, may continue if life expectancy is >10yrs
-High risk:
*parent, sibling or child with breast cancer start screening at ~40yrs
*BRCA1, BRCA2 mutation: 1-2x/yr screening and add MRI
Breast Cancer - Spread
-Progression of disease leads to:
*adherence to pectoral muscles/deep fascia
*adherence to skin causes retraction or dimpling of the skin or apple
-Lymphatic involvement may cause lymphedema causing skin thickening (peau d’orange)
-Distant metastasis may occur to almost any organ, up to many years later
*lung, skeleton, liver, adrenals, and brain are preferred sites
Breast Cancer - Prognosis
-Based on molecular and morphologic features and stage
-Size: <1.0cm excellent prognosis if no LN spread
-Lymph node involvement:
*sentinal node biopsy highly predictive of absence of metastatic CA in other nodes
*no axillary nodes - 5yr survival = 90%
*survival decreases with each positive node
-Distant metastasis - rarely curable
-Carcinoma grade and histologic type (ductal carcinomas have worst prognosis of subtypes)
-Hormone receptors- used to predict response to tamoxifen and aromatase inhibitors (aromatase turns androgen into estrogen)
-Targeted therapy of HER2/NEU (i.e. Herceptin) - getting better responses now
Oral Contraceptives
-Don’t increase breast cancer risk
-Increase risk of cervical cancer in women who are HPV+
-Increase risk of venous thrombosis and pulmonary thromboembolism because they increase coagulation factors
-Increase risk of cardiovascular disease in women smokers over 35 years
