1. Breast cancer pathology Flashcards
Histology of breast
- Breasts are modified apocrine grands.
- Terminal duct-lobular unit is the morpho-functional unit
- 2 layers of epithelium : luminal cell layer nad myoepithelial cell layer
- Majority of breast tissue is located in the upper outer quadrant (50% of cancers arise from this area)
Epidemiology
- Most frequent cancer in female population
- Risk is high with a wester lifestyle
- Incidence rate is progressively decrease
- Mortality slightly decreased due to early diagnosis and ttt but also due to overdiagnosis
- Less than 1/3 are represented by agressive lesions
Etiology
Multifactorial:
- Inheritance: BRCA1, 2, TP53
- Wester lifestyle
- Diabetes, obesity
- Hyperestrogenic/testosterone state
- Reproductive life characteristics (early menarche, nulliparous, artificial breast feeding, infertility, late menopause)
- HRT/estrogen based contraceptive
ER expression
- Evaluted through IHC
- 80% of breast cancers are ER-dependent
- Positivity goes from 1 to 100%, negativityjust in case of 0%
- Predictive factor for hormonal therapy response (tamoxiphene or aromatase inhibitors)
- > 1-10% intermediate responders to endocrine therapy - In normal breasts: present only in luminal cells, while myoepithelial and stem cells are negative for ER
PgR expression
- Depends on intact ER pathway
- Evaluted through IHC
- Present in 70% of breast cancers
HER-2/neu receptor
- Receptor encoded by the gene found on chr17q
- AMplified in 15-20% of cases
- Overexpression identified with IHC, that is the first line test for evaluation of anti-HER2 therapy (direct only in case of 3+)
- Positivity is intensity dependent, graded 1+,2+,3+ (the most common)
- Then gene amplification can be evaluated by FISH, CISH, SISH- Best parameter that indexes response to therapy but linear correlation with HER2 IHC expression
- TTT: mAb Trastuzumab (Herceptin) or TKI (Lapatinib)
- HER2 positivity is a negative prognostic factor, but benefit from antiHER2 therapy is more relevant
ER/PgR expression
ER+, PgR+ account for 70%
ER-, PgR- for 25%
- higher is the lebel of expression the greater is the benefit from HT
- ER, PgR positivity is a positive prognostic factor, that also benefits from HT
DIagnosis: 2 answers
Fine needle aspiration biopsy or biopsy (core biopsy or mammotome)
Fine neeldle aspiration biopsy
- 1st line tool
- Does not distinguish invasive from non-invasive
- Detects malignant tumor cells, in some cases cytological nuclear grading is added (low/high)
Biopsy
2nd level of investigation -> guide therapeutic or interventional procedure
- core biopsy: needle that yields a cylinder of tissue. it is used for diagnosis and evaluation for adjuvant therapues anticipaing or substituting surgery
- Mammotome: vaccum assisted breast biopsy, demolishes target lesion. guided by US or mammography. used to sample non palpable lesions especially in presence of calcifications. In situ lesions may become invasive -> procedure not indicated in patients that won’t receive surgery.
Classification of in situ tumors
Represent the 10%
- Ductal 8%, of which 5% non comedo and 3% comedo (high grade)
- Lobular 2%
Classification of invasive carcinoma
- Non special type (60%): ductal invasive carcinoma
- Special type (30%)
Inflammatory carcinoma
Associated with mastitis and many emboli in the dermal lymphatic channels
Elston-Ellis method
Grade invasive carcinoma, based on:
- Percent tubule formation
- Nuclear pleomorphism
- Mitotic counts per 10 HPF
Groups of breast cancers based on molecular signature
- Luminal A: ER +, PgR +, HER2 -, Ki67 <67% -> endocrine therapy only
- Luminal B: ER +, PgR +, HER2 +/-, Ki67 > 29% -> HT + chemotherapy + antiHER2
- HER2 enriched: hihgh Ki67 -> chemo with antiHER2
- Basal like / tripple negative: very high Ki67, >60% -> chemotherapy only
