Pathology - Breast Flashcards
Germ line mutations underlie what proportion of breast cancer?
What features suggest an underlying hereditary etiology?
12% of breast cancers.
Hereditary etiology is suggested in the setting of multiple affected first degree relatives, pre-menopausal cancers, or family members with specific malignancies.
What are the major risk factors for carcinoma of the breast?
Age and gender
Age at menarche (early menarche and late menopause increase risk)
First live birth
First degree relatives with breast cancer
Breast biopsies
Race
What proportion of breast cancers are attributable to BRCA genes?
About 25% of all familial cancers (3% of all breast cancers) can be attributed to two highly penetrant autosomal dominant genes: BRCA 1 and BRCA 2.
What are BRCA 1 and BRCA 2?
Where are they located?
What is their role?
BRCA 1 (17q21) and BRCA 2 (13q12-13) are two genes associated with the occurrence of breast and several other cancers.
Their exact role is unknown though they are known to be tumour suppressor genes as LoF leads to cancer.
Protein products of both genes are localised to the nucleus and are believed to be involved in transcription regulation.
What cancers is BRCA 1 associated with?
Breast cancer
Epithelial ovarian cancer (substantial)
Prostate and colon (slightly)
What cancers is BRCA 2 associated with?
Ovarian cancer (less than BRCA 1) Male breast cancer Melanoma Pancreatic tumours Stomach Bile ducts
What are the developmental roles Oestrogen plays in breast cancer?
Metabolites of oestrogen can cause mutations or generate DNA damaging free radicals.
Via its hormonal actions, oestrogens drive the proliferation of premalignant lesions as well as cancers.
Describe the broad classification of breast cancer:
Almost all breast malignancies are adenocarcinomas, all other types (phyllodes, sarcomas, lymphomas) make up fewer than 5%.
Carcinomas are divided into in-situ carcinomas or invasive (infiltrative) carcinomas. In situ lesions are limited to the ducts and lobules by the basement membrane. Invasive carcinoma has spread to the stroma.
DCIS constitutes what proportion of breast cancer in well screened populations?
How to they typically “present”?
15-30%
Most are detected mammographically, presenting with calcifications more often than periductal fibrosis. They are bilateral in 10-20% of cases.
Left untreated, what proportion of DCIS will progress to cancer?
1% per year.
Treatment option for DCIS?
Mastectomy is curative in 95% of patients.
Excision with adjuvant radiotherapy has slightly higher rates of recurrence related to grade, size, and margins.
Regardless of treatment, less than 2% of women with DCIS will die of breast cancer.
What is Paget’s disease of the nipple?
A rare occurrence 1-4%
Malignant cells extend from the DCIS into nipple skin without crossing the basement membrane. Manifests as an erythema tours eruption with a scaly crust.
Appearance of comedocarcinoma versus non-comedocarcinoma?
Comedocarcinoma is characterised by high grade pleomorphic cells, NC-DCIS has a monomorphic population of cells.
What is LCIS?
Comprises 1-6% of all breast cancers and is always an incidental finding since it does not manifest on mammography. It is bilateral in 20-40% of cases.
LCIS progresses to invasive cancer at a similar rate to DCIS; 1% per year.
What is the level of nodal involvement in palpable versus mammographically detected lesions?
If palpable: 50% of patients have nodal involvement
If detected on mammogram: 20% have nodal involvement
