17 - Breast Cancer Flashcards
Most common cancer in woman excluding non melanoma skin cancer
Invasive breast carcinoma
5 year survival of breast cancer
95%
Risk factors
- Gender
- Age (over 50)
- Previous breast carcinoma
- Oestrogen exposure
- Nulliparity
- Older age at first pregnancy
- Genetics
- Radiation
Estimating risk
Breast Cancer Risk Assessment Tool
Hereditary Breast Cancer
- 5-10% of all BC
- Younger at age, bilateral
- BRCA1/BRCA2
BRCA1/BRCA2
- Tumour suppressor genes
- Most common (47% of heritable BC syndromes)
- Highly penetrant, autosomal dominant pattern
- Lifetime risk of BC 50-85%
- Increased risk of other cancers (BRCA1- ovarian, colon, prostate; BRCA2- ovary, pancreas, prostate)
- Mutations rare in pathogenesis of sporadic BC
Well characterised heritable mutations beside BRCA1/BRCA2
- TP53
- ATM
- PTEN
- STK11
Benign lesions
- More common than BC
- Non proliferative and many proliferative breast disease have no increased risk, some do
Proliferative breast disease without atypia
- Associated with mild increase of BC (2x above general pop)
- Includes epithelial hyperplasia, columnar cell change, papilloma, radial scar
Proliferative breast disease with atypia
- Associated with moderate increased risk of BC (4-5x above general pop)
- Includes atypical papilloma, columnar cell change with atypia, atypical hyperplasia
- Exist toward the ‘benign’ end of a biologic continuum with low grade in situ and low grade invasive BC
Breast carcinoma in situ (CIS)
- Malignant BC cells confined to ductal lobular system without basement membrane invasion into stroma
- Cells are morphologically and genetically identical to invasive BC
- Associated with high risk of invasive BC (10x above general pop)
Classification of CIS
- Ductal (DCIS)
- Lobular (LCIS)
Difference between DCIS and LCIS
Different biology, clinical presentation, pathology and management
DCIS
- BC cells confined within duct spaces, occasionally lobular spaces
- Exist toward the ‘malignant’ end of a biologic continuum with ductal type BC
- No invasion thus no metastatic potential
DCIS histopathology
- Malignant cells
- Variable growth pattern (solid, cribriform, micropapillary etc)
- Necrosis
- Calcifications
DCIS prognosis
- Grade
- Extent of lesion
- Completeness of excision
Management of DCIS
Surgical excision with clear margins +/- radiotherapy
Paget’s disease of the nipple
- BC cells within epidermis of nipple
- Associated with underlying high grade DCIS, cells spread up lactiferous ducts
Clinical symptoms of Paget’s disease of the nipple
Red, weeping, “eczematous” nipple
Histopathology of Paget’s disease of the nipple
BC cells admixed with keratinocytes in epidermis
Management of Paget’s disease of the nipple
Surgical excision with clear margins including associated DCIS
Prognosis of Paget’s disease of the nipple
Dependant on features of associated DCIS (+/- invasive)
LCIS
- BC cells confined within lobular spaces, occasionally duct spaces
- The biologic nature and potential of classical LCIS is less clear cut than for DCIS
- Exist toward the ‘malignant’ end of a biologic continuum with
lobular type BC - Risk of subsequent BC is bilateral and the invasive BC may or may not be lobular type
Clinical features of LCIS
- Usually incidental finding
- 20-40% bilateral, often multifocal
Histopathology of LCIS
Expansion of lobules by discohesive, uniform neoplastic cells, with loss of E-cadherin expression
Management of LCIS
- Isolated in core biopsy (–> increased surveillance)
- Associated with mod-high risk lesion (e.g. DCIS) (–> dictated by the mod-high risk lesion)
- In surgical margins in excision (–>no action required)
- Consider anti-oestrogen risk reducing medication
Breast cancer
- Invasion of malignant epithelial cells beyond basement membrane into stroma
- Access to vessels and lymphatics leads to potential metastasis
Clinical features of BC
- Lump
- Pain
- Nipple change/discharge
- Skin changes (ulceration)
BC workup
- Examination (breast, axilla)
- Pathology (Fine needle aspiration or core biopsy)
- Radiology (MMG, US, MRI)
Pathology of BC
- Malignant cells, invasive into stroma
- Classifiers constitute important BC prognostic and predictive factors
How are BCs classified
- Type, grade, stage (degree of spread)
- Biomarker expression
- +/- molecular profile
‘special’ types of breast carcinoma with good prognosis
- Mucinous carcinoma
- Tubular carcinoma
‘special’ types of breast carcinoma with bad prognosis
- Micropapillary carcinoma
- Basal like carcinoma
Grading of BC
- Nottingham grade
- Based on Tubule formation, nuclear atypia and Mitotic rate
Staging of BC
- TNM
- Tumour size
- Nodal burden (number and size of deposits in draining nodes)
- Metastases
BC spread via lymphatics
Will usually manifest as axillary node deposit
Biomarkers
- Measurable biological characteristic
- Indicator of normal/pathologic process
- Prognosis or predictor of response to treatment
- Assessed by IHC or ISH
Three biomarkers in routine use in BCs
- ER (oestrogen receptor)
- PR (progesterone receptor)
- HER2
ER/PR pathways
Oestrogen and progesterone bind to ER/PR in cytoplasm, migrate to nucleus, transcribe DNA to protein and exert physiological effects
Physiological effects of ER/PR
- Promote growth and differentiation in normal
breast tissue - Promotes a growth advantage for overexpressing malignant cells
ER/PR prognostic and predictive
- ER+/PR+ BC improved survival vs ER-/PR- due to response to anti-oestrogen therapy (80% vs 10% response)
- ER in ~80% invasive BC
- PR in ~65% invasive BC
Example of anti-oestrogen therapy
tamoxifen
Her2
- Transmembrane tyrosine kinase (TK) protein
- Binds ligand (growth factors), forms heterodimers with other HER family proteins, activates
intracellular signals - Promote growth and differentiation in normal
breast tissue - Promotes a growth and survival advantage for overexpressing malignant cells
Intracellular signals activated by Her2
- Upregulates the RAS-MAPK pathway –> proliferation
and invasiveness - Upregulates the PI3K pathway –> inhibits cell death
Her2 prognostic and predictive
- Her2 positive BC poor survival vs Her2 negative BC
- Strong predictor of response to
anti-HER2 therapies (e.g Trastuzumab)
Four distinct BC subsets
- Luminal A
- Luminal B
- HER2 enriched
- Basal like
MC management
- Surgical excision with clear margins (Mastectomy or wide local excision)
- +/- axillary surgery
- +/- radiotherapy
- +/- chemotherapy (if high risk clinicopathological features)
+/- radiotherapy
- To the chest wall (if WLE or positive margins on mastectomy)
- To the axilla or supraclavicular nodes (if high nodal burden)
