CAP Breast Cancer and Molecular

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List 3 patient and 4 tumour features that affect Prognosis and treatment. 

Patient: age, menstual status, comorbidities; Tumour factors: N status, LVI, size, grade

Describe the histological grading system used for breast cancer. 

Nuclear pleomorphism, mitoses, and mitotic index (each scored 1-3), with cumulative grade 1(score 3-5), grade 2(score 6-7), and grade 3 (score 8-9)

Describe the genomic grading system used for breast cancer. 

Low grade path (+1q, -16q), High grade (17q12, 11q13, nad 1p21-p25)

What defines a positive ER by IHC for the purpose of determining Tamoxifen therapy? 

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what defines a positive HER2 for the purpose of treatment with Herceptin? 

HER2 IHC >30% with complete membranous staining OR HER2/CEP17 >2.2

What are the indications for chemotherapy for breast cancer patients? 

Low expression of ER/PR, Grade 3 histology, Ki67>20%, 4+ nodes positive, +LVI, and tumour >5cm]

What are the indications for hormonal therapy alone? 

high expression of ER, Grade 1, Ki67>40%, Node negative, LVI not identified, and tumour 1-2cm

What are the four categories of breast cancer using the molecular classification of gene expression? 

Luminal A, Luminal B, Basal, and Her2 OverExpression

What is the difference between unsupervised and supervised molecular classification of tumours? 

Supervised is based on seperating patients by clinical features (e.g. progression) and trying to identify common molecular characteristics within those groups. Unsupervised is the opposite, tumours are grouped by common molecular features and their behaviour examined based on these groups.

What are the four groups and list one gene for each used in the Oncotype Dx 21 Gene prognostic model. 

Invasion (Cathespin L2, Stromolysin), HER2 (Her2, GRB7), ER (BCL2, SCUBE2, ER, PR), Proliferation (Cyclin D1, Ki67, MYBL2, STK15, Survivin)

What are the features of Luminal A breast cancer? 

High ER/PR expression, low histological grade, low levels of proliferative genes, HER2neg, indolent clinical course, better prognosis, Tamoxifen responders, low recurrence score Oncotype Dx, minimal benefits of adjuvant chemotherapy.

What are the features of Luminal B breast cancer? 

low ER/PR expression (may be PR neg), over expression GFR(Her2 & EGFR), higher histological grade, more aggressive clinical course, worse prognosis, more likely positive lymph nodes, and high expression of proliferative genes (Ki67)

What are the features of Luminal B HER2 
ER+, HER2+, agressive clinical course, decrease response to tamoxifen, may benefit from chemo and tamoxifen, increased recurrence risk Oncotype Dx Score, some may benefit form Herceptin+Chemo+Tamoxifen
What are the features of Her2 Enriched breast cancers? 
GEP are ER neg, over expression of other genes in HER2 aplification, high proliferative index, increased probability of P53 mutation, high histological grade, younger age, agressive clinical course, Poor Px, good response to herceptin in combination with chemo, pathological complete response to chemo+herceptin


What are the features of Basal breast cancer?