cancer diagnoses (molecular pathology) Flashcards
What are the predictive biomarkers in breast cancer?
ER, PgR, HER2. These allow determination of which treatments to use, e.g. trastuzumab, gefitinib.
What are the preventative biomarkers in breast cancer?
BRCA1 and BRCA2 mutations are kind of preventative markers, as we can screen them if family history is present. BRCA1 mutation occurs in 2% of all breast cancer cases, and increases the risk of getting breast cancer cases by ~40-90%. BRCA2 mutations occur in 1% of all breast cancer cases, and increases the risk of getting breast cancer by ~30-90%.
What are the classifications of breast cancer based on their gene expression?
- Luminal A - ER+, low grade, best prognosis
- Luminal B - ER+, higher grade, worse prognosis
- HER-2, poor prognosis, high grade, however many successful treatments available.
- Basal-like - TNBC, high grade, poor prognosis. No expression to target therefore have to use just chemotherapy.
How can we test recurrence of cancers?
Oncotype DX is a new testing technique which uses RT-PCR to assess the RNA expression of 21 mutated genes associated with cancer. It produces a recurrence score. If low risk score is given, adjuvant chemotherapy will not be needed. If a high risk of recurrence is indicated, a more intensive therapy will be given. This is very useful if some aspects of results appear promising (e.g. ER+ tumour, no LN involvement, no metastasis) but some appear not good (e.g. intermediate prognosis based on NPI and intermediate/high grade).
What percentage of lung cancer cases are preventable?
89%
What are the subcategories of NSCLC?
Adenocarcinoma and Squamous Cell Carcinoma
What are the approaches for individualised therapy for NSCLC patients?
We can look at the recurrent driver mutations present in tumours, and further categorise them. We can then use specific therapies targeting these mutations, e.g. ALK, KRas, and EGFR mutations, rather than general chemotherapy treatments. This approach of personalised medicine was first started in the 1990’s
Name examples of diagnostic/therapeutic markers.
An example using the ER+ status of a tumour (breast cancer) determines whether patients will be eligible for tamoxifen treatment. This can be done for lung cancer also by testing for ALK expression. If expression is present, can use crezotinib - an ALK inhibitor.
How can the PD-1/PD-L1 axis be targeted for lung cancer?
Some tumour cells express PDL1 to bind to PD-1 on the surface of T cells to block T cell killing. If we were to block PDL1 or PD1 then we can prevent them binding and allow the T cell to kill the tumour. However, this could cause the T cells to bind and attack normal cells, resulting in autoimmune responses. Moreover, tumour cells can alter their PDL1 receptor to prevent drug binding, which can lead to resistance.
What are the markers of poor prognosis in colorectal cancer?
MSI-H and mismatch repair deficiencies are molecular factors of poor prognosis in colorectal cancer due to high frequency microsatellite instability. We can test for these using immunohistochemistry.
What are the predictive markers for colorectal cancer?
There are markers and genotypes associated with a safety response to chemotherapy, e.g. UGT1A1*28 genotype indicates irinotecan toxicity, therefore a different therapy should be offered.
What are the markers of advanced colorectal cancer?
KRas and BRAF mutations are indications of advanced cases. Therefore we can use these markers to determine specific treatment options which may be effective.
