Molecular Pathology - Breast cancer management Flashcards
High grade ductal carcinoma in situ
Which genetic test is done?
IHC for Estrogen receptor and progesterone receptor (ERPR)
HER2 is not tested for in-situ cancer, no need to do HER2 ISH and IHC
IHC of HER2 on breast cancer tissue is done on what specimen?
Paraffin section in 10% formalin for more than 6 hours
IHC score is 2+ for HER2 staining in breast CA.
Next step?
Score 2+ = Perform HER2 FISH on recurrent tumor
FISH for HER2 in breast cancer is performed.
HER2:CEP17 ratio is >2
Average HER2 per cell is >4
FISH result?
Treatment?
Positive
Give Herceptin
IHC score is 3+ for HER2 staining in breast CA.
Next step?
Score 3+ = give Herceptin
Histopathology:
- Invasive ductal carcinoma, grade I
- Low grade DCIS
- Size: 9mm
- No lymphovascular invasion
- No sentinel LN
- Margins: clear
IHC
- ERPR positive
- HER2 Equivocal/ score 2+
- Ki67 index: 12%
What additional test?
What specimen?
Reflex ISH for HER2
Done on INVASIVE component of formalin fixed paraffin embedded breast cancer tissue
+ve HER2 give Herceptin and lapatinib (TKI)
Patient with breast cancer is not eligible for HER2 treatment.
What additional molecular tests should be done to consider adjuvant chemotherapy?
Gene expression profiling
- Oncotype DX - 21 gene recurrence score *****
Predicts benefit of chemotherapy for ER+ve, early stage breast CA - MammaPrint - 70-gene prognosis signature
- Predictor analysis of Microarray (PAM) - 50 gene test
- High chance of recurrence = chemo
- Low chance of recurrence = avoid chemo
Which gene expression profiling tests to predict breast cancer response to chemotherapy is used most?
Which test is most tricky to conduct? Why?
Oncotype DX performed most
MammaPrint is hardest to conduct - Only test that uses fresh frozen tumour tissue sample, not paraffin embedded formalin fixed sample
Interpretation of Oncotype DX test score?
Recurrence score (RS) for early ER+ve breast cancer
RS <18 = Low risk = benefit from chemotherapy does NOT outweigh side effects, not recommend
RS >31 = High risk for recurrence = benefit for chemo outweighs side effects, recommend
RS between 18 - 31 = Intermediate risk of recurrence. Unclear recommendation.
Difference in treatment strategies for High RS and Low RS ER+ve breast cancer
Low Recurrence score = No benefit of adding Chemo
To reduce chemo side effects > give tamoxifen alone
High Recurrence score = Tamoxifen +/- chemo (though Tamoxifen alone already improves survival)
Case: 52/F Breast lump with total masectomy Grade III, bifoci invasive ductal carcinoma Size 4cm and 1.8cm No Lymphovascular invasion No sentinel LN Margins clear
IHC:
ERPR +ve
HER2 negative (Score 1+)
Ki-67 index 8%
Which gene expression test should be used?
Why?
Oncotype Dx
Create genetic profile and assess prognosis and predict response to therapy
Indication for Oncotype Dx in breast CA?
Early, Stage I or II
Node negative
ER+ve invasive breast cancer
Indication for neo-adjuvant chemotherapy and direct primary endocrine treatment of breast CA?
Neo-adjuvant = Very large tumour, reduce size
Primary endocrine treatment = elderly, conservative treatment, usually Estrogen receptor +ve
> > Secondary surgical resection after both therapy options
List 3 prognostic features of breast CA
Tumor size
LN status
Histological:
- Histologic type and grade
- Lymphovascualr invasion
- Margin of excision
List 2 predictive markers for breast CA and recommended therapy
ER+ve = tamoxifen
ER+ve with high RS: tamoxifen +/- chemo
HER2 = herceptin
Triple negative = adjuvant chemo
