Breast cancer Flashcards
What is the mean age at first diagnosis?
60 years
What are the screening programs in Aus?
Women aged 50-74 are invited for breast mammogram 2 years in Aus
- women aged 40-49 and >74 are not invited back have access to free screening
What clinical factors are associated with BRCA1/BRCA2 mutations?
Invasive breast Ca <30 years Triple negative breast ca <60 years Male invasive breast ca at any age Ovarian or primary peritoneal cancer Ashkenazi Jewish heritage
What is the function of BRCA1 and BRCA 2?
Tumour suppressor gene - Doubled-stranded DNA repair
Presence of mutation predisposition to homologous recombination deficiency
What is the difference in phenotype of the cancers predisposed by BRCA 1 vs BRCA 2
BRCA1 typically associated with triple negative breast cancers
BRCA 2 typically associated with increased risk of hormone-receptor positive breast cancers
What are some management options for BRCA positivity?
Risk reducing bilateral mastectomy or salpingo-oophorectomy once childbearing is complete
Increase surveillance - from aged 30 including breast MRI
Chemoprevention with tamoxifen/ anastrozole or exemestane
Which class of drugs can be used in BRCA positive patients? Why does it work?
PARP inhibitors
Knocking off another DNA repair mechanism (via PARP) causes flooding of mutations and cell death
What are the general principles of management?
Stage I-III that is resectable - curative intent
What are the stages in breast Ca?
Stage I-II - no lymph node involvement
Stage III - LN mets
Stage IV - distant mets
What is the implication of oligometastatic disease?
Treat all the mets with local therapy eg stereotactic radiotherapy
How is oestrogen/progesterone receptor vs HER2-amplification expression identified?
IHC
FISH - HER2
Which hormone/HER2 subtype has the best prognosis?
Hormone receptor +
HER2 negative
What are the treatments per cancer type?
Hormone receptor pos, HER2 neg: Endocrine therapy (+/- chemotherapy)
HER2-positive: HER2-targeted therapies. Chemo +/- endocrine
Triple negative breast cancer: Chemotherapy
Which subtype has low vs high late recurrence?
Triple negative low,
Hormone receptor positive high
What is the most important factor in determining whether adjuvant chemo should be given in early stage?
Lymph node status
What is dose dense chemo?
Increasing dose intensity facilitated by GCSF
Which targeted therapies targets HER2?
Trastuzumab
In selected high risk patients consider adding;
Lapatinib
Pertuzumab
Neratinib
What adjuvant can you use in lower risk patients?
In patients with tumour size <3cm, node neg, and HER2 pos
- Paclitaxel for 12 weeks with trastuzumab
What is the evidence for neoadjuvant?
No evidence currently
What the benefits of neoadjuvants?
Identify high risk disease that may benefit from more intense treatment in adjuvant setting
Convert tumour from unresectable to resectable
What are the adjuvant endocrine therapies?
Tamoxifen - selective oestrogen receptor modulator
Aromatase inhibitor - reduces oestrogen biosynthesis
When can’t aromatase inhibitors be used?
Pre-menopausal women (unless ovarian function suppression is given) as there can be rebound increased oestrogen production
What other adjuvant therapies are given?
Bisphosphonates
Denosumab
Why might you rebiopsy a patient with new met. disease?
Genetic change with time
What is the mechanism of CDK 4/6 inhibitor?
Cell cycle inhibition
What are the CDK 4/6 inhibitors?
Palbociclib
Ribociclib
Abemaciclib
What are the PI3-kinase inhibitors?
Alpelisib
What are the SE’s of alpelisib
Rash
Hyperglycaemia
N/V and diarrhoea
What is T-DM1? What are SE’s?
Trastuzumab conjugated to cytotoxic agent emtansine
Thrombocytopenia, liver toxicity
When is T-DM1 used?
2nd line for HER2 positive metastatic breast Ca
When is immune checkpoint blockage used in met. breast Ca?
Advanced triple negative breast cancer in combination with chemo
