Breast cancer Flashcards
What is BRCA 1 and 2 mode of inheritance ?
AD
What type of gene is BRCA 1/2?
tumour suppressor gene
Who do you refer for gene testing without strong family history ?
Breast cancer under 30 Triple negative breast cancer under 40 Male breast cancer under 60 Ovarian cancer under 70 All non-mucinous ovarian
What is mutation in Li-Fraumeni?
p53
What tumours do you get with Li-Fraumeni?
Breast > 90% Sarcoma Brain Adrenocortical Leukaemia Colon
What mutation in Peutz-jager?
STK11/LKB1
What mutation with Cowden?
PTEN
What mutation with diffuse gastric cancer (lobular breast ca)?
CDH1
What screening do you do for high risk breast ca ?
- 6/12 clinical breast exam
- Mammogram (or MRI) from 40 or 5 years younger than cancer age
What prophylaxis do you use for high risk Breast Ca?
Mastectomy - decrease by 90%
BSO - decrease by 50%
Pre men - SERM
Post men - AI or SERM
What 2 types of adjuvant chemo do you usually use in breast cancer?
Anthracycline e.g -rubicin
Anti-microtubules e.g. taxanes
When do you use adjuvant RTx for breast cancer?
Post WLE (provides similar recurrence rate to mastectomy) or if post mastectomy if > 5 cm or > 4LN
When do you use adjuvant endocrine therapy?
For all PR/ER +ve breast cancers
MOA Tamoxifen?
Tamoxifen is SERM ( antagonist at breast and uterus, agonist in lipids and bone)
What are the risks of Tamoxifen?
IHD, VTE, endometrial cancer
What is a positive side effect of Tamoxifen?
Increases BMD - less non vertebral fractures
How to Aromastase inhibitors work ?
The block the conversion of androstenedione and testosterone to oestrodial and and oestriol in fat, liver, muscle and breast tissue.
Who do you use AI in?
Post menopausal women, doesn’t stop ovarian oestrogen production
What are example of AI?
Letrozole, anastrazole, Exemestane
Side effects of AI?
Reduced BMD, hot flushes, arthralgia
How do you treat Her-2/neu positive breast cancer?
All get chemo + Tastuzumab
What does HER-2/neu 1+, 2+, 3+ mean on IHC?
1+ negative, 2+ equivocal, 3+ positive
What is Trastuzumab?
Herceptin
Monoclonal antibody against Her-2
What is the main AE of Trastuzumab?
Cardiac toxicity.
Reversible
Increased risk if used with anthracyclines
What is the approach to early breast cancer?
- WLE +RTX or Mastectomy + SLN Bx
- Adjuvant chemo if high risk
- Endocrine therapy if ER/PR +ve
- Trastuzumab if Her-2/neu positive
What is the approach to locally advance breast cancer?
Try and down stage with neo-adjuvant therapy
What are common sites of mets in breast cancer?
Bone, liver, lung, CNS
What is the approach to Metastatic breast cancer?
- If PR/ER positive try endocrine therapy first (unless advanced visceral disease)
- If Her-2/neu use targeted therapy
- Use chemo if this fails or rapidly advancing disease
- Treat bone mets to prevent SRE (not survival)
How do you treat hormone resistant metastatic breast cancer?
Evorolimus + exemestane - mtor pathway is often unregulated in AI resistance.
What do you use for Her-2/neu positive metastatic breast cancer who have been off trastuzumab for > 6/12?
Trastuzumab + Pertuzumab + Doxetaxal
How does Pertuzumab work ?
Monoclonal Ab against a different part of the Her-2/neu receptor , this often unregulated in trastuzumab resistant tumours
What do you use for Her-2/neu positive metastatic breast cancer who relapsed on trastuzumab ie. within 6/12?
Trastuzumab emtansine T-DM1
What is Trastuzumab emtansine?
Conjugate of trastuzumab with a microtubule inhibitor (DM1), allows targeted delivery of cytotoxic therapy to cancer cells.
