breast cancer Flashcards
What are the most common histological types of breast cancer?
ductal
lobular
If you see a triple negative tumour, what are you thinking? What are the associations?
Usually a high grade ductal Ca
Associated with BRCA
more aggressive
How long is adjuvant endocrine therapy administered?
5 years, or ten in select cases (for tamoxifen)
only ever 5 years for aromatase inhibitors
Always commenced after chemo, if this is being given
If metastatic disease and going well on aromatase inhibitor, just keep it going even after the 5 year mark
What are the side effects of tamoxifen?
Risk of breast cancer reduction far outweighs risk of endometrial cancer
VTE
Hot flushes
How does tamoxifen work?
Blocks binding of activated oestrogen receptors in nucleus to oestrogen response elements, which decreases downstream signalling
What impact does tamoxifen have on risk of death?
30% reduction risk of death
side effects of aromatase inhibitors?
arthralgias
bone loss- dexa at baseline and every2 years
no endometrial cancer or VTE risk like tamoxifen
AI reduce recurrence and death how much compared with tamoxifen?
Reduce recurrence by 4 percent
Reduce death by nothing
Indications for chemo
node positive
triple negative
younger premenopausal
large high grade even if node negative
greatest benefit for young women
What chemo is often given for breast ca?
doxorubicin and a taxane (docetaxel and paclitaxel)
Is herceptin oral or IV?
IV, three weekly, for a year!
Trastuzumab side effects
Decrease LVEF (usually asymptomatic)- check cardiac function every three months. ?Myocyte hibernation. Check LVEF every 3 months on therapy Sometimes intercept with antifailure therapy like and ACE
How long do metastatic breast cancer mets ppl live?
bone only- can live for years
visceral- months
Where do met’s usually happen?
Any correlation with histological subtype?
Bone, lung, liver
CNS especially HER2 positive disease
Unusual sites for lobular- gastric, peritoneal (not seen with ductal)
What do you do when hormone sensitive metastatic breast cancer becomes resistant to aromatase inhibitors, tamoxifen?
This is thought to be secondary to increased downstream activity in the mTOR pathway.
Hence can add in everolimus!! (new therapy)
In HER2 positive metastatic breast cancer, what drug is given?
Pertuzumab!
Recently listed in au! Now standard of care
Binds to another site on the HER2 extracellular region
If have progressed on trastuzumab, pertuzumb and docetaxel or have relapsed from trastuzumab within six months of completion of treatment, standard of care is trastuzumab emtansine (TDM-1)
If this progresses, lapatinib/capecitabine. Lapatenib acts IN the cell, ihibits TK domain of the HER2 receptor. It’s oral. Pimply rash, nail changes, finger skin splitting
What is a skeletal related event with bony mets?
Hyper calcaemia
spinal cord compression
pathological fracture
pain needing radiotherapy
Bony mets patients should be on what?
Zoledronic acid every 12 weeks (reduce skeletal related events by 15%)
small risk ONJ
NO impact on breast cancer survival
Denosumab monoclonal Ab against RANKL- greater reduction in SRE
Still can cause ONJ
Doesn’t have the same risk with renal impairment
When would you test for BRCA without strong FH?
under age 30
triple negative under age 40
ovarian cancer under age 70 for certain pathological subtypes
male breast cancer under age 60
Risks conferred by BRCA 1 and 2
1: 40-80% lifetime breast, 10-60% ovarian, also prostate
2: 40-80% breast, 10-40% ovarian, male breast, pancreas, prostate
who gets breast screening?
Breast cancer screening is two yearly from 50-79 for free but also free for 40-49 and over 75 but no invitations
premenopausal and mets to bone
-what extra gives survival benefit
tamoxifen and GnRH analogue
Which drug can you not be on with tamox?
parox or fluvox
as inhibit 2D6 and so tamox prodrug cannot be converted to active form
Aromatase inhibitor MOA
inhibit NZ in fat that blocks conversion of androgens to oestrogens
Li fraumneni mutation and cancers
p53
breast sarcoma brain colon leukaemia adrenocortical
cowden syndrome mutation
PTEN
breast
thyroid
endometrial
GU
PJ syndrome mutation
STKII/LKB1
BC small bowel colorectal uterine testicular
What fits in the normal risk bracket for breast ca?
one first degree over age 50
two second degree over age 50
one second degree under age 50
two first or second degree over 50 different sides family
do mammogram every 2 years 50-69
who is in high risk group
two first or second degree rel same side plus any of
another relative a jew breast and ovarian in same person breast under age 40 one sarcoma instead of the second cancer known BRCA bilateral breast cancer male breast
mastectomy
ovaries out reduces breast ca risk in pre men by half and ovarian by 90%
mammogram age 40 onwards
MRI yearly from 5 years younger than youngest relative
tamox can reduce risk 40%
OCP reduces OC risk but may increase breast risk
What does ER positive mean on IHC - 1 + ? 2+ ? 3+ ?
0/1+ is NEG
2+ is equiv
3+ is positive
TRICKY
