BREAST CANCER TREATMENT Flashcards
What are the three breast cancer treatments
- Selective oestrogen receptor modulators e.g. tamoxifen
- Aromatase inhibitors e.g. Anastrozole
- Oestrogen receptor downregulators / antagonist e.g. Fulvestrant
What is the moa of tamoxifen
Permits the AF1 transcription activation domain to bind to the basic
transcriptional machinery via adaptor (co-activator) proteins
* Prevents the AF2 transcription activation domain from binding to the basic
transcriptional machinery via adaptor (co-activator) proteins
ADRS of tamoxifen
Tamoxifen also binds to the ERβ receptor and acts as an
agonist enabling both AF1 and AF2 binding to adaptor
proteins leading to increased gene expression
* Results in:
* Hot flushes, fluid retention and menstrual irregularities
* And risk of:
* Endometrial cancer (due to uterine cell proliferation)
* Deep vein thrombosis
* Stroke
moa of anastrozole
Aromatase (CYP19A1) catalyses the synthesis of
estradiol from testosterone (the main source of
oestrogen in post menopausal women)
* Aromatase inhibitors block the synthesis of ALL
oestrogens from testosterone
* Anastrozole is a reversible inhibitor of CYP19A1
* Blocks oestrogen dependant cell division
what is adrs of anastrozole
ADRs associated with low oestrogen i.e. menopausal
symptoms
what does anastrozole decrease the risk of?
decreased risk of endometrial cancer, thrombosis
and stroke
what is the moa of fulvestrant?
- This binds to the receptor resulting in
- Receptor downregulation and
- Antagonises the ability of the receptor to bind to DNA
- May also inhibit aromatase
does fulvestrant have oestrogenic effects
no
what is pertuzumab
Prevents HER2 heterodimer formation with HER3
what are BRCA1 AND BRCA2
Mutation in both copies of the gene is required for inactivity, mutation is the second copy
is normally acquired by a somatic mutation
What is BRCA1
- Involved in double strand break repair
- Increases risk of breast cancer and ovarian cancer
- Increase risk of prostate cancer
WHAT IS BRCA2
Involved in homologous recombination
* Increased risk of gall bladder, bile duct, stomach cancer and melanoma
HOW IS BRCA CANCER TREATE
Fluorouracil (anti-metabolite)
* Epirubicin (topoisomerase inhibitor)
* Cyclophosphamide (DNA crosslinker)
* Docetaxel (microtubule inhibitor)
what are risk factors of breast cancer
increased estrogen exposure, advanced age, and genetic predisposition (e.g., BRCA1/BRCA2 mutations
if the tumor is ER or PR RECEPTOR positive what does this mean?
it can be treated systemically with hormone therapy (e.g., tamoxifen).
if the tumor is HER2 receptor positive what does this mean?
it should receive targeted therapy (e.g., trastuzumab
what are the side effects of trastuzumab
Cardiotoxicity; dilated cardiomyopathy
what is breast conserving surgery
a type of surgery that focuses on the removal of cancerous breast tissue only, in contrast to full-breast mastectomy
what is a mastectomy
A mastectomy involves the removal of the entire breast and, depending on the specific procedure, possibly other structures, such as lymph nodes and muscles.
what analysis can be used for HER2
FISH AND IHC
Her two (HER2) breasts can be treated with trastwozumab
Sid effects of tamoxifen
dvt
uterine sarcoma
