Cancer part 5 Flashcards
Where are breast cancers usually located?
Epithelial tumours of ductal or lobular origin.
what are the BRCA 1 and 2 responsible for?
These are genes that produce proteins that help repair damaged DNA. Everyone has two copies of each of these genes—one copy inherited from each parent.
Mutations in these genes can lead to faulty DNA damage repair leaving the patient susceptible to tumour growth.
what are the two types of ways oestrogen is produced in the body.
Oestrogen produced from the ovaries.
Oestrogen produced from androgens converted by the enzymes aromatase
what is the biggest risk factor of Breast cancer
Age
What percentage of Breast cancer and ovarian cancer is Linked to BRCA 1
> 70% breast cancer
> 40% ovarian
What is the main hormone that is attributed to breast cancer
Oestrogen
What system is used to classify Breast cancer
TNM system
Describe the normal process of oestrogen release in the reproductive system?
GnRh stimulates the pituitary
Release of FSH/LH
These causes the ovaries release of oestrogens and progesterone
What are the sources of oestrogen in the boyd
Ovary
Adrenal glands ——> Adipose tissue (Aromate enzymes)
Name the hormonal therapies
Zoladex (Goserline)
MOA of Zolades (Brand name?)
A GnRh agonist
Which initially releases Oestrogen but then stimulated the negative feedback pathway
Shuts down oestrogen production
Zoladex is used in ER+ Patients
What is the combined treatment of breast cancer
> Primary tumour removed by surgery (mastectomy/lumpectomy)
> Radiation therapy to remaining breast and/or axilla
> Adjuvant chemotherapy
> Hormonal therapy to eradicate any micro-neoplastic disease/prophylaxis
What did the TAILORx trial investiage
If the treatment of Hormone therapy alone is effective enough in early breast cancer patients
What was the results of the TAILORx trial
In low risk patient there was in difference survival
Groups reoccurrence score 11-25: NO benefit to chemotherapy
Groups with reoccurrence scores greater than 25 saw a benefit to chemotherapy
What was the purpose of RxPonder trial
To investigate treatment of hormone only vs Hormome + CCT in women with hormone receptor–positive, HER2-negative, node-positive early breast cancer
What was the overall result of the RxPonder trial
Addition of adjuvant chemo to endocrine therapy improved invasive disease–free survival among premenopausal women.
Postmenopausal women 0 to25 who have one to three positive axillary nodes there is no benefit to the use of chemotherapy
What is chemo-brain and is related to chemotherapy
Mental fog:
Include disorganized behaviour or thinking, confusion, memory loss, and trouble concentrating, paying attention, learning, and making decisions.
It was found in all test subject, irrespective of whether they were given chemotherapy
What are the first line hormonal treatments
Selective estrogen receptor modulators
What are Selective estrogen receptor modulators (SERMs)
Drugs that have both estrogenic and anti-estrogenic properties
They are antagonists of the Alpha oestrogen receptors and agonist of the Beta receptors
What are the two receptors that SERM can work on?
Alpha receptors (found in the breasts) and Beta receptors (found in the ovaries or uterine tissue).
How many types of oestrogen receptors are there and where are they found?
2:
>Alpha are found in the Breast
>Beta are found in the Ovaries
List some SERMs
Tamoxifen
Droloxifene
Toremifene
Raloxifene
Idoxifene
Risk of Tamoxifen
Increase the incidences of Endometrial cancer
Mechanism of SERMs
Bind to the oestrogen receptor and activates AF1 but not AF2 (dimer)
When this dimer binds to the ERE (Estrogen response element) only some co-factors are recruited
And so partially inactivates some transcription
How do SERMs prevent the activation of AF2
Due to improper dimerization
Which enzyme activates Tamoxifen and what is it metabolised to
CYP2D6
Converted to Endoxifen
How do SERDs work
Downregulates levels of oestrogen receptors by binding the active sites and preventing receptor dimerization.
rendering the receptor useless, the receptor is then degraded because it cannot be used.
Name a SERD
Fulvestrant (FASLODEX)
Can SERDs be used as first line treatment
No they are used to when Tamoxifen is resistant
What is Proteolysis Targeting
What is ARV-471
A selective protein degrader, it directly binds to
how can oestrogen production be reduced in women who are post-menopausal?
Inhibiting the androgen conversion by stopping the enzyme AROMATASE.
what are some examples of aromatase inhibitors?
Anastrozole
Letrozole
Exemestane
