Hormone Therapy (Breast cancer) Flashcards
(31 cards)
Most breast cancers are _ positive
oestrogen receptor
What occurs when oestrogen binds to an ER
Cascade molecules, co-activators ect
Estrogen response element is activated and causes specific proteins to be expressed
= changes in cell behaviour such as increased proliferation in breast and uterine tissue
What are the beneficial effects of oestrogen on the body
Breast = programs milk production
Liver/heart = Controls cholesterol
Uterus = Prepares for fetus
Bones = Preserves strength
What are the harmful effects of oestrogen on the body
Breast and Uterus = increases cancer risk
How can we modify oestrogenic environment in pre-menopausal women
Ovarian Ablation
Oestrogen receptor antagonist
How can we modify oestrogenic environment in post-menopausal women
Oestrogen receptor antagonist
Aromatase Inhibitors
Oestrogen receptor Downregulators
How is Oestradiol (E2) generated in the body
Androsterone -> Oestrone -> E2
Testosterone -> E2
Both reactions (bar E1->E2) are facilitated by aromatase
Why cant pre-menopausal women be given aromatase inhibitors
- Testosterone is needed in the body
- Lack of oestrogen causes menstrual cycle disruption
What is the mechanism of action of GnRH agonists
- produce a initial stimulation of the pituitary gland
-> Causes the production of FSH and LH in the ovary
-> Causes the release of oestrogen and progesterone
= This response is followed by down-regulation and inhibition of the pituitary-gonadal axis
What are the difference between GnRH agonist & antagonist
Antagonist - avoid the intial stimulatory phase. Discontinuation of treatment leads to a rapid+predictable recovery of Pit-Gonadal axis
Selective estrogen receptor modulators mechanism of action is __
Tissue specific
Depends on expression of CoActivators and/or CoRepressors
Breast = decrease proliferation
Uterine = increase
What is an example of a selective estrogen receptor modulator
Tamoxifen
Explains selective receptor receptor downregulators mechanism of action
They bind to and induce degradation of ER, thereby inhibiting dimerisation
and abolishing the ER signalling
What is an example of selective receptor downregulators
Fulvestrant
What is the mechanism of action of both aromatase inactivators/ inhibitors
Androstenedione isn’t converted to estrone
Testosterone isn’t converted to estradiol (active)
Androstenedione is still reversibly converted to testosterone
Estrone is still reversibly converted to estradiol
What are the subtypes of aromatase inhibitors/inactivators (+names)
Steroidal inactivators = Formestane, Exemestane
Androgen substrate = Androstenedione
Nonsteroidal inhibitors = Aminoglutethimide, letrozole, anastrozole
What did the ATLAS trial tell us about ER patients who take/taken tamoxifen
Continuous use of tamoxifen for 10 years decreases risk of recurrence and BC mortality compared to patients who seized tamoxifen treatment at 5 years
What side effects are there for endocrine therapy in ER+ Breast cancer
- Hair thinning (Aromatase/CDK4/6 inhibitors)
- Hot flashes/night sweats [treatment induced menopause]
- Cognitive difficulties (diminished neurocognitive function)
- Genitourinary/sexual health
- Accelerated osteoporosis
- Arthralgias (stiffness/acheness)
What are hot flashes/night sweats in endocrine therapy for ER+ BC linked to and how are they treated
Symptoms worse with tamoxifen than Aromatse Inhib
Lifestyle modification + use of SSRIs, oxybutynin or gabapentin
Therapies and supplements can also be used
What are Cognitive difficuties in endocrine therapy for ER+ BC linked to and how are they treated
RARE
symptoms normally abate over time
Referral for neuropsychiactric testing and evalution may be need
What are Arthalgias in endocrine therapy for ER+ BC linked to and how are they treated
Aromates inhib contribute to a symmetric stiffness/achiness that diffusely affect many joints+spine
Rheumatologic workup NOT indicated unless other indicators of rheumatoid disorders
Symptoms reduced physical activity, a acupuncture or by switching meds
What are Genitourinary/ sexual heath issues in endocrine therapy for ER+ BC linked to and how are they treated
Aromatase Inhi = Vaginal dryness/ atrophy
Tamoxifen = benign gyne bleeding, ovarinan cyst, uterine cancer
GnRH agonist = Dyspareunia, loss of libido/arousal
Routine Gyne care, vaginal moisturiser/lubricant, intravaginal oestrogen
What is osteoporosis in endocrine therapy for ER+ BC linked to and how are they treated
Tamoxifen = premenopausal
Aromatase inhib = postmenopausal
Weight-bearing exercise, calcium and vit D
Denosumab/biphosphonate can prevent bone loss due to treatment
Explain mTOR inhibitor use in breast cancer treatment
Approved and available in the UK
Treatment delayed disease progression however overall survival benefit is not demonstrated
Significant toxicity
