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Carcinogensis + Anticancer drugs > Hormone Therapy (Breast cancer) > Flashcards

Hormone Therapy (Breast cancer) Flashcards

1
Q

Most breast cancers are _ positive

A

oestrogen receptor

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2
Q

What occurs when oestrogen binds to an ER

A

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

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3
Q

What are the beneficial effects of oestrogen on the body

A

Breast = programs milk production
Liver/heart = Controls cholesterol
Uterus = Prepares for fetus
Bones = Preserves strength

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4
Q

What are the harmful effects of oestrogen on the body

A

Breast and Uterus = increases cancer risk

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5
Q

How can we modify oestrogenic environment in pre-menopausal women

A

Ovarian Ablation
Oestrogen receptor antagonist

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6
Q

How can we modify oestrogenic environment in post-menopausal women

A

Oestrogen receptor antagonist
Aromatase Inhibitors
Oestrogen receptor Downregulators

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7
Q

How is Oestradiol (E2) generated in the body

A

Androsterone -> Oestrone -> E2
Testosterone -> E2
Both reactions (bar E1->E2) are facilitated by aromatase

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8
Q

Why cant pre-menopausal women be given aromatase inhibitors

A
  • Testosterone is needed in the body
  • Lack of oestrogen causes menstrual cycle disruption
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9
Q

What is the mechanism of action of GnRH agonists

A
  • 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
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10
Q

What are the difference between GnRH agonist & antagonist

A

Antagonist - avoid the intial stimulatory phase. Discontinuation of treatment leads to a rapid+predictable recovery of Pit-Gonadal axis

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11
Q

Selective estrogen receptor modulators mechanism of action is __

A

Tissue specific
Depends on expression of CoActivators and/or CoRepressors
Breast = decrease proliferation
Uterine = increase

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12
Q

What is an example of a selective estrogen receptor modulator

A

Tamoxifen

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13
Q

Explains selective receptor receptor downregulators mechanism of action

A

They bind to and induce degradation of ER, thereby inhibiting dimerisation
and abolishing the ER signalling

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14
Q

What is an example of selective receptor downregulators

A

Fulvestrant

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15
Q

What is the mechanism of action of both aromatase inactivators/ inhibitors

A

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

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16
Q

What are the subtypes of aromatase inhibitors/inactivators (+names)

A

Steroidal inactivators = Formestane, Exemestane
Androgen substrate = Androstenedione
Nonsteroidal inhibitors = Aminoglutethimide, letrozole, anastrozole

17
Q

What did the ATLAS trial tell us about ER patients who take/taken tamoxifen

A

Continuous use of tamoxifen for 10 years decreases risk of recurrence and BC mortality compared to patients who seized tamoxifen treatment at 5 years

18
Q

What side effects are there for endocrine therapy in ER+ Breast cancer

A
  • 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)
19
Q

What are hot flashes/night sweats in endocrine therapy for ER+ BC linked to and how are they treated

A

Symptoms worse with tamoxifen than Aromatse Inhib
Lifestyle modification + use of SSRIs, oxybutynin or gabapentin
Therapies and supplements can also be used

20
Q

What are Cognitive difficuties in endocrine therapy for ER+ BC linked to and how are they treated

A

RARE
symptoms normally abate over time
Referral for neuropsychiactric testing and evalution may be need

21
Q

What are Arthalgias in endocrine therapy for ER+ BC linked to and how are they treated

A

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

22
Q

What are Genitourinary/ sexual heath issues in endocrine therapy for ER+ BC linked to and how are they treated

A

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

23
Q

What is osteoporosis in endocrine therapy for ER+ BC linked to and how are they treated

A

Tamoxifen = premenopausal
Aromatase inhib = postmenopausal
Weight-bearing exercise, calcium and vit D
Denosumab/biphosphonate can prevent bone loss due to treatment

24
Q

Explain mTOR inhibitor use in breast cancer treatment

A

Approved and available in the UK
Treatment delayed disease progression however overall survival benefit is not demonstrated
Significant toxicity

25
Q

PI3K inhibitors can be used treat breast cancer how?

A

Approved and available in the UK
Requires PIK3CA mutation test
Delays disease progression
Challenging toxicity

26
Q

Oestrogen resistance in breast cancer cause a new need for treatments

A

PI3K inhibitors
mTOR inhibitors

27
Q

what is the effect of ESR1 mutation

A

makes ER constitutively active, so not sensitive to oestrogen conc
Presence of an ESR1 mut + aromatase inhibitor cause decrease in women surviving progression free

28
Q

New oral selective oestrogen receptor degraders are being developed, what do they focus on

A

Patients whose cancer has acquired an ESR1 mutation
Mixed results

29
Q

How are CDK4/6 inhibitors used in breast cancer

A

Prolong control of disease when used in combination with ET
In both endocrine sensitive and resistant disease
Shown overall survival benefit and good toxicity profile
Expensive

30
Q

Outline the monarchE trial

A

Adjuvant CDK4/6 inhibitor combined with endocrine therapy for high-risk early BC
Increase invasive disease-free survival at 5 years compared to standard treatment

31
Q

How are AKT inhibitors used to treatment breast cancer

A

Stops mTOR production
oral AKT inhibitors approved by FDA in 2023
Increase % of progression free survial compared to placebo (when administered with fulvestrant)

Carcinogensis + Anticancer drugs (16 decks)

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