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Cancer > Cancer part 5 > Flashcards

Cancer part 5 Flashcards

1
Q

Where are breast cancers usually located?

A

Epithelial tumours of ductal or lobular origin.

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2
Q

what are the BRCA 1 and 2 responsible for?

A

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.

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3
Q

what are the two types of ways oestrogen is produced in the body.

A

Oestrogen produced from the ovaries.

Oestrogen produced from androgens converted by the enzymes aromatase

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4
Q

what is the biggest risk factor of Breast cancer

A

Age

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5
Q

What percentage of Breast cancer and ovarian cancer is Linked to BRCA 1

A

> 70% breast cancer

> 40% ovarian

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6
Q

What is the main hormone that is attributed to breast cancer

A

Oestrogen

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7
Q

What system is used to classify Breast cancer

A

TNM system

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8
Q

Describe the normal process of oestrogen release in the reproductive system?

A

GnRh stimulates the pituitary

Release of FSH/LH

These causes the ovaries release of oestrogens and progesterone

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9
Q

What are the sources of oestrogen in the boyd

A

Ovary

Adrenal glands ——> Adipose tissue (Aromate enzymes)

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10
Q

Name the hormonal therapies

A

Zoladex (Goserline)

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11
Q

MOA of Zolades (Brand name?)

A

A GnRh agonist

Which initially releases Oestrogen but then stimulated the negative feedback pathway

Shuts down oestrogen production

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12
Q
A

Zoladex is used in ER+ Patients

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13
Q

What is the combined treatment of breast cancer

A

> 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

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14
Q

What did the TAILORx trial investiage

A

If the treatment of Hormone therapy alone is effective enough in early breast cancer patients

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15
Q

What was the results of the TAILORx trial

A

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

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16
Q

What was the purpose of RxPonder trial

A

To investigate treatment of hormone only vs Hormome + CCT in women with hormone receptor–positive, HER2-negative, node-positive early breast cancer

17
Q

What was the overall result of the RxPonder trial

A

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

18
Q

What is chemo-brain and is related to chemotherapy

A

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

19
Q

What are the first line hormonal treatments

A

Selective estrogen receptor modulators

20
Q

What are Selective estrogen receptor modulators (SERMs)

A

Drugs that have both estrogenic and anti-estrogenic properties

They are antagonists of the Alpha oestrogen receptors and agonist of the Beta receptors

21
Q

What are the two receptors that SERM can work on?

A

Alpha receptors (found in the breasts) and Beta receptors (found in the ovaries or uterine tissue).

22
Q

How many types of oestrogen receptors are there and where are they found?

A

2:
>Alpha are found in the Breast
>Beta are found in the Ovaries

23
Q

List some SERMs

A

Tamoxifen

Droloxifene

Toremifene

Raloxifene

Idoxifene

24
Q

Risk of Tamoxifen

A

Increase the incidences of Endometrial cancer

25
Q

Mechanism of SERMs

A

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

26
Q

How do SERMs prevent the activation of AF2

A

Due to improper dimerization

27
Q

Which enzyme activates Tamoxifen and what is it metabolised to

A

CYP2D6

Converted to Endoxifen

28
Q

How do SERDs work

A

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.

29
Q

Name a SERD

A

Fulvestrant (FASLODEX)

30
Q

Can SERDs be used as first line treatment

A

No they are used to when Tamoxifen is resistant

31
Q

What is Proteolysis Targeting

A
32
Q

What is ARV-471

A

A selective protein degrader, it directly binds to

33
Q

how can oestrogen production be reduced in women who are post-menopausal?

A

Inhibiting the androgen conversion by stopping the enzyme AROMATASE.

34
Q

what are some examples of aromatase inhibitors?

A

Anastrozole
Letrozole
Exemestane

Cancer (18 decks)

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