Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHAM02 > Wk 14: Breast cancer > Flashcards

Wk 14: Breast cancer Flashcards

1
Q

What happens to the breast tissues with increasing age?

A

Involution changes due to altered sex steroid levels + decreasing ovarian function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What do the benign breast tumours comprise of?

A
  • Fibroadenomas (most common - proliferation of connective tissue stroma + glands in breast lobule)
  • Duct papillomas
  • Adenomas
  • Connective tissue tumours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Give examples of non-invasive carcinomas

A
  • Ductal carcinoma in situ (DCSI)
  • Lobular carcinoma in situ (LCIS)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Give examples of invasive carcinoma

A
  • Infiltrating ductal carcinoma
  • Invasive lobular carcinoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the tests for metastases?

A
  • Lymph node ultrasound/biopsy
  • MRI scan
  • CT scan
  • Liver ultrasound
  • Bone scan
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is ER, PR + HER2 identified?

A
  • Immunohistochemistry
  • If bound to enzyme, clear -> brown
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is tamoxifen?

A
  • SERM
  • Competitive inhibitor
  • Binds to ER + masks AF2 site -> less coactivator recruitment
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is a SERM? give examples

A
  • Selective estrogen receptor modulator
  • Tamoxifen + raloxifene
  • Antiestrogenic: mammary epithelium
  • Proestrogenic: uterine epithelium + bone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does tamoxifen resistance occur?

A
  • Loss of ER expression
  • Activating ER mutation
  • ER hypersensitivity to low oestrogen
  • Inc oestrogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is used in 2nd line treatment in oestrogen dependant breast cancer that are tamoxifen resistent?

A

Aromatase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Give examples of reversible aromatase inhibitors

A
  • Aminoglutethimide - reversible, poor selectivity
  • Anastrozole + letrozole - binds to haem of aromatase + prevents steroid binding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give an example of an irreversible aromatase enzyme inhibitors

A

Exemestane (lowers circulating oestrogens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the latest generation of ER antagonist?

A
  • Fulvestrant
  • Selective estrogen receptor degrader (SERD)
  • Binds tightly to ER
  • Masks both AF1 + AF2 -= receptor instability
  • ER degraded by proteome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is herceptin associated with?

A

Cardiovascular dysfunction - monitor cardiac function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What happens to HER2 in overexpressing cells?

A
  • HER2 receptor undergo proteolytic cleavage
  • Leads to ECD fragment being shed + activates p95 domain
  • Poor prognosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the mechanism of action of herceptin?

A
  • Blocks cleavage
  • Blocks dimerization
  • Endocytosis
  • Activation of antibody dependent cell mediated cytotoxicity (ADCC)
  • Blocks VEGF + tumour vascularisation
  • Upregulates p27
17
Q

How does herceptin illicit an immune response?

A
  • ADCC
  • Fc domain of herceptin binds to natural killer cells w/ Fc gamma receptor
  • Flags cells for immune attack
  • Tumour cell lysis occurs
18
Q

How does herceptin resistance occur?

A

Unable to bind to region 4 due to:

  • HER p95 fragment generation
  • Epitope masking by mucin
  • Epitope masking by CD44
19
Q

What is used in herceptin resistance?

A

Pertuzumab + trastuzumab emtansine

20
Q

What does pertuzumab do?

A
  • Binds to HER2 at region distinct from trastuzumab
  • Overcomes p95 cleavage + masking resistance
21
Q

What is trastuzumab emtansine (kadcyla)?

A
  • Trastuzumab linked to DM1 (microtubule inhibitor)
  • For: HER2 positive, unresectable, locally advance or metastatic breast cancer
22
Q

When do you give trastuzumab emtansine (kadcyla)?

A
  • Received prior therapy for locally advanced or metastatic disease
  • Developed disease recurrence during/w/in 6 months of completing adjuvant therapy
23
Q

What is the mechanism of action of trastuzumab emtansine (kadcyla)?

A
  • HER2 binding
  • Prevents dimerization
  • Prevents HER2 ECD cleavage ->p95
  • Blocks downstream signalling
  • ADCC
  • Prevents microtubule polymerisation
  • Initiates apoptosis
24
Q

What is used to target HER2 in tamoxifen resistant tumours?

A

Herceptin

PHAM02 (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions