Scott Breast Cancer Flashcards Preview

HRM Final Exam > Scott Breast Cancer > Flashcards

Flashcards in Scott Breast Cancer Deck (29)
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1
Q

What are the two epithelial layers of the breast?

A

Luminal and myoepithelium

2
Q

What epithelial layer in the breast has progenitor cells?

A

Luminal

3
Q

What epithelial layer in the breast is ER alpha negative?

A

Myoepithelial layer

4
Q

What epithelium in the breast is ER alpha positive?

A

Luminal layer

5
Q

What epithelial layer in the breast contains stem cells?

A

Myoepithelial cells

6
Q

What is the inheritance pattern of BRCA mutations?

A

Autosomal dominant

7
Q

Why does inactivation of BRCA1 or BRCA2 result in breast cancer susceptibility?

A

BRCA1/2 are essential components of homologous recombination arm of DNA repair machinery

8
Q

What does homologous recombination repair in the DNA?

A

Ds DNA breaks

9
Q

A repair defect in BRCA1/2 mutant cells results in what?

A

Genomic instability

10
Q

Genomic instability creates the opportunity for what?

A

accumulation of somatic cancer causing mutations

11
Q

In the absence of BRCA1, what cells accumulate?

A

Progenitor cells

12
Q

What other genes in the DNA damage repair pathway contribute to familial breast cancers?

A

PALB2, CHECK2, ATM

13
Q

What is microevolution?

A

Random somatic mutations that result in dysregulated proliferation and inappropriate survival are selected for

14
Q

What type of genetic change is the driving force in development of both familial and sporadic cancers?

A

Somatic genetic changes

15
Q

Estrogen binding to ER alpha promotes transcription of what in normal breast tissue?

A

Amphiregulin, a secreted growth factor

16
Q

What causes the transcription of amphiregulin?

A

ER binding ER alpha

17
Q

What is the effect of amphiregulin?

A

Acts on nearby cells to promote proliferation

18
Q

In the breast, there are cells that express ER and cells that don’t… which cells proliferate?

A

The cells without ER

19
Q

In tumor cells expressing ER, what effect does estrogen have when binding?

A

Estrogen promotes transcription of cell cycle regulators like cyclin D1; the cells expressing ER undergo proliferation

20
Q

How are tumor cells different than normal breast epithelial cells?

A

Tumor cells have increased expression of ER and change what genes are regulated (ie increase Cyclin D1 vs amphiregulin)

21
Q

Breast tumor cells and normal cells are similar in what way?

A

No mutations or amplifications of genes encoding estrogen or ER

22
Q

How does ER promote transcription of a different set of genes in breast cancer?

A

Overexpression of the pioneer transcription factor FOXA1

23
Q

What is FOXA1?

A

Binds closed chromatin and increases cyclin D1 transcription

24
Q

Cyclin D1 is a key regulator in the what transition of the cell cycle?

A

G1/S transition

25
Q

What is the MOA of tamoxifen?

A

Estrogen analog that bind ER; tamoxifen-ER complex bind DNA and INHIBIT transcription (favors interaction with co-repressors not co-activators)

26
Q

ERBB2 is part of what receptor family?

A

EGF - tyrosine kinase

27
Q

Why is overexpression of ERBB2 oncogenic?

A

Does not require ligand binding for activation

28
Q

What drug blocks activity of ERBB2 homodimers?

A

Trastuzumab

29
Q

What durg blocks EGFR-ERBB2 heterodimers?

A

Lapatinib - binds and blocks kinase at active site