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Diagnostic Molecular Pathology > 21 Breast cancer > Flashcards

21 Breast cancer Flashcards

1
Q

Which one has a better prognosis:
ER positive or PR positive

A

1) Both are associated with a better prognosis;

2) Showed benefit from hormone-targeted therapies like tamoxifen.

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2
Q

ER

A

estrogen recepter

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3
Q

PR

A

progesterone receptor

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4
Q

What is the original hormone receptor test used to detect the level of ER or PR in breast cancer?

A

Ligand-binding assays:
1) use fresh tissue;
2) inability to separate our the contribution of
noninvasive tissue from invasive;
3) use radioactive probe

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5
Q

What is still the standard hormone receptor testing for breast cancer?

A

IHC for hormone recepters

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6
Q

How is FISH used in breast cancer diagnosis?

A

1) Detect the gene amplification of HER2 (human epidermal growth factor receptor 2)

2) New standard practice

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7
Q

HER2

A

1) human epidermal growth factor receptor 2;

2) A transmembrane receptor tyrosine kinase;

3) located on chr. 17

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8
Q

Germline mutations testing for breast cancer

A

BRCA1 and BRCA2

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9
Q

Breast cancer risk management testing

A

Genetic testing:
1) BRCA1 and BRCA2;
2) test for resistance to endocrine therapy

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10
Q

single-marker testing for breast cancer

A

1) hormone receptor ER or PR testing;
2) HER2 FISH

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11
Q

% of breast cancer associated with HER2 overexpression

A

1) 10-15%;

2) HER2 overexpression drives an aggressive clinical course

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12
Q

what causes the HER2 overexpression in patient?

A

1) HER2 gene amplification;

2) leads to 40- to 100-fold increase of HER2 protein

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13
Q

HER2 positive breast cancer prognosis

A

aggressive and poor survival rate

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14
Q

Trastuzumab (aka. Herceptin)

A

1) The humanized monoclonal antibody;

2) Bind to HER2 and block downstream signaling pathways

3) Herceptin is for HER2 positive patient

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15
Q

HER2 testing CAP and ASCO guidelines

A

1) First HER2 overexpression IHC

2) if the result is equivocal (uncertain), do FISH or other in situ hybridization for HER2 overexpression

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16
Q

what causes HER2 IHC false positive?

A

over-staining or over interpretation

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17
Q

Describe HER2 FISH

A

1) use fluorescent-labeled DNA to detect:
– HER2 alone (single-probe);
– HER2 and centromere of chromosome 17 (CEP17) (dual-probe);

2) Specimen: FFPE;

3) need to make sure only the invasive carcinoma is scored;

4) Count the clusters with more than 10% of HER2 amplification;

5) Count a minimum of 10 cells/area, and count two areas at high power (oil immersion)

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18
Q

What is reported out for single-probe HER2 FISH?

A

HER2 copy number

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19
Q

What is reported out for dual-probe HER2 FISH?

A

1) CEP17 is used as an internal control;

2) Signals ratio of HER2:CEP17 is reported;

3) Mean HER2 and CEP17 absolute per cell counts are also reported

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20
Q

For FISH HER2 or HER2/CEP17, what is the criteria for “Positive HER2 amplification” category?

A

Ratio ≥ 2 and/or Gene copies ≥ 6

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21
Q

For FISH HER2 or HER2/CEP17, what is the criteria for “Equivocal HER2 amplification” category?

A

Ratio <2 and Gene copies 4.0 - 5.9

22
Q

For FISH HER2 or HER2/CEP17, what is the criteria for “Negative HER2 amplification” category?

A

Ratio <2 and Gene copies <4

23
Q

What are the nonclassical results of FISH HER2 considered as HER2 positive and eligible for treatment with HER2-targeted agents?

A

1) polysomy or coamplified cases (≥6 HER2 copies/cell with concurrent increases in CEP17);
2) Monosomy: cases with amplified ratio but less than 4 HER2 copies/cell;
3) Low amplified: cases with Ratio ≥ 2 but Gene copies 4.0 - 5.9;
4) Heterogenous: cases with a clustered subpopulation of cells with HER2 amplification in at least 10% of the total population

24
Q

Four main molecular/intrinsic subtypes of breast cancer

A

1) Luminal A: ER positive, PR +/-, HER2 -, low ki67;
2) Luminal B: ER positive, PR +/-, HER2 +/-, increased ki67
3) HER2-related: HER2 positive, ER +/-, PR +/-
4) Basal-like: triple negative (ER - , PR -, HER2 -)

25
Q

Which molecular subtypes of breast cancer are ER+?

A

Luminal A and B

26
Q

Which molecular subtype of breast cancer is triple negative?

A

Basal-like

27
Q

How can you differentiate luminal A and luminal B breast cancers?

A

luminal B has:
higher proliferation rate; increased ki67;
lower levels of hormone receptors

28
Q

Why is it important to identify ER+ breast cancers?

A

Patients can benefit form chemotherapy as an adjunct to hormone targeted therapies.

29
Q

What is the demographic of basal-like breast cancer?

A

Younger patients;
African-American women

30
Q

Are BRCA1-associated breast cancer associated more to luminal subtypes or basal-like?

A

Basal-like gene profile;

suggest a common pathways of carcinogenesis

31
Q

Can basal-like or triple negative breast cancers predict BRCA1 mutations in the patients?

A

No

32
Q

Can a patient HER2+ show luminal B molecular profile?

A

Yes;

Patient may not respond to HER2 targeted treatment but we should not withhold the treatment from these patient

33
Q

Which molecular breast cancer subtypes has Good prognosis?

A

Luminal A

34
Q

Which molecular breast cancer subtypes has Intermediate prognosis?

A

Luminal B

35
Q

Which molecular breast cancer subtypes has Worse prognosis?

A

HER2 and Basal-like

36
Q

What targeted therapy is used for luminal A and B breast cancers?

A

Tamoxifen;

Hormone therapies

37
Q

What targeted therapy is used for HER2 breast cancers?

A

Herceptin;

HER2-targeted therapies

38
Q

Which molecular breast cancer subtypes respond Better/Higher to chemotherapy?

A

HER2 and Basal-like

39
Q

Which molecular breast cancer subtypes respond Lower to chemotherapy?

A

Luminal A

40
Q

Which molecular breast cancer subtypes respond Intermediate to chemotherapy?

A

Luminal B

41
Q

Commercial molecular tests used to classify breast cancer

A

Prosigna PAM-50 uses NanoString’s nCounter technology;

Agendia BluePrint - microarray, 80 genes used;

Agendia MammaPrint - microarray, 70 gene classifier used

42
Q

What is NanoString’s Prosigna breast cancer assay?

A

1) based on the 50 gene expression signature;

2) The test outputs a risk of recurrence (ROR) score, risk category, and intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like).

3) In USA, FDA only approved reporting of ROR

43
Q

What is the technology used for NanoString’s Prosigna breast cancer assay?

A

1) NanoString’s nCounter technology:
uses a digital barcode that allows for direct multiplexed measurement of gene expression using color-coded probe pairs;

2) no amplification step

44
Q

How is a MammaPrint done?

A

1) MammaPrint tests for a group of 70 genes.
The results of the MammaPrint test help predict the chance of metastasis for some ER-positive, HER2-negative breast cancers;

2) categories of high or low risk of metastasis;

3) Used with BluePrint to further classify luminal breast cancers into A and B

45
Q

How well does PAM50 correlate with BluePrint?

A

1) correlation as low as 59%;

2) Both tests correlate well for Basal-like classification;

3) Variable in classify luminal A and B

46
Q

Commercial molecular tests used to predict outcomes in breast cancer

A

1) OncptypeDX:
- to determine which ER+ but lymph node-negative patients may not benefit from chemotherapy;
- RT-PCR of 16 cancer-related genes and 5 control genes;

2) MammaPrint/BluePrint: most useful in ER+ patients;

3) PAM50

47
Q

What kind of genes are used to predict recurrence risk of breast cancer by common commercial panels such as OncotypeDX, MammaPrint?

A

proliferative genes:
this makes sense since chemotherapy targeting rapidly dividing cells

48
Q

Example of genes detected by OncptypeDX

A

ER, PR, HER2, ki67, other proliferative genes

49
Q

What are the risk categories of OntotypeDX?

A

1) Low (RS<18)
2) Intermediate (RS=18-30)
3) High (RS>30)

50
Q

The limitation of molecular tests in comparison to IHC and ISH testing in breast cancer

A

1) the possibility of the contribution of noncancer tissue to confound results: intermixed inflammation, in situ carcinoma or desmoplastic stroma may influence the result

51
Q

Are there any genes can be used as molecular markers for tumor size or nodal status in breast cancer?

A

1) No.

2) prognostic information captured by histopathological method is not captured by current prognostic gene signatures

Diagnostic Molecular Pathology (12 decks)

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