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RACP Oncology 2020 > Breast Cancer > Flashcards

Breast Cancer Flashcards

1
Q

Breast screening programme in Australia

A

2 yearly mammogram for those between 50-74yo.

40-49, >75 are not invited, but have free access.

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2
Q

Features associated with BRCA1 or BRCA2 mutation

A 
Invasive Ca <30 yo
Triple -ve Br Ca <60 yo
Invasive male Br Ca any age
Ovarian/primary peritoneal Ca
Ashkenazi Jew
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3
Q

What does BRCA 1 or BRCA2 do?

A

tumour suppressor genes. Codes for Ds DNA break repair. Mutation predisposes to homologous recombination deficiency

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4
Q

BRCA1 is associated with what kind of Ca?

A

Triple negative Br Ca

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5
Q

BRCA2 increases the risk of what kind of Ca?

A

Hormone Receptor + Br Ca

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6
Q

How do you minimise risk of Br Ca in patients w/ BRCA 1/BRCA2 mutations?

A

Bilateral mastectomy
Salpingo-oophorectomy post childbearing
Increase surveillance
Chemoprevention of Br Ca (before they get invasive cancer)

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7
Q

How does PARP inhibitor work with those with BRCA mutations?

A

PARP inhibition leads to tumour selective cell death via synthetic lethality

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8
Q

What does TAM01 study show?

A

Low dose tamoxifen is useful in preventing invasive breast Ca in patients with pre-malignant ER+ tumours.

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9
Q

When do you decide about curative intent vs. non curative intent?

A

Stage I-III disease that is resectable (or potentially resectable) is typically treated with curative
intent
• More intensive treatment regimens with higher rates of toxicity may be considered to be acceptable
• Stage IV disease is generally still considered to be incurable and treatment is typically with
palliative intent
• Intensive treatment regimens with high rates of toxicity are only considered acceptable under certain
conditions

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10
Q

Different subtypes of Breast Ca

A

HR+/HER- (65%) - best prognosis, late recurrence
HER2 + (20%) - poor prognosis, improved w/ target therapy
Triple -ve (15%) - poorest prognosis, late recurrence uncommon

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11
Q

Which type of breast Ca is associated with late recurrence?

A

HR+ breast Ca

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12
Q

General treatment principles of breast Ca

A

Primary tx: surgery + RT

Secondary: neoadjuvant or adjuvant therapy (hormonal tx, anti HER2 or chemotherapy)

If no distinct mets - then treatment intent is always curative.

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13
Q

Types of non invasive breast cancer

A

Ductal carcinoma in situ

Lobular neoplasm in situ

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14
Q

How do you decide treatment?

A 
Prognostic factors ?rate of recurrence
Predictive features ?will it work
Anatomical features ?visual/physical findings
If no physical features -> TNM status
ER/PR status
HER status
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15
Q

Precision oncology

A

Identifying gene expression pattern. This can help refine prognostic estimate.

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16
Q

What is Oncotype Dx?

A

a 21 gene expression assay that stratify HR+, node-ve early breast cancer by likelihood of benefit to adjuvant chemotherapy

17
Q

Benefit of dose dense (neo) adjuvant chemotherapy

A

Most Node + BC will be treated with adjuvant chemotherapy (3rd generation anthracycline and taxane).

As per lancet 2019, Dose dense regimen can moderately reduce the risk of recurrence and death from breast Ca.

18
Q

What is neoadjuvant treatment?

A

treatment given prior to surgery (chemotherapy, HER2 targeted therapy or endocrine therapy.

19
Q

Rationale for neoadjuvant treatment

A
  • refine prognostic estimate
  • identify patient with complete pathological response (pCR)
  • identify high risk population that may benefit from escalation/change of adjuvant treatment
  • unresectable tumor more resectable
  • understand disease biology
20
Q

Mainstay adjuvant treatment for HR+, HER2- early breast Ca

A

endocrine therapy:

1st line: Aromatase inhibitor

2nd line: Tamoxifen

21
Q

Tamoxifen

MOA, side effect, toxicities, clinical utility

A

MOA: selective estrogen receptor modulator

S/E: menopausal - hot flushes, myalgia, vaginal atrophy

Risk: VTE + endometrial cancer

Utility: pre or post menopausal

22
Q

Aromatase inhibitor:

MOA, side effect, toxicities, clinical utility

A

MOA:

  • block endogenous conversion of androgen to estrogen
  • doesn’t inhibit ovarian estrogen
  • e.g. anastrazole, letrozole, exemastane (steroidal)

S/E: menopausal symptoms - hot flushes, myalgia, vaginal atrophy

Toxicities: accelerated bone loss

Clinical use: post menopausal, pre menopausal (w/ GnRH) as can cause paradoxical rise in estrogen level

23
Q

Benefit of ovarian function suppression (OFS)

A
  • OFS + tamoxifen in pre-menopausal symptoms show superior disease free survival.
  • OFS + exemestane is even greated DFS
  • greater benefit in high risk disease patient (adjuvant chemo, very young <35)
24
Q

Principle of combination chemotherapy treatment of metastatic disease

A
  • combination vs. sequential single agent chemo
  • single agent preferred in absence of rapid clinical progression, life threatening visceral mets, need for rapid symptom control.
25
Q

Cyclin dependen kInase 4/6 inhibitor

Example, MOA, Clinical use, side effect

A

“ciclib” - e.g. ribociclib, palbociclib

CDK4/6+CyclinD phosphorylates Rb, releasing E2F and progression of cell cycle.

Inhibiting this reduce Rb phosphorylation and prevent cell cycle progression.

FOr luminal breat Ca (HR+), 1st line w/ aromatase inhibitor.

S/E: neutropenia, LFT derangement, QTC prolongatin

26
Q

alpha P13K inhibitor

Example, MOA, Clinical use, side effect

A

e.g. alpelisib

MOA: P13K signaling pathway is complex and leads to proliferation. P1rK pathway is enriched in BrCa.

clinical use: endocrine resistant HR+ HER2- advance Br Ca

S/E: rash, hyperglycaemia, N+V/diarrhoea

27
Q

T-DM1

Example, MOA, Clinical use, side effect

A

e.g. trastuzumab-emtansine

MOA: antibody drug conjugate, when binds to HER2R, DM1 is internalised and is cytotoxic.

clinical use: 2nd line for advanced HER2+ Br Ca

S/E: thrombocytopenia, liver toxicity

28
Q

Immune check point blockade

Example, MOA, Clinical use, side effect

A

e.g. atezolizumab, pembrolizumab

MOA: Cancer upregulate PDL1 to promote immune escape. block PD1/PDL1 interaction between tumour cell+ cytotoxic T cell. so immune system can block this.

Clinical use: Atezolizumab+paclitaxel as first line therapy in triple negative breast Ca.

S/E: immune related - rash, colitis, etc

29
Q

Treatment of brain mets

A

common in triple negative + HER2+ breast Ca

whole brain radiotherapy only if surgery or sterotactic RT unsuitable.

RACP Oncology 2020 (4 decks)

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