Breast cancer

Question 1

What is BRCA 1 and 2 mode of inheritance ?

Answer 1

AD

Question 2

What type of gene is BRCA 1/2?

Answer 2

tumour suppressor gene

Question 3

Who do you refer for gene testing without strong family history ?

Answer 3

Breast cancer under 30 
Triple negative breast cancer under 40
Male breast cancer under  60
Ovarian cancer under  70
All non-mucinous ovarian

Question 4

What is mutation in Li-Fraumeni?

Answer 4

p53

Question 5

What tumours do you get with Li-Fraumeni?

Answer 5

Breast > 90%
Sarcoma
Brain
Adrenocortical
Leukaemia
Colon

Question 6

What mutation in Peutz-jager?

Answer 6

STK11/LKB1

Question 7

What mutation with Cowden?

Answer 7

PTEN

Question 8

What mutation with diffuse gastric cancer (lobular breast ca)?

Answer 8

CDH1

Question 9

What screening do you do for high risk breast ca ?

Answer 9

• 6/12 clinical breast exam

- Mammogram (or MRI) from 40 or 5 years younger than cancer age

Question 10

What prophylaxis do you use for high risk Breast Ca?

Answer 10

Mastectomy - decrease by 90%
BSO - decrease by 50%
Pre men - SERM
Post men - AI or SERM

Question 11

What 2 types of adjuvant chemo do you usually use in breast cancer?

Answer 11

Anthracycline e.g -rubicin

Anti-microtubules e.g. taxanes

Question 12

When do you use adjuvant RTx for breast cancer?

Answer 12

Post WLE (provides similar recurrence rate to mastectomy)
or if post mastectomy if > 5 cm or > 4LN

Question 13

When do you use adjuvant endocrine therapy?

Answer 13

For all PR/ER +ve breast cancers

Question 14

MOA Tamoxifen?

Answer 14

Tamoxifen is SERM ( antagonist at breast and uterus, agonist in lipids and bone)

Question 15

What are the risks of Tamoxifen?

Answer 15

IHD, VTE, endometrial cancer

Question 16

What is a positive side effect of Tamoxifen?

Answer 16

Increases BMD - less non vertebral fractures

Question 17

How to Aromastase inhibitors work ?

Answer 17

The block the conversion of androstenedione and testosterone to oestrodial and and oestriol in fat, liver, muscle and breast tissue.

Question 18

Who do you use AI in?

Answer 18

Post menopausal women, doesn’t stop ovarian oestrogen production

Question 19

What are example of AI?

Answer 19

Letrozole, anastrazole, Exemestane

Question 20

Side effects of AI?

Answer 20

Reduced BMD, hot flushes, arthralgia

Question 21

How do you treat Her-2/neu positive breast cancer?

Answer 21

All get chemo + Tastuzumab

Question 22

What does HER-2/neu 1+, 2+, 3+ mean on IHC?

Answer 22

1+ negative, 2+ equivocal, 3+ positive

Question 23

What is Trastuzumab?

Answer 23

Herceptin

Monoclonal antibody against Her-2

Question 24

What is the main AE of Trastuzumab?

Answer 24

Cardiac toxicity.
Reversible
Increased risk if used with anthracyclines

Question 25

What is the approach to early breast cancer?

Answer 25

1. WLE +RTX or Mastectomy + SLN Bx 2. Adjuvant chemo if high risk 3. Endocrine therapy if ER/PR +ve 4. Trastuzumab if Her-2/neu positive

Question 26

What is the approach to locally advance breast cancer?

Answer 26

Try and down stage with neo-adjuvant therapy

Question 27

What are common sites of mets in breast cancer?

Answer 27

Bone, liver, lung, CNS

Question 28

What is the approach to Metastatic breast cancer?

Answer 28

1. If PR/ER positive try endocrine therapy first (unless advanced visceral disease) 2. If Her-2/neu use targeted therapy 3. Use chemo if this fails or rapidly advancing disease 4. Treat bone mets to prevent SRE (not survival)

Question 29

How do you treat hormone resistant metastatic breast cancer?

Answer 29

Evorolimus + exemestane - mtor pathway is often unregulated in AI resistance.

Question 30

What do you use for Her-2/neu positive metastatic breast cancer who have been off trastuzumab for > 6/12?

Answer 30

Trastuzumab + Pertuzumab + Doxetaxal

Question 31

How does Pertuzumab work ?

Answer 31

Monoclonal Ab against a different part of the Her-2/neu receptor , this often unregulated in trastuzumab resistant tumours

Question 32

What do you use for Her-2/neu positive metastatic breast cancer who relapsed on trastuzumab ie. within 6/12?

Answer 32

Trastuzumab emtansine T-DM1

Question 33

What is Trastuzumab emtansine?

Answer 33

Conjugate of trastuzumab with a microtubule inhibitor (DM1), allows targeted delivery of cytotoxic therapy to cancer cells.