Breast cancer

Question 1

Risk factors for Breast Ca? (4)

Answer 1

1. FH - BRCA1/BRCA2 is the strongest RF
2. Obesity (most relevant from population perspective)
3. Longer exposures to oestrogen: early monarchy, late menopause, nulliparity, late first-pregnancy
4. Previous RTx (x10 RR if <30y age)

Question 2

What are the specific questions you need to ask in Breast Ca long-case in (“Current status”)? (3)

Answer 2

What impact does the Cancer have on patient, particularly

1. Sexual problems: vaginal atrophy, dyspareunia
2. Low-self esteem due to lack of breast/ scars or it’s appearance
3. Depression

Question 3

Breast cancer staging?

Answer 3

Stage 1: localised, small lesion (<2cm)

Stage 2: localised, larger lesion (>5cm) without nodes or smaller lesion with LN (1-3)

Stage 3: Large lesion (>5cm) with LN involvement or locally advanced disease (extending to chest wall or skin)

Stage 4: Mets.

Question 4

Prognosis of Breast Ca based on staging?

Answer 4

5y survival as below

I - 100%

II - 80%

III - 50%

IV - poor, 2 years overall survival (median)

Question 5

If patient had masectomy, lumpectomy (instead of breast conserving surgery) what useful information does it tell you?

Answer 5

Breast-conserving surgery is not recommended in below situations

1. Tumour was larger than 5cm
2. involvement of nipple or areola
3. Multi-focal

Hence the patient must have had high-risk features and mastectomy was performed to reduce the risk of recurrence.

Question 6

if the patient had RTx following surgery, what useful information does it tell you in the LC?

Answer 6

RTx is not usually indicated following surgery, except when high-risk features are present.

1. Margin not clear
2. Larger than 5cm
3. ≥4 LN involvement
4. Inflammatory Breast cancer

Question 7

What adjuvant endocrine therapies are given to pre vs. postmenopausal women with Hormone receptor +ve breast Ca following breast surgery?

Answer 7

Pre-menopausal: Tamoxifen (SERM)

Post-menopausal: Aromatase inhibitors

Question 8

Side effects of Tamoxifen? (4) how is Raloxifen beneficial compared with Tamoxifen?

Answer 8

VTE (1-2%)

Endometrial Ca (1%)

Hot flushes

Cataracts

Raloxifen: no endometrical Ca risk, lower risk of VTE and Cataracts.

Question 9

Side effects of aromatase inhibitors? (4)

Answer 9

Early (days to weeks): Vasomotor (Hot flushes), fluid retention, dyslipidaemia

Late: arthralgia, vaginal atrophy and Osteoporosis

Question 10

Specific side effects to ask about in Breast Ca long case for patients? 4

Answer 10

Cognitive dysfunction

Osteoporosis**

Sexual problems: dyspareunia, vaginal atrophy

Vasomotor symptoms: flushing

Question 11

Depression is common in patients with Breast Ca. Which anti-depressants must be avoided in patients who are on Tamoxifen?

Answer 11

Paroxetine, Fluoxetine - these are CYP2D6 inhibitors (hence impairs metabolism of Tamoxifen)

Question 12

Would you biopsy the recurrent breast tumour and why?

Answer 12

Yes - as secondary cancers usually have different hormone receptors hence would change management.

Question 13

Criteria for testing BRCA? (5)

Answer 13

Any of the:

1. ≥3 Breast or Ovarian Ca in family
2. 2 breast Ca <50y in family
3. Triple -ve & <50y
4. Bilateral breast Ca
5. Male Breast Ca

Question 14

What is the age-appropriate Breast Ca surveillance in non-BRCA population?

Answer 14

2 yearly Mamogram from 50-70.

Question 15

Surveillance protocol for BRCA patients?

Answer 15

Yearly Mamogram and MRI from age 30

Consider prophylactic bilateral salpingo-oophorectomy or mastectomy (if family completed) - improved survival and reduction in Breast Ca risk by 90%.

Question 16

Can a mamogram be used for younger patients (<40) for Breast Ca surveillance?

Answer 16

No, use USS or MRI as breasts are denser, MRI has higher sensitivity.

Question 17

What is the general principle of management of Breast Ca - early or locoregional disease (pharm)?

Answer 17

Surgery + Sentinal node biopsy +/- RTx then consider Adjuvant therapy depending on molecular/receptor profile.

Surgery

• WLE + RTx if no node involvement
• Mastectomy if big tumour without node (big or if many LN)
  
  • RTx if >5cm or ≥4 LN

Sentinal node biopsy - if +ve (met >2mm) → axillary node clearance

Adjuvant therapy

• Chemotherapy (taxanes): if node +ve or high-risk (triple -ve, high Ki67, HER2+)
• Hormone therapy (if ER or PR+)
  
  • Treat for 10y: Tamoxifen if pre, AI if post-menopausal
• Trastuzumab if HER2+, consider combination therapy with Lapatinib

Question 18

What are the risk factors for Cardiotoxicity with Trastuzumab use? (3)

Answer 18

1. Age
2. Baseline poor LVEF
3. Previous use of Anthracyclin (Daunorubicin - all -Rubicins)
   - Do not use it with Anthracyclins

Question 19

Pharmacological Tx of Metastatic Breast Ca?

Answer 19

ER/PR+: Hormonal therapy. At progression switch to another (e.g. AI to Tamoxifen, steroidal to nonsteroidal AI), can add mTOR inhibitor.

HER2+: trastuzumab + chemo +/- pertuzmab.

Bone metastasis: Denosumab > Zolendronic acid.

Question 20

Give some names of Aromatase inhibitors?

Answer 20

AIs work by inhibiting aromatase - which converts androgens to estrogens

Letrozole

Anastrozole

exemestane

Question 21

Definition of menopause? (2)

Answer 21

Prior Bilateral oophorectomy

No menstruation for 12 months - while undergoing ovarian suppression, tamoxifen, chemotherapy.

Question 22

Treatment options for hormone+ve, HER2-ve metastatic breast ca (postmenopausal women)?

• Low-burden
• Normo-burden
• High-burden

Answer 22

Postmenopausal - CDK 4/6 (Ribo/Pablocyclib) + AI (e.g. Letrozole)

Alternative = single agent AI: if patient prefers or cannot tolerate or have low burden disease

High-burden (rapidly progressive or extensive visceral mets with end-organ dysfunction): Chemotherapy

Question 23

Treatment options for hormone+ve, HER2-ve metastatic breast ca (premenopausal women)?

• Low-burden
• Normo-burden
• High-burden

Answer 23

Postmenopausal - Ovarian suppression + CDK 4/6 (Ribo/Pablocyclib) + Tamoxifen

Alternative = single-agent tamoxifen or OS/OA (ovarian suppression or ablation - check estradiol level) with tamoxifen if patient prefers or cannot tolerate or have low burden disease

High-burden (rapidly progressive or extensive visceral mets with end-organ dysfunction): Chemotherapy

Question 24

Treatment for HER2+ metastatic breast Cancer?

Answer 24

Combination Trastuzumab + Pertuzumab + Taxane

If not tolerated, dual Trastuzumab and Taxane

If Hormone +ve, ET + Trastuzumab is a reasonable alternative. However if high-burden or rapidly progressive disease, will need Chemo.

Question 25

General treatment strategy for triple -ve breast ca (early/locally advanced)?

Answer 25

Neoadjuvant or adjuvant chemotherapy + Surgery (if lesion >0.5cm)

Question 26

Treatment for metastatic triple -ve breast Ca? What are essential work up? (2)

Answer 26

PDL-1 expression

Germline BRCA mutations

If PDL-1 expression >1%, Atezolizumab + Nab-Paclitaxel (1b)

Germline BRCA mutations - above regime or PARPi

If all -ve, standard chemotherapy.

Question 27

CDK4/6 inhibitor (Ribociclib/Palbociclib) side effects? (5)

Answer 27

Cytopaenia

Hepatotoxicity

Cardiac - QT prolongation

Pulmonary Toxicity

Diarrhoea

Electrolytes: low Ca, K, Phos

Overall: a bit like immunotoxicity