Systemic treatment for IDC

Question 1

Indication for neoadjuvant therapy in IDC

Answer 1

• Locally advanced disease (to convert inoperable tumor to operable
  
  • Stage III or Stage IIB +T3 disease
• Early stage cancer to increase use of BCS

Question 2

Neoadjuvant chemotherapy regimen

Answer 2

• High risk patients (node positive / triple negative with tumor > 1cm) + HER-2 negative
  
  • Anthracycline based combination regimen
    
    • AC-T regimen: Doxorubicin + Cyclophosphamide, + Paclitaxel
  • Anthracycline free combination regiment (heart problems)
    
    • TC regimen: Docetaxel + Cyclophosphamide

Question 3

Benefits of neoadjuvant chemotherapy

Answer 3

• Downstage a disease to allow operability
• Downstage disease to allow BCS
• Reduce local recurrence
• Does not improve disease free or overall survival

Question 4

Determining suitable type of neoadjuvant therapy

Answer 4

• HER 2 status
  
  • +ve: chemo + HER2 directed therapy
  • -ve: →
• Menopausal status
  
  • Premenopausal + fit : NACT 6-8 cycles
  • Post menopausal: NACT vs Endocrine therapy
  • Medical frail: Endocrine therapy

Question 5

What hormonal profile is less likely to respond to neoadjuvant chemotherapy?

Answer 5

Hormone positive (esp luminal A), HER2 negative

Question 6

Indication for neoadjuvant endocrine therapy

Answer 6

HER2 negative, post-menopausal women

Question 7

Neoadjuvant endocrine regimen

Answer 7

• Aromatase Inhibitor (letrozole/anastrozole) for 16-18 weeks

Question 8

What is HER2?

Answer 8

Human epidermal growth factor receptor 2 is a tyrosine kinase protein present in all epidermal cells

It is overexpressed in 15-25% of breast cancers

Associated with tamoxifen resistance

Associated with increase sensitivity to anthracycline based regimen

Question 9

How is HER2 measured?

Answer 9

• immunohistochemistry: antibodies directed against HER2 protein are visualized with chromogenic detection
• FISH
• CISH

Question 10

What is FISH?

Answer 10

Fluorescence in-situ hybridization

Quantitative measure of gene amplification

Question 11

What is the mechanism of Trastuzumab?

Answer 11

recombinant human monoclonal antibody directed against the extracellular domain of the HER2

Prevents activation of cell signal pathway

inhibits cell proliferation

Question 12

Side effects of trastuzumab

Answer 12

• Cardiac toxicity (need pre-treatment echo with LVEF > 55%
  *

Question 13

Subtypes of IDC

Answer 13

• Tubular
• Lobular
• Ductal
• Ductal lobular
• Mucinous
• Medullary

Question 14

Molecular subtypes of IDC

Answer 14

• Luminal A
• Luminal B
• Triple negative/ basal-like
• HER2 +ve

Question 15

Types of aromatase inhibitors

Answer 15

• irreversible steroidal inhibitors (Exemestane)
• reversible non-steroidal competitive inhibitors (Anastrozole, Letrozole)

Question 16

Risks of Tamoxifen

Answer 16

Increase risk of endometrial cancer

Thromboembolic event (stroke, PE, DVT)

Question 17

Risks of Aromatase Inhibitor

Answer 17

Osteoporosis

Cardiac dysfunction

Question 18

Anthracycline (doxorubicin) risks

Answer 18

Cardiac toxicity

Question 19

Cyclophosphamide toxicity

Answer 19

Hemorrhagic cystitis

Immunosuppression

Question 20

Taxane toxicity

Answer 20

Peripheral neuropathy

Myelosuppression

Question 21

What are the indications for use of Pertuzumab?

Answer 21

• Pertuzumab + Trastuzumab + chemo in neoadjuvant treatment for HER2+ve breast cancer
• Pertuzuamb + Trastuzumab + Docetaxel in local recurrent breast CA or HER2+ metastasis not amenable to surgery that have not previously received adjuvant therapy

Question 22

What is Pertuzumab

Answer 22

recombinant monoclonal antibody

inhibits dimerisation of HER2, HER3, and other HER receptors

arrest cell growth and apoptosis