Breast cancer

Question 1

What is management of DCIS?

Answer 1

Lumpectomy + radiation +/- hormone therapy (if ER positive)
OR mastectomy

If bilateral mastectomy - dont need follow up endocrine therapy

Question 2

What is the management of invasive breast cancer?

Answer 2

Surgical excision + radiation

• WLE for cancers < 5cm, with clear margins and no skin involvement
• Mastectomy for high risk: > 5cm, inflammatory, BRCA1/2 positive, strong family history or when radiation is contraindicated
• Sentinel LN biopsy - if < 2 nodes involved and pt getting chemo + endocrine + radio tx no need for axillary LN clearance
• Can do neoadjuvant chemo or endocrine tx for breast conservation
• Radiation post op - recommended when tumour size > 5cm, positive margins, 4 or more LN involved, inflammatory breast cancer

Question 3

What are some side effects of axillary LN clearance?

Answer 3

Lymphoedema
Sensory loss
Shoulder abduction defects

Question 4

What is the management for invasive breast cancer women > 70 years ?

Answer 4

If tumour <2cm and ER+ve - WLE and endocrine therapy only

Question 5

What is Paget’s disease of the breast?

Answer 5

• A rare type of breast cancer that affects the lactiferous ducts and the skin of the nipple and areola
• Associated with underlying IDC or DCIS in 80-90% cases
• Clinical features: erythematous, scaly rash, nipple retraction and ulceration, blood tinged nipple discharge

Question 6

How is Paget’s disease of the breast diagnosed and treated?

Answer 6

• Diagnosed with punch /wedge biopsy of nipple tissue
• Followup imaging to look for IDC/ DCIS

Treatment:
Mastectomy OR breast conserving surgery with radiation

Question 7

What is inflammatory breast cancer ?

Answer 7

A rare form of advanced, aggressive invasive carcinoma characterized by dermal lymphatic invasion of tumor cells

Question 8

What are the clinical features of inflammatory breast cancer?

Answer 8

Peau d’orange
- erythematous, oedematous skin plaques with prominent hair follicles resembling orange skin peel –> caused by blocked lymphatics by the tumour
- Tenderness, burning sensation
- Blood-tinged nipple discharge
- Signs of metastatic disease (e.g., axillary lymphadenopathy
- Usually no palpable tumour

Question 9

What are the diagnostic criteria for inflammatory breast cancer?

Answer 9

All 4 criteria must be met:
1) Rapid onset of breast erythema, edema, warmth, and peau d’orange, with or without palpable mass on breast examination
2) Erythema involving at least one-third of the breast
3) Symptoms have been present for < 6 months
4) Core needle biopsy confirming the presence of invasive carcinoma

Question 10

What is the diagnostic workup for inflammatory breast cancer?

Answer 10

Patients who meet the diagnostic criteria should undergo at least two full-thickness skin punch biopsies
Further testing
Imaging: bilateral mammogram and ultrasound of regional lymph node
Receptor testing

Question 11

What is the management of inflammatory breast cancer?

Answer 11

modified radical mastectomy + ANLD with neoadjuvant and adjuvant systemic therapy and adjuvant radiation therapy

Question 12

What are some ddx of inflammatory breast cancer?

Answer 12

Mastitis
Paget’s disease of the breast
Breast abscess

Question 13

What are the 3 types of breast cancer depending on hormone and HER-2 status ?

Answer 13

ER/PR positive, HER-2 neg (65% of breast cancers)
HER-2 positive , variable ER/PR status (~20% of breast cancers)
Triple negative (ER/PR and HER-2 negative) - ~15% of breast cancers

Note: ER/PR positive if >= 1% cells have hormone receptors

Question 14

What are some features of ER/PR positive breast cancer in terms of prognosis and relapse?

Answer 14

Indolent course
Late recurrence with bone metastases
Responsible for the highest mortality of all breast cancer subtypes

Question 15

What are the general principles of therapy for the 3 molecular subtypes of breast cancer?

Answer 15

HR positive, HER-2 neg: endocrine tx +/- chemotx

HER-2 pos, HR pos or neg: HER-2 targeted tx + chemotx +/- endocrine tx

Triple neg: chemotherapy + immunotherapy

Question 16

What is the treatment for early stage breast cancer?

Answer 16

Curative intent
Surgery (mastectomy or WLE) +/- LN biopsy +/- ALND

Neoadjuvant therapy: Triple neg, HER-2 positive or large tumour size

Adjuvant therapy: can be Chemo +/- HER-2
Endocrine +/- CKD4/6 inhibitors
Radiotherapy
Bisphosphonates

Question 17

How does nodal status affect management?

Answer 17

Nodal involvement : neo or adj chemotx

No nodal involvement: role of chemotx (neo or adj) unclear and depends on other prognostic factors

Question 18

What did the TAILORx study show?

Answer 18

Study with 21 panel gene assay in HR positive, HER2 neg and node neg BC

Gave recurrence score estimates that were used to guide need for chemo

Post menopausal with recurrence score < 25 - only endocrine tx is enough

Question 19

What has been the change in delivery of neoadjuvant chemotx for breast cancer?

Answer 19

Usually nodal disease treated with anthracycline and taxane
Dose escalation not beneficial, better to shorten dose interval (2 weeks vs 3 weeks) with GCSF cover for myelosuppression

Question 20

What is the targeted therapy for HER-2 positive breast cancer?

Answer 20

Transtuzumab for 12 months (in early BC, and as maintenance in metastatic disease)
No benefit of addition of lapatinib and minimal benefit of adj addition of pertuzumab
Main SE: heart failure, compounded if co-administered with anthracycline drugs

2nd line : lapatinib with capecitabine chemo
Main SE: diarrhoea, hand–foot syndrome, anaemia and nausea

Question 21

What is the KATHERINE trial?

Answer 21

Failure with neoadj chemo and HER2 therapy and ongoing residual disease - did better with TDM-1 (anti -body with drug conjugate vs HER-2 ab alone)

Improvement in DFS and freedom from distant recurrence

Question 22

What are the endocrine therapies available for ER/PR +ve breast cancer, their duration of tx and side effects?

Answer 22

SERMS: tamoxifen and raloxifene
Aromatase inhibitors: anastrozole, letrozole, exemestane
Given for 5 - 10 years (ATLAS and ATTOM trial)
Common SE : hot flushes, arthralgias and vaginal atrophy
SERMs: VTE and endometrial ca
AI: osteoporosis
Small absolute benefit of AI> SERMs
SERMs: pre and post menopausal
AI: post menopausal or pre with ovarian suppression (otherwise causes paradoxical rise in oestrogen from ovaries if used premenopausal)

Adj BBP - zolendronic acid
Fertility preservation - cryopreservation
CDK 4/6 inhibitors (not PBS approved in HR pos BC)

Question 23

What is the treatment for metastatic breast cancer?

Answer 23

Palliative intent
- prolongation of life, QoL and symptom management

Consider re-biopsy as metastases may be discordant to primary tumour (HR, HER-2 status)

HR positive:
- endocrine +/- CDK4/6 inhibitors (abemaciclib, palbociclib, ribociclib)
- Chemo - sequential single agent
- bisphosphonates

HER-2 positive
- dual HER-2 - transtuzumab, pertuzumab
- chemotx
- ab- drug conjugates - transtuzumab emtansine and transtuzumab deruxtecan)

Triple neg
- chemotherapy + immunotherapy
- ab - drug conjugates - sacituzumab govitecan

Question 24

What are some examples of CDK4/6 inhibitors?

Answer 24

MONARCH: Abemaciclib
PALOMA: Palbociclib
MONALEESA: Ribociclib

All three showed PFS benefit in HR+, HER-2 neg advanced BC but only abemaciclib and ribociclib showed OS benefit - drug of choice

SE:
palbociclib: myelosuppression and fatigue

Ribociclib : myelosuppression, liver toxicity QTc

Abemaciclib: myelosuppression and diarrhoea

Question 25

What are some emerging therapies in BC?

Answer 25

PI3K inhibitors
- alpelisib (PIK3 aplha inhibitor) - only benefit if mutation present, not on PBS
SE: diarrhoea, rash, N/V, hyperglycaemia
and AKT inhibitors – clinical trials
mTOR for those resistant to endocrine tx + CDK4/6

Question 26

What is the role of immunotherapy in BC?

Answer 26

Used in advanced triple neg BC
- improvement in OS with pembrolizumab if high expression of PD-L1

Other checkpoint inhibitors like atezolizumab

Question 27

What are antibody-drug conjugates?

Answer 27

Ab + linker + highly potent cytotoxic agent (payload)

Ab - binds to tumour specific antigen
Linker - helps release payload (intracellular + extracellular)
Payload - induces apoptosis in target tumour cell + bystander effect in surrounding cells

Examples
Tranztuzumab - emtansine : HER2
Transtuzumab -deruxtecan : HER-2 (DESTINY 02)
SE: ILD, alopecia, nausea, diarrhoea
Sacituzumab-govitecan - TROP2 (ASCENT III)
SE: meylosuppression, diarrhoea, alopecia