Lecture 19 - Breast Cancer

Question 1

What 4 3’s do I need to know for the exam?

Answer 1

• Describe 3 risk factors for breast cancer
• Name 3 sub-types of breast cancer
• What is triple assessment?
• Discuss 3 treatment options

Question 2

Describe the incidence of breast cancer

Answer 2

• most common cancer in UK
• around 50,000 women and 400 men diagnosed each year
• 1/8 women will be diagnosed in her lifetime
• 12,000 women and 8- men will die from breast cancer each year

Question 3

What is the trend in incidence and mortality of breast cancer?

Answer 3

incidence = rising 
mortality = decreasing

Question 4

How does survival rate vary by stage? Why is this important?

Answer 4

survival decreases dramatically with each increasing stage

- early diagnosis essential

Question 5

What are the risk factors for breast cancer?

Answer 5

• age
• geographic location
• oestrogen exposure
• family history
• previous breast cancer
• exogenous hormones
• BMI
• ionising radiation

Question 6

Describe the NHS breast screening programme

Answer 6

• introduced in 1988
• 50-70
• 3 yearly intervals
• digital mammograms
• estimated 1000 deaths prevented

Question 7

What socioeconomic factors affect breast cancer risk?

Answer 7

• high SES
• age at first pregnancy - younger = protection
• number of children - more = protection

Question 8

What reproductive factors affect breast cancer risk?

Answer 8

• early onset menarche
• late menopause
• older age at first pregnancy
• nulliparity, each birth reduces the risk by 7% (15% in women with a twin birth)
• longer duration of breastfeeding

Question 9

What lifestyle factors affect breast cancer risk and the molecular basis for their risk?

Answer 9

Obesity
- activation of IGF-1 and insulin signalling pathways
- activation of PI3K/Akt/mTOR signalling pathways
- increased production of oestrogen
- increased production of adipokines (e.g. leptin)
Alcohol
- effect of actaldehyde
- epigenetic changes (DNA methylation)

Question 10

What is the prevalence of the BRCA genes?

Answer 10

0.2-0.3% in general population
3% in women with breast cancer
6% in women with breast cancer onset before age 40

Question 11

What subtype are most of the BRCA1 cancers?

Answer 11

• basal-like

Question 12

What gene is the major high-penetrance predisposition gene for luminal (ER positive) breast cancers?

Answer 12

BRCA2

Question 13

What are the two major histological types of breast cancer

Answer 13

Ductal carcinoma in situ = DCIS
- incidence increasing
- 30-50% chance of processing to invasive cancer
Lobule carcinoma in situ = LCIS
- marker of increased risk (8-10 fold) for ILC rather than a true precursor

Question 14

What are the main types of invasive breast cancer?

Answer 14

ductal/NST
lobular 
tubular
mucinous
papillary 
others

Question 15

Describe the transition from in situ to metastatic breast cancer

Answer 15

BM intact
in situ changes, including nuclear changes
invasion –> BM disruption
blood vessels and lymph invasion

Question 16

What are the major molecular subtypes of breast cancer?

Answer 16

• Basal-like (BRCA1/triple-begative)
• Luminal A (ER+, HER2-)
• Luminal B (ER+, HER2+)
• HER2
• Claudin-low
• Normal like

Question 17

Why is it important to find out the molecular characteristics of a breast cancer?

Answer 17

• guide treatment

- estimate prognosis

Question 18

Which is the worst and best molecular profile of a breast cancer?

Answer 18

triple negative = worst

O, P +ve = best

Question 19

What are the 3 things involved in the management?

Answer 19

diagnosis
surgery
adjuvant therapy

Question 20

Who forms part of the diagnostic team?

Answer 20

• breast clinician (consultant surgeon)
• radiologist and radiographer
• pathologist
• breast care nurse
• nurse practitioner
• clinic staff
• administrative staff
• dedicated MDT coordinator

Question 21

Who forms part of the treatment team?

Answer 21

• clinical oncologist
• medical oncologist
• breast surgeon
• medical geneticist
• data management personnel
• research nurse
• lymphedema specialist
• medical prosthetist
• clinical psychologist
• palliative care team

Question 22

What is the triple assessment?

Answer 22

1. Clinical
2. Radiological
3. Pathological

Question 23

Describe the clinical aspect of triple assessment

Answer 23

• inspection and palpation of the breast

- checking lymph nodes in the neck and axilla

Question 24

Describe the radiological aspect of triple assessment

Answer 24

mammogram and ultrasound

Question 25

Describe the pathological aspect of triple assessment

Answer 25

biopsy, FNA, core biopsy

Question 26

Describe the current treatment options for breast cancer

Answer 26

Neoadjuvant therapy 
- endocrine (aromatase inhibitors)
- chemotherapy (anthracyclines and taxanes)
- hercpetin/pertuzumab/lapatinib
Surgery
Adjuvant therapy 
- endocrine 
- chemotherapy 
- radiotherapy
- biological agents

Question 27

What are the surgical options?

Answer 27

• wide local excision (breast conserving surgery)
• mastectomy - simple vs skin sparing
• axillary lymph nodes - sentinel lymph node biopsy, axillary node sampling, axillary node clearance

Question 28

What are the three options for endocrine therapy?

Answer 28

Tamoxifen - a competitive inhibitor of estradiol
Aromatase inhibitors - significantly lower serum estradiol concentration
Ovarian suppression - GnRH agonists suppress ovarian function

Question 29

What are the two categories of biological therapies?

Answer 29

Extracellular mAbs
- herceptin/trastuzumab (HER2)
- pertuzumab (HER2)
Intracellular TKIs
- lapatinib (EGFR/HER2)

Question 30

What is the major new therapy for the future?

Answer 30

Tumour vaccines

• tumour antigens - MUC1, HER2
• tumour cells
• dendritic cells/T-cells
• exosomes

Oncolytic viral therapy?
Gene therapy?

Question 31

How does OCP and HRT affect breast cancer risk?

Answer 31

OCP –> 14% increase, baseline after 10 years

HRT –> 66% increase, baseline after 2 years