Lecture 19 - Breast Cancer Flashcards
What 4 3’s do I need to know for the exam?
- Describe 3 risk factors for breast cancer
- Name 3 sub-types of breast cancer
- What is triple assessment?
- Discuss 3 treatment options
Describe the incidence of breast cancer
- 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
What is the trend in incidence and mortality of breast cancer?
incidence = rising mortality = decreasing
How does survival rate vary by stage? Why is this important?
survival decreases dramatically with each increasing stage
- early diagnosis essential
What are the risk factors for breast cancer?
- age
- geographic location
- oestrogen exposure
- family history
- previous breast cancer
- exogenous hormones
- BMI
- ionising radiation
Describe the NHS breast screening programme
- introduced in 1988
- 50-70
- 3 yearly intervals
- digital mammograms
- estimated 1000 deaths prevented
What socioeconomic factors affect breast cancer risk?
- high SES
- age at first pregnancy - younger = protection
- number of children - more = protection
What reproductive factors affect breast cancer risk?
- 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
What lifestyle factors affect breast cancer risk and the molecular basis for their risk?
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)
What is the prevalence of the BRCA genes?
0.2-0.3% in general population
3% in women with breast cancer
6% in women with breast cancer onset before age 40
What subtype are most of the BRCA1 cancers?
- basal-like
What gene is the major high-penetrance predisposition gene for luminal (ER positive) breast cancers?
BRCA2
What are the two major histological types of breast cancer
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
What are the main types of invasive breast cancer?
ductal/NST lobular tubular mucinous papillary others
Describe the transition from in situ to metastatic breast cancer
BM intact
in situ changes, including nuclear changes
invasion –> BM disruption
blood vessels and lymph invasion
What are the major molecular subtypes of breast cancer?
- Basal-like (BRCA1/triple-begative)
- Luminal A (ER+, HER2-)
- Luminal B (ER+, HER2+)
- HER2
- Claudin-low
- Normal like
Why is it important to find out the molecular characteristics of a breast cancer?
- guide treatment
- estimate prognosis
Which is the worst and best molecular profile of a breast cancer?
triple negative = worst
O, P +ve = best
What are the 3 things involved in the management?
diagnosis
surgery
adjuvant therapy
Who forms part of the diagnostic team?
- breast clinician (consultant surgeon)
- radiologist and radiographer
- pathologist
- breast care nurse
- nurse practitioner
- clinic staff
- administrative staff
- dedicated MDT coordinator
Who forms part of the treatment team?
- clinical oncologist
- medical oncologist
- breast surgeon
- medical geneticist
- data management personnel
- research nurse
- lymphedema specialist
- medical prosthetist
- clinical psychologist
- palliative care team
What is the triple assessment?
- Clinical
- Radiological
- Pathological
Describe the clinical aspect of triple assessment
- inspection and palpation of the breast
- checking lymph nodes in the neck and axilla
Describe the radiological aspect of triple assessment
mammogram and ultrasound
Describe the pathological aspect of triple assessment
biopsy, FNA, core biopsy
Describe the current treatment options for breast cancer
Neoadjuvant therapy - endocrine (aromatase inhibitors) - chemotherapy (anthracyclines and taxanes) - hercpetin/pertuzumab/lapatinib Surgery Adjuvant therapy - endocrine - chemotherapy - radiotherapy - biological agents
What are the surgical options?
- wide local excision (breast conserving surgery)
- mastectomy - simple vs skin sparing
- axillary lymph nodes - sentinel lymph node biopsy, axillary node sampling, axillary node clearance
What are the three options for endocrine therapy?
Tamoxifen - a competitive inhibitor of estradiol
Aromatase inhibitors - significantly lower serum estradiol concentration
Ovarian suppression - GnRH agonists suppress ovarian function
What are the two categories of biological therapies?
Extracellular mAbs - herceptin/trastuzumab (HER2) - pertuzumab (HER2) Intracellular TKIs - lapatinib (EGFR/HER2)
What is the major new therapy for the future?
Tumour vaccines
- tumour antigens - MUC1, HER2
- tumour cells
- dendritic cells/T-cells
- exosomes
Oncolytic viral therapy?
Gene therapy?
How does OCP and HRT affect breast cancer risk?
OCP –> 14% increase, baseline after 10 years
HRT –> 66% increase, baseline after 2 years
