Breast Cancer Flashcards
Incidence
Most common cancer in the U.K.
50000 women 400 men
1 in 8 women will be diagnosed with BC in her lifetime
12000 women 80 men will die from breast cancer each year
Incidence inc of dec
Why
Inc
Women living longer age risk factor
Life styles
Mortality associated with BC
Low in comparison to diagnoses
More women diagnosed less are dying
Worldwide incidence
Geographical location matters
More likely in Europe than USA
Lifestyle and genetic factors
Migration studies
Chinese women same risk once emigrated
Survival by stage
Smaller the tumour better the chances of survival
Stage 1 - survive 10 years
Stage 4- mets unlikely to survive 10 years
Risk factors
Age Geographical location Oestrogen exposure Family history- BRCA1 Prev BC Exogenous hormone BMI high Ionising radiation
Nhs breast screening programme
47-73 every 3 years invitation
Socioeconomic factors and BC
High sat fats obesity
Age at first pregnancy lower less risk
Number of children
Reproductive factors
Early onset menarche Late menopause Older age at first pregnancy Nulliparity Longer duration breast feeding - reduces risk of BC
Lifestyle factors- obesity
Activation of IGF1 and insulin signalling pathways
Activation of PI3K Akt mTOR signalling pathways
Inc production of oestrogen
Inc production of adipokines
Lifestyle- alcohol
Effect of acetaldehyde Epigenetic changes (DNA methylation)
BRCA genes
Rare
Testing is expensive so only offered to certain groups
Younger women
Rare in women with BC
More common in BC onset before 40
Most of BRCA1 breast cancers are basal like subtypes
BRCA2 is the major high penetrance predisposition gene for luminal ER pos Bc
If BRCA pos very likely will get Bc by 70
Give a prophylactic/ risk reducing mastectomy
Prevent still 5% chance of getting cancer
Most common type of BC
Duct cancer
2nd common type of Bc
Lobule type
In situ bc can occur at multiple sites in one breast
DCIS
LCIS
DCIS
Incidence inc
30-50% chance of progressing to invasive cancer
LCIS - lobule carcinoma in situ
Marker of increased risk (8-10fold) for ILC rather than a true precursor
If find DCIS on biopsy
Treat more aggressive likely to result in cancer
If find LCIS on biopsy
Don’t necessarily have to treat as it is less aggressive/ likely to result in cancer
How many subtypes of invasive cancer
At least 17
DCIS likely or unlikely to metastasise
Unlikely
Basement membrane is still intact
If basement membrane breached
Metastasis of cancer can occur
Cancer can spread to blood vessels/ lymph nodes
Molecular subtypes of BC
Basal like (BRCA1/ triple negative 10-20%
Luminal A (ER+, HER2-) 50-60%
Luminal B ER+ and HER +
HER2 10-15%
Claudin low 12-14% Claudins are a family of proteins that are the most important components of tint junctions
Normal like 5-10%
3 markers for treatment planning
HER2 pos - herceptin
ER pos
Progesterone Pos
Management diagnosis, surgery, adjuvant therapy
Not just surgery need to prevent cancer fro returning
Involves MDT
Diagnostic team includes
Breast clinician
Radiologist and radiographer
40+ mammogram and Ultrasoind possibly MRI
Under 40 breast tissue v glandular and dense therefore mammogram is not informative
Mammogram more radiation
Under 40s x ray
Breast cancer nurse
Cancer treatment team includes
Clinical oncologist
Medical oncologist
Breast surgeon
Diagnosis triple assessment
Clinical
Radiological
Pathological
Clinical
Inspection and palpation if breasts - changes nipple, skin, visible lumps
Check lymph nodes in axilla and neck
Radiological
Mammogram USS Find lumps via imaging White - glandular tissue Black fatty tissue Older more white breasts look Cancer breast look more black Abnormal imaging - biopsy Image armpits too
Pathological
Biopsy with ultrasound guidance
Biopsy FNA or core biopsy
Biopsy lymph glands - localisation or spread
Mel adjuvant therapy
Before surgery - shrink lump as much as you can - conserve as much breast as you can Endocrine Chemo Radio Herceptin
Surgery
Before or with new- adjuvant surgery
2
1) wide local excision breast conserving
Remove cancer and a good margin of tissue around it -> if pathologist says the margin is clear - ok
2) mastectomy
Simple or skin sparing
Large tumour and small breast cannot shrink tumour with chemo recommend mastectomy
2 cancers in one breast mastectomy
BRCA gene carriers recommend as massive risk they will develop cancer during their lifetime
Auxiliary lymph node surgery
Always sample these
Check lymph nodes to see if pos or neg
If pos further treatment as cancer is spreading
Neg no further treatment needed
Sentinel lymph node - 1st node or group of nodes draining a cancer. In the case of established cancer met -> it is believed that the sentinel lymph nodes are the target organs first reached by metastasising cancer cells from the tumour
If Sentinel lymph node clear no cancer spread to it
Identify sentinel by using 2 dyes
1 radioactive the other blue if the blue met
Adjuvant therapies
Additional cancer treatment to lower risk cancer will come back
Which population most important to do this in
Young More metabolic activity Better blood supply More likely cancer cells to spread chemo shrink tumour Chemo through entire body Kills any cancer cells present
Types of adjuvant
Endocrine
Chemotherapy- iv injection sig SE
Radio therapy
Biological agents
Endocrine therapy
Tamoxifen - competitive inhibit E2
AI - lower E2 contents
Ovarian suppressors - GnRH agonist suppress ovarian function.
Radiotherapy when given
Following wide local excision
Still have breast tissue have not removed the breast
If don’t give radio more likely to get cancer again
Post mastectomy
Reduce recurrence by 70%
Chemotherapy when
Mel adjuvant or adjuvant
Adjuvant
Size grade lymph node status, receptor status
Cycles of chemo
Chemo SE
Bad
Suppresses normal cell numbers in blood counts, vomiting, hair loss
Who benefits most fro chemo
Young
Need to assay the cancer estimate how much a patient will benefit from chemotherapy
Done because chemo expensive
Can also make you feel more sick
Biological therapies
Herceptin/ trastuzumab
Pertuzumab
What do mab do
Attack her 2 Ag destroy cancer cells
Se mab
Cardiotoxic cannot use if ha heart problems
Intracellular RTK inhib
Laparinib
Expensive lots of se
Future - vaccines
Tumour Ag MUC1 HER2
Oncolytic viral therapy
Infects and kills cancer cells
