Describe incidence of Bc
- most common cancer in UK
- 2018 56,000 women got diagnosed and 375 mean
- 1 in 8 women diagnosed in lifetime
around 12,000 women die and 800 die each year
incidence has increased over time, and mortality has decreased slightly
What are the risk factors of breast cancer
- Age (non modifibale)
** - increase risk of breast cancer as you age
- people are living longer so more chances of developing breast cancer
- reasons: immunoscence, DNA changes
- location
** - if you live in developed countries
- socieocencomic
- diet→ obestiy → cancers
**- late 1st pregnancy
**- early menarche late menopause
- all factors mean more oestrogen exposure
**- oral contraceptive
** - oestrogen chance
- there’s a 14% increase because of pill
- family history
- previous breast cancer
- taking exogenous hormones
- HRT longer you use after menopause
- oestrogen stimulates breast cells to develop cancerous cell
- should not be on for long time, or high dosage
- BMI
- can be modified
- diet etc
- prior radiotherpay
- non hodgkins → radiotherpay to chest
- So may cause breast cancer????
- have to go through a screening
What is breast cancer screening, how it done, and how often
-introudced due to forrest report
-early diagnosis allows for a better outcome
- digital mammograms
- every 3 years
- done between ages 50-70 years
What reproductive factors can increase or decrease risk of bc
- Early onset menarche (I)
- Late menopause (i)
- Older age at first pregnancy (i)
- Nulliparity. Each birth reduces the risk by 7% (15% in women with a twin birth). (d)
- Longer duration of breastfeeding )d)
How does lifestyle factors i.e obesity + alcohol increase risk of breast cancer
looking more at signalling pathways
- Activation of IGF1 and insulin signalling pathways
- Activation of PI3K/Akt/mTOR signalling pathways
- Increased production of oestrogen from adipose tissue
- Increased production of adipokines (e.g. Leptin)
Alcohol
- alcohol metabolism produces → acetaldehyde → which reduced oestrogen metabolism
- Epigenetic changes (DNA methylation)
How can family history affect risk of bc
- Incidence goes up if you have family members that have breast cancer (24x more likely if you have one family member with breast cancer)
- certain genes like BRCA 1 and 2 have been implicated in breast cancer development
84x more likely to have breast cancer if one of these genes is mutated - BRCA 1 more likely to develop at younger age → more aggressive cancer -> have a basal like subtype
- BRCA 2 → more likely to be hormone recpetor positive cancer
- in general population
- 0.2-0.3 in general pop have these mutations
but 3% of women with breast cancer have mutations in these genes
Where in the breast does most brest cancer come from
most breast cancer comes from ducts
i.e dutcal cancer
want to know type→ because of behaviour
- lobular cancers→ hard to see on a mammogram
- metaplastic → most aggressive
What two catagories is breast cancer histology broken into
In situ
-DCIS, LCIS
Invasive
-around 17 subtypes
-i.r ductal, lobular, tubular, metaplastic etc
What is DCIS
how does it act etc
- ductal carconimia is classed as in situ
- happens just in cells
- it doesn’t breech basement membrane → wont go to other organs
- show up as calcium deposits
- three grades DCIS → if high grade have a chance of becoming invasive → so need to think fo removal
DCIS is considered a precursor for breast cancer, and its detection and treatment are important for preventing the development of invasive disease.
What is lobular cariconma in situ
marker for increased risk of invasive lobular caricinoma
What are the molecular subtypes of breast cancer
Basal‐like (BRCA1/ triple‐negative) – 10‐20%
Luminal A (ER+, HER2‐) – 50‐60%
Luminal B (ER+, HER2+) – 10‐20%
HER2 – 10‐15%
How do we diagnose breast cancer
Triple assesement
**- clinical
** - examine lump
- examine axilla → lymph nodes
- look for nipple change, skin chnages etc
**- radiological
** - mammogram
- MRI
**- pathological
** - bioposy
- FNA, core biopsy
What are the histological types of bc
- Invasive ductal NST cancer
- Invasive lobular cancer.
- Inflammatory breast cancer 1‐5% of all cancers.
- these are very aggressive
- spread into lymphatics and blocked it
- Pagets disease of the nipple
- looks like eczema
How do we treat bc
Neo‐adjuvant therapy
- Endocrine (aromatase inhibitors)
- Chemotherapy (anthracyclines and taxanes)
- Herceptin/Pertuzumab/Lapatinib
Surgery
Adjuvant therapy
- Endocrine
- Chemotherapy
- Radiotherapy
- Biological agents ( Immunomodulators)
How would we treat small cancer
- breast conserving operation → wide local excision
- limitation: if the cancer is large its difficulty, because the breast looks a bit different
- oncoplastic procedures
- move breast tissues around, and fill the defect
- mastectomy
- if there are multiple cancers in one breast
- or if they have a BRCA gene
- decrease the chance of reoccurrence
- small breast, reasonable cancer → removal
- can have two types of mastectomy → simple, skin sparing mastectomy
- axillary lymph nodes
- these are sampled
- sentienal lymph node biopsy
- node clearance
What endocrine therapies would you use to treat bc
- Tamoxifen – a competitive inhibitor of estradiol
- Aromatase inhibitors – significantly lower serum estradiol concentration
- Ovarian suppression – GnRH agonists suppress ovarian function (Grosselin)
- surgical oophorectomy to stop oestrogen → prevent cancer from returning
Why would do radiotherapy after wide local excison
point is to reduce local reoccurrence
When do we use chemo in bc and how do we decide
- neo-adjuvant chemo
- after operation
- Oncotype test
- test for certain genes so you don’t expose everyone to chemo
- score in the previous lecture before this
- adjuvant chemo
- look at size, grade, recpetor and lymph node status
- cycles
- side effects
decide using oncotype test
What biological therapies can you use to treat bc
Extracellular mAbs
- Herceptin/Trastuzumab (HER2)
- monoclonal antibody
-binds to HER 2 receptor to inhibit ligand binding
-promotes ADDC
-does not block dimmersaition
- monoclonal antibody
- Pertuzumab (HER2)
- binds to HER2 receptor to stop downstream signalling
- by blocking dimmeisation
Intracellular TKIs
- Lapatinib (EGFR/ HER2)
- targets tyrosine kinase
How can we prevent bc
- Diet
- Alcohol intake
- Regular exercise
immunotherapy and bc
- PDL1 → test breast cancer cells → mainly for triple therapy cancers which are hard to treat
- PDL1 → a protein on breast cancer cells
