Breast Cancer

Question 1

Incidence

Answer 1

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

Question 2

Incidence inc of dec

Why

Answer 2

Inc
Women living longer age risk factor
Life styles

Question 3

Mortality associated with BC

Answer 3

Low in comparison to diagnoses

More women diagnosed less are dying

Question 4

Worldwide incidence

Answer 4

Geographical location matters
More likely in Europe than USA
Lifestyle and genetic factors

Question 5

Migration studies

Answer 5

Chinese women same risk once emigrated

Question 6

Survival by stage

Answer 6

Smaller the tumour better the chances of survival
Stage 1 - survive 10 years
Stage 4- mets unlikely to survive 10 years

Question 7

Risk factors

Answer 7

Age
Geographical location 
Oestrogen exposure 
Family history- BRCA1 
Prev BC
Exogenous hormone 
BMI high 
Ionising radiation

Question 8

Nhs breast screening programme

Answer 8

47-73 every 3 years invitation

Question 9

Socioeconomic factors and BC

Answer 9

High sat fats obesity
Age at first pregnancy lower less risk
Number of children

Question 10

Reproductive factors

Answer 10

Early onset menarche 
Late menopause 
Older age at first pregnancy 
Nulliparity 
Longer duration breast feeding 
- reduces risk of BC

Question 11

Lifestyle factors- obesity

Answer 11

Activation of IGF1 and insulin signalling pathways
Activation of PI3K Akt mTOR signalling pathways
Inc production of oestrogen
Inc production of adipokines

Question 12

Lifestyle- alcohol

Answer 12

Effect of acetaldehyde 
Epigenetic changes (DNA methylation)

Question 13

BRCA genes

Answer 13

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

Question 14

Most common type of BC

Answer 14

Duct cancer

Question 15

2nd common type of Bc

Answer 15

Lobule type

Question 16

In situ bc can occur at multiple sites in one breast

Answer 16

DCIS

LCIS

Question 17

DCIS

Answer 17

Incidence inc

30-50% chance of progressing to invasive cancer

Question 18

LCIS - lobule carcinoma in situ

Answer 18

Marker of increased risk (8-10fold) for ILC rather than a true precursor

Question 19

If find DCIS on biopsy

Answer 19

Treat more aggressive likely to result in cancer

Question 20

If find LCIS on biopsy

Answer 20

Don’t necessarily have to treat as it is less aggressive/ likely to result in cancer

Question 21

How many subtypes of invasive cancer

Answer 21

At least 17

Question 22

DCIS likely or unlikely to metastasise

Answer 22

Unlikely

Basement membrane is still intact

Question 23

If basement membrane breached

Answer 23

Metastasis of cancer can occur

Cancer can spread to blood vessels/ lymph nodes

Question 24

Molecular subtypes of BC

Answer 24

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%

Question 25

3 markers for treatment planning

Answer 25

HER2 pos - herceptin ER pos Progesterone Pos

Question 26

Management diagnosis, surgery, adjuvant therapy

Answer 26

Not just surgery need to prevent cancer fro returning | Involves MDT

Question 27

Diagnostic team includes

Answer 27

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

Question 28

Cancer treatment team includes

Answer 28

Clinical oncologist Medical oncologist Breast surgeon

Question 29

Diagnosis triple assessment

Answer 29

Clinical Radiological Pathological

Question 30

Clinical

Answer 30

Inspection and palpation if breasts - changes nipple, skin, visible lumps Check lymph nodes in axilla and neck

Question 31

Radiological

Answer 31

``` 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 ```

Question 32

Pathological

Answer 32

Biopsy with ultrasound guidance Biopsy FNA or core biopsy Biopsy lymph glands - localisation or spread

Question 33

Mel adjuvant therapy

Answer 33

``` Before surgery - shrink lump as much as you can - conserve as much breast as you can Endocrine Chemo Radio Herceptin ```

Question 34

Surgery

Answer 34

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

Question 35

Auxiliary lymph node surgery

Answer 35

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

Question 36

Adjuvant therapies

Answer 36

Additional cancer treatment to lower risk cancer will come back

Question 37

Which population most important to do this in

Answer 37

``` 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 ```

Question 38

Types of adjuvant

Answer 38

Endocrine Chemotherapy- iv injection sig SE Radio therapy Biological agents

Question 39

Endocrine therapy

Answer 39

Tamoxifen - competitive inhibit E2 AI - lower E2 contents Ovarian suppressors - GnRH agonist suppress ovarian function.

Question 40

Radiotherapy when given

Answer 40

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%

Question 41

Chemotherapy when

Answer 41

Mel adjuvant or adjuvant

Question 42

Adjuvant

Answer 42

Size grade lymph node status, receptor status | Cycles of chemo

Question 43

Chemo SE

Answer 43

Bad | Suppresses normal cell numbers in blood counts, vomiting, hair loss

Question 44

Who benefits most fro chemo

Answer 44

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

Question 45

Biological therapies

Answer 45

Herceptin/ trastuzumab | Pertuzumab

Question 46

What do mab do

Answer 46

Attack her 2 Ag destroy cancer cells

Question 47

Se mab

Answer 47

Cardiotoxic cannot use if ha heart problems

Question 48

Intracellular RTK inhib

Answer 48

Laparinib | Expensive lots of se

Question 49

Future - vaccines

Answer 49

Tumour Ag MUC1 HER2

Question 50

Oncolytic viral therapy

Answer 50

Infects and kills cancer cells