FunMed Week 4: Breast

Question 1

1. Briefly describe the category of women who are invited for mammographic surveillance:
2. Who may be at an increased risk of developing breast cancer [1 mark]

Answer 1

• Younger women OR those between the ages of 30 and 49 (1/2 mark)
  who may be at a higher risk due to either a genetic predisposition to the disease OR a significant family history of breast cancer,
  OR
• previous supradiaphragmatic radiotherapy (e.g. treatment for Hodgkin’s disease) (1/2 mark).

Question 2

Briefly describe the category of women who are invited for mammographic surveillance:

​Who may be a at high risk of developing breast cancer [1 mark]

Answer 2

Older women (or those between the ages of 40 -70) (1/2 mark)
who have been diagnosed as carriers of mutated genes such as BRCA1 or BRCA2 (OR another gene such as p53) (1/2 mark)

Question 3

1. Identify the TWO types of epithelial cells that breast cancers can originate from. [1 mark]

Answer 3

Basal or luminal cells (1/2 mark each)

Question 4

1. Identify TWO other cancers that are routinely screened for in the UK. [1 mark]

Answer 4

Cervical cancer (1/2 mark)

Colorectal (1/2 mark)

Question 5

1. What is the difference between a proto-oncogene and an oncogene? [2 marks]

Answer 5

Proto-oncogene is a gene which facilitates normal cell growth OR diffrentaion OR division OR cell migration.[1 mark]

When a proto-oncogene is mutated it becomes an oncogene, there is a gain of function which drives the initation and pregression of cancer so e.g there would be uncontrolled growth.[1 mark]

Question 6

1. One of the functions of the BRCA genes is to facilitate repair of DNA damage. What type of DNA repair does BRCA1 and BRCA2 facilitate? [1 mark]

Answer 6

Homologous recombination (1/2 mark) of double-stranded DNA breaks (1/2 mark).

Question 7

1. Identify THREE reasons why a person may be referred to a genetic councillor [3 marks]

Answer 7

• There’s a history of some types of cancer in the family, such as breast cancer (e.g. BRCA1, BRCA2 or other genes such as p53) which affect family members at a young age, and members of the family want to know if they are at risk
• Parents know there’s a specific genetic disorder in the family and they would like specialist advice about the risks to them, their children
• There may be a genetic condition (other than cancer) in the family that needs specialist diagnosis
• A child has developmental delay that may have a genetic cause and need specialist diagnosis
• Prospective parents want advice on planning for a pregnancy

Pregnant women want to discuss an abnormal test result and understand their options

Question 8

what is the histology of breast tissue like? [4]

Answer 8

1. Each breast is made up of 15-25 secretory lobes, embedded in adipose tissue.
2. The mammary gland is like a modified sweat gland.
3. Each of theses lobes is a compound tubular acinar gland.
4. The acini empty into ducts, that are lined by cuboidal, or low columnar epithelial cells, and surrounded by myoepithelial cells
5. These ducts are surrounded by smooth muscle in the regon of the nipple, contraction of which makes the nipple become errect.

Breasts contain the mammary glands responsible for lactation in females.

Mammary glands are made up of 12 to 20 lobes, each of them containing many smaller lobules.

These smaller lobules have grape-like clusters of alveoli that contain mammary secretory epithelial cells, the milk producing cells of lactation.

These alveoli, lobules and lobes are connected through a network of ducts called the lactiferous ducts, and eventually form a unique lactiferous duct for each lobe which opens independently to the areola to drain the milk produced during lactation.

Each lactiferous duct has a dilated portion deep to the areola called the lactiferous sinus in which there’s a small drop of milk that accumulates or remains in a nursing mother, which becomes expelled from the areola when compressed during feeding.

Question 9

which chromosomes are BRCA1 & BRCA2 located on ? [2]

Answer 9

BRCA1: 17
BRCA2 : 13

Question 10

at what stage in DNA division do BRCA1 & BRCA2 work?

Answer 10

1. BRAC1 and BRAC2 repair damaged dsDNA crosslinks at the G2 / M checkpoint

Question 11

what is role of BRCA1?

• what does it trigger?
• what does deficiency lead to?

Answer 11

1. normally: triggers the activation of the CDK inhibitor: p21WAF-1 and p53, so can control cell cycle
2. Also involved in DNA repair
3. BRCA1 deficiency leads to the dysregulation of cell cycle checkpoint, abnormal centrosome duplication, genetic instability and eventually apoptosis

Question 12

what is role of BRCA2?

• normal?
• what does mutation in gene cause?

Answer 12

1. Normally facilitates HR of ds DNA breaks
2. BRAC2 deficient cells: can’t recruit RAD51 (protein that binds to ssDNA and needed in dsDNA repair)
3. mutations: cant repair ss and dsb DNA breaks

Question 13

what mode of inheritance is BRCA genes? [1]

Answer 13

autosomal dominant
BUT: If embryo has double BRCA gene then embryo tends not to develop so most common is heterozygous

Question 15

what are modifiable [5] and non-modifiable [5] risk factors for breast cancer?

Answer 15

1. Modifiable:
   
   1. Not being physically active
   2. Overweight / obese after menopause
   3. Hormones (HRT) during menopause (small increase of risk)
   4. Reproductive history. Pregnant after 30 increases risk
   5. Alcohol intake
2. Non-Modifiable
   
   1. Age (50+)
   2. Genetics
      
      1. Inheriting BRCA1/2 genes
      2. Heritage – Ashkenazi Jews have higher risk
   3. Dense breasts
      
      1. More connective tissue than fatty tissue – difficult to see tumours on mammograms
   4. Previous cases of breast cancer
   5. Previous treatment of radiation therapy

Question 16

how do you screen for breast cancer? [4]

Answer 16

1. Known gene mutation: Annual MRI scans from:
   
   1. Age 20 – TP53 mutation
   2. Age 30 for BRCA1/2
2. NHS Breast screening programme: all women 50-70 invited for screening every 3 years.
   
   1. Mammography (x-ray of the breast)
   2. 2 for each breast
3. Breast ultrasound
   
   1. For woman under 40 because have denser breasts – so mammogram isn’t as effective
4. Biopsy
   
   1. Needle: most common
      
      1. Can be guided by ultrasound
   2. Vacuum assisted biopsy / mammotome biopsy: needle attached to a gentle suction tube. Helps obtain sample and clear bleeding
   3. May need needle test on armpits (axilla) to see if spread
      5.

Question 17

what is a proto-oncogene?
what is an oncogene?
what is a tumour supressor gene?

Answer 17

• A Proto-oncogene is a normal gene that helps cells grow.
• An Oncogene is a gene that causes cells to divide uncontrolled causing cancer.
• A Protooncogene can undergo a mutation to become an oncogene.
• A tumour suppressor gene is a gene that encodes proteins which halt cell division. For example p53 or pRB

•

Question 18

Invasive breast cancer can be categorised into one of four molecular subtypes based upon gene expression. what are they? [4]

Answer 18

Luminal A

Luminal B

Basal

HER2

Question 19

which are two areas of the breast that are common for breast cancer to occur in? [2]

Answer 19

either the breast duct or lobe

Question 20

what is triple assessment of someone with suspected breast cancer? [3]

Answer 20

history & exam
imaging (mammography)
histopathology

Question 21

men with a BRCA gene are disposed to which types of cancer?

Answer 21

• breast cancer
• prostate cancer.

Question 22

explain how brca genes are inherited

Answer 22

- autosomal dominant:

• if have BRCA gene: have one altered and one working copy of the gene
• each time have a child: 50% chance pass on working copy and 25% chance

Question 23

what type of gene is BRCA 1/2

Answer 23

tumour suppressor gene

Question 24

what is different about BRCA breast cancers compared to other breast cancers?

Answer 24

. Breast cancers associated with a BRCA1 or BRCA2 mutation tend to develop in younger women and occur more often in both breasts than cancers in women without these mutations.

Question 26

describe the 3 different grades of cancer

Answer 26

GRADING

There are three grades of invasive breast cancer:

Grade 1 (well differentiated) – the cancer cells look most like normal cells: usually slow-growing

Grade 2 (moderately differentiated) – the cancer cells look less like normal cells: growing faster

Grade 3 (poorly differentiated) – the cancer cells look most change: usually fast-growing.

Question 27

what are the two ways can stage cancer? [2]

Answer 27

number staging
TNM staging

Question 28

Answer 28

Question 29

explain TMN staging

Answer 29

The T stages

TX means that the tumour size cannot be assessed

Tis means DCIS

T1 – The tumour is 2 centimetres (cm) across or less

T1mi – the tumour is 0.1cm across or less

T1a – the tumour is more than 0.1 cm but not more than 0.5 cm

T1b – the tumour is more than 0.5 cm but not more than 1 cm

T1c – the tumour is more than 1 cm but not more than 2 cm

T2 – The tumour is more than 2 centimetres, but no more than 5 centimetres across

T3 – The tumour is bigger than 5 centimetres across

T4 is divided into 4 groups

The N Stages

NX means that the lymph nodes cannot be assessed (example, if they were previously removed)

N0 – No cancer cells found in any nearby nodes

Isolated tumour cells (ITCs) are small clusters of cancer cells less than 0.2 mm across, or a single tumour cell, or a cluster of fewer than 200 cells in one area of a lymph node. Lymph nodes containing only isolated tumour cells are not counted as positive lymph nodes

N1 – Cancer cells are in lymph nodes in armpit but the nodes are not stuck to surrounding tissues

PN1mi – One or more lymph nodes contain areas of cancer cells called micro metastases that are larger than 0.2mm or contain more than 200 cancer cells but are less than 2mm

N2 is divided into 2 groups

N2a – there are cancer cells in the lymph nodes in the armpit, which are stuck to each other and to other structures

N2b – there are cancer cells in the lymph nodes behind the breast bone (the internal mammary nodes), which have either been seen on a scan or felt by the doctor. There is no evidence of cancer in lymph nodes in the armpit

N3 is divided into 3 groups

N3a – there are cancer cells in lymph nodes below the collarbone

N3b – there are cancer cells in lymph nodes in the armpit and behind the breast bone

N3c – there are cancer cells in lymph nodes above the collarbone

The M Stage

M0 means that there is no sign of cancer spread

CMo(i+) means there is no sign of the cancer on physical examination, scans or X-rays but cancer cells are present in blood, bone marrow, or lymph nodes far away from the breast cancer – the cells are found by laboratory tests

M1 – means the cancer has spread to another part of the bod

Question 30

explain number staging system

Answer 30

Stage 1 usually means that a cancer is small and contained within the organ it started in

Stage 2 usually means that the tumour is larger than in stage 1 but the cancer hasn’t started to spread into the surrounding tissues. Sometimes stage 2 means that cancer cells have spread into lymph nodes close to the tumour. This depends on the particular type of cancer

Stage 3 usually means the cancer is larger. It may have started to spread into surrounding tissues and there are cancer cells in the lymph nodes nearby.

Stage 4 means the cancer has spread from where it started to another body organ. For example to the liver or lung. This is also called secondary or metastatic cancer