Molecular Basis of Breast Cancer

Question 1

What is the most common form of cancer in women

Answer 1

Breast

Question 2

What are some of the activities that lead to increased breast cancer risk

Answer 2

Increased hormonal exposure, both endogenous and exogenous hormones can increase or decrease the risk of developing breast cancer

Question 3

How is breast cancer diagnosed?

Answer 3

It is done using mammograms, now there are 3D mammograms that are available, MRIs are also used, and finally also ultrasound. Ultrasound is usually used in combination with one or the other techniques

Question 4

What is the next step if a lump is detected in either the mammgogram, ultrasound or the MRI

Answer 4

A biopsy is done. There are 3 kinds of biopsy: 1. Fine needle biopsy, only a small number of cells are collected 2. Core needle biopsy, a punch biopsy 3. Surgical biopsy - complete removal of the lump

Question 5

What are the things that are determined in these biopsies

Answer 5

Type of cancer whether it is malignant or benign, grade of the cancer and receptors as to which receptors is the cancer sensitive to, whether it is estrogen, progesterone or HER2

Question 6

What is the structure of a breast

Answer 6

It comprises of ductal tissue and milk producing glands.

Question 7

What form of breast cancer is the most common

Answer 7

Invasive ductal carcinoma, it happens in the ductal tissue

Question 8

Why is obesity a risk factor for breast cancer

Answer 8

The fat tissue in the breast produces those hormones, increase in hormonal production increases the risk of developing breast cancer

Question 9

What does a mammogram detect

Answer 9

They detect lesions that are caused by ductal carcinoma in situ

Question 10

What stage is ductal carcinoma in situ

Answer 10

Stage 0, it has not evaded the basal membrane yet. However there is a 100% chance that it will evade the basal membrane and start invasion of the nearby tissue

Question 11

What is the controversy around mammogram

Answer 11

A lot of the DCIS doesn’t progress into malignant neoplasm so there is a controversy about over treatment.

Question 12

Primary area of metastasis for breast cancer

Answer 12

Bones, lung and liver, a small percentage also happens in the brain. Lymph has a whooping 88% metastasis

Question 13

What does TNM stand for in term of staging

Answer 13

T is for tumor, how big is it, N is for lymph nodes metastasis and M is for distant metastasis

Question 14

What are the different classes for TNM

Answer 14

T0: no tumor Tis: Intra ductal tumor T1: less than 2 cm T2: between 2 cm and 5 cm T3: larger than 5 cm T4: any size with direct extension to chest wall or skin N0: no regional lymph node metastasis N1, 2 and 3 is in different parts of the lymph nodes M0: no distant metastasis M1: distant metastasis

Question 15

What stage is an M1 cancer

Answer 15

Stage IV. Cancer has already metastasized

Question 16

What are the 3 genes involved in breast cancer

Answer 16

1. BRCA 1 and 2 2. Her2/neu 3. ER/PR

Question 17

How does estrogen (ER) and progesterone (PR) receptors work

Answer 17

They work by binding to their receptors which are suspended in the cytosol. By binding to the receptor, they regulate transcription and promotes cell proliferation

Question 18

How does ER and PR induce cell proliferation

Answer 18

It is important to know that they interact with a variety of different mechanisms in a cell, they interact with EGFR receptors which have downstream effect on a variety of cellular pathways that leads to cell proliferation

Question 19

What are the exact biochemical pathway through which the ER and PR work

Answer 19

They bind to their receptors, which then goes and bind to the parts of the DNA which are Estrogen receptor regulatory element or progesterone receptor regulatory elements that promotes cell proliferation

Question 20

What is the relationship of hormonal replacement therapy and breast cancer

Answer 20

Women who take estrogen and progesterone hormone therapy they are more likely to develop breast cancer. However she said women who only take estrogen are less likely to develop breast cancer and that is what her lab is studying right now

Question 21

What is HER2/neu

Answer 21

It is a tyrosine kinase receptor, mutation leads to breast cancer, it belongs to the EGFR family, receptors can dimerize and increase cell proliferation, 25% of the people with breast cancer are positive for HER2/neu mutation. There is amplification of the gene that leads to a lot of these receptors on the cell membrane leading to excessive cell proliferation

Question 22

How is HER2 amplification detected. Explain the mechanism of these tests

Answer 22

By immunohistochemistry test or by FISH. In IHC the monoclonal antibody binds to the HER2 receptors, if there are a lot of these present then we would know that a lot of the antibody is binding to the cells. In FISH, a part of the DNA that is fluorescent is put in a cell, that part of the DNA binds to its complementary DNA and since it is fluorescent it can be seen microscopically.

Refer to the picture

Question 23

What is the role of BRCA 1 and 2

Answer 23

BRCA 1 is for check point regulation and BRCA 2 is for DNA repair. They work together in sensing damage and working to repair the DNA

Question 24

How many breast cancer are sporadic and hereditary

Answer 24

90% are sporadic, 10% are hereditary

Question 25

What is an oncotype RX score

Answer 25

There is an RS score given to patient who undergo this genetic testing, A low RS score means patient has high chances of survival whereas a low RS score means that there are chances for breast cancer reoccurance and the patient has low chances of survival