Breast Cancer

Question 1

List the mechanisms by which obesity increases the risk of breast cancer.

Answer 1

1 - Increased activation of IGF1 and insulin signalling pathways.

2 - Increased activation of PI3K/Akt/mTOR signalling.

3 - Increased production of oestrogen from adipose tissue.

4 - Increased production of adipokines, e.g. Leptin, which interfere with oestrogen metabolism.

Question 2

List 2 mechanisms by which alcohol increases risk of breast cancer.

Answer 2

1 - Acetaldehyde (a metabolite of ethanol) reduces oestrogen metabolism.

2 - Epigenetic changes due to DNA methylation.

Question 3

What is the PALB2 gene?

Answer 3

• The PALB2 gene (partner and localiser of BRCA2) encodes a protein that has a function in double strand break repair.
• It binds to and colocalises with the BRCA2 gene, facilitating stable accumulation of BRCA2.

Question 4

With which breast cancers are mutations in BRCA genes associated?

Answer 4

Mutations in BRCA genes are associated with luminal (A and B) breast cancers.

Question 5

What is the difference between invase and in-situ breast cancers?

Answer 5

Invasive breast cancers invade tissue outside of the breast whereas in-situ breast cancers do not.

Question 6

List 4 histological types of breast cancer (2 in-situ and 2 invasive).

Answer 6

In-situ:

1 - Ductal carcinoma in-situ.

2 - Lobular carcinoma in-situ.

Invasive:

1 - Invasive ductal carcinoma.

2 - Invasive lobular carcinoma.

3 - Invasive tubular carcinoma.

*These are classified on the basis of their histology, whereas classifications such as luminal A are molecular subtypes.

Question 7

List the molecular subtypes of breast cancer.

Answer 7

1 - Luminal A.

2 - Luminal B.

3 - HER2.

4 - Triple-negative.

Question 8

List the receptors that are tested for in breast cancer.

Answer 8

Receptors tested for in breast cancer include:

1 - Oestrogen receptor.

2 - Progesterone receptor.

3 - HER2 receptor.

Question 9

What is involved in triple assessment of breast cancer?

Answer 9

1 - Clinical: inspection and palpation of the breasts and checking lymph nodes in the neck and axilla.

2 - Radiological: mammogram, ultrasound or MRI.

3 - Pathological: fine needle aspiration biopsy.

Question 10

List 4 types of treatment options available for breast cancer.

Answer 10

1 - Chemotherapy.

2 - Endocrine.

3 - Radiotherapy (following surgery).

4 - Surgery.

Question 11

List 3 chemotherapy drugs that are used to treat HER2-positive breast cancer.

Answer 11

Drug treatments for HER2-positive breast cancers include:

1 - Herceptin.

2 - Pertuzumab (an antibody against the HER2 receptor).

3 - Lapatinib (a tyrosine kinase inhibitor).

Question 12

Describe the mechanism of herceptin.

Answer 12

Herceptin is an antibody that binds to HER2 receptors on the cell surface, inducing an immune-mediated response that causes internalisation and downregulation of the HER2 receptor.

Question 13

List 3 endocrine treatments for breast cancer.

For each treatment, describe the mechanism.

Answer 13

1 - Tamoxifen (a competitive inhibitor of oestradiol).

2 - Aromatase inhibitors (for menopausal women, as the action of aromatase on testosterone is the primary source of oestrogen in menopausal women).

3 - Ovarian suppression (e.g. GnRH agonists such as goserelin for premenopausal women)

Question 14

List 4 surgical treatments for breast cancer.

Answer 14

1 - Wide local excision (a form of breast-conserving surgery).

2 - Mastectomy (removal of the breast).

3 - Axillary lymphadenectomy.