Research Projects

Genetic Screening of Triple Negative and Young Breast Patients in SA

Genetic Screening of Triple Negative and Young Breast Patients in SA

Prof Ans Baeyens

Project ended 31 March 2018

Prof Ans Baeyens

Title of the project

Genetic screening of triple negative and young breast patients in South Africa.

Project Description

Breast cancer is the leading cancer in women in South Africa with the National Cancer Registry of South Africa estimating a 1 in 32 lifetime risk of developing the disease breast cancer among South African women. South Africa is a country with diverse ethnic groups and the lifetime risk of developing breast cancer differs according to ethnicity.

The incidence of breast cancer is on the rise in South African women. This is typically due to increased life expectancies and urbanization that leads to lifestyle changes that elevate exposure to known risk factors for breast cancer. Due to low socio-economic status, limited access to diagnostic centers in rural areas, lack of awareness and lower standards of healthcare facilities, breast cancer is often diagnosed at an advanced stage in South Africa and results in higher mortality rates. Multiple factors influence breast cancer risk such as family history, hormonal factors and the presence of mutations in breast cancer susceptibility genes.

Breast cancers consist of a heterogenous group of tumours with different biologic characteristics, prognosis and response to treatment. Approximately 10-17% of breast cancers do not have expression of estrogen, progesterone and HER2/NEU receptors and are known as triple-negative (TN). These breast cancers are associated with poor prognosis and are hard to treat with hormonal and/or targeted therapy. Another subgroup of breast cancer patients with aggressive tumour progression, lack of receptor expression and poor prognosis are young breast cancer patients. Younger women of African descent are known to be in the high-risk group of breast cancer with decreased survival rates.

Two well-known high-risk breast cancer susceptibility genes, Breast Cancer gene 1 (BRCA1) and Breast Cancer gene 2 (BRCA2) are tumour suppressor genes. BRCA1 and BRCA2 are proteins involved in important cellular mechanisms such as cell cycle control, DNA repair and replication. BRCA mutations account for 20 to 25% of the familial breast cancers and about 5 to 10% of all breast cancers. PALB2 (partner and localiser of BRCA2) is a low-risk breast cancer susceptibility gene that interacts with BRCA2 and in this way is essential in DNA damage response pathways.

Women carrying pathogenic mutations in BRCA1 or BRCA2 can benefit from risk assessment and preventive strategies such as enhanced screenings or prophylactic mastectomy. Patients with BRCA mutations can also be treated with more specific therapies targeting these types of tumours. The main aim of this study is to investigate the prevalence of BRCA 1, BRCA2 and PALB2 mutations in a South African cohort of patients with triple negative breast cancer and/or young breast cancer patients.

The genotype information gained from this study might help in more screening strategies and early detection of breast cancer, might guide in therapy selection and thus lead to ameliorated treatment for triple negative and young breast cancer patients in the different South African ethnical groups. This study can also help in preventive measures for affected asymptomatic family members.

How this project was of value in the struggle against cancer:

As genetic screening of breast cancer was limited in South Africa, our study highlighted the importance of evaluating germline mutations in breast cancer genes in these cancer patients. Our results are particularly relevant for inherited cancer testing in the black population which was previously an under-researched group. The NGS approach applied in our study is also a cost effective approach which is very important in South African healthcare settings. This information is also important for family members who are not affected by the cancer but can be tested for the know mutations as a prevention measurement. The radio-sensitivity testing which was linked with this genetic screening creates opportunities to improve patient treatment and could alter treatment decisions for breast cancer patients. The radio-sensitive patients should be followed up more carefully and a personalised radiotherapy schedule could be planned in the near future.

Future plans for this research project:

We focused on identifying mutations in BRCA1, BRCA2 and PALB2 and the CHEK2 c.1100delC mutation, as the risks for the development of breast and associated cancers with these genes have been determined by analysing large study populations. The search for the remaining genetic contribution towards breast cancer has been carried out extensively, with numerous other genes being identified. However, at this time, the contribution and associated risks of mutations in most of these other genes is not yet well established. As the prevalence of mutations in each of these genes is much lower than germline BRCA1/2 mutations in the large cohorts of patients investigated up until now, more studies will be required to gain insight into the exact risks associated with mutations in these genes.

We will further also investigate the underlying mechanisms of the radio-sensitivity in breast cancer patients that are triple negative and positive for hormone receptors. Once more clarity on this is found, treatment schedules between positive and negative hormone receptor breast cancers can be altered and more specialised.


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