A Game Changer in the Fight Against Breast Cancer

Genetic Testing: A Game Changer in the Fight Against Breast Cancer

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Genetic testing has become a crucial element in managing breast cancer, offering insights into individual risk factors and guiding personalized treatment strategies. This process analyzes DNA to identify mutations that may predispose individuals to breast cancer, focusing primarily on hereditary mutations (changes in genes that occurs in a parent’s reproductive cells (egg or sperm) that affects the genetic makeup of their child ) like those in the BRCA1 and BRCA2 genes, as well as somatic mutations (mutations caused in cells other than sex cells- sperms and egg cells) that arise during a person’s lifetime. By understanding these genetic factors, healthcare providers can tailor prevention and treatment approaches, enhancing patient outcomes.

Importance of Genetic Testing

Approximately 5% to 10% of breast cancers are hereditary, with BRCA1 and BRCA2 mutations accounting for up to 30% of these cases. These mutations significantly increase the risk of developing breast and ovarian cancers, especially in individuals with a family history of these diseases. In addition to hereditary mutations, somatic mutations—those acquired during a person’s lifetime—also contribute to breast cancer development. These genetic changes can affect various genes involved in cell growth and repair, leading to uncontrolled cell division and tumor formation. Understanding these mutations is essential for risk assessment, early detection, and personalized treatment strategies in breast cancer management. Genetic testing can help identify at-risk individuals, enabling tailored surveillance and preventive measures.

Hereditary Mutations

Hereditary mutations are genetic changes that are passed down from parents to their children. The most well-known genes associated with hereditary breast cancer are BRCA1 and BRCA2. These genes produce proteins that help repair damaged DNA, functioning as tumor suppressors. When mutations occur in these genes, they can significantly increase the risk of breast and ovarian cancers.

  • BRCA1 and BRCA2: Individuals with a mutation in either of these genes have a markedly higher risk of developing breast cancer—over 60% by age 70, compared to about 13% in the general population. These mutations also elevate the risk for ovarian, pancreatic, and prostate cancers.
  • Other Genes: In addition to BRCA1 and BRCA2, several other genes have been identified that can increase breast cancer risk, including PALB2, CHEK2, and ATM. These are often assessed through multigene panel testing, which evaluates multiple genes simultaneously.

Somatic Mutations

Somatic mutations occur in non-germline cells (Somatic cells are all the cells in the body except for sperm and egg cells, which are known as germ cells) and are not inherited. These mutations can arise during a person’s lifetime due to environmental factors or errors in DNA replication. Unlike hereditary mutations, somatic mutations are specific to the tumor and cannot be passed on to offspring.

  • Tumor Testing: Genetic testing can also be performed on tumor samples to identify somatic mutations that may inform treatment options. For example, certain targeted therapies may be more effective against tumors with specific genetic alterations.

Demographics of BRCA Mutations in the Indian Population

The prevalence of BRCA1 and BRCA2 mutations in India has been the subject of various studies, revealing significant insights into the genetic landscape of breast cancer within the population. Understanding these demographics is crucial for risk assessment, early detection, and tailored treatment strategies.

Prevalence of BRCA Mutations

  • General Findings:
      • The prevalence of BRCA1 and BRCA2 mutations among Indian women diagnosed with breast cancer ranges from 2.9% to 28% across different studies. This variation can be attributed to factors such as sample size, geographic location, and population characteristics.
  • Specific Studies:
    • A study conducted in Pune reported that over 10% of breast and ovarian cancer patients carry pathogenic BRCA mutations.
    • Another study found a 29.1% prevalence of BRCA mutations among a cohort of 160 hereditary breast and ovarian cancer (HBOC) patients. This is notably higher than rates observed in Western populations.
    • A separate analysis indicated that 20.4% of patients had identified variants in the BRCA genes, with a significant proportion being pathogenic or likely pathogenic

Mutation Characteristics

  • Common Mutations:
      • The most frequently identified mutation in the Indian population is c.1961delA, also known as 185delAG, which accounts for a significant percentage of BRCA1 mutations.
      • Other notable mutations include c.68_69delAG, highlighting the presence of specific mutation hotspots unique to the Indian demographic.
  • Age and Mutation Correlation:
    • There is a positive correlation between younger age groups (20–45 years) and BRCA positivity, indicating that hereditary factors may contribute to earlier onset breast cancer in this population.

Non-BRCA Gene Mutations

While BRCA1 and BRCA2 are the primary focus for hereditary breast cancer risk, studies have also highlighted the importance of non-BRCA mutations:

  • Approximately 17.64% of patients with breast and ovarian cancers exhibited pathogenic mutations in non-BRCA genes, suggesting that genetic testing should encompass a broader panel beyond just BRCA genes to ensure comprehensive risk assessment.

Genetic testing for breast cancer involves a systematic process to identify mutations in genes associated with increased cancer risk. Here’s how the testing is typically carried out:

Steps in Genetic Testing

  1. Consultation: Speak with our Nutrigenomics counsellor to understand what to expect from genetic testing. You can connect with us here to get a better understanding.
  2. Informed Consent: Patients are required to provide informed consent, which includes understanding the testing procedure, benefits, limitations, and possible consequences of the results.
  3. Sample Collection: A biological sample is collected for analysis. This can be:
    • Blood: The most common method.
    • Saliva: Collected using a kit.
    • Cheek Swab: A buccal smear collects cells from the inside of the cheek.
    • Other Tissues: Such as skin or amniotic fluid.
  4. Laboratory Analysis:
    • The sample is sent to a certified laboratory where DNA is extracted.
    • Various testing methodologies are employed, including:Sequencing Tests
  5. Data Interpretation: Advanced computational tools analyze the sequencing data, comparing it against reference genomes to identify any mutations or variants.
  6. Results Reporting: The laboratory generates a report detailing the findings, which is then reviewed by the healthcare provider or genetic counselor. Results may indicate whether mutations are present and their significance regarding cancer risk.
  7. Follow-Up Counselling: Patients receive counseling to understand their results and discuss potential next steps, including risk management strategies or further testing for family members.

The need for an accredited Lab

It is crucial that genetic testing is performed in clinically-approved laboratories certified by relevant regulatory bodies (e.g., NABL) to ensure accuracy and reliability of results. This process not only aids in risk assessment but also informs treatment decisions for those diagnosed with breast cancer.

Importance of Genetic Testing

Genetic testing plays a crucial role in breast cancer management for several reasons:

  1. Risk Assessment: Identifying hereditary mutations allows individuals to understand their personal risk for developing breast cancer. This information is vital for making informed decisions about surveillance and preventive measures.
  2. Preventive Strategies: For individuals with known BRCA mutations, options such as increased surveillance (e.g., regular mammograms or MRIs), prophylactic surgeries (like mastectomy or oophorectomy), or chemoprevention can be considered to reduce cancer risk.
  3. Family Planning: Understanding one’s genetic status can also guide family planning decisions, as these mutations can be inherited. Genetic counseling can provide insights into the implications for children and other relatives.
  4. Tailored Treatment: For those diagnosed with breast cancer, knowing the specific genetic makeup of their tumor can help tailor treatment strategies, potentially leading to better outcomes.
  5. Emotional Support and Counseling: Engaging with a genetic counselor before testing can help individuals navigate the complexities of genetic information and its implications for themselves and their families.

The demographic data on BRCA mutations in the Indian population indicate a higher prevalence compared to Western countries, emphasizing the critical role of genetic testing for risk assessment and personalized treatment. By identifying both hereditary and somatic mutations, healthcare providers can tailor strategies for prevention, early detection, and effective management of breast cancer. As research progresses, understanding these genetic factors will be essential in addressing breast cancer within diverse populations.

About the Author:

Sarah Fathima is a passionate science educator turned genome analyst who worked in cancer genomics, and is now a biocurator and bioinformatician at Nugenomics. Inspired young minds as a school teacher. Contributed to cancer research and patient care through report generation. Currently curates genomic data to advance understanding of genetic influences on health. 

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