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Cracking the Genetic Code of Breast Cancer

Cracking the Genetic Code of Breast Cancer: What We Should Know

Submitted by: Surabhi Ganga ( MSc. Human Genetics, Cytogeneticist

As we observe Breast Cancer Awareness Month this October, there’s a growing focus on understanding how genetic testing is transforming the fight against breast cancer. Genetic tests can provide vital information about a person’s risk, guide early detection, and even help prevent the disease before it starts. While breast cancer remains a significant concern worldwide, the ability to unlock secrets hidden in our genes is offering new hope and empowering us to take control of our health.

A Genetic Test: What Is It?

A genetic test is a simple medical test that examines your DNA to search for alterations,ie mutations in specific genes that are linked to a higher risk of diseases like breast cancer. Some of the most commonly tested genes include BRCA1 and BRCA2, which are known to increase the chances of developing breast and ovarian cancers when mutated. This type of testing can help people understand whether they are more likely to develop cancer and take steps to catch it early or even prevent it.

In fact, the spotlight on genetic testing grew significantly after actress Angelina Jolie publicly shared her decision to undergo preventive surgery because of her BRCA1 mutation. Her story raised awareness, but genetic testing is now about much more than that—it’s about giving everyone the opportunity to learn their risk and act on it.

Genetic Tests: The Key to Unlocking Your Risk

Genetic tests can analyze your DNA to check for mutations in several important genes, including BRCA1, BRCA2, TP53, and PALB2. These genes play a crucial role in controlling cell growth, and mutations can increase the likelihood of developing breast cancer, sometimes even at a young age.

If a person tests positive for a mutation in one of these genes, it doesn’t mean they will definitely develop breast cancer,but it does mean their risk is higher. If you carry a BRCA1 or BRCA2 mutation, regular screenings—like mammograms or MRIs—begin earlier, giving you a head start in detecting any abnormal growths. In some cases, women opt for preventive surgeries. This personalized approach helps women—and men—take control of their health, whether through more frequent screenings or lifestyle changes.

Advances in Genetic Testing Technology

So, how does genetic testing work? These tests use advanced techniques like Next-Generation Sequencing (NGS), a powerful tool that can quickly analyze large sections of DNA. This technology looks for mutations in multiple genes at once, making it easier to detect high-risk genetic variations. For more complex mutations, Multiplex Ligation-dependent Probe Amplification (MLPA) is used to detect larger genetic changes that might otherwise be missed.

Thanks to these technologies, genetic testing has become faster, more precise, and more widely available than ever before, giving more people access to this life-saving information.

The Role of the HER2 Gene in Breast Cancer

Beyond BRCA mutations, another major breakthrough in breast cancer research is the identification of the HER2 (Human Epidermal Growth Factor Receptor 2) gene. While not inherited like BRCA, HER2 is an important player in breast cancer progression. HER2-positive tumors grow faster, but identifying this gene through genetic testing allows for precise, targeted treatments. Tests like the HER2/neu test use Immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) to determine HER2 status in tumors, helping doctors decide whether targeted therapies like trastuzumab (Herceptin) should be used.

Beyond BRCA: New Discoveries and Emerging Tools

While BRCA1 and BRCA2 mutations are well-known risk factors, scientists are continually discovering new genes and genetic variations that contribute to breast cancer.

·       Lifestyle Factors and Gene Expression (Epigenetics)
Recent studies suggest that while you can’t change your genes, lifestyle factors such as diet, exercise, and environmental exposures can influence how your genes are expressed. This field of study, known as epigenetics, shows that even individuals with genetic predispositions might reduce their cancer risk through healthy living, such as maintaining a balanced diet, avoiding smoking, and exercising regularly.

·       Polygenic Risk Scores (PRS)
In addition to single-gene mutations like BRCA1 and BRCA2, scientists are now developing polygenic risk scores (PRS) that consider multiple small genetic variations scattered throughout the genome. PRS can provide a more nuanced understanding of breast cancer risk by calculating how a combination of minor genetic factors contributes to overall risk. This is especially helpful for those without major mutations but who still want to assess their long-term risk.

·       Genetic Testing for Non-Hereditary Cancer Risk
While BRCA1 and BRCA2 are associated with hereditary breast cancer, only about 5–10% of all breast cancer cases are linked to these genes. For the majority of breast cancer cases, which are non-hereditary, genetic testing still plays a role. These tests focus on somatic mutations in the cancer cells themselves, helping doctors determine the most effective treatment, such as whether the cancer might respond well to hormone therapies or targeted treatments like Herceptin.

Not All Mutations Lead to Cancer: The Importance of Counseling

One important thing to remember is that not every mutation detected by a genetic test is dangerous. Some gene variations are classified as “variants of unknown significance” (VUS), meaning their impact on cancer risk is unclear. In these cases, genetic counseling can help explain the results, ensuring that patients receive accurate information without unnecessary worry.

Genetic counsellors work with patients to interpret test results and develop a plan based on their individual risk, providing much-needed support and guidance through what can be a complicated process.

Looking to the Future: AI and Genetic Testing

As technology continues to advance, artificial intelligence (AI) is playing a larger role in genetic testing. AI can help analyze huge amounts of genetic data and predict the impact of lesser-known mutations, providing more accurate and comprehensive assessments of cancer risk. This is an exciting area of development that promises to further enhance the accuracy and usefulness of genetic testing.

 

Conclusion: Knowledge is Power, Not Fear

Breast cancer is one of the most common cancers worldwide, but the good news is that we now have powerful tools, like genetic testing, to detect it early and even prevent it. Genetic tests give individuals the ability to understand their risk and take action—whether that means more frequent screenings, preventive treatments, or lifestyle changes.

As we mark Breast Cancer Awareness Month this October, it’s important to remember that knowledge is the key to empowerment. Genetic testing is not something to fear—it’s a tool that allows us to protect our health, make informed decisions, and live without the unknown hanging over us. The future of breast cancer prevention is here, and it’s in our DNA!.

 

References:

1.       Pritzlaff M, et al. Male breast cancer in BRCA mutation carriers. Breast Cancer Res Treat. 2017.

2.       Mardis ER. The Impact of Next-Generation Sequencing on Cancer Genomics. Genome Med. 2017.

3.       Easton DF, et al. Genes, environment and cancer risk: the contribution of BRCA1 and BRCA2 to breast cancer. J Clin Oncol. 2015.

4.       Ebbesen KK, et al. Epigenetics and breast cancer: Role of environmental factors. Carcinogenesis. 2019.

5.       Mavaddat N, et al. Polygenic risk scores for prediction of breast cancer. Am J Hum Genet. 2019.

6.       Kruglyak KM, et al. Somatic mutations in breast cancer: Predictive value for personalized medicine. Nat Rev Clin Oncol. 2017.

7.       Li Y, et al. AI-driven insights in interpreting genetic variants of unknown significance. Nat Biotechnol. 2021.

8.       Venetis, K., Pescia, C., Cursano, G., Frascarelli, C., Mane, E., De Camilli, E., et al. (2024). The Evolving Role of Genomic Testing in Early Breast Cancer: Implications for Diagnosis, Prognosis, and Therapy. International Journal of Molecular Sciences, 25, 5717.