A large new study published in BMC Cancer has uncovered something important for how we think about inherited breast cancer risk in India: most of the genetic risks would be missed if doctors only test for the famous BRCA genes.
When people hear about genetic testing for breast cancer, they usually hear about BRCA1 and BRCA2. These genes are well known for increasing breast and ovarian cancer risk, and most hospital testing focuses only on them. But this new research, which studied nearly 500 Indian women with breast cancer using a broad genetic scan called whole-exome sequencing, shows that this narrow approach may overlook a large part of the story.
The researchers found that about 1 in 4 women in the study carried an inherited genetic change that increases cancer risk. But here’s the striking part: only a small fraction of these were in BRCA1 or BRCA2. The majority were in other cancer-related genes that are not routinely checked in standard tests. This means that if these women had only received traditional BRCA testing, most of their inherited risk would never have been detected.
This is especially important because genetic patterns differ between populations. Much of what we know about breast cancer genetics comes from Western studies. This Indian study revealed several rare and population-specific genetic changes that are not commonly seen in global databases. In simple terms, the genetic “fingerprint” of breast cancer risk in Indian patients may look quite different from what global guidelines are based on.
The study also uncovered something that goes beyond cancer risk. Around 3% of women carried a gene variant that can cause severe side effects from certain common chemotherapy drugs. These women, if treated without this knowledge, could suffer serious toxicity from medicines like fluorouracil or capecitabine. But if doctors know about this in advance, they can choose safer treatment options. This is an example of how genetic testing can directly influence treatment decisions—not just risk prediction.
Even more surprisingly, over one in five women had important genetic findings unrelated to cancer at all. These were gene changes linked to other serious health conditions, such as heart rhythm disorders or inherited metabolic problems. Discovering these “incidental” findings could allow patients and their families to take preventive action for other health risks they didn’t know they had.
So what does this mean in practice?
For clinicians, it suggests that testing only for BRCA1/2 is no longer enough, especially in Indian patients. Broader genetic panels—or more comprehensive approaches—can reveal far more useful information that can guide cancer screening, treatment choices, and advice to family members.
For patients, it means you are not simply “BRCA positive” or “BRCA negative.” Your genetic risk may lie in many other genes that are currently not being looked at in routine testing. More complete testing could provide a clearer understanding of your cancer risk, safer treatment pathways, and valuable information for your relatives.
This study signals a shift in thinking: genetic testing in breast cancer is not just about two genes anymore. In India, especially, a wider lens reveals a much richer—and more clinically useful—genetic picture.
References
Peter J, Jolly B, Raha R, Jothi J, Chakraborty A, Raman SG, Radhakrishnan S, Sivasubbu S, Scaria V, Mahalingam S. Germline mutational landscape in a large cohort of Indian breast cancer. BMC Cancer. 2025 Dec 1;26(1):48. doi: 10.1186/s12885-025-15360-w. https://link.springer.com/article/10.1186/s12885-025-15360-w