Researchers in India have identified a key genetic defect that may explain why some breast cancer patients stop responding to standard hormone therapy within a year of treatment. This discovery offers new insights into treatment resistance and could pave the way for more personalized cancer care.
Focus on a Common Breast Cancer Subtype
The study, led by Dr Amit Dutt from University of Delhi South Campus, focused on hormone receptor-positive, HER2-negative breast cancer. This subtype accounts for nearly 70% of breast cancer cases in India, with close to two lakh new cases reported annually. The findings were published in the British Journal of Cancer.
Why Standard Hormone Therapy Fails
Doctors typically treat HER2-negative breast cancer using hormone therapy drugs such as tamoxifen, aromatase inhibitors, and fulvestrant. These medications block estrogen, which fuels tumour growth. Initially, they prove effective; however, in nearly 40% of patients, the cancer eventually becomes resistant, returns, and becomes more difficult to treat.
According to Dr Sudeep Gupta, Director at Tata Memorial Centre and co-author of the study, this resistance remains a major clinical challenge.
The Role of the CDKN1B Gene
As reported by TOI, the research team traced this resistance to the loss of a gene called CDKN1B, which produces a protective protein known as p27. To investigate further, scientists analysed tumour samples from 186 Indian patients.
They found that the CDKN1B gene was either damaged or missing in many patients whose cancers no longer responded to hormone therapy. In contrast, this defect was absent in patients who continued to respond well to treatment. According to lead author Suhail Ahmad, this finding revealed a clear biological pathway driving treatment resistance.
Laboratory Validation Confirms Findings
To strengthen their conclusions, the researchers recreated the genetic defect in breast cancer cells in the laboratory. When they switched off the CDKN1B gene, the cells became resistant to hormone therapy drugs. However, when they restored the missing p27 protein, the cancer cells regained sensitivity to treatment. This experiment confirmed the gene’s direct role in therapy resistance.
Implications for Personalized Treatment
Importantly, the discovery opens new possibilities for more precise treatment strategies. Since p27 levels can be measured through routine pathology tests, clinicians may be able to identify high-risk patients early. Consequently, doctors could initiate stronger or combination therapies before relapse occurs.
Dr. Dutt emphasized that this approach could significantly improve patient outcomes by preventing or delaying resistance.
Significance of India-Specific Research
Furthermore, the study highlights the importance of region-specific cancer research. Dr. Gupta noted that tumour genetics can vary across populations, making Indian patient data crucial for developing effective treatment strategies. The research received support from the Department of Biotechnology’s Virtual National Cancer Institutes initiative.
A Step Toward Better Outcomes
Overall, the study identifies a critical molecular “switch” that drives resistance to hormone therapy. By linking this mechanism to an existing treatment pathway, the researchers have taken an important step toward improving outcomes for patients with relapsed breast cancer.