Mumbai: Local scientists have identified a genetic defect that could explain why some breast cancer patients stop responding to standard hormone treatment after a year of starting treatment.
Led by Dr Amit Dutt of University of Delhi South Campus, who was formerly associated with Tata Memorial Centre (TMC), the study looked at hormone receptor-positive, HER2-negative breast cancer, which accounts for 70% of breast cancer cases in India — nearly two lakh new breast cancer cases are reported annually in India. The study was published in the British Journal of Cancer, an indexed medical journal.
HER2-negative breast cancer is treated with hormone therapy drugs such as tamoxifen, aromatase inhibitors and fulvestrant, which block estrogen that helps these tumours grow. These medicines are often effective at first, but in four out of every 10 patients, the cancer eventually becomes resistant, returns and is harder to treat, according to TMC director Dr Sudeep Gupta, who is an author of the study.
The team traced this “resistance” to the loss of a gene called CDKN1B, which produces a protective protein known as p27.
They analysed tumour samples from 186 Indian patients and found the CDKN1B gene was damaged or missing in many women whose cancers stopped responding to the standard treatment. It was not seen in patients who remained sensitive to therapy. According to the study’s main author, Suhail Ahmad, this pointed to a pathway of resistance.
The team confirmed the finding by recreating the defect in breast cancer cells in the laboratory. Once CDKN1B was switched off, the cells became resistant to hormone drugs. “But when the missing p27 protein was restored, the medicines started working again,” said Dr Dutt.
The discovery could lead to more precise treatment. “Since p27 levels can be checked through routine pathology tests, we may be able to identify high-risk patients early and start stronger combination therapy before the relapse,” added Dr Dutt.
Dr Gupta told TOI that the research, supported by the Department of Biotechnology’s Virtual National Cancer Institutes, highlights the importance of Indian patient data, as genetic makeup of tumours may differ in the Indian population.
According to a release, the research identified a molecular switch. “It has been functionally validated, and linked to an existing, effective treatment. That is a meaningful step forward for patients whose cancers have relapsed,” Ahmad added.
