Testing breast cancer tumors for BRCA1 may guide therapy

Testing tumors in women with breast cancer for the BRCA1 gene could increase the effectiveness of chemotherapy dramatically, researchers said on Thursday.

In laboratory tests, scientists from the Cancer Research Centre, Queen’s University Belfast, found tumor cells reacted very differently to anti-cancer agents depending on how well the gene was working within the cells. A functioning BRCA1 gene made cells more than 1,000 times more sensitive to drugs, such as Taxol and Taxotere, which work by blocking the final stage of cell division. But the same cells were between 10 and 1,000 times more resistant to drugs, such as cisplatin, which work by damaging DNA within tumors. “Essentially, cancer cells with functional BRCA1 are highly resistant to one type of chemotherapy but extremely sensitive to another,” said senior researcher Paul Harkin. “It’s very exciting, because knowing a tumor’s BRCA1 status may be invaluable in deciding which type of chemotherapy to use.” The BRCA1 gene plays an important role in stopping cancer developing, and it has long been known that women who inherit a damaged version of the gene have a high risk of developing breast cancer.But BRCA1 may also get switched off in as many as 30% of tumours, even in patients who inherited a normal version of the gene. Unlocking the genetic reasons why some cancer patients respond to treatment while others do not is a central goal of medical research. Some progress has already been made, with Genentech Inc’s Herceptin, for example, reserved for patients whose tumours over-express the HER2 gene. But Harkin said many more such markers were needed to make cancer treatment more effective. “This is the challenge for oncology over the next few years. We have lots of really good drugs now. The problem is we need to know why one patient responds and another patient with an apparently identical tumour does not,” he told Reuters in a telephone interview. Harkin and colleagues plan to conduct a clinical trial over the next two years to confirm their laboratory findings. They will assess the effectiveness of Aventis SA’s Taxotere in breast cancer patients whose tumours show differing BRCA1 levels.(Source: Reuters Health: Ben Hirschler: September 25, 2003: Oncolink)