About half of women whose breast cancer is treated with standard chemotherapy have their cancer return within five years. Furthermore, most chemotherapeutic drugs have undesirable side effects, but there has been no way to predict who would benefit from taking the drugs and who would not. Fortunately, new research findings from the University of Southern California (USC) /Norris Comprehensive Cancer Center could change that.
The researchers have discovered a new biological marker in tumors that can help indicate whether a woman’s breast cancer will respond to the most commonly prescribed chemotherapy drugs.
Dr Amy Lee, professor of biochemistry and molecular biology in the Keck School of Medicine at USC, isolated the gene for the GRP78 protein (78-kDA glucose-regulated protein) in 1980. It normally helps protect cells from dying, particularly when they are under stress from a lack of glucose.
In her current research, Dr Lee has found that breast cancer tumors with high levels of GRP78 are protected from a common chemotherapy regimen based on adriamycin, a topoisomerase inhibitor.
Dr Lee and her colleagues analyzed records of 432 women with stage II or III breast cancer treated at the USC/Norris Cancer Hospital, of whom 209 received adriamycin-based chemotherapy. Tumor samples were collected from 127 of the women before they received chemotherapy. The samples were analyzed using antibodies to detect and stain GRP78 protein. Review of the samples under a microscope showed that two-thirds (67%) of the tumors tested had high levels of GRP78.
Subsequent analysis of the patients’ records showed that women whose tumors had higher levels of GRP78 were more likely to have had the cancer recur. That was particularly likely if the women received adriamycin-based chemotherapy and no further treatment with the chemotherapy drug taxane, regardless of their tumor stage.
Likewise, women who had mastectomies followed by adriamycin-based therapy were more likely to have the cancer return if their tumors had elevated levels of GRP78, compared to identically treated patients with low levels of GRP78.
Conversely, the study also suggests that women who received adriamycin-based therapy followed by additional treatment with taxane had a lower risk of cancer recurrence if their tumors had elevated levels of GRP78.
Dr Lee hopes others will confirm her findings in subsequent research, and that it will eventually lead to a standard laboratory test that can screen all women diagnosed with breast cancer.
The study is anticipated to have broad implications since other types of cancers have also been found to have elevated levels of GRP78. To that end, Dr Lee is also collaborating with USC/Norris pathologist Dr Richard Cote on a study of the protein’s role in prostate cancer.