Molecular subtyping of breast cancer can better identify women at high risk of recurrence

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A method called molecular subtyping can help doctors better determine which of their breast cancer patients are at high risk of getting breast cancer again, according to a new study reported at the Miami Breast Cancer Conference, held March 6-9, 2014, in Miami Beach, Florida. This sophisticated genetic profiling of a person's specific tumor offers an additional resource to help identify patients who would most benefit from chemotherapy and those who would not.

"The most important takeaway for our colleagues in breast cancer diagnosis and treatment is the potential value of molecular subtyping to personalize and improve each woman's treatment," said principal investigator Charles E. Cox, MD, of the University of South Florida.

Molecular subtyping is a way of classifying breast cancer tumors into one of four genetically distinct categories, or subtypes: luminal A, luminal B, basal (a subset of triple-negative), and human epidermal growth factor receptor 2 (HER2)-type. Each subtype responds differently to different kinds of treatments, and some subtypes indicate a higher risk of disease recurrence.

"Our data showed that a substantial number of breast cancer patients—classified as low risk by one particular genomic test—turn out to be at high risk of recurrence once we determined their subtype," said Cox. "These are mostly luminal B patients, and their physicians might not fully understand their patient's situation unless they do subtyping."

The study examined why different genomic tests for breast cancer sometimes provide contradictory information about risk of recurrence. The key findings involved the 70-gene MammaPrint test; the 21-gene Oncotype DX test, which is an earlier commercially available test; and Mammostrat, a gene-profiling test performed on slides of the breast tumor by a pathologist. The tests have generally been assumed to provide equivalent information about recurrence risk, but that is proving not to be the case.

Researchers examined tumor samples from a total of 148 patients. The greatest discordance (lack of agreement) about risk of disease recurrence occurred in a group of 51 patients. Of those 51, all were stratified by MammaPrint as high risk of recurrence, while Oncotype classified 18 of them (35%) as low risk.

BluePrint, an 80-gene test to identify a tumor's molecular subtype, was also used for those stratified by MammaPrint. This process revealed that the 51 patients were luminal B, a molecular subtype with a high risk of recurrence.

Patients with a high risk of recurrence are normally counseled to receive chemotherapy following surgery to prevent the cancer from returning. In contrast, women whose subtype has a low risk of recurrence (luminal A) will not benefit from the addition of chemotherapy. They may thus be able to safely avoid chemotherapy and its potentially damaging side effects. At the same time, they can be prescribed treatments such as hormonal therapy known to benefit those with their subtype.

Cox clarified that discordance does not necessarily show that some genomic test results were wrong.

"These tests use different genes and were validated on different types of populations," he said. "But if physicians use molecular subtyping as we did in this study, they will have valuable, additional information to guide the appropriate treatment for each patient."

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