The Mayo Clinic has identified genes that may help predict whether the drug trastuzumab will prevent the recurrence of breast cancer in some women, according to a study presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.
Trastuzumab is used alone or along with chemotherapy to prevent cancer recurrence, improving survival in a large number of women with early stage HER2-positive breast cancer, which tends to be more aggressive than others types of cancer and less responsive to hormone treatment. However, trastuzumab does not stop tumors from returning in about 25 percent of patients, and until now, oncologists didn't have a way to identify these women before treatment.
Led by oncologists at the Mayo Clinic campus in Florida, researchers discovered 27 genes that are significantly linked to positive results in patients using trastuzumab and chemotherapy for breast cancer treatment. They also identified five other genes linked to a poor outcome using the same treatment regimen.
The Expert Take
“Over the past few years a lot of information has become available related to new techniques to interrogate or evaluate gene profiles in breast cancer that may help us understand why breast cancer develops, why breast cancer behaves in different ways for different persons, and why persons may derive benefit from treatment versus not deriving benefit,” said Edith Perez, M.D., deputy director at large of the Mayo Clinic Comprehensive Cancer Center and director of the Breast Cancer Translational Genomics Program.
Perez said that, in in terms of clinical significance, the implications of this study are quite broad.
“If we can collaborate our data, we may be able to—in the next few years—develop a brand new test that will incorporate genomic profiling when a patient is diagnosed with early stage HER2-positive breast cancer,” she said.
This kind of testing could be used to inform the patient and her doctor about how she'll respond to chemotherapy and trastuzumab, providing an avenue to incorporate other treatments into standard patient management.
According to breastcancer.org, about one in eight women in the U.S. will develop invasive breast cancer over the course of her lifetime. Next to lung cancer, breast cancer death rates are higher than those of any other cancer.
Perez said that this study, along with future analysis, could lead to novel methods of cancer-management and predictive tests to help oncologists select the best treatment for HER2-positive patients. In fact, researchers have already found that the genes linked to cancer patient outcomes can be grouped into different categories that affect tumor cell function.
Source and Method
The study was funded by grants from the National Cancer Institute and the Mayo Clinic, with support from the Breast Cancer Research Foundation and the 26.2 with Donna Foundation. Analysis was conducted on patients who participated in the N9831 clinical trial.
The team treated patients who had been diagnosed with early stage HER2-positive breast cancer with either chemotherapy or chemotherapy aided by trastuzumab. Along with data from other studies, researchers determined the best clinical outcome for patients who received a combination of chemotherapy and trastuzumab.
A genome analysis of the 24,000 genes present in human cells was conducted on trial participants, and researchers determined that 353 of these genes were related to patient outcome. They further narrowed this number to 32, based on statistical evaluation, and found that of those 32 genes, 27 were correlated with a positive outcome.
In a study published in 2012 in The Lancet, researchers analyzed event-free survival in patients with HER2-positive breast cancer receiving chemotherapy with or without one year of trastuzumab. They found that within a three-year period, 71 percent of the participants had an event-free survival with trastuzumab, versus 56 percent without the drug.
Based on the fact that the use of trastuzumab has been linked to cardiac toxicity, in a study published in The New England Journal of Medicine in 2011, researchers evaluated the efficacy and safety of a new nonanthracycline regimen with trastuzumab. They concluded that the addition of one year of trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer.
Another study, published in 2010 in The Lancet, investigated whether trastuzumab in combination with chemotherapy would work as a treatment for HER2-positive advanced gastric cancers. Researchers determined that “trastuzumab in combination with chemotherapy can be considered as a new standard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer.”