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Overall, breast cancer accounts for about 40,000 deaths in the United States annually. The mortality rate, and survival rates, differ for the different types of breast cancer, and can be linked to the presence or absence of receptors (e.g., estrogen, progesterone, or HER2) on the tumors. For example, the five year survival rate for women with estrogen receptor positive (ER+) tumors is better than for women who are ER-. Yet, some women with ER+ tumors who have been treated successfully with Aromatase inhibitors (AI — drugs which lower the body's production of estrogen ) will experience a recurrence of their disease, which can metastasize to other parts of the body — leading to a poor prognosis.
A recent report in JAMA Oncology presents an investigation of mutations that seem to be linked to the chance that a woman with ER+ disease will have a recurrence, and to her survival. Dr. Sarat Chandarlapaty, from Memorial Sloan Kettering Cancer Center in New York City, and colleagues analyzed cell-free DNA (cDNA) from women who had participated in an international study of breast cancer treatments. All were postmenopausal, had metastatic breast cancer, and had been treated with an AI.
The women had been randomly assigned to receive one of 2 treatments: exemestane (an AI) plus everolimus (an immune system suppressor) or the exemestane plus placebo. Dr. Chandarlapaty and colleagues examined the cDNA from 541 of these patients, looking at mutations in their estrogen receptors to see if they were linked to the women's survival time. They found that 29 percent had the D538G mutation, 13 percent had the Y5378 mutation, and 30 of the women had both. These mutations are known to be associated with activation of the estrogen receptor, even if the estrogen itself isn't present.
Progression-free survival for the women was 32 months for those with neither mutation. With the D538G mutation it was 26 months, with the Y5378 mutation it was 20 months, and for those with both mutations it was only 15 months. Women who had been treated with both the AI and the immune suppression drug, even if they had the D538G mutation, had progression-free survival similar to the women who had neither mutation.
In their discussion, the authors note that the cDNA assay used in their study would be relatively easy to use in clinical practice. They state, "With this information [provided by such assays], clinicians and investigators facing a wide range of outcomes may identify clinically valuable information regarding prognosis and prediction about treatments under consideration."
While this study hasn't found a "cure" for breast cancer, it suggests a new means of providing a longer life for women with ER+ tumors — even if metastasis has occurred.
