Genetic testing selects patients with ER+ breast cancer for extended hormone therapy

Genetic testing selects patients with ER+ breast cancer for extended hormone therapy
Genetic testing selects patients with ER+ breast cancer for extended hormone therapy

Genetic analyses of results from 1,125 postmenopausal women being treated for estrogen-responsive breast cancer have shown that some women are more likely than others to have a late recurrence of their cancer and might benefit from 10 years of hormone therapy rather than 5. This study was presented at the European Breast Cancer Conference in Glasgow, Scotland.

The research found that women whose tumors were negative for the human epidermal growth factor protein (HER2­–) but were very sensitive to estrogen had more than double the risk of their cancer recurring between 5 and 10 years postsurgery after receiving adjuvant hormone therapy for 5 years.

"Our data suggest that these patients, who are those that appear to benefit most from the current standard 5 years of endocrine treatment, may also benefit from adjuvant hormone treatment that extends beyond that 5 years," said Mitch Dowsett, PhD, of The Institute of Cancer Research and of The Royal Marsden NHS Foundation Trust, both in London, United Kingdom.

The findings are the latest to come from the ATAC trial (Arimidex, Tamoxifen Alone, or in Combination), a double-blinded phase 3 clinical trial that randomly assigned postmenopausal women with early, estrogen receptor positive (ER+) breast cancer to receive the hormone therapies anastrozole or tamoxifen, or a combination of the two.

This study used data from the OncotypeDx 21-gene Recurrence Score that are not usually available from this test to analyze the genetic make-up and to predict the likelihood of cancer recurring within 10 years in these women.

"The OncotypeDx result is reported as a single score, but it is made up of 16 informative genes and five control or housekeeper genes that we have studied in detail. Some of the 16 are considered as groups rather than individual genes, and one of these is the E-module, which consists of four genes that are related to estrogen signalling, including the estrogen receptor itself," Dowsett explained.

OncotypeDX has been used for more than 350,000 tests and the ATAC team had previously shown that its prediction of recurrence was poorer in the second 5 years after a patient's diagnosis than in the first 5 years. The researchers wanted to find out the reason for this. To do so, they determined the relationship between the expression of the individual genes and gene modules and early (up to 5 years) and late (between 5 and 10 years) recurrence rates in women with ER+ HER2– breast cancer.

They found that recurrence rates were highest in the first 5 years for women with HER2+ breast cancer, compared with the subsequent 5 years, but for women with HER2– cancer, the recurrence rates were higher between 5 and 10 years.

The findings could change clinical practice: women with HER2–, high estrogen signalling breast cancer might be considered for adjuvant hormone therapy that is extended to 10 years. However, the results need to be confirmed in other sets of tumors first.

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