SAN FRANCISCO – A new gene-based biomarker assay may help to estimate prognosis and make decisions about extended endocrine therapy in women with estrogen receptor–positive early breast cancer, new data suggest.
Researchers tested the biomarker, the Breast Cancer Index (BCI), among 249 women with estrogen receptor–positive early breast cancer from the MA.17 trial, in which women received 5 years of adjuvant tamoxifen therapy and, if still disease free, were then randomized to an additional 5 years of either letrozole (Femara) or placebo.
Study results, reported at a breast cancer symposium sponsored by the American Society of Clinical Oncology, showed that with each 5-unit increase in the 10-unit BCI score, women’s odds of late recurrence nearly tripled.
The index as a whole was not helpful in predicting the benefit of added letrozole therapy in reducing recurrence risk. But one of its components, called H/I, was helpful: Women having a high H/I were about half as likely to have a recurrence if they received letrozole instead of placebo.
In the future, these findings might be used to develop a management algorithm for women with estrogen receptor–positive breast cancer, according to lead investigator Dr. Dennis C. Sgroi, director of breast pathology at the Massachusetts General Hospital in Boston.
"If patients are disease free after 5 years of adjuvant endocrine therapy, we might be able to then test them with the BCI. If this assay identifies these patients to be at low risk, there will be no further therapy for these patients. However, if they are at high risk by BCI, we can then explore the H/I component," he explained.
"If they have high H/I, that indicates that these patients are likely to benefit from extended adjuvant therapy," he continued. "For patients who have low H/I, one might consider using extended adjuvant therapy, or these patients might be considered as a future focus for research in clinical trials."
The investigators identified 83 women from the MA.17 trial who had had a recurrence and had primary tumor tissue available. They then matched the women by age, N stage, T stage, and prior receipt of chemotherapy in a 1:2 ratio with 166 women who had not had a recurrence and had primary tumor tissue available. Tissue was analyzed by reverse transcriptase–polymerase chain reaction to determine the BCI.
The BCI has two components, Dr. Sgroi explained. The HOXB13/IL17BR (H/I) component is based on expression of two genes regulated by estradiol. The molecular grade index (MGI) component is based on five genes related to pathological grade.
"We have shown in the past that these two biomarkers are complementary, as the combination of the two biomarkers outperforms each individually," he noted. "In addition, we have shown that the combination biomarker outperforms standard clinicopathological parameters currently used to predict disease recurrence."
In a multivariate analysis, with each 5-unit increase in the BCI score, women’s odds of recurrence increased 2.91-fold (P = .014). The findings were similar when categories were used: Women with high or intermediate scores had 2.21-fold higher odds of recurrence than did their counterparts with low scores (P = .019).
The BCI as a whole did not predict the benefit of extended therapy with letrozole, but the H/I component did, Dr. Sgroi reported. In a multivariate analysis, women who had a high H/I had a 58% reduction in the odds of recurrence if they received letrozole instead of placebo (P = .037).
"Most notably, there was a statistically significant interaction between the H/I biomarker and treatment (P = .02), indicating that the magnitude of letrozole benefit depends on the expression level of H/I," he said. "These results suggest that patients with tumors expressing high H/I will benefit from extended endocrine therapy."
Dr. Sgroi reported receiving research funding from bioTheranostics Inc. The study was supported in part by Novartis, the manufacturer of letrozole.