Genomic assay may predict ovarian function suppression benefit in breast cancer subset
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SAN ANTONIO — A genomic assay identified risk for distant recurrence among certain premenopausal women with hormone receptor-positive, early-stage breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
The Breast Cancer Index assay (Hologic/Biotheranostics) also identified which of these patients may derive greater benefit from the addition of ovarian function suppression therapy to primary adjuvant endocrine therapy.
“Given the potential short- and long-term toxicities of this more intensive treatment approach in premenopausal women, as well as the high lack of adherence, it's important for us to be able to identify those women who receive benefit from ovarian function suppression versus those who do not. Honing in on a biomarker helps us do just that,” researcher Ruth O’Regan, MD, chair of medicine and Charles A. Dewey professor at University of Rochester, told Healio.
The Breast Cancer Index evaluates risk for late distant recurrence — 5 to 10 years after diagnosis — among patients with hormone receptor-positive, early-stage breast cancer.
The index incorporates a gene expression signature called molecular grade index and the H/I ratio, or the expression ratio of the HOX13 gene to the IL17BR gene. The H/I ratio is used to predict which patients with this breast cancer subtype may benefit from extended endocrine therapy.
O’Regan and colleagues evaluated the Breast Cancer Index in a subgroup of patients (n = 1,687) enrolled in the SOFT trial to evaluate whether it could predict prognosis, as well as the value of ovarian function suppression, for premenopausal women with hormone receptor-positive, early-stage breast cancer who underwent endocrine therapy with or without chemotherapy.
After 12 years of follow-up, results showed prognostic value of the index for distant recurrence.
An analysis of women without lymph node involvement showed those with high Breast Cancer Index scores had a 98% increased risk for distant recurrence compared with those with low Breast Cancer Index scores. Results showed a comparable increase among women whose cancer had spread to one, two or three lymph nodes.
In addition, among patients with low H/I ratios, women who received ovarian function suppression in addition to exemestane or tamoxifen exhibited a reduced risk for recurrence after 12 years than those who received tamoxifen alone (7.3% vs. 11.6%; P < .01).
Investigators observed this predictive benefit regardless of age, lymph node involvement or receipt of chemotherapy.
“Previously, high H/I ratio has been shown to predict which patients benefit from longer durations of endocrine therapy, which could indicate sensitivity to such therapy. However, benefiting from [ovarian function suppression] may not be related to endocrine sensitivity,” O’Regan said. “It is possible that patients with endocrine-resistant cancers may benefit more from [ovarian function suppression], which could explain our findings. If validated, the H/I ratio may be useful to determine which premenopausal patients require [ovarian function suppression], thereby avoiding additional toxicity in those who are unlikely to benefit.”
Researchers acknowledged study limitations, including the small sample size and the need to validate the findings in a larger population.
“The sample provided greater understanding about the predictive capabilities of the [Breast Cancer Index] test. Plans to validate our findings in other patients are underway,” O’Regan told Healio. “We will continue to investigate the test’s utility to help inform ovarian function suppression treatment decisions in the future.”
Perspective
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Azka Ali, MD
Ovarian function suppression along with endocrine therapy is effective for treating high-risk, early -stage premenopausal women with hormone-sensitive breast cancer. However, ovarian function suppression is not benign and does predispose women to several adverse effects from premature suppression of ovarian function. It would be ideal to identify patients who would benefit from ovarian function suppression by using genomic assays. O’Regan and colleagues attempted to answer this question using the Breast Cancer Index assay. The Breast Cancer Index (BCI) has been validated in evaluating risk for late recurrence (5 to 10 years) and benefit from extended adjuvant endocrine therapy by incorporating a five-gene molecular grade index and H/I ratio. Previously, the BCI H/I-high group had been shown to derive benefit from extended adjuvant endocrine therapy.In this study, investigators evaluated if BCI H/I predicted benefit from the addition of ovarian function suppression to endocrine therapy in a subgroup of patients with or without chemotherapy enrolled in the SOFT trial (n= 1,687). At 12-year follow-up, results showed a noted prognostic value of the BCI. Interestingly, there was a predictive benefit of BCI H/I-low, with a 12-year absolute benefit in aromatase inhibitor plus ovarian function suppression arm of 13.2% (vs. tamoxifen) and a 7.4% benefit in the tamoxifen plus ovarian function suppression arm (vs. tamoxifen alone). This was a surprising finding that patients with BCI H/I-low group derived benefit from the addition of ovarian function suppression while the BCI H/I-high group did not. It is possible that the BCI H/I high group indicates an endocrine-resistant population and, therefore, these patients derived a larger benefit from ovarian function suppression. These are interesting and thought-provoking findings that need further follow-up for right-sizing of therapies going forward.
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O’Regan R. Abstract GS1-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 6-10, 2022; San Antonio.
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