A prospective-retrospective translational study reported in JAMA Oncology by Ruth M. O’Regan, MD, and colleagues confirmed the prognostic value of the Breast Cancer Index (BCI) in a Suppression of Ovarian Function Trial (SOFT) trial–derived population of premenopausal women with early-stage, hormone receptor–positive breast cancer.
“The benefit from ovarian function suppression–containing adjuvant endocrine therapy was greater for patients with BCI HOXB13/IL17BR ratio–low vs –high tumors,” the investigators remarked. “BCI HOXB13/IL17BR ratio–low status may identify premenopausal patients who are likely to benefit from this more intensive endocrine therapy.”
Ruth M. O’Regan, MD
Study Details
In brief, the phase III multicenter SOFT trial evaluated both ovarian function suppression and the aromatase inhibitor exemestane as adjuvant therapies for premenopausal patients with early-stage, hormone receptor–positive breast cancer. A total of 3,066 patients were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus ovarian function suppression, or exemestane plus ovarian function suppression. Those with available formalin-fixed paraffin-embedded tumor tissue samples yielding sufficient RNA for BCI testing (n = 1,687) were included in the present study cohort.
The BCI gene-expression analysis by reverse transcription polymerase chain reaction was performed blinded to clinical data and outcome. The BCI signature consists of two functional biomarker panels: the ratio of the HOXB13 and IL17BR genes for measuring estrogen signaling, and the five-gene Molecular Grade Index for assessing tumor proliferation. Integration of these panels provides a single prognostic score that quantifies the risk of distant recurrence.
In this analysis, the investigators primarily sought to evaluate the predictive performance of the BCI HOXB13/IL17BR ratio; assessing the prognostic performance of the continuous BCI score was their secondary objective. The primary endpoints were breast cancer–free interval and distant recurrence–free interval, respectively, for the predictive and prognostic analyses.
Key Findings
KEY POINTS
- Premenopausal patients with BCI HOXB13/IL17BR ratio–low vs –high early-stage hormone receptor–positive breast cancer seemed to derive a greater benefit from ovarian function suppression–based adjuvant endocrine therapy.
- A higher BCI continuous index appeared to be associated with poorer prognosis.
- Pending validation in additional studies, the BCI may inform adjuvant endocrine therapy decision-making in this population.
Follow-up data were provided for a median of 12 years. A total of 57.6% and 42.4% of patients were found to have BCI HOXB13/IL17BR ratio–low and –high tumors, respectively. Those with BCI HOXB13/IL17BR ratio–low tumors exhibited a 12-year absolute benefit in breast cancer–free interval of 11.6% with exemestane plus ovarian function suppression (hazard ratio [HR] = 0.48; 95% confidence interval [CI] = 0.33–0.71) and 7.3% with tamoxifen plus ovarian function suppression (HR = 0.69; 95% CI = 0.48–0.97) vs tamoxifen alone. In contrast, neither adjuvant treatment with exemestane (absolute benefit = −0.4%; HR = 1.03; 95% CI = 0.70–1.53; P for interaction = .006) nor tamoxifen (absolute benefit = −1.2%; HR = 1.05; 95% CI = 0.72–1.54; P for interaction = .11) plus ovarian function suppression appeared to confer a benefit in their counterparts with BCI HOXB13/IL17BR ratio–low status.
According to the investigators, the BCI continuous index for distant recurrence–free interval was significantly prognostic in the subgroup of patients with N0 disease (n = 1,110; P = .004). The 12-year distant recurrence–free interval rates were 95.9%, 90.8%, and 86.3% in those with BCI low-risk, intermediate-risk, and high-risk cancers, respectively.
The investigators concluded: “The potential adverse effects of ovarian function suppression make it critical to determine which premenopausal patients derive the greatest benefit from ovarian function suppression–containing adjuvant endocrine therapy. To our knowledge, this prospective-retrospective translational study of patients enrolled in SOFT was the first study in which a genomic assay was able to predict which premenopausal patients were most likely to benefit from ovarian function suppression. Although these results revealed intriguing novel possible predictive capabilities of the BCI HOXB13/IL17BR ratio, further validation is needed before expanding the use of the BCI to aid with ovarian function suppression decision-making.”
Meredith M. Regan, ScD, of Harvard Medical School, Boston, is the corresponding author of the JAMA Oncology article.
Disclosure: This translational research study was supported by Biotheranostics and others. For full disclosures of the study authors, visit jamanetwork.com.
