The invited discussant of the SOFT analysis was Polly Niravath, MD, Associate Professor and Director of the Cancer Survivorship Program at Houston Methodist Hospital in Texas. She noted that the study evaluated the use of the Breast Cancer Index (BCI) as a prognostic tool in early hormone receptor–positive breast cancer and its HOXB13/IL17BR (H/I) ratio as a marker of benefit from ovarian suppression.
Polly Niravath, MD
“The results were predictive for benefit of ovarian suppression—however, not in the way that was anticipated,” she commented. “It turns out that BCI (H/I)–low patients actually benefited more from ovarian suppression plus an aromatase inhibitor vs tamoxifen, and BCI (H/I)–high patients did not have this differential benefit. Interestingly, this trend stubbornly held in every subset analysis, including patients who had prior chemotherapy or did not, those who are node-positive or node-negative, and regardless of age or HER2 status.”
To “make sense of these surprising results,” Dr. Niravath described some of the biology that underlies the use of the H/I ratio and found it fitting. She noted that estrogen suppresses HOXB13 expression and increases IL-17BR expression. In premenopausal untreated women, a low H/I ratio would predict for estrogen-responsive disease, she said.
“And, in the clinical sense, we know that H/I ratio has been validated to predict for tumors that benefit from standard endocrine therapy because of endocrine responsiveness and late risk of recurrence. Using that information, we can then deduce that perhaps H/I-low tumors essentially have a high risk of early recurrence. This means augmented endocrine therapy in the first 5 years may be more effective for these tumors, whereas H/I-high tumors—because of their greater risk for later recurrence—may not derive as much benefit from early aggressive therapy. Perhaps these patients also need longer follow-up to reflect their ultimate outcomes,” Dr. Niravath proposed.
If the data are reliably reproduced and validated, she said, the future treatment algorithm for estrogen receptor–positive premenopausal breast cancer may look like this: patients with BCI (H/I)–low scores may be treated with ovarian suppression plus an aromatase inhibitor for 5 years, and those with BCI (H/I)–high scores would be treated with tamoxifen for 5 years, after which they may opt for extended endocrine therapy (tamoxifen for years 6–10 if they remain premenopausal or an aromatase inhibitor for 2–5 more years if they are naturally postmenopausal).
Virginia Kaklamani, MD
Press briefing moderator Virginia Kaklamani, MD, Professor of Medicine at UT Health San Antonio and leader of the Breast Cancer Program at UT Health San Antonio MD Anderson Cancer Center, said she was “pretty impressed with the results” of the SOFT analysis. She is currently using the BCI for women who complete 5 years of endocrine therapy as a means of determining their need for extended endocrine treatment but could visualize BCI being useful in earlier stages, should the SOFT results be validated.
“Obviously, for many of our patients, we already obtain a genomic score, whether it’s OncotypeDX or MammaPrint, to decide whether to give them chemotherapy. My concern is if I use the BCI earlier, will insurance companies pay for two genomic tests, or will this be put upon the patient? On the other hand, how much does giving an LHRH [luteinizing hormone-releasing hormone] agonist for 5 years cost? These are expensive tests, so this is definitely something that needs validation.”
DISCLOSURE: Dr. Niravath reported no conflicts of interest. Dr. Kaklamani has served as a consultant to or a speaker for Puma Biotechnology, AstraZeneca, Daiichi Sankyo, Menarini, Gilead Sciences, Pfizer, Genentech, Exact Sciences, Novartis, and Seagen and has received research support from Eisai.
