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Extended adjuvant letrozole benefitted women with high HOXB13/IL17BR biomarker index
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Women with ER-positive breast cancer who had primary tumors with a high HOXB13/IL17BR biomarker index and were disease free within 4.5 to 6 years of treatment with extended adjuvant tamoxifen receive benefit from extended adjuvant letrozole therapy, according to results of a prospective-retrospective, nested case-control study.
The HOXB13/IL17BR biomarker has previously been shown to predict the risk for recurrence in women with ER-positive, lymph node-negative breast cancer.
In the current study, researchers assessed 83 recurrences and compared them with 166 nonrecurrences among patients assigned to letrozole or placebo.
Researchers used reverse-transcription polymerase chain reaction to determine HOXB13/IL17BR expression within primary tumors. They then used multivariable conditional logistic regression to investigate the predictive ability of HOXB13/IL17BR in determining benefit from letrozole.
Results indicated that an increase in HOXB13/IL17BR was significantly associated with a decrease in late breast cancer recurrence among those assigned to letrozole (OR=0.35; 95% CI, 0.16-0.75). Further, data from an adjusted model with standard clinicopathological factors indicated an increase in HOXB13/IL17BR was significantly associated with benefit from letrozole (OR=0.33; 95% CI, 0.15-0.73).
Patients with increased HOXB13/IL17BR had a 16.5% decrease in the absolute risk for recurrence at 5 years (P=.007). The interaction between the HOXB13/IL17BR biomarker and letrozole was statistically significant (P=.03), according to the researchers.
“In the absence of extended letrozole therapy, high HOXB13/IL17BR identifies a subgroup of ER-positive patients disease free after 5 years of tamoxifen who are at risk for late recurrence,” the researchers wrote. “When extended endocrine therapy with letrozole is prescribed, high HOXB13/IL17BR predicts benefit from therapy and a decreased probability of late disease recurrence.”
The ability to identify which patients are vulnerable to a late recurrence, as well as which patients may benefit from extended therapy, is of substantial clinical value, the researchers said.
“Our biomarker should allow many women to avoid unnecessary treatment and for the focus to center on those in most need of therapy,” they wrote. “This, in turn, could improve compliance with medication and further improve outcomes.”
Disclosure: The study was funded by grants from the Avon Foundation, the NIH, the Breast Cancer Foundation, the Department of Defense Breast Cancer Research Program, the NCI SPORE in breast cancer at Massachusetts General Hospital, and Novartis.
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