The combination of a 21-gene recurrence score and quantitative estrogen receptor expression may help clinicians identify patients with estrogen receptor–positive breast cancer who are most likely to benefit from hormonal therapy extended beyond the customary 5 years, according to researchers.
Long-term follow-up of patients with recurrence score information from two National Surgical Adjuvant Breast and Bowel Project (NSABP) studies showed that recurrence score is strongly prognostic for late distant recurrences among patients with higher quantitative estrogen receptor expression (ESR1) levels, reported Dr. Norman Wolmark and colleagues from the NSABP Operations Centers and other institutions.
“These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high [recurrence score] with higher ESR1 expression at initial diagnosis,” they wrote (J Clin Oncol. 2016 May 23. doi: 10.1200/JCO.2015.62.6630).
HconQ/ThinkStock
The authors looked at data on patients with recurrence score information who were enrolled in the tamoxifen-only arm of the NSABP B-14 trial and in the B-28 trial, which compared four cycles of doxorubicin plus cyclophosphamide (AC) with four cycles of AC followed by four cycles of paclitaxel plus 5 years of tamoxifen for hormone receptor–positive patients. The recurrence score cohorts for the studies included 668 and 1,065 patients, respectively.
After a median follow-up of 11.2 years in B-28, recurrence score was associated with both early (0 to 5 years) and distant recurrence (P less than .001 and P = .02, respectively), regardless of ESR1 expression.
The investigators then used B-28 to establish a quantitative ESR1 cut-point to identify patients for whom recurrence scores predicted late distant recurrences. They determined it to be 9.1 normalized expression cycle threshold units (CT), and then validated this cutoff in B-14.
In the B-14 cohort, a recurrence score of less than 18 CT was associated with a distant recurrence rate in years 5 through 15 of 6.8%, a score from 18 to 30 was associated with a 11.2% rate, and a score of 31 or greater was associated with a 16.4% rate (P less than .01).
The results “confirm studies of other molecular assays in postmenopausal patients and extend these findings to premenopausal women: at-risk patients have varying rates of [late distant recurrence], and a low-risk group with less than a 5% risk of recurrence in the second [5 years] can be identified,” the researchers wrote.
The data also confirm and extend results of foundational gene expression studies showing that highly proliferative, high-ER-gene–expressing tumors are at the greatest risk of late relapse, they said.
However, additional studies are needed before clinicians can rely on genomic factors to predict which patients require only 5 years of hormonal therapy, they cautioned.
The study was supported by National Cancer Institute grants, Susan G. Komen for the Cure grants, Bristol-Myers Squibb, Pharmaceutical Research Institute, AstraZeneca, and Genomic Health. Several authors disclosed relationships with various pharmaceutical companies, and five are employed by Genomic Health.