More from TAILORx investigators

 By Peggy Peck, Editor-in-Chief, BreakingMED

CHICAGO — Clinical risk — high versus low risk — integrated into a genomic risk model is prognostic of distant recurrence of breast cancer in women whose 21-gene score puts them in the moderate to high risk category, according to the latest results from the TAILORx trial.

But factoring in clinical risk was not predictive of adjuvant chemotherapy benefit, said Joseph A. Sparano, MD, of New York’s Montefiore Medical Center, who reported the findings here at the American Society of Clinical Oncology meeting. The results were also published in The New England Journal of Medicine.

The calculus of deciding which women will gain the greatest benefit from adjuvant chemotherapy is far from straightforward, and the conclusions that Sparano offered are actually based on a subgroup analysis of a secondary objective from a trial that enrolled almost 10,000 women with early stage breast cancer who were followed for roughly 9 years.

The 21-gene recurrence score is an assay of 21 genes, the results of which are graded on a score of 0-100, with higher scores indicating worse prognosis or a greater benefit from chemotherapy. The 9,427 women in the trial had hormone receptor positive (HR+), human epidermal growth receptor-2 (HER-2) negative, axillary node-negative breast cancer.

The report here is a second bite of the apple for the TAILORx investigators, who almost exactly a year ago published the initial TAILORx findings that found endocrine therapy was noninferior to chemoendocrine therapy in women considered at intermediate risk for distant recurrence. The new analysis was an attempt to further hone the risk prediction model to identify any subgroups that might benefit from more effective antiestrogen therapy.

“There was a significant interaction between chemotherapy treatment, age (≤50 vs >50 years) or menopausal status, and recurrence score, suggesting a modest but clinically meaningful reduction in the rate of distant recurrence with chemotherapy among younger or premenopausal women who had a recurrence score of 16 to 25. Similar findings were noted in a population-based study indicating a chemotherapy benefit emerging at a recurrence score above 15 in women who were 50 years of age or younger and above 25 in women who were older than 50 years,” Sparano said.

Sparano and colleagues used a clinical risk classification scheme also used in another trial —MINDACT (Microarray in Node-Negative Disease May Avoid Chemotherapy) —that rates breast cancer recurrence as low or high on the basis of the tumor size and histologic grade.

Most of the premenopausal women younger than 50 had initial endocrine therapy with tamoxifen.

Among the findings:

  • Women whose 21-gene risk score is in the 11-25 range have a 5% absolute risk of distant recurrence, irrespective of chemotherapy use.
  • All women whose risk was in the 26-100 range had chemotherapy and endocrine therapy, but still had a 10% absolute risk of distant recurrence.
  • Clinical risk did not predict chemotherapy benefit for women in the 10-25 group treated with chemotherapy and endocrine therapy.
  • The absolute chemo benefit was greatest among premenopausal women ages 41-50 with genomic risk scores in the 16-25 range.

Vered Stearns, MD, co-director of the Breast and Ovarian Cancer Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who served as discussant for Sparano’s presentation, said the findings need to be interpreted with caution, noting that additional studies are needed to validate the findings.

But TAILORx does, Stearns said, provide “a rich resource for new explorations, other biomarkers, models, and machine learning.”

ASCO breast cancer spokesperson Harold J. Burstein, MD, PhD of the Dana-Farber Cancer Institute in Boston told BreakingMED that, when one looks at the universe of breast cancer, “about half are hormone positive HER2 negative and tumors generally respond to antiestrogen therapy often with ovarian suppression, and we are looking at 10 year recurrence-free survival in the 85-90% range … but there is still that 10%-15% and we are still seeking ways to identify that segment and find effective treatment.”

TAILORx algorithms and other biomarker tools aid in guiding therapy and predicting outcome, he said.

Sparano offered this conclusion:

“Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy.”



TAILORX was funded by the National Cancer Institute.

Sparano reported grants from National Cancer Institute during the conduct of the study.


Sparano JA, et al “Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer” N Eng J Med 2019; Published online June 3 DOI: 10.1056/NEJMoa1904819.

Sparano JA, et al “Impact of clinical risk category on prognosis and prediction of chemotherapy benefit in early breast cancer (EBC) by age and the 21-gene recurrence score (RS) in TAILORx” ASCO 2019; Abstract 503.


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