21-Gene Assay Can TAILORx Chemotherapy for Select Low-Risk Breast Cancer Patients

Select breast cancer patients with a low gene expression assay recurrence score may be spared adjuvant chemotherapy

medwireNews: A 21-gene expression assay can guide clinicians on the need for adjuvant chemotherapy in women with invasive breast cancer that is axillary node-negative, hormone receptor-positive and HER2-negative, research confirms.

“In patients who were found to have a low risk of recurrence on the basis of genetic-assay results and who were thus assigned to receive endocrine therapy alone, the risk of the recurrence of breast cancer at a distant site was less than 1% and the risk of any recurrence was less than 2% at 5 years”, report Joseph Sparano, from Montefiore Medical Center in New York, USA, and co-workers.

They believe their study “supports the clinical validity of the 21-gene assay in identifying patients who may be safely spared adjuvant chemotherapy.”

For the Trial Assigning Individualized Options for Treatment (TAILORx), 10,253 patients aged 18–75 years were assigned a recurrence score based on a previously validated, commercially available, Oncotype DX reverse-transcriptase–polymerase chain reaction assay carried out on RNA extracted from a tumour sample.

The current results, reported simultaneously at the European Cancer Congress in Vienna, Austria and in The New England Journal of Medicine, describe the outcomes of the 15.9% of women with a low-risk recurrence score, defined as 10 or below out of a possible 100, and followed up for a median of 69 months after mastectomy or lumpectomy.

These 1626 patients were given an aromatase inhibitor (AI, 59%), tamoxifen (34%), sequential tamoxifen then AI therapy (1%), ovarian suppressive therapy (3%) or another endocrine treatment (3%) but the protocol stated they were not to be treated with adjuvant chemotherapy.

After 5 years, 88 patients had developed invasive cancer or died, giving an invasive disease-free survival rate of 93.8% and a freedom from distant breast cancer recurrence rate of 99.3%. The 5-year rate of freedom from recurrence was 98.7% and the overall survival rate was 98.0%.

After adjusting for age, tumour size, histological grade and surgery type, only histological grade was significantly predictive of freedom from recurrence (hazard ratio=8.07 for intermediate vs low; 4.73 for high vs low).

But histological grade did not significantly predict 5-year rates of mortality associated with invasive disease or freedom from distant occurrence, the authors report.

“These findings provide additional evidence supporting expert-derived clinical practice guidelines that recommend the use of this assay in patients with hormone-receptor–positive, axillary node–negative invasive breast cancer”, the researchers write, but note that the results apply to only a small proportion of patients enrolled in the TAILORx trial.

“Approximately 67% of the patients enrolled in the trial had a midrange score of 11 to 25 and were randomly assigned to receive chemotherapy plus endocrine therapy or endocrine therapy alone”, they explain. “Continued follow-up is required in order to determine the effect of chemotherapy in this larger group of patients.”

In an accompanying editorial, Clifford Hudis, from Memorial Sloan Kettering Cancer Center in New York, USA, describes the findings as “both reassuring and frustrating”, noting that previous studies of this test have shown that patients with a recurrence score of below 18 did not benefit from adjuvant chemotherapy, while those with a score above 31 did derive benefit.

“[F]or many physicians already using this test, the gap between this cutoff point of 10 and the higher ‘standard’ cutoff point of 18 may be a concern”, he writes.

If chemotherapy is later shown to benefit patients with this newly defined intermediate score of 11–25 there will be “two conflicting guides to treatment that need to be reconciled”, Clifford Hudis explained, making further research in this population “critical”.


Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med 2015; Advance online publication 28 September. DO I: 10.1056/NEJMoa1510764

Hudis CA. Biology before anatomy in early breast cancer – Precisely the point. N Engl J Med 2015; Advance online publication 28 September. DOI: 10.1056/NEJMe1512092

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