The recurrence score (RS) derived from a 21-gene expression assay may indicate which patients with early-stage hormone receptor-positive (HR+) breast cancer can maintain freedom from distant recurrence for longer with the inclusion of an anthracycline in adjuvant chemotherapy, suggests a post hoc analysis of the phase III TAILORx trial presented at SABCS 2024.

Among women with RS ≥31 in the studied trial population with HR+, HER2-negative, axillary node-negative disease (n=2,549), the inclusion of an anthracycline in the taxane plus cyclophosphamide regimen (TAC) was associated with an improved distant recurrence-free interval (DRFI), showing a significant 5.1-percent absolute benefit in the DRFI rate at 5 years (96.1 percent vs 91 percent; adjusted hazard ratio [aHR], 0.32; p=0.009).

In contrast, among women with RS <31, those receiving TAC and those receiving taxane plus cyclophosphamide alone (TC) had similar 5-year DRFI rates (97 percent vs 97.6 percent; aHR, 1.24; p=0.484). The interaction between chemotherapy treatment and RS was statistically significant (p for interaction=0.009). [SABCS 2024, abstract GS3-03]

The relative DRFI benefit from anthracyclines increased progressively with an increasing RS from 15 to 50. At RS of 15, DRFI was identical between TAC and TC (aHR, 1.00, 95 percent confidence interval [CI], 0.51?1.95), with a trend increasingly favouring TAC at higher RS. At RS of 45, a significant benefit from anthracyclines could be demonstrated (aHR, 0.52, 95 percent CI, 0.27?0.98), and the magnitude of benefit increased further at RS of 50 (aHR, 0.45, 95 percent CI, 0.21?0.96).

“Increasing RS of ≥31 corresponded to an increased benefit from the addition of anthracyclines,” said Dr Nan Chen from the Section of Hematology/Oncology, Department of Medicine, University of Chicago in Illinois, US. “Anthracyclines should be considered in patients with high genomic risk, HR+, lymph node-negative disease.”

Survival outcomes

DRFI in TAILORx was defined as the time from chemotherapy allocation to distant recurrence of breast cancer or death with distant recurrence, if death is its first manifestation. [N Engl J Med 2018;379:111-121]

In the RS ≥31 group, improved distant recurrence-free survival (DRFS) was also observed in those receiving TAC vs those receiving TC, with an absolute benefit of 5.6 percent in the 5-year survival rates (95.4 percent vs 89.8 percent; aHR, 0.47; p=0.031).

The benefit of anthracyclines was more pronounced in those with tumour size >2 cm for both DRFI (HR, 0.29, 95 percent CI, 0.10?0.87) and DRFS (HR, 0.23, 95 percent CI, 0.08?0.69), while a detrimental effect relative to TC on DRFS could not be ruled out for tumours ≤2 cm (HR, 1.32, 95 percent CI, 0.51?3.43).

There was a trend towards an overall survival benefit with the inclusion of anthracyclines among women with RS ≥31 (5-year rates 97.3 percent vs 93.5 percent; aHR, 0.546; p=0.167).

Genomic and clinical risk

It is noteworthy that the benefits from anthracyclines among high genomic risk patients were evident despite clinical risk factors such as age, menopausal status, tumour size, disease grade, and progesterone receptor status generally disfavouring the TAC group overall, a bias that arose because TAILORx was not designed to randomize patients to different chemotherapy regimens.

“One of the things we wanted to highlight was the use of RS as opposed to some clinical or pathological factors that we typically use,” added Chen. “Patient stratification is important, and certainly, that is a patient population where TC would be more reasonable (eg, RS ≥31 but small tumours).”