When to Use Anthracyclines in Early Breast Cancer

SAN ANTONIO — Patients with early-stage, node-negative, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and a high risk for recurrence benefited more from adding adjuvant anthracyclines to taxane-based chemotherapy than from taxane-based chemotherapy alone, according to a post-hoc analysis of the TAILORx study.

More specifically, patients with a recurrence score ≥ 31, as determined by Oncotype DX genomic test, demonstrated improved distant recurrence-free survival, a longer distant recurrence-free interval and recurrence-free interval, as well as a trend towards improved 5-year overall survival when adding adjuvant anthracycline therapy to taxane-based chemotherapy.

“Anthracyclines should be considered in patients with high genomic risk HR-positive, HER2-negative, lymph-node–negative disease,” said Nan Chen, MD, University of Chicago, Illinois, when presenting the post hoc findings at the San Antonio Breast Cancer Symposium (SABCS) 2024. 

The role of chemotherapy in the adjuvant setting of high-risk, early-stage HR-positive, HER2-negative breast cancer continues to evolve.

While patients with this type of breast cancer generally receive either adjuvant taxane-based regimens or more intensive chemotherapy with taxane- and anthracycline-based regimens, there is limited data to guide the use of the more intensive strategy, Chen explained.

Chen and her colleagues analyzed data on patients from the TAILORx trial who received a taxane plus cyclophosphamide chemotherapy (TC) or an anthracycline-taxane combination (T-AC), including anthracycline with cyclophosphamide followed by a taxane, concurrent anthracycline, cyclophosphamide, and docetaxel, or other anthracycline with taxane combinations.

Patients in the trial had stage I or II, node-negative disease, and all received a recurrence score based on the Oncotype DX 21-gene recurrence-score assay, with scores ranging from 0 to 100 and higher scores predictive of chemotherapy benefit.

Patients with a recurrence score between 11 and 25 were randomized to endocrine therapy or endocrine therapy plus chemotherapy of physicians’ choice, whereas patients with a recurrence score of ≥ 26 received endocrine therapy plus chemotherapy. 

The post hoc analysis included 438 patients who received T-AC and 2111 who received TC. 

Compared to patients receiving TC, those who had T-AC were generally younger (mean age, 53 vs 55 years), premenopausal, and more likely to have larger tumors that were high-grade and progesterone receptor-negative. Patients receiving T-AC also had higher recurrence scores (mean, 29.6 vs 9.5 for those receiving TC). 

For the primary survival outcome of 5-year distant recurrence-free interval, patients with recurrence scores under 31 did not experience a statistically meaningful benefit with the addition of anthracycline (97.0% with T-AC vs 97.6% with TC), Chen reported. 

However, among those with a recurrence score of 31 or higher, the 5-year distant recurrence-free interval was 96.1% among those receiving T-AC vs 91.0% among those who received TC (adjusted hazard ratio [aHR], 0.32; P = .009). 

In this patient group, the addition of an anthracycline led to a significant 5-year distant recurrence-free survival benefit — 95.5% with T-AC vs 89.8% with TC (aHR, 0.47; P = .31). 

Patients receiving anthracycline also showed a trend towards improved overall survival, with the 5-year overall survival rate at 97.3% in the T-AC group vs 93.5% in the TC group (P = .167)

In subgroup analyses, the benefit of T-AC in patients with a recurrence score of 31 or higher was greatest in patients with tumors ≥ 2 cm. 

A similar benefit of adding anthracycline was observed in premenopausal and postmenopausal patients, which suggests that the effect is not due to the ovarian suppressive effects of anthracyclines, Chen said. 

Chen noted that the benefit of adding anthracycline therapy increased as the recurrence score increased in those with scores > 31.

But less than 5% of patients in TAILORx had a recurrence score ≥ 31, “so we recognize that this is not an extremely common scenario,” Chen said. Still, “I think it’s important to identify a subset of patients with HR-positive, HER2-negative breast cancer who may benefit from anthracycline therapy.”

Commenting on the data, briefing moderator Carlos, Arteaga, MD, noted that clinicians “tend to use anthracyclines in this patient population anyway.”

“What this study provides is a rigorous demonstration that there’s benefit for the addition of anthracyclines for patients with high recurrence scores,” said Arteaga with Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, Texas.

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Research Foundation, and the Lynn Sage Breast Cancer Foundation. Chen reports receiving consultant fees from Guardant Health, Daiichi Sankyo, Stemline Therapeutics, Seagen, AstraZeneca, and Novartis. Arteaga reported relationships with Pfizer and Lilly.