When Should Anthracyclines Be Used in Early-Stage Breast Cancer?

In patients with early-stage, node-negative, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer at high risk of recurrence, adding adjuvant (postoperative preventive) anthracyclines to taxane-based chemotherapy provided greater benefit than taxane-based chemotherapy alone. This finding came from a subsequent subgroup analysis of the TAILORx trial.

The Oncotype DX genomic test is a molecular diagnostic test that analyzes the expression of 21 genes to assess recurrence risk and predict chemotherapy response in certain cancers, including breast cancer. It is performed on a tissue sample obtained through surgical biopsy.

In particular, patients with an Oncotype DX recurrence score ≥ 31 experienced longer recurrence-free survival and longer intervals before recurrence when adjuvant anthracyclines were added to taxane-based chemotherapy, as well as a trend toward improved overall health at 5 years.

Presenting the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024, Dr. Nan Chen said, "Anthracyclines should be considered in HR-positive, HER2-negative, node-negative patients with high genomic risk."

The Evolution of Adjuvant Chemotherapy in High-Risk Patients

The role of adjuvant chemotherapy in high-risk, early-stage HR-positive, HER2-negative breast cancer continues to develop. These patients are generally treated with either taxane-based regimens or more intensive taxane- and anthracycline-based chemotherapy. However, evidence guiding use of the more intensive strategy is limited.

Dr. Chen and colleagues analyzed TAILORx patients who received taxane and cyclophosphamide (TC) or an anthracycline-taxane combination (T-AC). T-AC was given in several forms, including anthracyclines combined with cyclophosphamide followed by a taxane, or concurrent anthracycline, cyclophosphamide, and docetaxel.

Treatment Based on Oncotype DX and Risk Scores

All TAILORx participants received a score from the Oncotype DX 21-gene recurrence score test. Scores ranged from 0 to 100, with higher scores predicting chemotherapy benefit. Patients with scores of 11-25 were randomized to endocrine therapy alone or endocrine therapy plus chemotherapy selected by the physician. Those with scores ≥ 26 received endocrine therapy and chemotherapy.

The subgroup analysis included 438 patients receiving T-AC and 2111 receiving TC. T-AC recipients were generally younger (mean age 53 vs 55), premenopausal, and had higher-grade, progesterone receptor-negative, larger tumors. Their mean recurrence score was also higher (29.6 vs 9.5).

Main Findings

For the study's primary endpoint, 5-year distant metastasis-free survival , adding anthracyclines did not produce a statistically significant difference among patients with scores below 31 (97.0% T-AC vs 97.6% TC). However, the rates differed significantly among those with scores of 31 or higher: 96.1% (T-AC) vs 91% (TC) (adjusted hazard ratio [aHR], 0.32; P = 0.009).

In subgroup analyses, the benefit of T-AC among patients with recurrence scores of 31 or higher was most pronounced in those with tumors ≥ 2 cm. Similar benefits were observed in premenopausal and postmenopausal patients, suggesting that the effects were not due to the ovarian-suppressing effects of anthracyclines.

Chen emphasized that the benefit of anthracycline treatment increased with the recurrence score. However, in TAILORx, fewer than 5% of patients had a recurrence score ≥ 31. "Although this is an uncommon scenario, it is important to identify a subgroup of patients with HR-positive, HER2-negative breast cancer who may benefit from anthracyclines," she said.

Commentary

In early-stage breast cancer, the Oncotype DX score has become one of the most important guides for patients and physicians when determining the need for postoperative chemotherapy. This study clearly demonstrates the substantial benefit of adding anthracyclines in patients with high recurrence scores, particularly scores of 31 or above. The findings allow more precise treatment planning in this group, potentially directing patients toward effective therapy while minimizing unnecessary toxicity. They are valuable in showing how personalized medicine continues to shape adjuvant chemotherapy.