HR-positive, HER2-negative Breast Cancer Patients With High Risk of Recurrence May Benefit From Addition of Anthracyclines to Taxane- based Chemotherapy

Genomic testing helped identify which patients with node-negative, HR-positive, HER2- negative breast cancer could benefit from the addition of anthracyclines to chemotherapy regimen

SAN ANTONIO – Patients with early-stage, node-negative, hormone receptor (HR)-positive, HER2- negative breast cancer who have a high risk of recurrence based on the OncotypeDX genomic test had better outcomes when treated with adjuvant anthracycline- plus taxane-based chemotherapy regimens compared with those receiving adjuvant taxane-based chemotherapy regimens alone, according to results presented at the San Antonio Breast Cancer Symposium (SABCS), held December 10-13, 2024.

“HR-positive, HER2-negative is the most common type of breast cancer in the United States and we frequently need to decide whether or not adjuvant chemotherapy would be beneficial, and if so, what type of chemotherapy would be beneficial,” explained Nan Chen, MD, assistant professor of internal medicine at the University of Chicago Medicine, who presented the study. Chen said that while patients with this type of breast cancer generally receive either adjuvant taxane-based regimens or taxane- and anthracycline-based regimens, there is limited data to guide the use of more intensive chemotherapy via the addition of anthracyclines.

Chen and her colleagues analyzed data from the TAILORx trial to compare outcomes of patients with stage I/II, node-negative, HR-positive, HER2-negative breast cancer who received either taxane with anthracycline/cyclophosphamide and similar regimens (T-AC) or taxane with cyclophosphamide (TC) chemotherapy after surgery. Within the trial, the OncotypeDX test was used to help predict which patients might benefit from chemotherapy. This commonly used gene assay provides a recurrence score (RS) between 0 and 100, with lower scores indicating a smaller risk of recurrence and thus a less likely benefit from adjuvant chemotherapy relative to its side effects.

Patients with an RS between 11 and 25 were randomly assigned to receive endocrine therapy alone or endocrine therapy plus a chemotherapy regimen chosen by the physician, while those with an RS over 26 received endocrine therapy plus a chemotherapy regimen chosen by the physician. Out of 2,639 eligible cases, 2,197 patients received TC while 442 were treated with T-AC, which included one of three regimens: anthracycline with cyclophosphamide followed by taxane; concurrent anthracycline, cyclophosphamide, and docetaxel; or other anthracycline with taxane combinations.

After controlling for age, grade, tumor size, and estrogen/progesterone receptor status, the use of T-AC in patients with an RS 31 or greater and tumors 2 cm or greater was associated with improved survival outcomes after five years.

Among patients with an RS 31 or greater, compared with those who received TC, patients who received T-AC had a higher distant recurrence-free interval (90.7% vs. 96.1%), distant recurrence-free survival (89.5% vs. 95.4%), recurrence-free interval (89.1% vs. 94.1%), and a trend towards improved recurrence- free survival (87.9% vs. 93.4%) and overall survival at five years (93.1% vs. 97.3%).

The benefit of anthracycline therapy was also found to increase as the RS increased above 31, while no trend toward benefit was seen in patients with a score between 26 and 30.

Chen and colleagues found a similar benefit of anthracycline regimens in premenopausal and postmenopausal patients, which she said suggests that the effect is not due to the ovarian suppressive effects of anthracyclines.

“These results are in line with current clinical practice, where we give anthracyclines more readily in tumors biologically closer to triple-negative disease,” Chen said. “While most HR-positive, HER2-negative tumors do not have RS 31 or greater, many of the highest RS tumors may have less estrogen receptor expression, higher proliferation, and are closer along the spectrum towards triple-negative disease, a subset in which the benefit of anthracyclines has been much more clearly demonstrated.”

Chen added that while some of the secondary endpoints, such as distant recurrence-free survival, only increased for T-AC when the tumor was larger than 2 cm, the primary endpoint of distant recurrence-free interval increased with T-AC regardless of tumor size. She and her colleagues will continue to validate these findings and examine the use of anthracyclines in other patient groups.

“We believe that these findings have some implications for clinical care with caution,” Chen said. “Previous trials have shown the early benefit in recurrence reduction with anthracyclines may be offset by late risk of non-breast cancer deaths such as leukemia, so longer-term follow-up will be needed, and these risks should be discussed with patients before considering anthracycline-based chemotherapy.”

Limitations of this study include the fact this is a posthoc analysis of the TAILORx study, which was not specifically designed to evaluate the benefit of anthracyclines and could bias results. Additionally, the benefits of anthracyclines in lower-risk patients (RS 26-30) may have been difficult to measure because of the overall lower risk of recurrence in this population.

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.

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