Evolving Treatment Algorithms for Early-Stage Hormone Receptor–Positive Breast Cancer
Key Points
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The Oncotype DX score is important in the early-stage setting for hormone receptor (HR)–positive breast cancer treatment decision-making.
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Premenopausal patients with an Oncotype DX score less than 25 remain a challenging population to treat, but the OFSET trial may provide crucial answers.
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Adjuvant ribociclib and abemaciclib have transformed the management of higher-risk disease, with many patient-provider considerations, such as toxicity, before therapy selection.
Treatment of early-stage HR–positive breast cancer has significantly evolved over the past several decades. Historically, anthracycline-based chemotherapy was routinely given to most patients with breast cancer because of its proven efficacy. However, the significant toxicities associated with anthracyclines have prompted a more selective approach, explained Erica Mayer, MD, MPH, of Dana-Farber Cancer Institute, in an Oncology Brothers podcast discussion. Dr. Mayer shared her insight on treatment algorithms for early and locally advanced HR-positive disease with cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center.
Anthracycline use has declined across breast cancer subtypes but remains common in triple-negative breast cancer. In HR–positive disease, Dr. Mayer explained that there has been a gradual pullback, which began around the time of the ABC trials, a pooled analysis comparing anthracycline-based chemotherapy with taxane-based chemotherapy (docetaxel/cyclophosphamide [TC]) across subtypes and stages.
Data From TAILORx
The TAILORx trial, presented at the 2024 San Antonio Breast Cancer Symposium, examined chemotherapy selection—AC-T (Adriamycin and Cyclophosphamide followed by Taxol) or TC—and, although not randomized, the data were compelling enough to influence practice for certain high-risk patients, Dr. Mayer said. She explained that in her practice, a patient with an Oncotype score of 54 may reasonably be offered AC-T, whereas the benefit may be less convincing for someone with a score of 31.
Disease Management in Premenopausal Populations
Management becomes more challenging in premenopausal women with node-positive disease and low genomic risk scores. The role of chemotherapy in this population remains contentious, Dr. Mayer said. Trials such as OFSET are investigating whether chemotherapy provides benefit beyond endocrine strategies in premenopausal women with N1 disease and low Oncotype scores (less than 25).
She stressed the importance of ovarian function suppression (OFS) as a powerful therapeutic tool in HR–positive disease. Long-term, 15-year follow-up data from the landmark SOFT and TEXT studies confirmed the durability of benefit with OFS-based endocrine therapy, Dr. Mayer said.
At Dana-Farber, Dr. Mayer shared that they don’t automatically administer chemotherapy to every premenopausal, node-positive patient. A tumor board reviews the size, grade, node involvement, degree of estrogen receptor staining, Ki-67 (if relevant), and patient preferences. They also obtain genomic assays and, in some cases, defer chemotherapy in favor of an intensified endocrine approach that includes OFS, an aromatase inhibitor, and a CDK4/6 inhibitor.
CDK4/6: Ribociclib Versus Abemaciclib
The adjuvant use of CDK4/6 inhibitors has further transformed management of higher-risk HR–positive breast cancer. Ribociclib and abemaciclib have demonstrated strong efficacy based on data from the monarchE and NATALEE trials.
In patients with one to two positive nodes, choosing between the agents may come down to toxicity profiles and patient preference, Dr. Mayer explained. Abemaciclib is more commonly associated with gastrointestinal toxicity, such as diarrhea, while ribociclib carries the risk of liver function test abnormalities. Dr. Mayer said that proactive toxicity management is crucial. For ribociclib, liver enzymes should be monitored at baseline and every 2 weeks for the first 8 weeks. For abemaciclib, strategies such as gradual dose escalation may reduce early discontinuation and improve tolerability.
Dr. Mayer shared data from the single-arm, phase 2 TRADE study, which she served as the primary investigator for, that assessed the tolerability of abemaciclib dose escalation in early-stage HR–positive/HER2–negative breast cancer. At 12 weeks, investigators observed a low discontinuation rate (about 6%), suggesting that starting at a lower dose and titrating upward enabled more patients to complete therapy.
The doctors rounded out their conversation with a discussion on additional advances in high-risk early-stage disease, including adjuvant olaparib for selected patients and emerging agents such as giredestrant currently under investigation.