Professors Li Wang & Jianbin Li: Choosing Adjuvant Therapy for Intermediate-Risk HR+ Early Breast Cancer

Editor’s Note: For patients with intermediate-risk hormone receptor–positive early breast cancer (HR+ EBC), should adjuvant therapy prioritize chemotherapy plus an aromatase inhibitor (AI), or an AI combined with a CDK4/6 inhibitor? At the 2025 Summer Breast Cancer Forum · Northern Salon, Professors Li Wang of Xingtai People’s Hospital and Jianbin Li of the General Hospital of the PLA debated this question in the “Debate” session. Here, in Oncology Frontier’s “In-Depth” column, they further share their perspectives based on evidence.

Weighing the Options

Professor Li Wang: Chemotherapy + AI as First Choice

In my view, chemotherapy combined with AI remains the preferred adjuvant option for patients with intermediate-risk HR+/HER2− early breast cancer. My reasoning rests on two main points.

First, regarding the role of chemotherapy: although a traditional modality, chemotherapy continues to be the cornerstone of treatment for most breast cancer patients. Numerous clinical studies confirm that chemotherapy confers a survival advantage compared with no chemotherapy. While CDK4/6 inhibitors have achieved remarkable results in both advanced and early disease, and exploring their substitution for chemotherapy is a logical step forward, current evidence is insufficient to completely replace chemotherapy. Importantly, in pivotal trials such as monarchE and NATALEE, 95% and 88% of enrolled patients, respectively, had already received chemotherapy. It is therefore premature to remove chemotherapy from the treatment algorithm.

Second, should every patient receive CDK4/6 inhibitors? While NATALEE demonstrated benefit in intermediate-risk patients, ribociclib has not yet been included in national reimbursement schemes. For many patients, treatment costs represent a heavy financial burden. Moreover, fewer than 70% of patients (62.8%) in NATALEE completed the planned three years of ribociclib therapy, and the outcomes for those who discontinued remain unclear. Taken together, these considerations support chemotherapy + AI as the current first-choice regimen for intermediate-risk patients.

Professor Jianbin Li: AI + CDK4/6 Inhibitors as Preferred Approach

Our debate today essentially centers on whether CDK4/6 inhibitors can replace chemotherapy. In the past, during the era of endocrine therapy alone, high-risk patients identified by genomic testing or clinical features did not necessarily achieve better outcomes with chemotherapy compared with intensified endocrine therapy. Subsequent trials—including SOFT/TEXT, NATALEE, and monarchE—have steadily demonstrated the growing effectiveness of endocrine-based strategies.

As for the cost factor, I believe this challenge may be resolved soon. Ongoing national reimbursement negotiations could make ribociclib more widely accessible. At the same time, multiple clinical studies are being conducted for patients currently unable to afford ribociclib, aiming to reduce both the financial burden and the toxicities associated with chemotherapy. With these considerations, I advocate for AI + CDK4/6 inhibitor therapy as the more appropriate option to strengthen adjuvant treatment.

Seeking the Best Fit for Each Patient

Professor Li Wang: As clinicians, our responsibility is to select treatment based on each patient’s overall situation rather than adopting a “one-size-fits-all” approach. If you had the option, for which patients would you consider omitting chemotherapy and moving directly to intensified endocrine therapy?

Professor Jianbin Li: Currently, intermediate-risk HR+/HER2− EBC is defined as N1 disease without additional risk factors, or N0 disease with large tumors or high-risk genomic features. For patients with T3–4 disease or high genomic risk, chemotherapy cannot be omitted; the main decision lies in whether to intensify or de-escalate endocrine therapy. For patients outside these scenarios, however, chemotherapy exemption can be considered.

Professor Li Wang: Indeed, clinical studies in China are underway to evaluate the strategy of skipping chemotherapy and directly using CDK4/6 inhibitors. We look forward to these results. At the same time, I hope genetic testing can be adopted more rapidly and made more affordable nationwide. Widespread access will enable more patients, including those in lower-resource settings, to benefit from precision treatment. This is a direction for us all to work toward in the future.