Editor's Note: On July 14, the "8th Yunnan Breast Cancer Summit Forum" was held in Kunming, coinciding with the 40th anniversary of the Yunnan Cancer Hospital. This event, organized by the Yunnan Anti-Cancer Association and the China Medical Education Association, and co-hosted by eight institutions including the Peking University Cancer Hospital Yunnan Branch, Yunnan Cancer Hospital, and the Third Affiliated Hospital of Kunming Medical University, brought together the latest advances in breast cancer. At the conference, "Oncology Frontier" invited Dr. Zhaoqing Fan from Peking University Cancer Hospital to provide an overview of the treatment landscape for HR+/HER2- breast cancer and to discuss the prospects of immunotherapy in early-stage patients based on the CheckMate 7FL and KEYNOTE-756 studies, guiding the future direction of new drug development for neoadjuvant therapy.01
Oncology Frontier: Could you introduce the current treatment landscape for HR+/HER2- breast cancer patients?
Dr. Zhaoqing Fan: HR+/HER2- breast cancer accounts for about 60%-70% of all breast cancer cases. Surgical treatment strategies for these patients are influenced by breast cancer subtypes, with endocrine therapy achieving long-term systemic or local tumor control and generally good prognosis. This biological characteristic affects both systemic and local treatment strategies. For HR+/HER2- patients with small tumors, sentinel lymph node biopsy may be omitted while preserving the breast; for patients with low lymph node burden, such as those with 1-2 lymph node metastases or micrometastases, axillary lymph node dissection may be avoided if the patient consents to breast-conserving treatment.
In terms of systemic treatment, endocrine therapy is the cornerstone for HR+/HER2- breast cancer. A good disease-free survival can be achieved with five years of endocrine therapy. For some patients with relatively poor prognosis, intensified treatment may be necessary. For example, young breast cancer patients with high-risk factors might consider ovarian function suppression combined with endocrine therapy, while postmenopausal patients might benefit from the combination of CDK4/6 inhibitors and endocrine therapy.
During the long-term treatment of HR+/HER2- breast cancer, there is a small peak of recurrence around 5-8 years. Therefore, extending endocrine therapy should be considered, such as 10 years of tamoxifen, 5 years of tamoxifen followed by 5 years of aromatase inhibitors (AI), or even 10 years of AI therapy.
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Oncology Frontier: How do you view the prospects of immunotherapy in early-stage HR+/HER2- breast cancer?
Dr. Zhaoqing Fan: Immunotherapy has been a hot topic in recent years, showing good results in triple-negative breast cancer by increasing the pathological complete response (pCR) rate and extending event-free survival (EFS). In HR+/HER2- breast cancer, studies like CheckMate 7FL and KEYNOTE-756, reported at the 2023 SABCS, have shown that immunotherapy can increase the pCR rate to over 20%. However, overall survival (OS) data is not yet available, so the application of immunotherapy in HR+/HER2- breast cancer remains immature.
The CheckMate 7FL and KEYNOTE-756 studies have conducted exploratory analyses to identify biomarker-defined populations that are more sensitive to immunotherapy, aiming to further increase the pCR rate. The CheckMate 7FL study showed that as the CPS score increases, the pCR rate significantly improves. For patients with a combined positive score (CPS) ≥20, the pCR rate reached 78.9%. Unfortunately, the CPS ≥20 population is very small among HR+/HER2- patients, and immunotherapy has some unacceptable adverse effects, so it may not be worth administering immunotherapy to all HR+/HER2- patients.
In summary, for immunotherapy in HR+/HER2- patients, we need to continue identifying the most responsive populations and await the survival results of related studies to find a balance between efficacy and side effects. Only then can we consider the clinical application of immunotherapy.
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Oncology Frontier: Based on data from CheckMate 7FL and KEYNOTE-756, what types of drugs do you think can be added to the neoadjuvant treatment field for early-stage HR+/HER2- breast cancer in the future?
Dr. Zhaoqing Fan: In the field of neoadjuvant treatment for early-stage HR+/HER2- breast cancer, traditional chemotherapy has been the mainstay, and neoadjuvant endocrine therapy can achieve results equivalent to chemotherapy, leading to similar downstaging and breast-conserving rates. Currently, a series of new drugs are being explored: for example, the application of CDK4/6 inhibitors in neoadjuvant treatment is a promising direction, and relevant genetic testing or mid-term effect evaluations can play supportive roles. Immunotherapy, as seen in the initial successes of CheckMate 7FL and KEYNOTE-756, still requires clear identification of the most responsive populations. Additionally, antibody-drug conjugates (ADCs) targeting low HER2 expression have shown some effectiveness in advanced HR+/HER2- breast cancer, and their application in early-stage disease is a future direction to consider.
Overall, the prognosis of HR+/HER2- breast cancer is relatively good. For some patients requiring downstaging, neoadjuvant therapy opens a window when we explore how to implement subsequent intensified adjuvant treatment strategies.
Dr. Zhaoqing Fan
- PhD, Chief Physician, Associate Professor, Master’s Supervisor
- Deputy Director of the Breast Cancer Prevention and Treatment Center, Peking University Cancer Hospital
- Standing Member of the Breast Cancer Professional Committee, Chinese Anti-Cancer Association
- Standing Member of the Breast Surgery Committee, Chinese Medical Doctor Association
- Director of the Breast Cancer Multidisciplinary Diagnosis and Treatment Group, China Medical Education Association
- Standing Member of the Breast Disease Branch, China International Exchange and Promotive Association for Medical and Health Care
- Vice President of the Beijing Cancer Prevention and Treatment Society
