Breast cancer is one of the most common malignant tumors among women worldwide, and its treatment has been a key focus in the medical field. With ongoing research, significant progress has been made in treatment options for HR+/HER2- advanced breast cancer, especially with the application of CDK4/6 inhibitors combined with endocrine therapy (ET), offering patients longer survival periods. However, the optimization of treatment plans and the improvement of patient survival and quality of life remain critical issues in the field of breast cancer treatment. At the 2025 North-South Summit – 7th Breast Cancer Forum, Oncology Frontier had the privilege of interviewing Dr. Man Li from The Second Affiliated Hospital of Dalian Medical University, who shared insights into recent research progress and discussed her participation in the “2025 International Breast Cancer Consensus Prospective Voting” session.Oncology Frontier: CDK4/6 inhibitors have shown significant efficacy in the treatment of HR+/HER2- advanced breast cancer. How do you view the role of CDK4/6 inhibitors in future treatment strategies? Are there any new combination therapies worth anticipating?
Dr. Man Li: With the publication of the results from series studies like PALOMA, MONALEESA, MONARCH, and DAWNA, CDK4/6 inhibitors combined with endocrine therapy (ET) have become the first-line treatment of choice for HR+/HER2- advanced breast cancer. The combination not only improves progression-free survival (PFS) but also has the potential to translate PFS into overall survival (OS) benefits, thus extending survival for more patients.
In clinical practice, when treating HR+/HER2- advanced breast cancer patients, we typically opt for CDK4/6 inhibitors combined with ET as the first-line treatment. However, regrettably, many patients—particularly those with primary or secondary endocrine resistance—experience relatively short PFS with CDK4/6 inhibitors in the first-line setting. This raises the important question of how to select the next line of treatment for these patients.
With the publication of the INAVO120 clinical study results, we may have found a better answer. This study included patients with PIK3CA mutations and HR+/HER2- breast cancer who had localized recurrence or distant metastasis within 12 months after postoperative endocrine therapy, and who had not previously received CDK4/6 inhibitors. Patients were randomized in a 1:1 ratio to receive either the Inavolisib group (Inavolisib + Palbociclib + Fulvestrant) or the placebo group (placebo + Palbociclib + Fulvestrant) as first-line treatment. The results showed that the PFS of the Inavolisib + Palbociclib + Fulvestrant group was almost doubled compared to the placebo group (median PFS: 15.0 months vs. 7.3 months, HR 0.43, P<0.001). These results suggest that for patients who initially receive CDK4/6 inhibitors, additional therapies may be needed in the future. For those with primary or secondary endocrine resistance and PIK3CA mutations, it may be a good choice to combine CDK4/6 inhibitors with PI3K inhibitors and ET.
Oncology Frontier: For HR+/HER2- advanced breast cancer patients, endocrine therapy remains the cornerstone of treatment. What innovations and breakthroughs do you foresee in endocrine therapy? How can we better improve patient adherence to treatment and quality of life?
Dr. Man Li: Indeed, endocrine therapy remains a cornerstone treatment for HR+/HER2- breast cancer. With the widespread use of aromatase inhibitors (AIs) and Fulvestrant, endocrine therapy has become the best companion for CDK4/6 inhibitors. However, the efficacy of endocrine therapy is limited, and there is considerable potential for further optimization and innovation.
With the publication of the EMERALD trial results, we can see that oral SERDs (Selective Estrogen Receptor Degraders), such as Elacestrant, show better treatment outcomes in the post-CDK4/6 inhibitor era. The presentation of the EMBER-3 study results at the 2024 SABCS meeting also highlighted the extended PFS in ESR1 mutation patients when using Imlunestrant combined with Abemaciclib, compared to Imlunestrant monotherapy (9.4 months vs. 5.5 months, HR 0.57, P<0.01). This indicates that oral SERD drugs, especially in combination with other treatments, are a promising option in the future.
Additionally, other new endocrine therapy agents, such as selective estrogen receptor antagonists, complete estrogen receptor antagonists, and proteolysis-targeting chimeras, are also promising. Clinical trials for these drugs are currently underway in phases I and II. In the future, these new endocrine therapy agents will provide more hope for HR+/HER2- advanced breast cancer patients.
Oncology Frontier: As an expert participant in the “2025 International Breast Cancer Consensus Prospective Voting,” could you share with us which aspects of HR+/HER2- breast cancer treatment you focused on during the voting session?
Dr. Man Li: The treatment of breast cancer, especially for patients with different molecular subtypes, has always been a major focus in clinical practice. Many issues are worth further exploration and discussion. Personally, I am particularly concerned with the adjuvant therapy for breast cancer patients.
For HR+/HER2- early breast cancer, especially those with 1 to 3 positive lymph nodes, there is still much room for discussion regarding treatment strategies. With the application of CDK4/6 inhibitors, a new issue has arisen: For patients at intermediate to high risk of recurrence, how long should endocrine therapy continue? Should we stick to the traditional 5-year treatment regimen, or is there a need to extend the treatment duration? Additionally, the treatment path following CDK4/6 inhibitor therapy is also an area that requires serious consideration.
Moreover, for HR+/HER2- early breast cancer patients with BRCA1/2 mutations and a high risk of recurrence, we face a dilemma in drug selection. Should we prioritize PARP inhibitors or CDK4/6 inhibitors? Should we consider combining these treatments, or should they be administered sequentially? These are important questions that need to be thoroughly explored, and I hope that the relevant votes and research will provide us with answers.
Dr. Man Li
- MD, Professor, PhD Supervisor
- Director of Oncology, Second Affiliated Hospital of Dalian Medical University
- Director of the Clinical Trial Unit (Phase I)
- Liaoning Provincial Distinguished Professor
- Standing Council Member of the Chinese Clinical Oncology Society
- Deputy Chair of the Breast Cancer Rehabilitation Professional Committee, Chinese Anti-Cancer Association
- Standing Committee Member of the Breast Cancer Expert Committee, Chinese Clinical Oncology Society
- Deputy Chair of the Oncology Branch, Liaoning Medical Association
- Deputy Chair of the Breast Cancer Professional Committee, Liaoning Anti-Cancer Association
- Chair of the Oncology Branch, Dalian Medical Association
