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Updated: Aug 16, 2025
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Endocrine Therapy-Based Strategies for Metastatic Breast Cancer with Different Endocrine Sensitivity Statuses: A
Jiani Wang1, Yiqun Han1, Jiayu Wang1
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Background:
Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (mBC).
Methods:
We performed a systematic search with a predefined search strategy in PubMed, Embase and Cochrane CENTRAL databases to perform a network meta-analysis and evaluate the relative efficacies of ET-based treatment regimens in HR+/HER2- mBC patients with different endocrine sensitivity statuses. The study was registered in the PROSPERO database (CRD42021235570).
Results:
A total of 47 trials (20,267 patients) were included. Analysis of progression-free survival (PFS) in endocrine therapy-sensitive (ETS) patients revealed cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) + fulvestrant 500 mg (Ful 500) (random effect (RE): hazard ratio (HR), 0.46; 95% credibility interval (CrI), 0.27-0.78; surface under the cumulative ranking curve (SUCRA), 0.93; fixed effect (FE): HR, 0.48; 95% CrI, 0.40-0.58; SUCRA, 0.99) to be the best therapy followed by CDK4/6i + aromatase inhibitors (AIs) (RE: HR, 0.53; 95% CrI, 0.40-0.72; SUCRA, 0.86; FE: HR, 0.54; 95% CrI, 0.48-0.61; SUCRA, 0.91). Chemotherapy followed by CDK4/6i + Ful 500 appears to be the most effective option for the endocrine therapy-resistant (ETR) group. Analysis of overall survival revealed CDK4/6i + Ful 500 (SUCRA: 0.99) and AKTi + Ful 500 (SUCRA: 0.87) to be the first-rank regimen for the ETS group and ETR groups, respectively.
Conclusion:
Our comprehensive analysis suggests that CDK4/6i combined with ETs may be the best treatment option in terms of PFS for ETS patients and chemotherapy for ETR patients with HR+/HER2- mBC. Different endocrine sensitivity statuses required various optimal treatment strategies, which may provide guidance for clinical practice.
Insights
For hormone receptor-positive/HER2-negative metastatic breast cancer, cyclin-dependent kinases 4/6 inhibitors plus endocrine therapies improve progression-free survival in endocrine-sensitive patients. Chemotherapy is recommended for endocrine-resistant patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advancements in endocrine therapies (ETs) and targeted regimens have significantly improved outcomes for hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (mBC).
- Tailoring treatment strategies based on endocrine sensitivity is crucial for optimizing patient outcomes in HR+/HER2- mBC.
Purpose of the Study:
- To evaluate the relative efficacies of various ET-based treatment regimens for HR+/HER2- mBC patients.
- To compare treatment outcomes based on different endocrine sensitivity statuses (endocrine-sensitive vs. endocrine-resistant).
Main Methods:
- A systematic literature search was conducted across PubMed, Embase, and Cochrane CENTRAL databases.
- A network meta-analysis was performed on data from 47 trials involving 20,267 patients.
- Progression-free survival (PFS) and overall survival were analyzed as primary endpoints.
Main Results:
- In endocrine-sensitive patients, cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) + fulvestrant demonstrated superior PFS compared to other regimens.
- For endocrine-resistant patients, chemotherapy followed by CDK4/6i + fulvestrant emerged as the most effective option for PFS.
- CDK4/6i + fulvestrant and AKT inhibitors + fulvestrant showed the best overall survival outcomes for endocrine-sensitive and endocrine-resistant groups, respectively.
Conclusions:
- CDK4/6i combined with ETs represents a highly effective treatment strategy for improving PFS in endocrine-sensitive HR+/HER2- mBC.
- Chemotherapy is a viable and effective option for endocrine-resistant HR+/HER2- mBC patients.
- Treatment decisions should be individualized based on the patient's endocrine sensitivity status to optimize therapeutic strategies.
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