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Open research questions in Advanced Breast Cancer Therapies

118 unresolved questions extracted from the limitations and future-work sections of 339 Advanced Breast Cancer Therapies papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The lack of effective treatment options for triple-negative breast cancer. The need for new, potent, and less toxic therapeutic modalities. The limited understanding of the molecular mechanisms underlying TNBC.

    Untargeted metabolomics and network pharmacology unveil AKT1 inhibition by Kanchanara Guggulu in triple-negative breast cancer · 2026 · DOI

  • The study notes that spontaneous reporting data cannot establish causality or estimate incidence. The analysis is limited by the spontaneous reporting nature of FAERS and the absence of reliable exposure denominators.

    Distinct renal adverse event profiles among CDK4/6 inhibitors: a comparative pharmacovigilance analysis · 2026 · DOI

  • Further studies are needed to establish causality and estimate incidence of renal adverse events, - Investigation of the mechanisms underlying the heterogeneous renal toxicities associated with CDK4/6 inhibitors, - Comparison of renal adverse event reporting patterns among different patient populations

    Distinct renal adverse event profiles among CDK4/6 inhibitors: a comparative pharmacovigilance analysis · 2026 · DOI

  • The MAP kinase ERK5 promotes tumor progression by driving cell-cycle progression, yet its functional interplay with CDK4/6-dependent cell cycle control remains poorly defined.

    ERK5 inhibition triggers CDK6 proteasomal degradation and enhances palbociclib efficacy in cancer cells · 2026 · DOI

  • This therapy is not always effective, and in every patient, resistance ultimately occurs, but the underlying resistance mechanisms remain unclear.

    Gene expression analysis in circulating tumour cells to determine resistance to CDK4/6 inhibitors plus endocrine therapy in HR + /HER2- metastatic breast cancer patients · 2025 · DOI

  • Encapsulated papillary carcinoma (EPC) is a rare subtype that typically exhibits indolent behavior, but its aggressive course remains poorly understood.

    Case Report: Pure Encapsulated Papillary Carcinoma of the Breast in a Centenarian: A Case Report of Distant Metastasis After Surgery, and review of literature · 2025 · DOI

  • However, optimal therapy after tumor progression to ET plus CDK4/6i remains unclear.

    Survival Following CDK4/6 Inhibitor Therapy for Hormone Receptor–Positive, ERBB2–Negative Metastatic Breast Cancer · 2025 · DOI

  • The pathogenesis of a malignant tumor is complex and has not been fully elucidated.

    Cell cycle checkpoint revolution: targeted therapies in the fight against malignant tumors · 2024 · DOI

  • However, the efficacy and safety of this approach in elderly patients (≥70 years) remain unclear, particularly in the context of real-world clinical practice.

    Evaluating CDK4/6 Inhibitor Therapy in Elderly Patients with Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer: A Retrospective Real-World Multicenter Study · 2024 · DOI

  • Further investigation of the BMX-E2F1 axis as a potential target for overcoming chemoresistance in SCLC. The development of novel therapies targeting the BMX-E2F1 axis.

    BMX inhibition overcomes small cell lung cancer chemoresistance by stabilizing E2F1 via ERK1/2-Cyclin D1/CDK4/6 axis · 2026 · DOI

  • The lack of effective treatments for SCLC due to chemoresistance. The need for novel therapeutic targets for SCLC.

    BMX inhibition overcomes small cell lung cancer chemoresistance by stabilizing E2F1 via ERK1/2-Cyclin D1/CDK4/6 axis · 2026 · DOI

  • Accurate receptor evaluation is necessary for guiding treatment selection. Triple-negative breast cancer has limited treatment options. Hormone receptor-negative tumours have poorer prognoses.

    Prognostic Features and Clinical Outcomes Across Breast Cancer Subtypes Defined by Hormone Receptor and HER2 Status: A Literature Review · 2026 · DOI

  • There is a need to understand the differences in treatment response and prognosis between hormone-responsive and unresponsive breast cancer subtypes. There is a need for accurate receptor evaluation in guiding treatment selection.

    Prognostic Features and Clinical Outcomes Across Breast Cancer Subtypes Defined by Hormone Receptor and HER2 Status: A Literature Review · 2026 · DOI

  • The absence of molecular profiling is a major limitation of this case. The patient declined further genetic testing for personal and financial reasons. The study is based on a single case report.

    Sequential CDK4/6 inhibition in bone-only metastatic HR+/HER2- breast cancer: a case of prolonged disease control with abemaciclib after clinical progression on palbociclib-based therapy · 2026 · DOI

  • Limited evidence is available for the efficacy of sequential CDK4/6 inhibition in patients with bone-only metastatic HR+/HER2- breast cancer. The optimal treatment strategy for patients with bone-only metastatic HR+/HER2- breast cancer remains unclear.

    Sequential CDK4/6 inhibition in bone-only metastatic HR+/HER2- breast cancer: a case of prolonged disease control with abemaciclib after clinical progression on palbociclib-based therapy · 2026 · DOI

  • Further investigation of the molecular characteristics of individual tumors to inform personalized medicine approaches. Development of new therapeutic strategies targeting specific resistant cell-states.

    Endocrine therapy-specific lineage and partial epithelial-mesenchymal reprogramming defines divergent resistant cell-states in ER+ breast cancer · 2026 · DOI

  • Acquired resistance to CDK4/6i remains a major challenge. Identifying patients who derive limited benefit from CDK4/6i is crucial. The lack of reliable biomarkers for prognostic stratification.

    Positron-emission tomography as a predictor of response to first-line cyclin-dependent kinase 4/6 inhibitors in patients with metastatic ER-positive HER2-negative breast cancer · 2026 · DOI

  • The lack of reliable biomarkers for prognostic stratification in patients receiving CDK4/6i. The need for novel approaches to identifying individuals at elevated risk of early disease progression. The importance of investigating the prognostic value of SUVmax in patients with ER-positive HER2-negative breast cancer.

    Positron-emission tomography as a predictor of response to first-line cyclin-dependent kinase 4/6 inhibitors in patients with metastatic ER-positive HER2-negative breast cancer · 2026 · DOI

  • The lack of standardized therapeutic approaches for TNBC. The need for non-invasive predictors of chemotherapy sensitivity in TNBC patients.

    Prediction of response to neoadjuvant chemotherapy for triple-negative breast cancer using nuclear magnetic resonance-based urine metabolomics and self-organizing maps · 2026 · DOI

  • The safety of omitting ALND is contingent upon the administration of appropriate radiotherapy. In resource-limited settings, the direct application of the SENOMAC protocol requires caution. The small absolute gain of 0.7 months in the postMONARCH trial raises questions about its universal clinical utility.

    Breast cancer in 2025: navigating new horizons of precision-guided de-escalation · 2026 · DOI

  • The field of locoregional management is undergoing a paradigm shift towards surgical de-escalation. The narrative has shifted from the initial adoption of CDK4/6 inhibitors to refining their use in the adjuvant setting.

    Breast cancer in 2025: navigating new horizons of precision-guided de-escalation · 2026 · DOI

  • CDK4/6i treatment can be associated with adverse events. Patients with metastatic cancer at initial diagnosis may have a poorer prognosis. The optimal dosing and scheduling of CDK4/6i is unclear.

    Real-World Data on the Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced/Metastatic Breast Cancer · 2026 · DOI

  • There is a need for real-world data on the use of CDK4/6i in HR+/HER2- a/mBC patients. Previous studies have been limited to randomized clinical trials.

    Real-World Data on the Use of Cyclin-Dependent Kinase 4/6 Inhibitors in Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced/Metastatic Breast Cancer · 2026 · DOI

  • Future research should investigate the long-term outcomes of patients receiving palbociclib and ribociclib. Future research should explore the factors that influence progression-free survival rates in larger patient populations.

    Real world experience with cyclin dependent kinase inhibitors in metastatic breast cancer in India · 2026 · DOI

  • The study identifies a gap in understanding the real-world experience with cyclin dependent kinase 4/6 inhibitors in India. The study highlights the need for more research on the effectiveness of these inhibitors in Indian patients.

    Real world experience with cyclin dependent kinase inhibitors in metastatic breast cancer in India · 2026 · DOI

Most-cited papers in Advanced Breast Cancer Therapies

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118 open questions have been extracted from the limitations and future-work passages of 339 Advanced Breast Cancer Therapies papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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