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Open research questions in Advanced Breast Cancer Therapies

288 gap statements mined from Advanced Breast Cancer Therapies papers in our 7.9M-paper local library, which holds 1,374 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.

Choosing where to publish on Advanced Breast Cancer Therapies? See the ranked Medicine journals.

What the literature leaves open

  • To our knowledge, no studies have quantified health care resource utilization (HRU) or economic burden following CDK4/6i initiation in the Medicare population.

    Health care resource utilization and costs of Medicare-enrolled patients with HR+/HER2− metastatic breast cancer treated with a CDK4/6i in the first-line setting · 2025 · DOI

  • Biomarker analyses to optimally identify patients suitable for this approach yielded inconsistent findings that do not apply to daily clinical decision making.

    Unveiling the Potential of Cyclin-Dependent Kinases 4 and 6 Inhibitors Beyond Progression in Hormone Receptor Positive/Human Epidermal Growth Factor Negative Advanced Breast Cancer – A Clinical Review · 2024 · 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

  • 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 fact that the study group under examination was quite heterogeneous is a limitation of this study, but it also shows how RWD can differ from RCTs and illustrates the benefit of this analysis.

    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 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

  • The treatment of HR+/HER2- breast cancer is complex and involves multiple factors. The use of CDK4/6 inhibitors is associated with increased toxicity. The paper highlights the need for individualized risk–benefit assessment in EBC.

    Efficacy and Toxicity of CDK4/6 Inhibitors in Early and Metastatic HR+/HER2− Breast Cancer: An Updated Meta-Analysis of Phase III Trials · 2026 · DOI

  • Future research should focus on optimizing treatment sequences and identifying predictive biomarkers to guide therapy selection, ultimately improving outcomes for patients with HR+/HER2- MBC.

    Subsequent Treatments After Progression on Cyclin-Dependent Kinase 4/6 Inhibitors: A Review of the Evidence and a Real-World Data Perspective From Portuguese Hospitals · 2026 · DOI

  • 4% of patients, it demonstrated a survival advantage that warrants further investigation, especially given the limitations of CDK4/6i trials in addressing optimal sequencing.

    Subsequent Treatments After Progression on Cyclin-Dependent Kinase 4/6 Inhibitors: A Review of the Evidence and a Real-World Data Perspective From Portuguese Hospitals · 2026 · DOI

  • Further investigations should be carried out in tackling other CDKs such as CDK2, CDK9, and utilizing the PROTAC technology to degrade the proteins of CDK. The development of next-generation, highly selective inhibitors remains a critical objective. Although the CDK4/6 inhibitors have been successful, there is a clear need for other oncogenic CDK (e.g., CDK2, or CDK9) inhibitors with little off-target activity.

    Targeting Cyclin-Dependent Kinases (CDKs) for Cancer Therapy: An In-Depth Review of Molecular Candidates, Their Synthesis, Evaluation, and Future Directions · 2026 · DOI

  • The clinical implications of BMI in patients with hormone receptor–positive, HER2-negative metastatic breast cancer remain incompletely defined, particularly in the context of CDK4/6 inhibitor therapy.

    Association between obesity and outcomes of first-line CDK4/6 inhibitor therapy in metastatic breast cancer: a multicenter real-world study · 2026 · DOI

  • This is a single-case clinical observation, which has limited generalizability. The rarity of primary metastatic ulcerative breast cancer makes it difficult to draw conclusions.

    An Extreme Clinical Diagnosis: Primary Metastatic Breast Cancer with Complete Bilateral Breast Contour Elimination and Ulceration · 2026 · DOI

  • Limited understanding of the clinical benefit of palbociclib retreatment after abemaciclib exposure in hormone receptor-positive, HER2-negative metastatic breast cancer. Need for evaluation of overall survival and time to treatment failure on CDK4/6i retreatment in different patient cohorts.

    Clinical benefit of palbociclib retreatment after abemaciclib exposure in hormone receptor positive, HER2 negative metastatic breast cancer · 2026 · DOI

  • Vitiligo-like lesions are a rare and underrecognized dermatologic adverse event associated with CDK4/6i.

    Late-onset Vitiligo Associated with Prolonged Ribociclib Therapy in Metastatic Breast Cancer: A Case Report · 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

  • There are no specific evidence-based treatment guidelines available for primary metastatic ulcerative breast cancer. Published studies on therapeutic strategies for fungating and ulcerating breast cancers have high heterogeneity and low level of evidence.

    An Extreme Clinical Diagnosis: Primary Metastatic Breast Cancer with Complete Bilateral Breast Contour Elimination and Ulceration · 2026 · 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

  • 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

  • Limited number of cases in cohort 1, - Retrospective design of the study, - No patients were treated for adjuvant disease, - Ribociclib was not included…

    Clinical benefit of palbociclib retreatment after abemaciclib exposure in hormone receptor positive, HER2 negative metastatic breast cancer · 2026 · DOI

Most-cited papers in Advanced Breast Cancer Therapies

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Open questions raised by papers listed on this page include: (1) The lack of effective treatments for SCLC due to chemoresistance (“BMX inhibition overcomes small cell lung cancer chemoresistance by stabilizing…”, 2026); (2) There is a need to understand the differences in treatment response and prognosis between hormone-responsive and unresponsive breast cancer subtypes (“Prognostic Features and Clinical Outcomes Across Breast Cancer Subtypes Defined…”, 2026); (3) The lack of reliable biomarkers for prognostic stratification (“Positron-emission tomography as a predictor of response to first-line…”, 2026); (4) Future research should investigate the long-term outcomes of patients receiving palbociclib and ribociclib (“Real world experience with cyclin dependent kinase inhibitors in metastatic…”, 2026); (5) Future research should focus on optimizing treatment sequences and identifying predictive biomarkers to guide therapy selection, ultimately improving outcomes for patients with HR+/HER2- MBC (“Subsequent Treatments After Progression on Cyclin-Dependent Kinase 4/6…”, 2026). 288 gap statements have been mined from Advanced Breast Cancer Therapies papers in our 7.9M-paper local library, which holds 1,374 papers on the topic; the gaps come from whichever of those papers state one. They are mostly the research gaps the authors state and the papers' abstracts, plus future-work, limitations and challenges passages. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one, so you can read the original claim in context.

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