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New Strategies in Metastatic Hormone Receptor-Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies.

ABSTRACT: Although major advances in our understanding of the molecular underpinnings of hormone receptor-positive (HR+) breast cancer have led to new therapies that have substantially improved patient outcomes, endocrine-resistant disease still remains a leading cause of breast cancer mortality. Comprehensive molecular profiling of breast cancers has highlighted tremendous tumor heterogeneity, and analysis of paired primary and metastatic tumors has shown the evolution that can occur during acquired resistance to systemic therapies. Novel techniques for monitoring tumor load under treatment pressure, including "liquid biopsy" techniques, such as circulating free tumor DNA (cfDNA) and circulating tumor cells, have shown promise as biomarkers to direct treatment without invasive tumor biopsies. However, more research is needed to deepen our understanding of breast cancer alterations under treatment pressure to reveal mechanisms of drug resistance and apply precision medicine in biomarker-driven clinical trials. Clin Cancer Res; 23(5); 1126-31. ©2016 AACR.

SUBMITTER: Jankowitz RC

PROVIDER: S-EPMC5350010 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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New Strategies in Metastatic Hormone Receptor-Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies.

Jankowitz Rachel C RC Oesterreich Steffi S Lee Adrian V AV Davidson Nancy E NE

Clinical cancer research : an official journal of the American Association for Cancer Research 20161215 5

Although major advances in our understanding of the molecular underpinnings of hormone receptor-positive (HR<sup>+</sup>) breast cancer have led to new therapies that have substantially improved patient outcomes, endocrine-resistant disease still remains a leading cause of breast cancer mortality. Comprehensive molecular profiling of breast cancers has highlighted tremendous tumor heterogeneity, and analysis of paired primary and metastatic tumors has shown the evolution that can occur during ac ...[more]

PMID: 27979914

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Project description:We aimed to explore what kind of endocrine treatments are optimal for hormone receptor-positive and human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer in some specific clinical situations. We searched randomized controlled trials in Embase, Medline, the Cochrane library, and PubMed from inception to April 1, 2020 and performed a network meta-analysis based on a Bayesian fixed-effects model. Progression-free survival (PFS) with hazard ratios and corresponding 95% confidence interval was defined as the primary endpoint, while overall survival (OS), objective response rate (ORR), clinical benefit rate and serious adverse events were used as secondary endpoints. A total of 35 studies involving 12,285 patients and 24 treatment options were included. In general, most co-treatment options prolonged PFS compared to single-agent therapy, of which aromatase inhibitor (AI) plus everolimus and fulvestrant plus palbociclib were probably the most effective agents, and the latter had the best safety record. However, despite the superior efficacy of fulvestrant plus capecitabine for PFS and OS, palpable toxic effects have been demonstrated for this treatment, so its application must be scrupulously considered. The results of subgroup analysis indicated that fulvestrant combined with palbociclib improved prognosis for phosphatidylinositol 3-kinase (PI3K)-mutated patients, PI3K-unmutated patients, patients with endocrine therapy resistance, and visceral metastatic patients, while no obvious improvement was detected in OS. Moreover, the efficacy of fulvestrant plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors was slightly better than that of AI plus CDK4/6 inhibitors, while AI plus everolimus was more efficacious than fulvestrant combined with everolimus in terms of PFS, OS, and ORR. In conclusion, our results provide moderate evidence that fulvestrant plus palbociclib and AI plus everolimus were the most effective treatments, while the efficacy and safety of fulvestrant plus palbociclib was obviously superior in some specific clinical situations.

Dataset Information

New Strategies in Metastatic Hormone Receptor-Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies.

Publications

New Strategies in Metastatic Hormone Receptor-Positive Breast Cancer: Searching for Biomarkers to Tailor Endocrine and Other Targeted Therapies.

Similar Datasets

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