Dataset Information

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis.

ABSTRACT: BACKGROUND:To investigate the efficacy of neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET) and neoadjuvant chemoendocrine therapy (NCET) on the tumour response, including pathological complete response (pCR) rate and overall response rate (ORR), in postmenopausal women with hormone receptor (HR)-positive breast cancer. METHODS:Based on a PRISMA-IPD statement, the PubMed, Embase and Cochrane Library databases were used to identify eligible trials published from inception to 7 May 2019. Pooled odds ratio (OR) with 95% confidential interval (CI) was calculated to assess the pCR rate and ORR of tumours among those three treatments via fixed- or random-effect Mantel-Haenszel models in terms of a Heterogeneity Chi2 test with a significant level of p?

SUBMITTER: Wang Y

PROVIDER: S-EPMC6993383 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis.

Wang Yaling Y He Lin L Song Yuhua Y Wu Qian Q Wang Haiji H Zhang Biyuan B Ma Xuezhen X

BMC women's health 20200131 1

<h4>Background</h4>To investigate the efficacy of neoadjuvant chemotherapy (NCT), neoadjuvant endocrine therapy (NET) and neoadjuvant chemoendocrine therapy (NCET) on the tumour response, including pathological complete response (pCR) rate and overall response rate (ORR), in postmenopausal women with hormone receptor (HR)-positive breast cancer.<h4>Methods</h4>Based on a PRISMA-IPD statement, the PubMed, Embase and Cochrane Library databases were used to identify eligible trials published from i ...[more]

PMID: 32005117

Similar Datasets

Project description:BackgroundResistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.MethodsIn this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.ResultsBaseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval [CI], 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).ConclusionsEverolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).

Project description:Breast cancer (BC) is currently the most frequently diagnosed cancer and the primary cause of cancer-related death among women worldwide. Human epidermal growth factor receptor type 2 (HER2)-positive BC accounts for 14.5-15% of all BCs, with a relatively poor prognosis. Neoadjuvant therapy (NAT) has become a preferred treatment option for HER2+ BCs. With the continuous emergence of various clinical trials and new treatment concepts in BC, the NAT model has changed from chemotherapy alone to the neoadjuvant combination of anti-HER2-targeted therapy with chemotherapy, neoadjuvant endocrine therapy, and so on. Therefore, an up-to-date review is needed to inform the selection of NAT strategies for HER2+ BCs. This review was administrated with literature from the PubMed database. Manuscripts were searched using the following keywords: "neoadjuvant" or "preoperative", "breast cancer" or "breast neoplasm", "HER2+" or "HER2-positive", titles and abstracts were screened and evaluated independently by two authors. Information relating to the efficacy and safety profile of NAT for patients with HER2+ BCs were included and analyzed qualitatively. Only English-language articles were included. This review discusses the neoadjuvant situation for the surgical management of HER2-positive BCs around the world. In this paper, we describe the efficacy assessment of NAT, analyze clinical effect and toxicity of chemotherapy, and targeted therapy, including monoclonal antibody, tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), and other neoadjuvant treatments in HER2+ BC. The data shows while overall survival is the standard endpoint for efficacy, pathological complete response have been implemented more and more frequently in clinical trials for its convenience. Dual-targeted therapy plus chemotherapy exhibited favorable efficacy in most cases, meanwhile other treatment strategies such as combinations without chemotherapy or including CDK4/6 agents may be applicable in specific situation. As an important part of BC treatment, NAT is lingering in the stage of continuous development, especially for patients with HER2-positive BC. The challenges we are facing today in this field are dose de-escalation without reducing efficacy and choose suitable combination of agents in clinical practice. Moreover, new biomarkers are warrant for individualize treatment.

Project description:BackgroundAndrogen receptors (AR) are frequently expressed in breast cancers, but their implication in cancer growth is still controversial. In the present study, we further investigated the role of the androgen/AR pathway in breast cancer development.MethodsAR expression was evaluated by immunochemistry in a cohort of 528 postmenopausal breast cancer patients previously examined for the association of serum testosterone levels with patient and tumor characteristics. AR expression was classified according to the percentage of stained cells: AR-absent (0%) and AR-poorly (1%-30%), AR-moderately (>30%-60%), and AR-highly (>60%) positive.ResultsStatistical analysis was performed in 451 patients who experienced natural menopause. AR-high expression was significantly related with low histologic grade and estrogen receptor (ER)- and progesterone receptor (PR)-positive status (P trend<0.001). Mean testosterone levels were significantly higher in the AR-high category than in the other categories combined (P=0.022), although a trend across the AR expression categories was not present. When women defined by ER status were analyzed separately, regression analysis in the ER-positive group showed a significant association of high testosterone levels with AR-highly-positive expression (OR 1.86; 95% CI, 1.10-3.16), but the association was essentially due to patients greater than or equal to 65 years (OR 2.42; 95% CI, 1.22-4.82). In ER-positive group, elevated testosterone levels appeared also associated with AR-absent expression, although the small number of patients in this category limited the appearance of significant effects (OR 1.92; 95% CI, 0.73-5.02): the association was present in both age groups (<65 and ≥65 years). In the ER-negative group, elevated testosterone levels were found associated (borderline significance) with AR-absent expression (OR 2.82, 95% CI, 0.98-8.06). In this ER-negative/AR-absent subset of tumors, elevated testosterone levels cannot stimulate cancer growth either directly or after conversion into estrogens, but they probably induce increased synthesis of some other substance that is responsible for cancer growth through binding to its specific receptor.ConclusionsThe findings in the present study confirm that testosterone levels are a marker of hormone-dependent breast cancer and suggest that the contemporary evaluation of ER status, AR expression, and circulating testosterone levels may identify different subsets of cancers whose growth may be influenced by androgens.

Project description:BackgroundPostmenopausal women with large, hormone receptor (HR)-positive/HER2-negative and low-proliferative breast cancer derived a benefit from neoadjuvant endocrine therapy (NET) in the CARMINA02 trial. This study was designed to correlate gene expression and mutation profiles with both response to NET and prognosis.MethodsGene expression profiling using RNA sequencing was performed in 86 pre-NET and post-NET tumor samples. Targeted next-generation sequencing of 91 candidate breast cancer-associated genes was performed on DNA samples from 89 patients. Molecular data were correlated with radiological response and relapse-free survival.ResultsThe transcriptional profile of tumors to NET in responders involved immune-associated genes enriched in activated Th1 pathway, which remained unchanged in non-responders. Immune response was confirmed by analysis of tumor-infiltrating lymphocytes (TILs). The percentage of TILs was significantly increased post-NET compared to pre-NET samples in responders (p = 0.0071), but not in non-responders (p = 0.0938). Gene expression revealed that lipid metabolism was the main molecular function related to prognosis, while PPARγ is the most important upstream regulator gene. The most frequently mutated genes were PIK3CA (48.3%), CDH1 (20.2%), PTEN (15.7%), TP53 (10.1%), LAMA2 (10.1%), BRCA2 (9.0%), MAP3K1 (7.9%), ALK (6.7%), INPP4B (6.7%), NCOR1 (6.7%), and NF1 (5.6%). Cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway were altered significantly more frequently in non-responders than in responders (p = 0.0017 and p = 0.0094, respectively). The average number of mutations per sample was significantly higher in endocrine-resistant tumors (2.88 vs. 1.64, p = 0.03), but no difference was observed in terms of prognosis. ESR1 hotspot mutations were detected in 3.4% of treatment-naive tumors.ConclusionsThe Th1-related immune system and lipid metabolism appear to play key roles in the response to endocrine therapy and prognosis in HR-positive/HER2-negative breast cancer. Deleterious somatic mutations in the cell cycle and apoptosis pathway and PIK3CA/AKT/mTOR pathway may be relevant for clinical management.Trial registrationThis trial is registered with ClinicalTrials.gov ( NCT00629616 ) on March 6, 2008, retrospectively registered.

Dataset Information

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis.

Publications

The tumour response of postmenopausal hormone receptor-positive breast cancers undergoing different types of neoadjuvant therapy: a meta-analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets