scholarly journals The Predictive Role of PIK3CA Mutation Status on PI3K Inhibitors in HR+ Breast Cancer Therapy: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Mingming Wang ◽  
Jin Li ◽  
Jiangsheng Huang ◽  
Mei Luo

Aim. To evaluate the impact of PIK3CA mutation status on clinical outcomes of HR+ breast cancer treated with PI3K inhibitors. Methods. A comprehensive literature search was conducted in online databases from inception to December 31, 2019. The main characteristics and prognostic data of each eligible study were extracted. The odds ratio (OR) for the overall response rate (ORR) and hazard ratio (HR) for progression-free survival (PFS) were estimated using the fixed-effects Mantel-Haenszel model. Results. A total of 8 studies involving 2670 patients were included for analysis. Overall, the clinical outcomes of PI3K inhibitors were significantly influenced by PIK3CA mutation status in HR+ breast cancer. After the treatment of PI3K inhibitors, HR+ breast cancer patients with PIK3CA mutations presented better ORR (PIK3CA-mutated group: OR=1.98 [95% CI, 1.46 to 2.70]; PIK3CA wild-type group: OR=1.09 [95% CI, 0.78 to 1.53]) and better PFS (PIK3CA-mutated group: HR=0.65 [95% CI, 0.55 to 0.76]; PIK3CA wild-type group: HR=0.87 [95% CI, 0.70 to 1.09]). No publication bias was detected for ORR and PFS in our analysis. Conclusion. In this meta-analysis, it suggests that the association between clinical outcomes of PI3K inhibitors and PIK3CA mutation status is dramatic. PIK3CA mutations were a favorable factor in the clinical outcomes of HR+ breast cancer treated with PI3K inhibitors.

2017 ◽  
Vol 17 (2) ◽  
pp. 217-225 ◽  
Author(s):  
Kejia Hu ◽  
David Frederick Callen ◽  
Jiayuan Li ◽  
Hong Zheng

Studies have shown that vitamin D could have a role in breast cancer survival; however, the evidence of the relationship between patients’ vitamin D levels and their survival has been inconsistent. This meta-analysis explores possible dose-response relationships between vitamin D levels and overall survival by allowing for differences in vitamin D levels among populations of the various studies. Studies relating vitamin D (25-OH-D [25-hydroxyvitamin D]) levels in breast cancer patients with their survival were identified by searching PubMed and Embase. A pooled HR (hazard ratio) comparing the highest with the lowest category of circulating 25-OH-D levels were synthesized using the Mantel-Haenszel method under a fixed-effects model. A two-stage fixed-effects dose-response model including both linear (a log-linear dose-response regression) and nonlinear (a restricted cubic spline regression) models were used to further explore possible dose-response relationships. Six studies with a total number of 5984 patients were identified. A pooled HR comparing the highest with the lowest category of circulating 25-OH-D levels under a fixed-effects model was 0.67 (95% confidence interval = 0.56-0.79, P < .001). Utilizing a dose-response meta-analysis, the pooled HR for overall survival in breast cancer patients was 0.994 (per 1 nmol/L), Pfor linear trend < .001. At or above a 23.3 nmol/L threshold, for a 10 nmol/L, 20 nmol/L, or 25 nmol/L increment in circulating 25-OH-D levels, the risk of breast cancer overall mortality decreased by 6%, 12%, and 14%, respectively. There was no significant nonlinearity in the relationship between overall survival and circulating 25-OH-D levels. Our findings suggest that there is a highly significant linear dose-response relationship between circulating 25-OH-D levels and overall survival in patients with breast cancer. However, better designed prospective cohort studies and clinical trials are needed to further confirm these findings.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1521-1521
Author(s):  
April Ann Nicole Rose ◽  
Christine Elser ◽  
Pamela Jean Goodwin

1521 Background: Vitamin D (VitD) is a circulating hormone known to regulate gene transcription in breast cancer (BC) cells. The association between VitD and BC risk has been extensively studied. Until recently, however, the role of VitD in BC progression and its association with clinical outcomes among BC patients was poorly understood. To assess these new developments, a systematic review and meta-analysis was performed. Methods: A systematic review and meta-analysis by searching MEDLINE (1982 – 2012), ASCO, and SABCS for abstracts (2009 – 2012), with the following keywords: “breast cancer” and “prognosis” or “survival”, and “vitamin D” or ”calcitriol.” Abstracts were scrutinized for reports correlating serum VitD levels with breast cancer clinical outcomes, including: disease-free survival (DFS) and overall survival (OS). Studies were included if serum VitD samples were taken shortly after diagnosis and survival data were reported. Meta-analyses were performed using an inverse-variance weighted fixed-effects model. Results: We identified 7 studies reporting correlative data between serum VitD levels and BC survival. These data included 4,885 patients evaluated for DFS and 3858 patients evaluated for OS. VitD-deficiency was defined as <30ng/mL, <20ng/mL, and <14ng/mL in 3, 3, and 1 studies, respectively, and was identified in an average of 48.1% of patients (range: 17.9-87.8%). VitD deficiency was associated with a pooled hazard ratio (HR) of 2.13 (CI: 1.64 - 2.78) and 1.76 (CI: 1.35 - 2.30) for DFS and OS, respectively. Conclusions: To our knowledge, this is the first report of a meta-analysis of the relationship between serum VitD and BC prognosis. The prevalence of VitD-deficiency varied widely across studies and may reflect differences in geographic location, race, and rates of supplementation across patient populations. These findings support the hypothesis that VitD-deficient breast cancer patients have poorer clinical outcomes than VitD sufficient patients; but do not establish whether this relationship is causative. Further studies are warranted to investigate the possible protective effects of VitD supplementation on survival among VitD-deficient BC patients.


2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shu Wang ◽  
Mingyue Liu ◽  
Siheng Lian ◽  
Naiming Liu ◽  
Guibin Zhang ◽  
...  

Objective. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a promising treatment target for patients with breast cancer (BC). Our study aimed to evaluate the most effective and safe PI3K inhibitor for patients with BC, especially in PIK3CA mutation. Methods. Electronics databases were systematically searched from their inception to June 2020 for published randomized controlled trials (RCTs) comparing PI3K inhibitor therapy versus non-PI3K inhibitor therapy in patients with BC that mentioned or reported data of PIK3CA-mutated patient subgroups. Eligible RCTs had to report at least one of the following clinical outcomes: objective response rate (ORR), progression-free survival (PFS), or adverse events (AE). Results. Nine eligible RCTs involving 3872 BC patients and four PI3K inhibitor therapy arms (i.e., alpelisib, buparlisib, pictilisib, and taselisib) were included. In evaluating ORR, beneficial significant results of PI3K inhibitors could be found in the PIK3CA mutated group (1.952, 1.012 to 3.766); analogous results could also be found in 6m-PFS (1.519, 1.144 to 2.018) and PFS from HR data (-0.346, -0.525 to -0.168). From pairwise and network meta-analyses, buparlisib showed the most favorable ORR, as it was significantly different from fulvestrant in the PIK3CA-mutated patient group (2.80, 1.56 to 5.03). Alpelisib ranked first in the assessment of 6m-PFS and was significantly different from fulvestrant in the PIK3CA-mutated group (2.33, 1.45 to 3.44). The above PI3K inhibitors had good safety with few serious AEs. PROSPERO registration CRD42020193932. Conclusion. The PI3K inhibitors alpelisib and buparlisib appear to have superior efficacy and safety therapeutic choices for patients with BC, especially in PIK3CA-mutated patients.


2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lingling Qiu ◽  
Ya li Xu ◽  
Song hu Kong ◽  
Jie xiu Zhao

Objective Breast cancer is one of the most common malignant tumors that threaten the physical and mental health and even life-threatening of women worldwide.Chronic inflammation plays a key role in the occurrence, progression and recurrence of cancer.Several sources of evidence indicate that exercise during and after breast cancer could positively modulate the tumor microenvironment. The purpose of this meta-analysis is to determine the impact of exercise training on inflammatory factors in breast cancer patients. Methods We systematically searched the relevant randomized controlled trials published from January 1990 to June 2017 and analyzed them by Pubmed、Embase、Web of Science and Cochrane Library.The combination of Breast Cancer and Exercise is used for retrieval.The search term used for Pub Med is:(Exercise[Me SH] OR Physical Activity[Text Word] OR Training [Text Word] OR Activity [Text Word] OR Sport[Text Word] AND Breast Cancer[Text Word] OR Breast Tumor [Text Word] OR Breast Neoplasm [Text Word] OR Mammary Cancer [Text Word] OR Malignant Neoplasm of Breast [Text Word] OR Breast Carcinoma [Text Word] AND Interleukins [Text Word] OR IL [Text Word]).And manually check the references in the article to identify additional articles. Examination of titles and abstracts of papers based on pre-set inclusion criteria.Eleven high-quality trials were included. Results Pooled analyses revealed compared with the control group, the exercise group significantly improved the serum concentration of IL-8(Z=0.07,SMD=-0.02, 95%CI:[-0.47,-0.44],p=0.946)and TNF-α(Z=2.10, SMD=-0.60,95%CI:[-1.16,-0.04],p=0.036). No significant differences were found in the serum concentrations of IL-2(Z=1.96,SMD=-0.69,95%CI:[-1.37,0.00],p=0.05),IL-6(Z=0.40,SMD=-0.12, 95%CI: [-0.69,0.45],p=0.686),IL-10 (Z=1.73,SMD=-0.45,95%CI:[-0.95,0.06],p=0.084)or C-reactive protein(Z=0.18, SMD=-0.03,95%CI:[-0.35,0.41],p=0.861). Conclusions Exercise training can effectively improve some inflammatory factors in breast cancer patients and may affect tumor microenvironment. These findings provide a theoretical basis for the promotion of sports in this population.


BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e047957
Author(s):  
Qiong Zhou ◽  
Jie Dong ◽  
Qingqing Sun ◽  
Nannan Lu ◽  
Yueyin Pan ◽  
...  

ObjectiveThe neutrophil-to-lymphocyte ratio (NLR) is recognised as a suitable prognostic biomarker in patients with breast cancer. Nevertheless, the efficacy of this biomarker in predicting the pathological complete response (pCR) and survival in patients with breast cancer receiving neoadjuvant chemotherapy (NACT) is still controversial. This meta-analysis aimed to identify the association between baseline NLR and the prognosis of patients with breast cancer treated with NACT.DesignMeta-analysis.Data sourcesRelevant literature published before 1 May 2021 was searched using the Cochrane Library, Embase, PubMed and the Web of Science databases.Eligibility criteriaAll studies involving patients with breast cancer treated with NACT and peripheral blood pretreatment NLR recorded as a dichotomous variable were included.Data extraction and synthesisTwo researchers independently extracted and evaluated OR/HR and its 95% CIs of survival outcomes and clinicopathological parameters.ResultsA total of 19 studies were identified. From each study, the impact of NLR on the pCR, OR and HR, with their 95% CIs were extracted and combined using either a random or fixed-effects model. The results indicate that a higher pCR in patients with a low NLR (OR 1.620, 95% CI 1.209 to 2.169, p<0.001). In addition, an elevated NLR predicted lower disease-free survival (HR 2.269, 95% CI 1.557 to 3.307, p<0.001) and overall survival (HR 1.691, 95% CI 1.365 to 2.096, p<0.001) in patients with breast cancer treated with NACT.ConclusionsNLR is a suitable biomarker for predicting pCR and survival in patients with breast cancer receiving NACT.


2020 ◽  
Vol 50 (3) ◽  
pp. 230-240
Author(s):  
Naomi Gondo ◽  
Masataka Sawaki ◽  
Masaya Hattori ◽  
Akiyo Yoshimura ◽  
Haruru Kotani ◽  
...  

Abstract Objective The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. Methods Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is &lt;18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, &gt;30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. Results From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1–149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38–4.28; P &lt; 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15–6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11–3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15–11.04; P &lt; 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52–13.34; P &lt; 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02–4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. Conclusion Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.


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