Background: Sulfotransferase (SULT) plays an important role in the formation of estrogen which is usually conferred as a risk factor for breast cancer. Polymorphism of the SULT1A1 may be closely associated with breast cancer. However, studies on the association between polymorphism and breast cancer have yielded inconsistent results. We performed a meta-analysis including ethnic subgroup and menopausal statue subgroup to investigate the association of SULT1A1 Arg213His polymorphism with breast cancer. Methods: PubMed, EBSCO and Web of Science databases were searched for the correlative articles up to January 2010 (10362 breast cancer patients and 14250 controls). The risk (odds ratio, OR) was used to estimate the association between SULT1A1 polymorphism and breast cancer risk. All of the data from each study use either fixed-effects or random-effects. Results: We found that SULT1A1 Arg213His had no exact effect to increase the risk of breast cancer (OR = 1.07, 95% CI: 0.97-1.17, P = 0.164), but it did increase the risk of breast cancer among postmenopausal women in the dominant model (OR = 1.28, 95%CI: 1.04-1.58, P = 0.019). No similar effect was found among premenopausal breast cancer women (OR = 1.06, 95%CI: 0.88-1.27, P = 0.537). There was a significant increase in breast cancer risk among Asian women (OR = 2.03, 95% CI: 1.00-4.14, P = 0.051) but not Caucasian women in recessive model. There was publication bias among postmenopausal women subgroup (P = 0.002), however by using the trim and fill method, if the publication bias was the only source of the funnel plot asymmetry, it needed two more studies to be symmetrical. The value of Log OR did not change too much after the adjustment and the fail-safe number of missing studies that would bring the P-value changed was 17. Conclusions: We concluded that the polymorphism of SULT1A1 Arg213His might be one of the high risk factors for breast cancer in Asian women and in postmenopausal women for all races. We should point out that the publication bias among postmenopausal women may partly account for the result, but the conclusion might not affected deeply by the publication bias.
CYP2D6 gene polymorphism has a profound impact upon the effect of tamoxifen as adjuvant endocrine therapy in breast cancer. However, it had never been reported whether the adverse drug reactions vary by CYP2D6 metabolic status for patients treated with tamoxifen or toremifene. We conducted a retrospective study in breast cancer patients to investigate the impact of CYP2D6 metabolic status on liver dysfunction events, gynecological events and dyslipidemia events. According to CYP2D6*10 (100C → T) genotype, the enrolled patients were further categorized into four cohorts (extensive metabolizers taking tamoxifen [EM + TAM], extensive metabolizers taking toremifene [EM + TOR], intermediate metabolizers taking tamoxifen [IM + TAM], and intermediate metabolizers taking toremifene [IM + TOR]). A total of 192 patients were included in the study, with a median follow-up time of 26.2 months. In EM + TAM cohort, the risks of liver dysfunction events (P = .004) and gynecological events (P = .004) were significantly higher compared to EM + TOR cohort. In IM + TAM cohort, the risks of liver dysfunction events (P = .14) and gynecological events (P = .99) were not significantly different from IM + TOR cohort. A significant decrease of total cholesterol was observed in EM + TAM cohort around 1 year after taking tamoxifen (P < .001). Significant interactions between CYP2D6 metabolic status and endocrine agents were observed in terms of liver dysfunction events (P-interaction = .007) and gynecological events (P-interaction = .026). These findings suggested that CYP2D6 gene polymorphism played a significant role in predicting liver dysfunction, gynecological diseases and lipid metabolism changes among patients taking tamoxifen or toremifene.
We aimed to explore the value of contrast-enhanced ultrasound (CEUS) in early prediction of pathologic complete response (pCR) and recurrence-free survival (RFS) in locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NAC). LABC patients who underwent CEUS before and during NAC from March 2014 to October 2018 were included and assessed. Logistic regression analysis and the Cox proportional hazards model were used to identify independent variables associated with pCR and RFS. Among 122 women, 44 underwent pCR. Molecular subtype, peak intensity (PEAK) and change in diameter were independent predictors of pCR after one cycle of NAC (area under the receiver operating characteristic curve [AUC], 0.81; 95% CI: 0.73, 0.88); Molecular subtype, PEAK and change in time to peak (TTP) were independently associated with pCR after two cycles of NAC (AUC, 0.85; 95% CI: 0.77, 0.91). A higher clinical T (hazard ratio [HR] = 4.75; 95% CI: 1.75, 12.87; p = 0.002) and N stages (HR = 3.39; 95% CI: 1.25, 9.19; p = 0.02) and a longer TTP (HR = 1.06; 95% CI: 1.01, 1.11; p = 0.02) at pre-NAC CEUS were independently associated with poorer RFS. CEUS can be used as a technique to predict pCR and RFS early in LABC patients treated with NAC.
Background Capecitabine is effective and indicated for the salvage treatment of metastatic breast cancer. Therefore, it is essential to evaluate the efficacy of capecitabine in the adjuvant setting. There have been two large randomized studies to determine whether patients with high-risk early breast cancer benefit from the addition of capecitabine to standard chemotherapy, but they have yielded inconsistent results. We first undertook a meta-analysis to evaluate the efficacy of the addition of capecitabine over standard treatment. Methods PubMed, EBSCO, Web of Science, conference proceedings and key trials were searched from 1998 to 2011. The hazard ratio (HR) was used to evaluate the efficacy of a taxane-anthracycline regimen and a taxane-anthracycline-capecitabine regimen in early breast cancer. All of the data from each study use either fixed-effects or random-effects by Stata. Findings We found significant improvement in the additional capecitabine arm versus control in disease-free survival (DFS) (HR = 0.83, 95% CI: 0.71–0.98, P = 0.027), overall survival (OS) (HR = 0.71, 95% CI: 0.57–0.88, P = 0.002), distant recurrence (HR = 0.79, 95% CI: 0.66–0.94, P = 0.008) and the death from breast cancer only (HR = 0.65, 95% CI: 0.51–0.83, P = 0.001). Meanwhile, the subgroup analysis revealed that capecitabine improved the DFS in triple negative (HR = 0.71, 95% CI: 0.53–0.96, P = 0.028), hormone receptor negative (HR = 0.73, CI: 0.56–0.94, P = 0.017) and HER2 negative (HR = 0.81, CI: 0.67–0.98, P = 0.034) patients. Conclusion Due to the synergistic effect of taxane and capecitabine, taxane-anthracycline-capecitabine regimen may effectively improve the efficacy in the adjuvant setting and may be a novel generation of adjuvant chemotherapy regimen. The results of the current meta-analysis support this hypothesis and indicate that taxane-based regimen with capecitabine may be an effective, convenient, and well tolerated regimen in patients with early breast cancer.
There is a growing population of patients with inflammatory bowel diseases (IBD) in Asia in recent years. The present investigation intended to obtain a better understanding of the current situation on drug therapy and monitoring for IBD from physicians’ viewpoints in Asian areas. A questionnaire investigation about drug therapy and monitoring for IBD was conducted in Asia before the sixth Annual Meeting of Asian Organization for Crohn’s and Colitis (AOCC). Questionnaires were sent to AOCC members to fill out via email between March and May 2018. One hundred and sixty-nine physicians of 132 medical centres from Mainland China, Hong Kong, Taiwan, Japan, South Korea, India, Malaysia, Singapore and Thailand responded to the survey, in which 74 centres from all parts of Mainland China except Tibet participated. The average number of consultant gastroenterologists with specialist IBD experience of the investigated centres was 4.8 in Taiwan, which was the most among the surveyed regions. Mainland China had the largest average number of 2.5 of IBD specialist nurses in their centres. 5-aminosalicylic acid (5-ASA)/sulfasalazine (SASP) (99.41%) was the most preferred first-line choice for mild–moderate ulcerative colitis (UC), then followed by steroids (34.9%) and azathioprine (8.9%). Steroids (84.7%) were widely applied for severe UC, followed by infliximab (29.8%), 5-ASA/SASP (20.3%), azathioprine (14.9%) and ciclosporin A (11.9%). The first-line medication for Crohn’s disease (CD) markedly varied among the responders as steroids (69.1%) were the most preferred in Mainland China, Japan and South Korea, followed by infliximab (52.3%), azathioprine (46.5%), 5-ASA/SASP (42.5%) and adalimumab (11.4%). Step-up strategy for mild–moderate UC was adopted by a large majority of physicians (96.4%) while it was only favoured by 36.1% physicians for severe UC. For CD, top-down treatment was adopted by 51.5% physicians while 39.1% chose step-up. For therapeutic drug monitoring, only 19.4%, 37.1%, 41.2%, 25.9% and 17.7% of the centres were able to test blood concentration of 6-mercaptopurine, FK506, ciclosporin A, infliximab and antibody to infliximab, respectively. The frequency for monitoring adverse events of IBD medication varied from 1 week to 6 months according to responders’ answers. The quantity of medical personnel with specialist IBD experience, the availability of IBD drugs and the preferences for drug choice vary from region to region in Asia. Therapeutic drug monitoring is insufficient in most investigated areas, which suggests little optimism in quality of drug therapy. Asian version of recommended indicators for drug therapy and monitoring is encouraged to be established for further improvement of IBD management.
Background Adjuvant trastuzumab therapy has yielded conflicting results for overall survival, concerns about central nervous system (CNS) metastasis, and questions about optimal schedule. Therefore, we carried out a meta-analysis to assess the benefits of concurrent or sequential trastuzumab with adjuvant chemotherapy for early breast cancer patients with HER2-positive tumors. Methods Computerized and manual searches were performed to identify randomized clinical trials comparing adjuvant chemotherapy with or without trastuzumab in HER2-positive early breast cancer patients. Odds ratios were used to estimate the association between the addition of trastuzumab to adjuvant chemotherapy and various survival outcomes. The fixed-effects or random-effects model was used to combine data. Findings With six eligible studies identified, this analysis demonstrated that patients with HER2-positive breast cancer derived benefit in disease-free survival, overall survival, locoregional recurrence and distant recurrence (all P<0.001) from the addition of trastuzumab to adjuvant chemotherapy, whereas trastuzumab did worse in CNS recurrence as compared to the control group (P = 0.018). Furthermore, concomitant use of trastuzumab significantly lowered the hazard of death (P<0.001) but bore a higher incidence of CNS recurrence (P = 0.010), while statistical significance failed to be discerned for either overall survival (P = 0.069) or CNS metastasis (P = 0.374) between the sequential and observation arms. Conclusion This analysis verifies the efficacy of trastuzumab in the adjuvant setting. Additionally, our findings indirectly corroborate the superiority of concurrent trastuzumab to sequential use and also illuminate that prolonged survival is the possible reason for the higher incidence of CNS with trastuzumab versus observation.
Objective:Phosphatase and tensin homolog (PTEN) loss or activating mutations of phosphoinositol-3 (PI3) kinase (PIK3CA) may be related to trastuzumab resistance in in vitro studies; however, this issue in clinical studies is controversial. Therefore, we conducted a meta-analysis to assess the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in HER2-positive breast cancer patients.Methods:A computerized search was performed through the PubMed database, the online proceedings of the American Society of Clinical Oncology Annual Meetings, the San Antonio Breast Cancer Symposium and the International St. Gallen Breast Cancer Conference. Ten eligible studies including 1889 cases were identified.Results:In HER2-positive locally advanced breast cancer patients, neither PTEN loss, PIK3CA mutation nor PI3K activation was associated with the response rate of trastuzumab-based neoadjuvant treatment (PTEN loss: RR = 0.687, 95% CI: 0.439–1.074, P = 0.099; PIK3CA mutation: RR = 1.114, 95% CI: 0.453–2.735, P = 0.814; PI3K activation: RR = 0.787, 95% CI: 0.417–1.484, P = 0.459; RR = 0.772, 95% CI: 0.387–1.539, P = 0.462). In HER2-positive early stage breast cancer patients, PTEN loss was not associated with the disease-free survival (DFS) rate of trastuzumab-based adjuvant treatment (HR = 1.096, 95% CI: 0.706–1.700, P = 0.684). In HER2-positive recurrent or metastatic breast cancer patients, PTEN loss was significantly correlated with poorer efficacy of trastuzumab-based salvage treatment (RR = 0.682, 95% CI: 0.550–0.846, P = 0.000).Conclusions:In HER2-positive recurrent or metastatic breast cancer patients PTEN loss might indicate resistance to trastuzumab-based salvage treatment. Due to the small sample size and the considerable heterogeneity in the chemotherapy treatment regimens, further research is needed to clarify the association between PTEN loss, PIK3CA mutation and the efficacy of trastuzumab-based treatment in neoadjuvant and adjuvant settings.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)