Tingting Yan

The efficacy of zoledronic acid in breast cancer adjuvant therapy: A meta-analysis of randomised controlled trials

BACKGROUND The effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomised controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy. METHODS We searched PubMed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992-2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004-2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end-points were the disease free survival (DFS). Secondary end-points were overall survival (OS), distant or loco-regional recurrence free survival and bone metastasis free survival. FINDINGS Compared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival, disease free survival, bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (relative risk (RR) = 0.763, 95% confidence interval (CI) 0.658-0.884, p < 0.001) and reduce the risk of distant (RR = 0.744, 95%CI 0.611-0.906, p = 0.003) and locoregional recurrence (RR = 0.508, 95%CI 0.340-0.760, p = 0.001). INTERPRETATION Adjuvant zoledronic acid did not significantly improve the prognosis of breast cancer patients. Due to the highly variable definitions of menopause utilised in different studies, we hypothesise that zoledronic acid may have a potential effect on postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal counterparts, differing disease stages and various pathological types of breast cancer.

Site-specific relapse pattern of the triple negative tumors in Chinese breast cancer patients

BackgroundIt has been reported that triple negative phenotype is characterized by aggressive clinical history in Western breast cancer patients, however its pattern of metastatic spread had never been reported in the Chinese population. Considering racial disparities, we sought to analyze the spread pattern for different sites of first recurrence in Chinese triple negative breast cancers.MethodsA retrospective study of 1662 patients was carried out from a large database of breast cancer patients undergoing surgery between January 1, 2000 and March 31, 2004 at the Cancer Hospital, Fudan University, Shanghai, China. Survival curves were generated using the Kaplan-Meier method and annual relapse hazards were estimated by the hazard function.ResultsWe found a statistically significant difference in relapse-free survival (RFS) for locoregional and visceral recurrence (P = 0.007 and P = 0.025, respectively) among the triple negative, ERBB2+ and HR+/ERBB2- subgroups in univariate analysis. In the multivariate Cox proportional hazards regression analysis, RFS for either locoregional or visceral relapse in the triple negative category was inferior to that in HR+/ERBB2- patients (P = 0.027 and P = 0.005, respectively), but comparable to that in ERBB2+ women (both P > 0.05). Furthermore, the early relapse peak appeared later in the triple negative group than that in the ERBB2+ counterpart for both locoregional and visceral relapse. On the other hand, when compared with triple negative breast cancers, a significantly lower risk of developing bone relapse was discerned for ERBB2+ women (P = 0.048; HR = 0.384, 95% CI 0.148-0.991), with the borderline significance for HR+/ERBB2- breast cancers (P = 0.058; HR = 0.479, 95% CI 0.224-1.025). In terms of bone metastasis, the hazard rate remained higher for the triple negative category than that for the ERBB2+ subtype.ConclusionBased on the site-specific spread pattern in different subgroups, the triple negative category of breast cancers in the Chinese population exhibits a different pattern of relapse, which indicates that different organotropism may be due to the different intrinsic subtypes. A better knowledge of the triple negative category is warranted for efficacious systemic regimens to decrease and/or delay the relapse hazard.

Association of sulfotransferase SULT1A1 with breast cancer risk: a meta-analysis of case-control studies with subgroups of ethnic and menopausal statue

BackgroundSulfotransferase (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.MethodsPubMed, 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.ResultsWe 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.ConclusionsWe 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.

The clinical significance of Ki-67 as a marker of prognostic value and chemosensitivity prediction in hormone-receptor-positive breast cancer: a meta-analysis of the published literature

Abstract Objectives: Hormone-receptor (HR)-positive breast cancer is associated with a poor response to adjuvant chemotherapy. Thus, it is important to identify HR-positive patients who can benefit from chemotherapy and the Ki-67 index may help to predict chemotherapy efficacy in such populations. However, controversies exist regarding the prognostic and predictive role of Ki-67 and its exact cut-off value in HR-positive patients. Therefore, we conducted this study. Methods: The meta-analysis included 4512 patients in five trials. Due to different data formats provided by studies, we classified the trials into two groups to facilitate analysis. Group 1 included the PACS01, USON 01062, and IBCSG VIII and IX trials, while Group 2 included the BCIRG001, USON 01062, and IBCSG VIII and IX trials. Results: In Group 1, Ki-67 high patients had a worse prognosis in disease-free survival (DFS) than Ki-67 low counterparts (risk ratio [RR] = 1.62, 95% confidence index [CI] = 1.36–1.94, P < 0.001). In Group 2, Ki-67 high patients had a better prognosis in DFS (RR = 0.53, 95% CI = 0.45–0.61, P < 0.001) and overall survival (OS) (RR = 0.32, 95% CI = 0.25–0.42, P < 0.001). In Ki-67 high patients administered anthracycline/taxane-based chemotherapy, the experimental group (FAC → T, AC → TX) achieved a better DFS than the control group (FAC, AC → T, respectively) (RR = 0.60, 95% CI = 0.39–0.90, P = 0.014). With a cut-off point ≥19%, Ki-67 high patients achieved a worse DFS (RR = 1.49, 95% CI = 1.28–1.72, P < 0.001). Conclusion: This study had limitations due to its retrospective nature and the lack of standardized Ki-67 measurement methods. Nevertheless, our findings indicate that Ki-67 high patients have a worse prognosis and may be more sensitive to anthracycline/taxane-based regimens. The ideal Ki-67 cut-off point for predicting chemosensitivity may be a certain value among a range of values ≥19% in HR-positive patients.

First Efficacy Results of Capecitabine with Anthracycline- and Taxane-Based Adjuvant Therapy in High-Risk Early Breast Cancer: A Meta-Analysis

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.

Postoperative Fever: The Potential Relationship with Prognosis in Node Negative Breast Cancer Patients

Background Postoperative fever may serve as an indirect sign to reflect the alterations of the host milieu caused by surgery. It still remains open to investigation whether postoperative fever has a bearing on prognosis in patients with lymph node negative breast cancers. Methods We performed a retrospective study of 883 female unilateral patients with lymph node negative breast cancer. Fever was defined as an oral temperature ≥38 in one week postoperation. Survival curves were performed with Kaplan-Meier method, and annual relapse hazard was estimated by hazard function. Findings The fever patients were older than those without fever (P<0.0001). Hypertensive patients had a propensity for fever after surgery (P = 0.011). A statistically significant difference was yielded in the incidence of fever among HR+/ERBB2-, ERBB2+, HR-/ERBB2- subgroups (P = 0.012). In the univariate survival analysis, we observed postoperative fever patients were more likely to recur than those without fever (P = 0.0027). The Cox proportional hazards regression analysis showed that postoperative fever (P = 0.044, RR = 1.89, 95%CI 1.02–3.52) as well as the HR/ERBB2 subgroups (P = 0.013, HR = 1.60, 95%CI 1.09–2.31) was an independent prognostic factor for relapse-free survival. Conclusion Postoperative fever may contribute to relapse in node negative breast cancer patients, which suggests that changes in host milieu related to fever might accelerate the growth of micro-metastatic foci. It may be more precise to integrate both tumor- and host-related factors for the evaluation of relapse risk.

P3-16-10: The Efficacy of Zoledronic Acid in Breast Cancer Adjuvant Therapy: A Meta-Analysis of Randomized Controlled Trials.

Background: The effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomized controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy. Methods: We searched Pubmed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992–2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004–2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study endpoints were the DFS. Secondary endpoints were OS, distant or loco-regional recurrence free survival and bone metastasis free survival. Results: Compared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival (OS), disease free survival (DFS), bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (RR=0.763, 95%CI 0.658−0.884, p Discussion: Adjuvant zoledronic acid may potentially improve the prognosis of postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal couterparts, differing disease stages, and various pathological types of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-10.

Epidemiology of Triple Negative Breast Cancer in China.

Background:The classification of tumors based on the gene expression may define intrinsic breast cancer subtypes in which the effect of risk factors could be more obvious. We sought to assess the risk factors for triple negative breast cancer on Chinese population.Methods: A retrospective study of 5761 patients was carried out from a large database of breast cancer patients undergoing surgery between January 1, 1991 and June 31, 2008 in Cancer Hospital, Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test of Student9s t test and multivariate analyses by logistic regression.Results: A total of 1108 women were identified as having triple negative breast cancer and were compared with the 4653 women with non-triple negative. Regardless the pathological discrepancy, women with triple negative breast cancers were significantly more likely to be younger age(P=0.001; OR=1.615, 95%CI=1.207-2.160), premenopausal (P = 0.003; OR = 1.570, 95% CI = 1.171-2.106) and parous women (P = 0.001; OR = 1.741, 95% CI = 1.269-2.387).There seems no associations with increasing risk of triple negative breast cancer for breastfeeding (P=0.126), younger age at menarche (P=0.129), first degree family history (P=0.111) and oral contraceptive usage (P=0.251).Conclusion:Based on this large population study in Chinese breast cancer patients, the risk factors for triple negative phenotype may be somewhat different from those for Western women. Therefore, a better knowledge of this issue is warranted due to it may have impact on clinical outcomes and may offer some insight into the process of carcinogenesis and therapeutic efficacy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2065.