Extracellular Matrix 1 (ECM1) Expression Is a Novel Prognostic Marker for Poor Long-Term Survival in Breast Cancer: A Hospital-Based Cohort Study in Iowa

Introduction  Previous work in a small, unselected series showed that up to 83% of breast carcinomas overexpress ECM1 by immunohistochemistry (IHC) and that tumors with lymph node metastases are more likely to be ECM1-positive. We sought to further evaluate ECM1 expression and its effect on prognosis in an unselected cohort of patients with breast cancer. Methods   ECM1 expression was examined by IHC in 134 women diagnosed with invasive breast cancer between 1986 and 1989 and correlated with clinical parameters and outcomes, including disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using Cox proportional hazards regression. Results  During follow-up, 83 of 134 (66%) patients died. The median follow-up was 211 (range, 183–245) months for surviving patients. Based on a previously described cutoff of 10% staining, 47% of breast cancers were ECM1-positive. ECM1-positive tumors were associated with increasing patient age (P = 0.01). In multivariate analyses, while controlling for age, ER status, tumor grade, stage, and treatment, ECM1 expression emerged as a significant predictor of DSS (hazard ratios, 4.16 (P = 0.009) and 11.6 (P = 0.01) at 10 and 15 years, respectively) and DFS (hazard ratio, 3.08 (P = 0.03) at 15 years) with ECM1 overexpression predicting poorer survival. Conclusions   ECM1 was overexpressed in approximately half of invasive breast carcinomas and is an important prognostic marker, particularly for predicting poorer DSS, with its predictive value increasing with time from diagnosis. Further work is needed to confirm these findings and determine whether ECM1 expression is predictive of response to specific therapy.     

Patients 35 years old or younger with operable breast cancer are more at risk for relapse and survival: a retrospective matched case-control study

It has long been suggested that younger women with breast cancer have less favorable prognostic factors and poorer outcomes. Our main objectives were to determine whether poor prognosis among young women was independent of other common clinicopathologic parameters. We retrospectively analyzed 551 young patients (≤35 years, Group I) and 551 older patients (36–50 years, Group II), matched for year of diagnosis, family history of breast cancer, pathologic stage, hormone receptor expression and application of adjuvant therapy. Patients in Group I had significantly shorter disease-free survival (DFS) than Group II (median 23.2 months vs. 28.4 months, P = 0.024). Five-year DFS rate(63.7% vs. 74.7%, P < 0.001) and overall survival (OS) rate (79.5% vs. 85.6%, P = 0.024) in Group I was inferior to those in Group II. Multivariate analysis showed that young age was a significantly negative predictor for DFS and OS. Our study thus shows that age (≤35 y/o) is an independent risk factor for prognosis in operable breast cancer.     

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

BackgroundPrevious studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.ResultsA total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.ConclusionBCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.     

T1期乳腺癌的临床病理特征及预后危险因素分析

背景与目的：T1期乳腺癌患者总体生存预后良好,但仍有少部分患者具有高度侵袭性,早期容易出现复发转移与死亡等不良生存结局,预后较差。本研究探讨影响T1期乳腺癌的临床病理特征及预后的危险因素,旨在早期识别高风险的T1期乳腺癌患者,为临床决策提供参考。方法：回顾性分析中南大学湘雅医院2011年1月—2015年12月经手术治疗的1 250例T1～T3期原发性浸润性乳腺癌患者资料,分析T1期与非T1期患者的临床病理学特征差异,单因素及多因素Cox风险模型分析影响T1期乳腺癌患者复发转移及死亡的危险因素,Kaplan-Meier法分析不同危险因素下T1期乳腺癌患者总生存（OS）和无病生存（DFS）的差异,Log-rank检验比较组间生存曲线差异。结果：1 250例原发性浸润性乳腺癌患者中,T1期261例（20.88%）,非T1期（T2和T3期） 989例（79.12%）。与非T1期比较,T1期患者BMI值低、腋窝淋巴结转移数目少、不利生物学特性少、生存预后好（均P<0.05）。T1期患者随访期间共15例死亡,40例出现复发转移。中位OS时间为94 (5～132)个月,2、5、10年OS率分别...     

Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese breast cancer

The prognostic significance of preoperative carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels in breast cancer is controversial. This study evaluated the prognostic value of preoperative serum CEA and CA15-3 levels in Chinese breast cancer patients. A total of 470 patients with breast cancer had preoperative CEA and CA15-3 concentrations measured. The relationships between preoperative concentration and clinicopathological factors and outcomes were determined. CEA and CA15-3 levels were increased in 34 (7.2%) and 58 (12.3%) patients, respectively. Elevations of serum CEA and CA-15-3 levels correlated with the primary tumor size and axillary lymph node status. CEA levels were lower in patients with triple-negative breast cancer than in those with other subtypes (P = 0.002). The 5-year distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of CEA-negative vs. CEA-positive patients were 84.1% vs. 54.5% (P < 0.001), 82.7% vs. 54.8% (P < 0.001), and 89.7% vs. 78.5% (P = 0.007), respectively. The 5-year DMFS, DFS, and OS of CA15-3-negative vs. CA15-3-positive patients were 84.0% vs. 69.6% (P = 0.002), 83.0% vs. 66.2% (P < 0.001), 90.9% vs. 74.2% (P = 0.005), respectively. Multivariate analysis of prognosis indicated that CEA and CA15-3 levels were independent prognostic factors for DMFS (P = 0.021) and DFS (P = 0.032), and DFS (P = 0.014) and OS (P = 0.032), respectively. Serum levels of CEA and CA15-3 may differ in breast cancer molecular subtypes and preoperative levels of CEA and CA15-3 have a significant effect on prognosis in Chinese women with breast cancer.     

Breast cancer after hormone replacement therapy--does prognosis differ in perimenopausal and postmenopausal women?

Hormone replacement therapy (HRT) has been associated with higher incidence of breast cancer in postmenopausal women, but it is unclear if breast cancers developing after HRT use have different prognosis. 1053 women with hormone receptor positive non-metastasized breast cancer were analyzed in a retrospective trial, stratifying by HRT use before diagnosis. Postmenopausal HRT users had significantly more early tumor stages (p < 0.001). HRT in postmenopausal patients was associated with longer time to progression (TTP) (HR 0.81, 95%CI 0.55–1.19, p = 0.28) and overall survival (OS) (HR 0.68, 95%CI 0.45–1.02, p = 0.059). Perimenopausal HRT users showed shorter TTP and OS (HR 1.99, 95%CI 0.57–6.91, p = 0.28 and HR 4.59, 95%CI 0.91–23.25, p = 0.06 respectively). Higher BMI was significantly associated with poorer prognosis in perimenopausal women only (TTP: HR = 1.16; OS: HR = 1.31). In this retrospective analysis postmenopausal HRT users seemed to have a better breast cancer prognosis. For perimenopausal HRT users however, a trend towards worse prognosis was found.     

Outcomes and utilization of postmastectomy radiotherapy for T3N0 breast cancers

BackgroundThe role of postmastectomy radiotherapy (PMRT) for women with pT3N0M0 breast cancer is controversial. We sought to determine the benefit of PMRT in this cohort using the National Cancer Database (NCDB).MethodsWe analyzed women with pT3N0M0 breast cancer who received mastectomy with or without PMRT between 2004 and 2012. We excluded men, women ≤18 years, neoadjuvant or unknown radiation or chemotherapy status, unknown estrogen or progesterone receptor status, unknown surgical margin status, histology other than invasive ductal or lobular carcinoma, and if death occurred <3 months after diagnosis. A total of 4291 patients was included for analysis. Chi-squared analysis was used to compare patient characteristics. Univariate (UVA) and multivariate (MVA) Cox proportional hazards modeling was used to identify factors associated with survival. Propensity score matching was performed to address confounding variables. Survival analysis was performed using Kaplan-Meier and shared frailty models.ResultsOf the 4291 women analyzed, 2030 (47%) received PMRT. On MVA, PMRT (HR 0.72, p < 0.001), chemotherapy (HR 0.51, p < 0.001), and hormone therapy (HR 0.63, p < 0.001) were associated with improved overall survival (OS). After propensity score matching, a matched cohort of 2800 women was analyzed. At 5 years, OS was 83.7% and 79.8% with and without PMRT, respectively (p < 0.001). This difference in OS benefit increased with time. At 10 years, OS was 67.4% and 59.2% with and without PMRT, respectively.ConclusionsPMRT was associated with improved OS in women with pT3N0M0 breast cancer, which strongly suggests PMRT may provide a survival advantage and should be considered.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

Lower recurrence risk through mammographic screening reduces breast cancer treatment costs

Mammographic screening is associated with a reduced risk of breast cancer recurrence. The objective of the study was to evaluate treatment costs due to breast cancer recurrence in relation to patients’ use of mammographic screening, consecutively collected in a defined population. The study included 418 women exposed to screening and 109 women unexposed to screening diagnosed with stage I–III breast cancer. During the first eight years after primary diagnosis, 19% (N = 80) of the exposed women and 33% (N = 36) of the unexposed women developed recurrent disease, P = 0.002. In the exposed group, 41% of the 8-year treatment costs were for the treatment of patients who developed recurrent disease, compared with 52% in the unexposed group, P = 0.039. Among the relapsed patients, the mean post-recurrence costs were EUR14,950, accounting for 65% of their total 8-year costs. The mean post-recurrence costs were comparable for both exposure groups irrespective of the detection method.     

Four cycles of docetaxel and cyclophosphamide as adjuvant chemotherapy in node negative breast cancer: A real-world study

IntroductionThe optimal number of cycles of adjuvant docetaxel and cyclophosphamide (DC) in patients with node negative breast cancer is not known. We aimed to analyse the survival outcomes of patients with node negative and human epidermal growth factor receptor (HER2)-negative breast cancer treated with four cycles of DC.MethodsPatients with node negative and HER2-negative breast cancer treated with four cycles of DC after surgery in a large Canadian province from 2008 to 2012 were identified. We analysed the 4-year and 9-year invasive disease free survival (iDFS) and overall survival (OS). Cox regression models were constructed to examine the associations of clinical characteristics with survival outcomes.ResultsA total of 657 patients were eligible for the current analysis. The median age was 53 years and 71.2% of patients had hormone receptor-positive breast cancer. Approximately three-fourths of patients had grade III tumours. At a median follow-up of nine years, the 4-year iDFS and OS were 91.0% and 95.5% and the corresponding 9-year rates were 80.5% and 88.0%, respectively. On multivariable Cox regression analysis, grade III tumour predicted worse iDFS (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.09–4.21; P = 0.026) and OS (HR, 3.15; 95% CI, 1.18–8.45; P = 0.022).ConclusionsAdjuvant chemotherapy with four cycles of DC in a select population of node negative breast cancer was associated with encouraging long-term survival. In the absence of a randomized comparison between four and six cycles of DC, this study presents real-world evidence to consider four cycles of DC as a reasonable option.     

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Background  We sought to determine the significance of Ki-67, one of the tumor cell proliferation markers, as a useful prognostic factor in early breast cancer. Methods  A total of 1080 consecutive patients with stage I or II breast cancer that underwent surgery between 1998 and 2003 were enrolled. Patients were categorized on the basis of the 2007 St. Gallen consensus and Adjuvant! Online. The expression of Ki-67 in the tumor was assayed by immunohistochemistry (cutoff value, 10%). Results  Univariate analysis determined that tumor size, lymph node involvement, histologic grade, estrogen receptor, progesterone receptor, bcl-2, and Ki-67 (≥10%) were statistically significant for both overall survival (OS) and distant metastasis-free survival (DFS). Of these factors, lymph node involvement and high Ki-67 expression were identified as independent prognostic factors for OS and DFS on the basis of multivariate analysis. The survivals of intermediate- and high-risk groups according to 2007 St. Gallen consensus were further separated by Ki-67 expression level (5-year DFS rate = 91.9% vs. 86.3% for Ki-67 < 10% and ≥10%, respectively in intermediate-risk group (P = .01); 5-year DFS rate = 82.5% vs. 61.4% for Ki-67 < 10% and ≥10%, respectively in high-risk group (P = .01)). The survivals of low- and high-risk groups according to Adjuvant! Online were further separated by Ki-67 expression level (5-year DFS rate = 97.8% vs. 89.5% for Ki-67 < 10% and ≥10%, respectively in low-risk group (P = .02); 5-year DFS rate = 9.4% vs. 82.6% for Ki-67 < 10% and ≥10% in high-risk group (P = .005)). Conclusions  Ki-67 is an independent prognostic factor for DFS and OS in early breast cancer and can provide additional prognostic information on the risk stratification with the use of the 2007 St. Gallen consensus and Adjuvant! Online. S.-Y. Jung and W. Han contributed equally to this work.     

Effect of primary tumor resection on overall survival in patients with stage IV breast cancer

We aimed to evaluate the effect of primary tumor resection on overall survival in stage IV breast cancer patients. In total, 284 breast cancer patients presenting with breast cancer at stage IV at initial diagnosis, between 2001 and 2014, were enrolled in the study. Patients were divided into two groups based on surgical resection of the primary tumor. Overall survival (OS) between the two groups was analyzed. Patients in the surgery group (n = 92) had smaller tumors than those in the no‐surgery group (n = 192, T0‐1:17.7% vs 34.8%, P < 0.001). The surgery group more often had negative nodal status (5.7% vs 33.7%, P < 0.001). Multiple metastatic organ sites were more common in the no‐surgery group than in the surgery group (55.7% vs 15.2%, P < 0.001). The surgery group showed a better OS than the no‐surgery group (P = 0.01). Multivariate analysis showed that surgical resection of primary tumors tended to be associated with improved OS (HR = 0.67, P = 0.055). T stage, ER, HER2 and metastatic organ sites were independent prognostic factors for OS in multivariate analysis. Surgical resection of the primary tumor may be a treatment option for patients with stage IV disease and may not have a negative effect on overall survival.     

Primary tumor resection in metastatic breast cancer: A propensity‐matched analysis, 1988‐2011 SEER data base

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988‐2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score‐matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score‐matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity‐matched analysis.     

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.     

REG1A Expression is an Independent Factor Predictive of Poor Prognosis in Patients with Breast Cancer

Background  Regenerating gene I alpha (REG1A) is a growth factor known to affect pancreatic islet β cells. Although REG1A expression has also been observed in various malignant tumors, the correlation between REG1A expression and the clinicopathological characteristics of breast cancer and patient prognosis has not been evaluated. Methods  Resected breast cancer tissues obtained at surgery from 150 breast cancer patients was stained with anti-REG1A antibody, after which the relative area occupied by stained tumor cells was evaluated under a light microscope and correlated with known clinicopathological factors. Results  Whereas tumor cells were frequently stained with anti-REG1A antibody, cells from normal breast tissue were not stained. REG1A expression in tumors of breast cancer patients with HER2-positive disease was higher than those with HER2-negative disease (P = .0009). The 10-year disease-specific survival rate among patients with lower levels of REG1A was significantly better than among those with higher levels (P = .0002 by log rank test). Multivariate Cox proportional hazard analyses revealed REG1A (hazard ratio, 2.07; 95% confidence interval, 1.93 to 11.29; P = .0005) and axillary lymph node status (hazard ratio, 4.44; 95% confidence interval, 1.52 to 11.29; P = .0003) to be independent factors affecting the 10-year disease-specific survival rate. Conclusion  High levels of REG1A expression within tumors are an independent predictor of poor prognosis in patients with breast cancer.     

Different prognostic significance of CD24 and CD44 expression in breast cancer according to hormone receptor status

Objective

CD44⁺CD24^−/low-expressing tumor cells have been studied as tumorigenic stem cells in vitro study. This study was designed to determine the clinical implication of the CD44 and CD24 expression in breast cancer.

Methods

Tissue microarray blocks containing 643 consecutive cases of invasive breast carcinomas from 1993 to 1998 were immunostained for CD44 and CD24. The median follow-up period was 127 months.

Results

CD44⁻CD24⁺ phenotype was associated with frequent hormone receptor positivity and Her2/neu positivity (P = 0.000; Both). The CD44⁺CD24⁻ phenotype was inversely associated with lymph node metastasis (P = 0.002), and it showed positive associations with prolonged disease-free survival (DFS; P = 0.003) and overall survival (OS; P = 0.002). 10-year DFS and OS were 68.9% and 74.6% for CD24 negative group, 55.6% and 60.9% for CD24 positive group (P = 0.001; Both). 10-year DFS and OS were 62.2% and 68.1% for CD44 negative group, 73% and 77.7% for CD44 positive group (P = 0.012, P = 0.013, respectively). In a multivariate analysis, CD24 expression was negatively related to OS only in the receptor positive group (Hazard ratio = 2.03; P = 0.003; 95% CI: 1.27-3.24) and CD44 expression was positively related to OS only in the hormone receptor negative group (hazard ratio = 0.58; P = 0.022; 95% CI: 0.36-0.92).

Conclusions

The CD44⁺CD24⁻ group is considered a favorable prognostic subgroup in breast cancer. CD24 expression was a poor prognosis marker in hormone receptor positive breast cancer, and CD44 expression was a good prognostic marker in the receptor negative group.     

Radiotherapy concurrent versus sequential with endocrine therapy in breast cancer: A meta-analysis

IntroductionThis study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer.Materials and methodsEligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS.ResultsEleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92–1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46–2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75–2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79–1.28, P = 0.26), (RR 0.86, 95% CI 0.66–1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96–1.06, P = 0.65), (RR 0.98, 95% CI 0.93–1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes.ConclusionRadiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing.     

Use of Bisphosphonates and Risk of Breast Cancer

A decreased risk of breast cancer has been reported among patients given bisphosphonates. The present aims were to study potential associations between different antiosteoporosis drugs, including bisphosphonates, and the risk of breast cancer before and after start of treatment and to appraise possible dose–effect relationships. From national Danish registers, all female users of bisphosphonates aged ≥40 years and other drugs against osteoporosis between 1996 and 2006 were identified (n = 87,104). This cohort was compared with a control group, where each patient was matched on age with three nonexposed women from the general population (n = 261,322). Before start of most drugs against osteoporosis an increased risk of breast cancer was seen compared to controls (e.g., adjusted OR = 1.09, 95% CI 1.04–1.16 for alendronate). This excess risk was higher in younger women (e.g., OR = 4.48, 95% CI 2.98–6.75 for alendronate in women ≤50 years) and disappeared in women older than 70 years (e.g., OR = 0.95, 95% CI 0.88–1.01 for alendronate). In contrast, a decreased risk of breast cancer was seen after start of alendronate (HR = 0.53, 95% CI 0.38–0.73), etidronate (HR = 0.80, 95% CI 0.73–0.89), and raloxifene (HR = 0.53, 95% CI 0.38–0.73). No dose–response relationship was present for alendronate and etidronate, whereas a decreasing risk was seen with increasing daily dose of raloxifene. Bisphosphonate treatment in women was associated with a reduced risk of breast cancer. However, no causal relationship seemed to be present.     

Worsened oncologic outcomes for women of lower socio-economic status (SES) treated for locally advanced breast cancer (LABC) in Pakistan

Two hundred and thirty-seven women, undergoing multimodality treatment for locally advanced breast cancer (LABC), were retrospectively analyzed for age, menopausal status, socio-economic status (SES), tumor size, nodal involvement, tumor grade, estrogen and progesterone receptor (ER, PR) status and tumor stage. Primary purpose was to assess outcomes of these patients treated in a low-income country as defined by the World Bank and using limited-level treatment resources as defined by Breast Health Global Initiative (BHGI) guidelines. Secondary objectives included correlation of predictive and prognostic features with event-free survival (EFS) and overall survival (OS) at 5 years.Predictors of decreased EFS or OS included lower SES [P = 0.05 (95%CI 0.34–1.0) and P = 0.1 (CI 0.29–1.14)], larger tumor size [P = 0.01 (95%CI 1.06–1.59) and P = 0.3 (CI 0.86–1.50)] and positive lymph node status [P = 0.04 (95% CI 1.0–1.55) and P < 0.0001 (CI 1.37–2.64).In women diagnosed with LABC in Pakistan, patients with lower SES had larger, more aggressive tumors with worsened survival outcomes. Optimal breast cancer care warrants consideration for health care policies that address access to diagnostic and treatment services for financially disadvantaged women.     

Efficacy of anthracycline/taxane‐based neo‐adjuvant chemotherapy on triple‐negative breast cancer in BRCA1/BRCA2 mutation carriers

This study aims to estimate the pathologic complete response (pCR) rate after neo‐adjuvant chemotherapy and to compare disease‐free survival (DFS) and overall survival (OS) between pCR and non‐pCR groups of patients with triple‐negative breast cancer (TNBC) and deleterious BRCA1 or BRCA2 mutation. We carried out a retrospective analysis of 53 patients including 46 BRCA1, 6 BRCA2, and 1 combined BRCA1 and BRCA2 mutation. All patients had been diagnosed with triple‐negative breast cancer (TNBC) between 1997 and 2014. Neo‐adjuvant therapy consisted of regimens that were based on anthracycline or an anthracycline‐taxane doublet. DFS included any relapse or second cancer. The Kaplan‐Meier method and the log‐rank test were used to compare pCR and non‐pCR groups. A pCR was observed in 23 (42.6% [95% CI, 29.2%‐56.8%]) of the TNBC included. The pCR rate was 38.3% [95% CI, 26%‐55%] among BRCA1 mutation carriers, and 66% among the 6 BRCA2 mutation carriers. Median follow‐up was 4.4 years (range 0.62‐16.2 years) and did not differ between the groups (P = .25). Fifteen relapses and six second cancers were recorded during the follow‐up period. Eleven deaths occurred, all of which were in the non‐pCR group. DFS (P < .01) and OS (P < .01) were significantly better in the pCR group than the non‐pCR group. This study shows a high pCR rate after neo‐adjuvant therapy in BRCA‐mutated triple‐negative breast cancer, and the survival results confirm the prognostic value of pCR in this group. These outcomes should be considered as a basis of comparison to be used by future studies about new therapies in this domain.