Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.     

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

BackgroundThis meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody.MethodsThe NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999–November 2017. Treatment arms with shorter PFS were considered as the “control” arm, whereas those with longer PFS as the “test” arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses.ResultsTwenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68–0.78) and median OS (HR = 0.82, 95% CI: 0.77–0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p < 0.001) and linearly correlated, which was not found with any non-anti-HER2 antibody drug differences.ConclusionsAnti-HER2 antibody in patients with HER2-positive mBC prolonged OS more than PFS and mandates further investigation.     

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study

PurposeIn the MONALEESA-3 Phase III trial of patients with hormone receptor–positive human epidermal growth factor receptor–negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL).MethodsPatients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant. Time to definitive 10% deterioration (TTD) from baseline in HRQOL (global health status [GHS] from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan-Meier estimates; a stratified Cox regression model was used to estimate the hazard ratio (HR) and 95% CIs.ResultsDeterioration ≥10% in the EORTC-QLQ-C30 GHS was observed in 33% of patients in the ribociclib group vs 34% of patients in the placebo (reference) group (HR for TTD ≥ 10% = 0.81 [95% CI, 0.62–1.1]). Similar findings were noted for TTD ≥5% (HR = 0.79 [95% CI, 0.61–1.0]) and TTD ≥15% (HR = 0.81 [95% CI, 0.60–1.08]). TTD ≥10% in emotional functioning (HR = 0.76 [95% CI, 0.57–1.01]) trended in favor of the ribociclib group, whereas results for fatigue and pain were similar between arms. TTD ≥10% in BPI-SF pain severity index score (HR = 0.77 [95% CI, 0.57–1.05]) and worst pain item score (HR = 0.81 [95% CI, 0.58–1.12]) trended in favor of ribociclib vs placebo.ConclusionsIn addition to significantly prolonging PFS and OS compared with placebo plus fulvestrant, adding ribociclib to fulvestrant maintains HRQOL.     

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis

PurposeThe aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.MethodsA total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed.ResultsPatients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737).ConclusionOlder female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.     

Systemic inflammation response index (SIRI) as a predictive factor for overall survival in advanced soft tissue sarcoma treated with eribulin

BackgroundEribulin is a tubulin and microtubule-targeting drug that has clinical benefit in overall survival (OS) for patients with advanced soft tissue sarcoma. Eribulin's efficacy has been confirmed in several clinical trials, although no clinically useful biomarkers have been identified. We therefore sought to clarify the predictive factor of eribulin treatment, while focusing on systemic inflammation and immune response values.MethodsThis study included 33 advanced STS patients treated with eribulin between March 2016 and September 2019. We evaluated the associations of clinical factors influencing the efficacy of eribulin treatment and systemic inflammatory and immune response, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the systemic inflammation response index (SIRI), and the prognostic nutrition index (PNI), with progression-free survival (PFS) and OS using the Kaplan–Meier method and log–rank test.ResultsNLR, LMR, PLR, SIRI, and PNI were unassociated with PFS. Compared with patients with SIRI <1.5, those with an SIRI ≥1.5 had a significantly shorter OS [median OS 15 months (95% confidence interval [CI] 8–not reached) vs. 7 months (95% CI 3–14), P = 0.04]. Moreover, the PFS tended to be shorter for patients with SIRI ≥1.5 who received chemotherapy after eribulin treatment than in those with SIRI >1.5 [median PFS 92.5 days (95% CI 27–204) vs. 133 days (95% CI 36–507), P = 0.08].ConclusionsHigh SIRI values may predict poorer overall survival and the efficacy of subsequent drugs after eribulin treatment among patients with advanced soft tissue sarcoma.     

The efficacy of neutralizing monoclonal antibodies in transplant recipients with mild-to-moderate COVID-19

IntroductionTransplant recipients (TRs) are at high risk for severe coronavirus disease 2019 (COVID-19). Neutralizing monoclonal antibodies (mAbs) are used for treating mild-to-moderate COVID-19. However, reports comparing the efficacy of COVID-19 treatment without/with mAbs in TRs are limited. We assessed the efficacy of casirivimab/imdevimab against mild-to-moderate COVID-19 in TRs.MethodsForty-one patients were retrospectively evaluated. The duration until defervescence, oxygen (O₂) requirement ≥5 L, and neutralizing antibody levels were compared in TRs with COVID-19 without/with casirivimab/imdevimab.ResultsCasirivimab/imdevimab was correlated with shorter duration until defervescence and non-requirement of O₂ ≥ 5 L in TRs with COVID-19 [mean: without/with: 6 vs. 2; P = 0.0002, hazard ratio (HR) = 0.3333, 95% confidence interval (CI) = 0.1763–0.6301; 15 vs. 8; P < 0.0001, HR = 0.5333, 95% CI = 0.2878–0.9883; P = 0.0377, HR = 0.1502, 95% CI = 0.02511–0.8980]. Casirivimab/imdevimab was associated with early defervescence after adjusting for sex and age (P = 0.013, HR = 0.412, 95% CI = 0.205–0.826). The antibody levels between patients without/with casirivimab/imdevimab on the day of hospitalization were not significantly different (P = 0.1055), including 13 TRs with vaccination. Antibody levels were higher in patients with casirivimab/imdevimab at 3–5 days after hospitalization than in those without, at 7–9 days after hospitalization (P < 0.0001, mean, without/with: 414.9/40000 AU/mL).ConclusionCasirivimab/imdevimab was effective and increased the neutralizing antibody in TRs with mild-to-moderate COVID-19, it may contribute toward preventing the progression.     

Prognostic value of hypocholesterolemia in patients with gastric cancer

BackgroundAccording to previous studies, low serum total cholesterol (TC) is associated with higher cancer incidence and mortality. However, the prognostic implications of preoperative TC in patients with gastric cancer (GC) remain to be determined.MethodsA total of 1251 patients with GC, who underwent radical gastrectomy between 2005 and 2008, were recruited. Propensity score weighting (PSW) based on a generalized boosted method (GBM) was used to control for selection bias.ResultsAfter balancing the preoperative and operative covariates, low TC was associated with high incidence of complications (severe complication rate: 15.2% (Low TC) vs. 4.7% (Normal TC) vs 5.5% (High TC); p = 0.004). In multivariable analysis, lowering TC was associated with poor OS and RFS in weighted population. [OS: hazard ratio (HR) = 0.92; 95% CI = 0.867–0.980; P = 0.009 and RFS: HR = 0.93; 95% CI = 0.873–0.988; P = 0.02].ConclusionsPreoperative TC is a useful predictor of postoperative survival and postoperative complications in patients with stage I–III GC and may help to identify high-risk patients for rational therapy, including nutritional support, and timely follow-up.     

Influence of age as a continuous variable on the prognosis of patients with pT1-2N1 breast cancer

PurposeTo assess the influence of age as a continuous variable on the prognosis of pT1-2N1 breast cancer and examine its decision-making value for postmastectomy radiotherapy (PMRT).MethodsWe retrospectively evaluated 5438 patients with pT1-2N1 breast cancer after mastectomy in 11 hospitals. A multivariable Cox proportional hazards regression model with penalized splines was used to examine the relationship between age and oncologic outcomes.ResultsThe median follow-up was 67.0 months. After adjustments for confounding characteristics, nonsignificant downward trend in locoregional recurrence (LRR) risk was observed with increasing age (P-non-linear association = 0.640; P-linear association = 0.078). A significant non-linear association was found between age and disease-free survival (DFS) and overall survival (OS) (P-non-linear association <0.05; P-linear association >0.05, respectively). The DFS and OS exhibited U-shaped relationships, with the hazard ratios (HRs), reaching a nadir at 50 years old. A decreased risk of LRR with PMRT vs. no PMRT (HR = 0.304, 95% CI: 0.204–0.454) was maintained in all ages. The HR of PMRT vs. no PMRT for DFS and OS gradually increased with age. In patients ≤50 years old, PMRT was independently associated with favorable LRR, DFS, and OS, all P < 0.05). In patients >50 years old, PMRT was independently associated with reduced LRR (P = 0.004), but had no effect on DFS or OS.ConclusionsAge was an independent prognostic factor for pT1-2N1 breast cancer; PMRT provided survival benefits for patients ≤50 years old, but not for patients >50 years old.     

Comparison between doublet agents versus single agent in metastatic breast cancer patients previously treated with an anthracycline and a taxane: A meta-analysis of four phase III trials

AimTo compare doublet agents with single agent as salvage treatment in metastatic breast cancer (MBC) patients pre-treated with an anthracycline and a taxane.MethodsWe systematically searched for randomised clinical trials that compared doublet agents with single agent in MBC patients pre-treated with an anthracycline and a taxane. The primary end point was overall survival (OS). Secondary end points were progression-free survival, overall response rate and grade 3 or 4 toxicity. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 10.0 software (Stata Corporation, College Station, TX, USA).ResultsFour trials comprising 2373 patients were eligible for inclusion. Meta-analysis showed that there was significant improvement in progression-free survival (PFS) (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.72–0.86, P = 0.000) and overall response rate (risk ratio (RR) 1.47, 95%CI 1.13–1.91; p = 0.004) in doublet agents group, though the pooled HR for OS (HR 0.96, 95%CI 0.87–1.05; p = 0.356) showed no significant difference. Subgroup analysis also favoured capecitabine-based doublet agents therapy in terms of PFS (HR 0.77, 95%CI 0.70–0.86; p = 0.000) and overall response rate (ORR) (RR 1.65, 95%CI 1.06–2.56; p = 0.026), but gemcitabine-based doublet agents therapy gained no clinical benefits. There were more incidences of grade 3 or 4 anaemia (RR 1.610, 1.212–2.314, p = 0.01), neutropenia (RR 2.239, 1.231–4.071, p = 0.008), thrombocytopaenia (RR 2.401, 1.595–3.615, p = 0.000), fatigue (RR 2.333, 1.338–4.006, p = 0.000) and nausea and vomiting (RR 2.233, 1.558–3.199, p = 0.000) in the combination group. With regard to the risk of grade 3 or 4 stomatitis (RR 1.666, 0.818–3.392, p = 0.160), diarrhoea (RR 0.739, 0.542–1.008, p = 0.056) and hand–foot syndrome (RR 1.002, 0.835–1.203, p = 0.983), equivalent frequencies were found between the two groups.ConclusionCombination chemotherapy offered a significant improvement in PFS and ORR in patients with MBC pre-treated with an anthracycline and a taxane but did not benefit OS. With present available data from randomised clinical trials, we were still unable to clearly set the role of combination therapy in the treatment of MBC in this setting.     

Concurrent versus sequential adjuvant chemo-endocrine therapy in hormone-receptor positive early stage breast cancer patients: a systematic review and meta-analysis

BackgroundAlthough in clinical practice adjuvant chemotherapy (CT) and endocrine therapy (ET) are administered sequentially in patients with hormone-receptor positive breast cancer, the optimal timing, i.e. concurrent or sequential administration, of these treatments has been scarcely investigated. To better clarify this issue we conducted a systematic review and meta-analysis of randomized studies comparing these two modalities of administrations in terms of disease-free survival (DFS) and overall survival (OS).MethodsRelevant studies were identified by searching PubMed, Web of Knowledge and the proceedings of the major conferences with no date restriction up to March 2016.The summary risk estimates (pooled hazard ratio [HR] and 95% confidence intervals [CI]) for DFS and OS were calculated using random effect models (DerSimonian and Laird method).ResultsA total of three randomized studies were eligible including 2021 breast cancer patients. Overall, 755 DFS events were observed, 365 in the sequential arm and 390 in the concomitant arm, with a pooled HR of 0.95 (95% CI = 0.76 to 1.18, P = 0.643).No association between timing of treatment and OS was observed (HR = 0.95; 95% CI = 0.80 to 1.12, P = 0.529).ConclusionOur pooled analysis showed no association between the timing of administration of adjuvant CT and ET and DFS and OS in breast cancer patients candidates for both adjuvant treatments. Because of the small number of published trials, the lack of data on the timing with modern adjuvant treatments, i.e. taxane-containing CT and aromatase inhibitors, this topic remain still controversial and requires further studies to be clarified.     

Effects of postmastectomy radiotherapy on survival in different age groups for patients with T3N0M0 breast cancer

BackgroundPostmastectomy radiotherapy (PMRT), as an important regional treatment, improves the survival rate of patients with T3N0M0 breast cancers. However, the therapeutic effect of PMRT on T3N0M0 patients in different age groups is unclear.MethodsUsing Surveillance, Epidemiology, and End Results database, we identified 4840 T3N0M0 patients between 2000 and 2015. The primary and secondary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Survival outcomes were compared using Kaplan-Meier survival test, COX regression analysis, propensity score matching and forest plot, which present the relationship between age and PMRT.ResultsSurvival analysis demonstrated that for young patients (aged 18–45 and 46–55), there was no significant difference in OS between with and without PMRT. However, for patients older than 65 years, PMRT could significantly improve survival time (P < 0.001). Multivariate Cox analysis of OS showed older patients with PMRT had a lower hazard ratio (HR) than those without PMRT (aged 56–65: HR = 0.67, P = 0.014; aged >65: HR = 0.60, P < 0.001), and little benefit for young patients. The consistent results were also observed in 1:1 matched cohort. Subgroup analysis revealed the survival HRs of with versus without PMRT for patients older than 65 years were significant in most subgroups.ConclusionThe effect of PMRT in T3N0M0 patients is related to the age. PMRT is associated with improved survival in older patients with T3N0M0 breast cancer, especially those older than 65 years. While the benefit of PMRT is limited in T3N0M0 patients of young age. The observation suggests the importance of age for T3N0M0 patients when individualized treatment is made.     

Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

BackgroundLocoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).MethodsRCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.ResultsAnalyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72–1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14–0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65–1.43), triple negative (HR 1.4, 95% CI 0.50–3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68–1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58–1.62) and in visceral disease (HR = 1.02, 95% CI 0.77–1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.ConclusionsLRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.     

The role of tumor phenotype in the surgical treatment of early-stage breast cancer

BackgroundWe investigated whether tumor phenotype influences surgical decision-making, and how that may impact overall survival (OS) for early-stage breast cancer.MethodsWomen aged 18–69 with cT0-2/cN0/cM0 breast cancer in the National Cancer Database (2010–2017) were included. A generalized logistic model was used to identify factors associated with surgery type. A Kaplan-Meier curve was used to visualize unadjusted OS, and the log-rank test was used to test for differences in OS between surgery types.ResultsOf 597,149 patients, 58% underwent lumpectomy with radiation (BCT), 25% unilateral mastectomy (UM), and 17% bilateral mastectomy (BM). After adjustment, HER2+ and triple-negative (TN) tumors were less likely to undergo UM than BCT, versus hormone receptor-positive tumors (OR = 0.881, 95% CI = 0.860–0.903; OR = 0.485, 95% CI = 0.470–0.501). UM and BM had worse 5-year OS versus BCT (UM: 0.926, vs BM: 0.952, vs BCT: 0.960).ConclusionsBCT is increasingly used to treat HER2+ and TN tumors. More extensive surgery is not associated with better survival outcomes, regardless of tumor phenotype.     

Topoisomerase II-�� as a predictive factor of response to therapy with anthracyclines in locally advanced breast cancer

Background

Topoisomerase II-?? is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-?? expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-?? overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients.

Material and methods

Topoisomerase II-??, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-?? status and dose intensity.

Results

Tumors from 40 patients (36%) showed topoisomerase II-?? overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-?? expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-?? (P = 0.010 and 0.027, respectively). Negative PR (P = 0.041), positive HER2 (P = 0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-?? negative shown no significance (HR = 0.92, IC 95% 0.39-2.15, P = 0.839) while the multivariate analysis in topoisomerase II-?? positive, dose intensity shown to be statistically significant (HR = 2.725, IC 95% 1.07-6.95, P = 0.036).

Conclusions

Our data do not support a correlation between topoisomerase II-?? expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-?? may experience better clinical benefit with higher anthracycline dose intensity.     

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive,HER2-negative metastatic breast cancer: A study of the National Cancer Center,China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population.MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test.ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.     

Smoking and survival of breast cancer patients: A meta-analysis of cohort studies

ObjectivesPublished articles reported controversial results about the association of breast cancer survival with smoking. Hence, a meta-analysis was performed to investigate this association.MethodsA comprehensive search was performed to identify relevant cohort studies (up to May 31st, 2016). In the current smoking and former smoking v. never smoking analyses, the fixed- or random-effect model was selected based on the heterogeneity test among studies. And the heterogeneity was measured using Q test and I² statistic. Publication bias was estimated using Egger's regression asymmetry test.ResultsThirteen articles with 44 studies were included. Compared with never smokers, current smokers have a higher breast cancer-specific mortality and all-cause mortality, with pooled hazard ratio (HR) (HR = 1.30 95%CI: 1.16–1.45; I² = 52.4%) and (HR = 1.59, 95%CI: 1.41–1.78; I² = 87.1%), respectively. While former smokers tend to have a moderately increased all-cause mortality (HR = 1.10, 95%CI: 1.07–1.12; I² = 0.0%), but there was no significant association between former smoking and breast cancer-specific mortality (HR = 0.95, 95%CI: 0.90–1.02; I² = 0.0%).ConclusionThe present evidence indicates that current smoking leads to higher breast cancer-specific mortality and all-cause mortality than never smoking in breast cancer patients. However former smoking just causes a mild increase in all-cause morality, but not breast cancer-specific mortality.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.     

Impact of locoregional treatment on survival in patients presented with metastatic breast carcinoma

ObjectivesIn this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC).Materials and methodsThe medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27–83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n = 50; breast conserving surgery (BCS), n = 4] and 132 (70%) had surgery (mastectomy, n = 119; BCS, n = 13) followed by locoregional RT.ResultsThe median follow-up time was 35 months (range, 4–149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS (p < 0.001). Median survival was 67 months and 37 months, respectively.ConclusionOur study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT.     

Response to treatment and long‐term outcomes in kidney transplant recipients with acute T cell–mediated rejection

The recent recognition of complex and chronic phenotypes of T cell–mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR—a condition previously considered to lack relevant consequences for allograft survival—to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy‐proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92‐0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10‐1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00‐1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13‐4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i‐IF/TA) (HR = 1.87; 95% CI = 1.08‐3.25; P = .025), and donor‐specific anti‐HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46‐4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41‐0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i‐IF/TA, and anti‐HLA DSAs (cross‐validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody‐mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.     

Predictive Factors for Revision and Survivorship Analysis of a Prevalent 36-mm Metal-on-Metal Total Hip Replacement System: A Large Single-Center Retrospective Cohort Study

BackgroundTo our knowledge, this is the largest single-center cohort of the 36-mm Corail-Pinnacle metal-on-metal total hip replacements system, aiming to determine 10-year survivorship and identify predictors of revision. We further assessed year of implantation given reports of manufacturing variations affecting shells made after 2006 predisposing these components to increasing wear.MethodsAll Corail-Pinnacle 36-mm metal-on-metal hips implanted in a single center (2005-2012). The effect of patient and implant-related variables, and year of implantation on revision risk was assessed using Kaplan-Meier, Cox regression, and interrupted time series analysis.ResultsIn total, 1212 metal-on-metal total hip replacements were implanted with a 10-year survival rate of 83.4% (95% confidence interval [CI] = 81.3-85.5). Mean follow-up duration was 7.3 years with 61% of patients reaching a minimum of 7 years of follow-up. One hundred nineteen patients required revision surgery (9.8%). Univariate analysis identified female gender (hazard ratio [HR] = 1.608, CI = 1.093-2.364, P = .016), age at implantation (HR = 0.982, CI = 0.968-0.997, P = .019), smaller 50-mm to 54-mm cup diameter (HR = 1.527, CI = 1.026-2.274, P = .037), and high-offset stems (HR = 2.573, CI = 1.619-4.089, P < .001) as predictors of revision. Multivariate modeling confirmed female gender and high-offset stems as significant predictors of revision. For components implanted after 2007, the number of revisions showed no statistically significant step increase compared to pre-2007 implantation.ConclusionWe observed a high 10-year failure rate (16.6%) with this implant, mostly due to adverse reaction to metal debris. Female gender and high femoral offset stems were significant predictors for all-cause revision. Year of implantation was not significantly associated with an increasing number of revisions from 2007 onwards, although further studies to validate the impact of manufacturing discrepancies are recommended.