Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent.
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ABSTRACT:
SUBMITTER: Yu KD
PROVIDER: S-EPMC5542291 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
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Project description:ImportanceAdjuvant chemotherapy improves outcomes of patients with breast cancer. However, the optimal timing of chemotherapy initiation is unknown. Delayed administration can decrease the benefit of cytotoxic systemic therapies.ObjectiveTo identify the determinants in delayed chemotherapy initiation and to determine the relationship between time to chemotherapy (TTC) and outcome according to breast cancer subtype. We hypothesized that prolonged TTC would be associated with adverse outcomes.Design, setting, and participantsIn an observational, population-based investigation using data from the California Cancer Registry, we studied a total of 24 843 patients with stage I to III invasive breast cancer diagnosed between January 1, 2005, and December 31, 2010, and treated with adjuvant chemotherapy. Data analysis was performed between August 2014 and August 2015.Main outcomes and measuresTime to chemotherapy was defined as the number of days between surgery and the first dose of chemotherapy, and delayed TTC was defined as 91 or more days from surgery to the first dose of adjuvant chemotherapy. We evaluated overall survival and breast cancer-specific survival. Logistic regression and Cox proportional hazard models were used.ResultsIn all, 24 843 patients were included. Median age at diagnosis was 53 years, and median was TTC was 46 days. Factors associated with delays in TTC included low socioeconomic status, breast reconstruction, nonprivate insurance, and Hispanic ethnicity or non-Hispanic black race. Compared with patients receiving chemotherapy within 31 days from surgery, there was no evidence of adverse outcomes among those with TTC of 31 to 60 or 60 to 90 days. Patients treated 91 or more days from surgery experienced worse overall survival (hazard ratio [HR], 1.34; 95% CI, 1.15-1.57) and worse breast cancer-specific survival (HR, 1.27; 95% CI, 1.05-1.53). In a subgroup analysis according to subtype, longer TTC caused patients with triple-negative breast cancer to have worse overall survival (HR, 1.53; 95% CI, 1.17-2.00) and worse breast cancer-specific survival (HR, 1.53; 95% CI 1.17-2.07).Conclusions and relevanceFor patients with breast cancer, adverse outcomes are associated with delaying initiation of adjuvant chemotherapy 91 or more days. Delayed TTC was particularly detrimental among patients with triple-negative breast cancer. The determinants of delays in chemotherapy initiation appeared to be sociodemographic, and clinicians should provide timelier care to all patients.
| S-EPMC5920529 | biostudies-literature
Project description:BackgroundAdjuvant chemotherapy benefits early-stage breast cancer (BC) patients. Older women receive guideline-adherent treatment less frequently and experience treatment delays more frequently. We evaluated factors associated with delaying adjuvant chemotherapy and the delays' survival impact in a large population-based cohort of elderly BC patients.MethodsPatients age >66 years diagnosed 2001-2015 with localized or regional BC were identified in the SEER-Medicare and Texas Cancer Registry-Medicare databases. Time from surgery to chemotherapy (TTC) was categorized into four groups: 0-30, 31-60, 61-90, and >90 days. We identified predictors of delays, estimated overall (OS) and BC-specific (BCSS) survival, and determined the association between TTC and outcome adjusting for other variables.ResultsAmong 28,968 women (median age 71 years), median TTC was 43 days. 10.7% of patients experienced TTC >90 days. Older age, Black or Hispanic race/ethnicity, unmarried status, more comorbidities, hormone receptor-positivity, mastectomy, Oncotype DX testing, and full state buy-in were associated with increased risk of delay. Five-year OS estimates by TTC group were 0.82, 0.81, 0.80, and 0.74, respectively (p<.001). BCSS demonstrated a similar trend (p<.001). Chemotherapy delay was associated with worse OS (HR=1.33, 95%CI 1.25-1.40) and BCSS (HR=1.39, 95%CI 1.27-1.53). In subgroup analysis, delayed chemotherapy was associated with worse OS and BCSS among patients with hormone receptor-positive (HR=1.56, 95%CI 0.97-2.51), HER2-positive (HR=1.99, 95%CI 1.04-3.79), and triple-negative (HR=2.15, 95%CI 1.38-3.36) tumors.ConclusionChemotherapy delays are associated with worse survival in older BC patients. Providers should avoid delays and initiate chemotherapy ≤90 days after surgery regardless of patients' BC subtype or age.
| S-EPMC7541132 | biostudies-literature
Project description:ImportanceAdjuvant chemotherapy offers a survival benefit to a number of staging scenarios in non-small-cell lung cancer. Variable recovery from lung cancer surgery may delay a patient's ability to tolerate adjuvant chemotherapy, yet the urgency of chemotherapy initiation is unclear.ObjectiveTo assess differences in survival according to the time interval between non-small-cell lung cancer resection and the initiation of postoperative chemotherapy to determine the association between adjuvant treatment timing and efficacy.Design, setting, and participantsThis retrospective observational study examined treatment-naive patients with completely resected non-small-cell lung cancer who received postoperative multiagent chemotherapy between 18 and 127 days after resection between January 2004 and December 2012. The study population was limited to patients with lymph node metastases, tumors 4 cm or larger, or local extension. Patients were identified from the National Cancer Database, a hospital-based tumor registry that captures more than 70% of incident lung cancer cases in the United States. The association between time to initiation of adjuvant chemotherapy and survival was evaluated using Cox models with restricted cubic splines.ExposuresAdjuvant chemotherapy administered at different time points after surgery.Main outcomes and measuresEffectiveness of adjuvant chemotherapy according to time to initiation after surgery.ResultsA total of 12 473 patients (median [interquartile range] age, 64 [57-70] years) were identified: 3073 patients (25%) with stage I disease; 5981 patients (48%), stage II; and 3419 patients (27%), stage III. A Cox model with restricted cubic splines identified the lowest mortality risk when chemotherapy was started 50 days postoperatively (95% CI, 39-56 days). Initiation of chemotherapy after this interval (57-127 days; ie, the later cohort) did not increase mortality (hazard ratio [HR], 1.037; 95% CI, 0.972-1.105; P = .27). Furthermore, in a Cox model of 3976 propensity-matched pairs, patients who received chemotherapy during the later interval had a lower mortality risk than those treated with surgery only (HR, 0.664; 95% CI, 0.623-0.707; P < .001).Conclusions and relevanceIn the National Cancer Database, adjuvant chemotherapy remained efficacious when started 7 to 18 weeks after non-small-cell lung cancer resection. Patients who recover slowly from non-small-cell lung cancer surgery may still benefit from delayed adjuvant chemotherapy started up to 4 months after surgery.
| S-EPMC5824207 | biostudies-literature
Project description:The relationship between survival and time to the start of adjuvant chemotherapy (AC) among breast cancer patients is unclear. In order to illustrate the effect of delaying the initiation of AC on survival we have undertaken a systematic review and meta-analysis. We identified 12 available studies in the meta-analysis including 15 independent analytical groups. This meta-analysis showed that a 4-week delay before AC was associated with a significantly worse overall survival (OS)(HR=1.13; 95% confidence interval [CI], 1.08-1.19) and disease free survival (DFS)(HR=1.14; 95%CI, 1.05-1.24). Two studies categorized patients into hormone receptor-positive, ERBB2-positive, and triple-negative breast cancer (TNBC) patients according to the clinicopathological features of breast cancer. The HRs for OS between waiting time (WT) ≤30 days and 31-60 days in the subgroups were extracted and analyzed. The analysis demonstrated that a WT of 31-60 days was related to worse OS among patients with TNBC (HR, 1.26; 95% CI, 1.08-1.48), but had no significant effect on OS among those with hormone receptor-positive (HR, 1.02; 95% CI, 0.89-1.15) or ERBB2-postive (HR, 0.95; 95%CI, 0.79-1.14) tumors. In this meta-analysis of the eligible literatures reviewing the time to AC, a longer waiting time to adjuvant chemotherapy may lead to worse survival in breast cancer patients, especially in TNBC patients.
| S-EPMC5788675 | biostudies-literature
Project description:PurposeAdiposity has been linked with increased breast cancer risk and mortality. It is established that etiologic associations for adiposity vary by tumor subtype, but the influence of adiposity on subtype-specific survival is unknown.MethodsStudy participants were 1,109 invasive breast cancer participants in the population-based Carolina Breast Cancer Study, diagnosed between 1993 and 2001, and with tissue blocks available for immunohistochemical subtyping. General and central adiposities were assessed by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, based on in-person measurements after diagnosis. Vital status as of 2011 was determined using the National Death Index (median follow-up = 13.5 years). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer (BC)-specific and all-cause mortalities.ResultsAmong all patients, high WHR (≥0.84), but not BMI, was associated with all-cause mortality (adjusted HR 1.50, 95% CI 1.11-2.05, <0.77 as reference). No significant association between adiposity and BC-specific mortality was detected, although there was a suggestion of increased mortality risk among high-BMI (≥30 kg/m(2)) patients with basal-like tumors (adjusted HR 2.44, 95% CI 0.97-6.12, <25 kg/m(2) as reference). Quantitative differences in all-cause mortality were observed by subtype, with BMI associated with basal-like mortality and WHR associated with luminal mortality. The associations were attenuated by tumor characteristics.ConclusionsOur study confirms the association of adiposity and unfavorable overall survival in breast cancer patients and suggests that this association may vary by intrinsic subtype and adiposity measure.
| S-EPMC5057532 | biostudies-literature
Project description:BACKGROUND: We assessed the sensitivity to adjuvant chemotherapy in cell cycle checkpoint kinase 2 (CHEK2) vs non-CHEK2 breast cancer patients by comparing the contralateral breast cancer incidence and distant disease-free and breast cancer-specific survival between both groups, stratified for adjuvant chemotherapy. METHODS: One Dutch hereditary non-BRCA1/2 breast cancer patient cohort (n=1220) and two Dutch cohorts unselected for family history (n=1014 and n=2488, respectively) were genotyped for CHEK2 1100delC. Hazard ratios for contralateral breast cancer, distant disease-free and breast cancer-specific death for mutation carriers vs noncarriers were calculated using the Cox proportional hazard method, stratified for adjuvant chemotherapy. RESULTS: The CHEK2 mutation carriers (n=193) had an increased incidence of contralateral breast cancer (multivariate hazard ratio 3.97, 95% confidence interval 2.59-6.07). Distant disease-free and breast cancer-specific survival were similar in the first 6 years in mutation carriers compared with noncarriers, but diverted as of 6 years after breast cancer diagnosis (multivariate hazard ratios and 95% confidence intervals 2.65 (1.79-3.93) and 2.05 (1.41-2.99), respectively). No significant interaction between CHEK2 and adjuvant chemotherapy was observed. CONCLUSIONS: The CHEK2 1100delC-associated breast cancer is associated with a higher contralateral breast cancer rate as well as worse survival measures beyond 6 years after diagnosis. No differential sensitivity to adjuvant chemotherapy was observed in CHEK2 patients.
| S-EPMC4150261 | biostudies-other
Project description:We investigated whether GSTT1 ("null" allele), GSTM1 ("null"allele), GSTP1 (A313G), RFC1 (G80A), MTHFR (C677T), TS (2R/3R) polymorphisms were associated with toxicity and survival in patients with early breast cancer (EBC) treated with adjuvant chemotherapy (CT).This prospective trial included patients with stage I-III BC subjected to CT with CMF or FEC regimens. PCR-RFLP was performed for MTHFR, RFC1 and GSTP1, while PCR for TS, GSTT1 and GSTM1 genes.Among the 244 patients consecutively enrolled, 48.7% were treated with FEC and 51.3% with CMF. Patients with TS2R/3R genotype showed less frequently severe neutropenia (G3/G4) than those with TS2R/2R and 3R/3R genotype (p = 0.038). Patients with MTHFRCT genotype had a higher probability of developing severe neutropenia than those with MTHFR CC genotype (p = 0.043). Patients with RFC1GG or GSTT1-null genotype or their combination (GSTT1-null/RFC1GG) were significantly associated with a shorter disease free survival (DFS) (p = 0.009, p = 0.053, p = 0.003, respectively) and overall survival (OS) (p = 0.036, p = 0.015, p = 0.005, respectively). Multivariate analysis confirmed the association of RFC1GG genotype with a shorter DFS (p = 0.018) and of GSTT1-null genotype of a worse OS (p = 0.003), as well as for the combined genotypes GSTT1-null/RFC1GG, (DFS: p = 0.004 and OS: p = 0.003).Our data suggest that TS2R/2R and 3R/3R or MTHFR CT genotypes have a potential role in identifying patients with greater risk of toxicity to CMF/FEC and that RFC1 GG and GSTT1-null genotypes alone or in combination could be important markers in predicting clinical outcome in EBC patients.
| S-EPMC5530465 | biostudies-literature
Project description:It is unknown whether racial differences exist in adjuvant chemotherapy initiation among women with similar oncotype DX (ODX) risk scores. We examined whether adjuvant chemotherapy initiation varied by race. Data come from the Phase III, Carolina Breast Cancer Study, a longitudinal, population-based study of North Carolina women diagnosed with breast cancer between 2008 and 2014. We used modified Poisson regression and report adjusted relative risk (aRR) and 95% confidence intervals (95%CI) to estimate the association between race and adjuvant chemotherapy initiation across ODX risk groups among women who received the test (n = 541). Among women who underwent ODX testing, 54.2, 37.5, and 8.3% of women had tumors classified as low-, intermediate-, and high-risk groups, respectively. We observed no racial variation in adjuvant chemotherapy initiation. Increasing ODX risk score (aRR = 1.39, 95%CI = 1.22, 1.58) and being married (aRR = 2.92, 95%CI = 1.12, 7.60) were independently associated with an increased likelihood of adjuvant chemotherapy in the low-risk group. Among women in the intermediate-risk group, ODX risk score (aRR = 1.15, 95%CI = 1.11, 1.20), younger age (aRR = 1.95, 95%CI = 1.35, 2.81), larger tumor size (aRR = 1.70, 95%CI = 1.22, 2.35), and higher income were independently associated with increased likelihood of adjuvant chemotherapy initiation. No racial differences were found in adjuvant chemotherapy initiation among women receiving ODX testing. As treatment decision-making becomes increasingly targeted with the use of genetic technologies, these results provide evidence that test results may drive treatment in a similar way across racial subgroups.
| S-EPMC4562432 | biostudies-literature
Project description:Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30?days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30?days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30?days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30?days were more likely than those with TTC within 30?days to die within 10?years after surgery (HR 1.69 (95% CI 1.22-2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10?years overall survival between those with TTC within or beyond 30?days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30?days (HR 1.04 (95% CI 0.84-1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30?days is associated with decreased 10?years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted.
| S-EPMC7317578 | biostudies-literature
Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC.MethodsWe retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20-83 days]).ResultsPatient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334-6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081-3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160-3.862) were significantly associated with shorter OS.ConclusionsAdjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications.
| S-EPMC5354454 | biostudies-literature