Chemotherapy for early-stage breast cancer: a brief history.
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ABSTRACT:
SUBMITTER: Verrill M
PROVIDER: S-EPMC2752226 | biostudies-other | 2009 Sep
REPOSITORIES: biostudies-other
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Project description:BackgroundOlder women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older.MethodsWe randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival.ResultsWhen the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%).ConclusionsStandard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)
| S-EPMC3082436 | biostudies-literature
Project description:To compare the risk of hospitalization between patients with early-stage breast cancer who received different chemotherapy regimens.We identified 3,567 patients older than age 65 years from the SEER/Texas Cancer Registry-Medicare database and 9,327 patients younger than age 65 years from the MarketScan database who were diagnosed with early-stage breast cancer between 2003 and 2007. The selection was nonrandomized and nonprospectively collected. We categorized patients according to the regimens they received: docetaxel (T) and cyclophosphamide (C), doxorubicin (A) and C, TAC, AC + T, dose-dense AC + paclitaxel (P) or AC + weekly P. We compared the rates of chemotherapy-related hospitalizations that occurred within 6 months of chemotherapy initiation and used multivariable logistic regression analysis to identify the factors associated with these hospitalizations.Among patients younger than age 65 years, the hospitalization rates ranged from 6.2% (dose-dense AC + P) to 10.0% (TAC), and those who received TAC and AC + T had significantly higher rates of hospitalization than did patients who received TC. Among patients older than age 65 years, these rates ranged from 12.7% (TC) to 24.2% (TAC) and the rates of hospitalization of patients who received TAC, AC + T, AC, or AC + weekly P were higher than those of patients who received TC.TAC and AC + T were associated with the highest risk of hospitalization in patients younger than age 65 years. Among patients older than age 65 years, all regimens (aside from dose-dense AC + P) were associated with a higher risk of hospitalization than TC. Results may be affected by selection biases where less aggressive regimens are offered to frailer patients.
| S-EPMC4164758 | biostudies-other
Project description:Breast cancer is the most common cancer among women worldwide, and survival rates are increasing. Chemotherapy-associated peripheral neuropathy (PN) is clinically important because of effects on quality of life (QOL) and potential effects on dose limitations. This adverse drug reaction is associated with certain classes of chemotherapy and commonly presents as peripheral sensory neuropathy whose natural course is largely unknown. The literature was reviewed to determine the frequency and characteristics of PN associated with adjuvant chemotherapy in early-stage breast cancer (ESBC) to explore the potential impact on long-term (one or more years after diagnosis) health outcomes and QOL. MEDLINE, PubMed, Embase, and the Cochrane Library were searched for relevant English-language randomized controlled trials, systematic reviews, meta-analyses, and case-control and cohort studies published between January 1990 and July 1996. Included studies were limited to current adjuvant regimens (eg, anthracyclines, taxanes, cyclophosphamide, platinum compounds). Two investigators independently reviewed abstracts, full-text articles, and extracted data from fair- and good-quality studies. Discrepancies in quality assessment and data extraction were resolved by consensus. We identified 364 articles; 60 were eligible for full-text review. Only five reports of four studies provided data beyond one year post-treatment initiation. Studies used different measures to assess PN. Neuropathic symptoms persisted in 11.0% to more than 80% of participants at one to three years following treatment. There is a paucity of data describing persistent PN in ESBC patients. Consistent use of validated measures and well-conducted randomized clinical trials or observational studies are needed to evaluate the incidence, persistence, and QOL associated with the long-term effects of PN.
| S-EPMC5825681 | biostudies-other
Project description:Importance:Several types of cancer have been linked to a higher risk of developing atrial fibrillation (AF). Fewer data exist regarding early-stage breast cancer (EBC), for which cardio-oncology concerns are more pertinent. Objective:To investigate the association of EBC and subsequent chemotherapy with the risk of developing AF. Design, Setting, and Participants:This was a population-based, retrospective, matched cohort study conducted in Toronto, Ontario, Canada, of 68 113 women diagnosed with EBC between April 2007 and December 2016 who were matched 1:3 to a cancer-free control group based on birth year and receipt of breast imaging. Prevalence of AF before the index date (date of EBC diagnosis) was compared between the cohorts using the McNemar test. Cumulative incidence function curves were used to describe the AF incidence. To study preexisting AF, participants were matched before exclusion for prior AF. For the remaining analyses, we excluded women with prior AF before matching. An analysis was conducted beginning 1 year after the index date (ie, excluding AF diagnoses in year 1), which we stratified by chemotherapy exposure. Multivariable cause-specific regression was used to determine the hazard ratio (HR) associated with EBC relative to the controls and the association of chemotherapy with AF in patients with EBC. Exposures:Breast cancer and chemotherapy. Main Outcomes and Measures:Incidence of AF. Results:A total of 68?113 women with EBC and 204?330 cancer-free controls were included in the study; both groups had a mean (SD) age of 60 (13) years. Of the women with EBC, 44.3% were diagnosed as having stage I breast cancer; 38.7%, stage II; and 13.4%, stage III; cancer stage information was missing for 3.6% of the patients. No difference was observed in preexisting AF prevalence (5.3% in the EBC cohort vs 5.2% in controls; P?=?.21). At 10 years after the index date, the AF incidence was 7.4% (95% CI, 7.1%-7.7%) for women with EBC and 6.8% (95% CI, 6.7%-7.0%) for the controls (P?<?.001). The adjusted cause-specific HR was significantly elevated at year 1 (HR, 2.16; 95% CI, 1.94-2.41) and after year 5 (HR, 1.20; 95% CI, 1.11-1.30) but not during years 2 through 5. Analyses beginning 1 year after diagnosis showed attenuated differences that remained statistically significant: the cumulative incidence of AF at 9-year follow-up was 7.0% (95% CI, 6.7%-7.3%) for patients with EBC and 6.5% (95% CI, 6.3%-6.7%) for the cancer-free controls. The rate of AF was higher in women who received chemotherapy (adjusted HR, 1.23; 95% CI, 1.13-1.35) but was not associated with exposure to anthracyclines or trastuzumab. Conclusions and Relevance:This study's findings suggest that patients with EBC may not have a higher prevalence of AF before cancer diagnosis. A higher rate of AF was observed in the first year and after 5 years following the EBC diagnosis. The rate of AF was higher in patients who received chemotherapy but appeared to not be associated with specific cardiotoxic agents. These findings suggest that the early and late periods of increased AF risk in EBC survivors warrant focused research to better understand the underlying causes and subsequent implications.
| S-EPMC6755537 | biostudies-literature
Project description:Background:There is growing concern about overtreatment of breast cancer as outcomes have improved over time. However, little is known about how chemotherapy use and oncologists' recommendations have changed in recent years. Methods:We surveyed 5080 women (70% response rate) diagnosed with breast cancer between 2013 and 2015 and accrued through two Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles) about chemotherapy receipt and their oncologists' chemotherapy recommendations. We surveyed 504 attending oncologists (60.3% response rate ) about chemotherapy recommendations in node-negative and node-positive case scenarios. We conducted descriptive statistics of chemotherapy use and patients' report of oncologists' recommendations and used a generalized linear mixed model of chemotherapy use according to time and clinical factors. All statistical tests were two-sided. Results:The analytic sample was 2926 patients with stage I-II, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. From 2013 to 2015, keeping other factors constant, chemotherapy use was estimated to decline from 34.5% (95% confidence interval [CI] = 30.8% to 38.3%) to 21.3% (95% CI = 19.0% to 23.7%, P < .001). Estimated decline in chemotherapy use was from 26.6% (95% CI = 23.0% to 30.7%) to 14.1% (95% CI = 12.0% to 16.3%) for node-negative/micrometastasis patients and from 81.1% (95% CI = 76.6% to 85.0%) to 64.2% (95% CI = 58.6% to 69.6%) for node-positive patients. Use of the 21-gene recurrence score (RS) did not change among node-negative/micrometastasis patients, and increasing RS use in node-positive patients accounted for one-third of the chemotherapy decline. Patients' report of oncologists' recommendations for chemotherapy declined from 44.9% (95% CI = 40.2% to 49.7%) to 31.6% (95% CI = 25.9% to 37.9%), controlling for other factors. Oncologists were much more likely to order RS if patient preferences were discordant with their recommendations (67.4%, 95% CI = 61.7% to 73.0%, vs 17.5%, 95% CI = 13.1% to 22.0%, concordant), and they adjusted recommendations based on patient preferences and RS results. Conclusions:For both node-negative/micrometastasis and node-positive patients, chemotherapy receipt and oncologists' recommendations for chemotherapy declined markedly over time, without substantial change in practice guidelines. Results of ongoing trials will be essential to confirm the quality of this approach to breast cancer care.
| S-EPMC5946952 | biostudies-literature
Project description:PurposeTo investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer.Patients and methodsWe retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cut-off value of interval time from surgery to the start of chemotherapy was calculated by Maxstat.ResultsThe median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cut-off value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes.ConclusionFor women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes.
| S-EPMC7538693 | biostudies-literature
Project description:Many women with early-stage breast cancer are working at the time of diagnosis and survive without disease recurrence. The short-term impact of chemotherapy receipt on employment has been demonstrated, but the long-term impact merits further research.The authors conducted a longitudinal multicenter cohort study of women diagnosed with nonmetastatic breast cancer between 2005 and 2007, as reported to the population-based Los Angeles and Detroit Surveillance, Epidemiology, and End Results program registries. Of 3133 individuals who were sent surveys, 2290 (73%) completed a baseline survey soon after diagnosis and of these, 1536 (67%) completed a 4-year follow-up questionnaire.Of the 1026 patients aged?<?65 years at the time of diagnosis whose breast cancer did not recur and who responded to both surveys, 746 (76%) worked for pay before diagnosis. Of these, 236 (30%) were no longer working at the time of the follow-up survey. Women who received chemotherapy as part of their initial treatment were less likely to be working at the time of the follow-up survey (38% vs 27%; P?=?.003). Chemotherapy receipt at the time of diagnosis (odds ratio, 1.4; P?=?.04) was found to be independently associated with unemployment during survivorship in a multivariable model. Many women who were not employed during the survivorship period wanted to work: 50% reported that it was important for them to work and 31% were actively seeking work.Unemployment among survivors of breast cancer 4 years after diagnosis is often undesired and appears to be related to the receipt of chemotherapy during initial treatment. These findings should be considered when patients decide whether to receive adjuvant chemotherapy, particularly when the expected benefit is low.
| S-EPMC4047155 | biostudies-literature
Project description:There is a lack of sufficient evidence-based data defining the optimal adjuvant systemic therapies in older women. Recommendations are mainly based on retrospective studies, subgroup analyses within larger randomised trials and expert opinion. Treatment decisions should consider the functional fitness of the patient, co-morbidities, in addition to chronological age with the aim to balance risks and potential benefits from treatment(s). In this review, we discuss assessment tools to aid clinicians to select elderly patients who are 'fit' for chemotherapy, and review the literature on the use of chemotherapy and of the anti-HER 2 antibody trastuzumab in this population. We will also review two commonly used prediction models to assess their accuracy in predicting survival outcomes in elderly patients. Ongoing clinical trials specifically focusing on older patients may help to clarify the absolute benefits and risks of adjuvant systemic therapy in this age group.
| S-EPMC5220141 | biostudies-literature
Project description:Copy number alteration profiling of human early-stage (stage I and II) breast cancers. We aimed to describe the commonly occurred chromosome alterations in early-stage breast cancer (stage I and II) and to explore the implications of the recurrently altered regions (RAR) on the patient prognosis. For this purpose, we analyzed the DNA copy number alterations (CNAs) across the whole genome using oligoarray-comparative genomic hybridization (CGH) in the discovery set of EBC patients.
2012-05-09 | GSE37839 | GEO
Project description:Copy number alteration profiling of human early-stage (stage I and II) breast cancers. We aimed to describe the commonly occurred chromosome alterations in early-stage breast cancer (stage I and II) and to explore the implications of the recurrently altered regions (RAR) on the patient prognosis. For this purpose, we analyzed the DNA copy number alterations (CNAs) across the whole genome using oligoarray-comparative genomic hybridization (CGH) in the discovery set of EBC patients. 48 cases of early-stage breast cancer were used in this study.
2012-05-08 | E-GEOD-37839 | biostudies-arrayexpress