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Delayed initiation of adjuvant chemotherapy in older women with breast cancer.

ABSTRACT: BACKGROUND:Adjuvant 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. METHODS:Patients 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. RESULTS:Among 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. CONCLUSION:Chemotherapy 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.

SUBMITTER: Smith-Graziani D

PROVIDER: S-EPMC7541132 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Delayed initiation of adjuvant chemotherapy in older women with breast cancer.

Smith-Graziani Demetria D Lei Xiudong X Giordano Sharon H SH Zhao Hui H Karuturi Meghan M Chavez-MacGregor Mariana M

Cancer medicine 20200807 19

<h4>Background</h4>Adjuvant 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.<h4>Methods</h4>Patients age >66 years diagnosed 2001-2015 with localized or regional BC were identified in the SEER-Medicare and Texas C ...[more]

PMID: 32767723

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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.

Project description:PurposeOlder women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions.MethodsThis was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival.ResultsThree hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; P = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; P < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; P < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank P = .02).ConclusionOne in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.

Project description:PurposeOlder cancer patients are at increased risk of cancer-related cognitive impairment. The purpose of this study was to assess the alterations in intrinsic brain activity associated with adjuvant chemotherapy in older women with breast cancer.MethodsChemotherapy treatment (CT) group included sixteen women aged ≥ 60 years (range 60-82 years) with stage I-III breast cancers, who underwent both resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological testing with NIH Toolbox for Cognition before adjuvant chemotherapy, at time point 1 (TP1), and again within 1 month after completing chemotherapy, at time point 2 (TP2). Fourteen age- and sex-matched healthy controls (HC) underwent the same assessments at matched intervals. Three voxel-wise rs-fMRI parameters: amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity, were computed at each time point. The changes in rs-fMRI parameters from TP1 to TP2 for each group, the group differences in changes (the CT group vs. the HC group), and the group difference in the baseline rs-fMRI parameters were assessed. In addition, correlative analysis between the rs-fMRI parameters and neuropsychological testing scores was also performed.ResultsIn the CT group, one brain region, which included parts of the bilateral subcallosal gyri and right anterior cingulate gyrus, displayed increased ALFF from TP1 to TP2 (cluster p-corrected = 0.024); another brain region in the left precuneus displayed decreased fALFF from TP1 to TP2 (cluster level p-corrected = 0.025). No significant changes in the rs-fMRI parameters from TP1 to TP2 were observed in the HC group. Although ALFF and fALFF alterations were observed only in the CT group, none of the between-group differences in rs-fMRI parameter changes reached statistical significance.ConclusionsOur study results of ALFF and fALFF alterations in the chemotherapy-treated women suggest that adjuvant chemotherapy may affect intrinsic brain activity in older women with breast cancer.

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Delayed initiation of adjuvant chemotherapy in older women with breast cancer.

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Delayed initiation of adjuvant chemotherapy in older women with breast cancer.

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