Influence of Timing of Initiation of Adjuvant Chemotherapy Over Survival in Breast Cancer: A Negative Outcome Study by the Spanish Breast Cancer Research Group (GEICAM)

Sánchez, Carlos Jara; Ruı́z, Amparo; Martín, Miguel; Antón, Antonio; Munárriz, Blanca; Plazaola, Arrate; Schneider, J.; Prado, Purificación Martínez del; Alba, Emilio; Fernández-Aramburo, Antonio

doi:10.1007/s10549-006-9282-0

Cited by 55 publications

(21 citation statements)

References 18 publications

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“…Reports are conflicting since some studies have found no relationship between TTC and outcome. 11,15,25 However, these studies 11,15,25 were small, reported on single-institution data, and do not reflect contemporary breast cancer systemic management.…”

Section: Discussionmentioning

confidence: 98%

Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer

et al. 2016

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IMPORTANCE Adjuvant 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. OBJECTIVE To 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 PARTICIPANTS In 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 MEASURES Time 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. RESULTS In 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 RELEVANCE For 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.

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Section: Discussionmentioning

confidence: 98%

Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer

et al. 2016

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“…In other relevant studies of association between time to AC and survival but not included in this meta-analysis due to low validity, inconsistent results were presented. Studies by Buzdar et al [28], Shannon et al [29], Samur et al [4], and Sanchez et al [30] failed to show inferior outcome for chemotherapy started later after surgery compared with chemotherapy stared early. In contrast, Alkis et al [31] reported that OS was significantly better in patients who started AC within 44 days.…”

Section: Discussionmentioning

confidence: 99%

Association between delayed initiation of adjuvant CMF or anthracycline-based chemotherapy and survival in breast cancer: a systematic review and meta-analysis

Huang

Zhang

et al. 2013

BMC Cancer

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BackgroundAdjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes.MethodsPubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (between January-1 1978 and January-29, 2013) were searched for eligible studies. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) corresponding to a continuous representation per 4-week delay of AC. Most used regimens of chemotherapy in included studies were CMF (cyclophosphamide, methotrexate, and fluorouracil) or anthracycline-based. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity.ResultsWe included 7 eligible studies with 9 independent analytical groups involving 34,097 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 4 hospital-/population-based retrospective study. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.15; 95% confidence interval [CI], 1.03-1.28; random-effects model) and DFS (HR = 1.16; 95% CI, 1.01-1.33; fixed-effects model). One study caused a significant between-study heterogeneity for OS (P < 0.001; I2 = 75.4%); after excluding that single study, there was no heterogeneity (P = 0.257; I2 = 23.6%) and the HR was more significant (HR = 1.17; 95% CI, 1.12-1.22; fixed-effects model). Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS.ConclusionsLonger time to AC is probably associated with worse survival in breast cancer patients.

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“…Five of eight studies analysing institutional or registry datasets (level III‐2 evidence) demonstrated no survival impact of TTC, with maximum delay intervals of 35 days, 9 weeks, and 3 months . Of those reporting a negative prognostic impact of delayed TTC, reduced survival was observed at measured delay intervals of >45, 60, 70 and 98 days .…”

Section: Methodsmentioning

confidence: 96%

“…Of these, nine papers were included in the final review to answer the question of whether TTC impacts survival outcomes in breast cancer. All studies reported outcomes based on the TTC interval from date of surgery to commencement of adjuvant chemotherapy . No studies were available in the setting of neoadjuvant or palliative chemotherapy – a notable evidence gap.…”

Section: Methodsmentioning

confidence: 99%

Timely initiation of chemotherapy: a systematic literature review of six priority cancers – results and recommendations for clinical practice

Alexander

Blum

Burbury

et al. 2017

Internal Medicine Journal

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This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.

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Influence of Timing of Initiation of Adjuvant Chemotherapy Over Survival in Breast Cancer: A Negative Outcome Study by the Spanish Breast Cancer Research Group (GEICAM)

Cited by 55 publications

References 18 publications

Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer

Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer

Association between delayed initiation of adjuvant CMF or anthracycline-based chemotherapy and survival in breast cancer: a systematic review and meta-analysis

Timely initiation of chemotherapy: a systematic literature review of six priority cancers – results and recommendations for clinical practice

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