Specific Adverse Events Predict Survival Benefit in Patients Treated With Tamoxifen or Aromatase Inhibitors: An International Tamoxifen Exemestane Adjuvant Multinational Trial Analysis

2013 ◽  
Vol 31 (18) ◽  
pp. 2257-2264 ◽  
Author(s):  
Duveken B.Y. Fontein ◽  
Caroline Seynaeve ◽  
Peyman Hadji ◽  
Elysée T.M. Hille ◽  
Willemien van de Water ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Endocrine Therapy ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Cox Proportional Hazards ◽  
Endocrine Treatment ◽  
Survival Outcomes ◽  
Cox Proportional Hazards Models

Purpose Specific adverse events (AEs) associated with endocrine therapy and related to depletion or blocking of circulating estrogens may be related to treatment efficacy. We investigated the relationship between survival outcomes and specific AEs including vasomotor symptoms (VMSs), musculoskeletal adverse events (MSAEs), and vulvovaginal symptoms (VVSs) in postmenopausal patients with breast cancer participating in the international Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Patients and Methods Primary efficacy end points were disease-free survival (DFS), overall survival (OS), and distant metastases (DM). VMSs, MSAEs, and VVSs arising in the first year of endocrine treatment were considered. Patients who did not start or who discontinued their allocated therapy and/or had an event (recurrence/death) within 1 year after randomization were excluded. Landmark analyses and time-dependent multivariate Cox proportional hazards models assessed survival differences up to 5 years from the start of treatment. Results A total of 9,325 patients were included. Patients with specific AEs (v nonspecific or no AEs) had better DFS and OS (multivariate hazard ratio [HR] for DFS: VMSs, 0.731 [95% CI, 0.618 to 0.866]; MSAEs, 0.826 [95% CI, 0.694 to 0.982]; VVSs, 0.769 [95% CI, 0.585 to 1.01]; multivariate HR for OS: VMSs, 0.583 [95% CI, 0.424 to 0.803]; MSAEs, 0.811 [95% CI, 0.654 to 1.005]; VVSs, 0.570 [95% CI, 0.391 to 0.831]) and fewer DM (VMSs, 0.813 [95% CI, 0.664 to 0.996]; MSAEs, 0.749 [95% CI, 0.601 to 0.934]; VVSs, 0.687 [95% CI, 0.436 to 1.085]) than patients not reporting these symptoms. Increasing numbers of specific AEs were also associated with better survival outcomes. Outcomes were unrelated to treatment allocation. Conclusion Certain specific AEs are associated with superior survival outcomes and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy.

scholarly journals Candidate methylation sites associated with endocrine therapy resistance in ER+/HER2- breast cancer

2020 ◽  
Author(s):  
Maryam Soleimani ◽  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Pernette J. Verschure ◽  
Stefan Wiemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Endocrine Therapy ◽  
Proportional Hazards ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Cox Proportional Hazards ◽  
Endocrine Treatment ◽  
Endocrine Therapy Resistance ◽  
Cox Proportional Hazards Models

Abstract Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+/HER2- tumours from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AI or TAM) that patients received (N=210 and N=172, respectively). We also identified multivariable methylation signatures associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of tumour stage, age, AI treatment, and luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Also at the gene set level, several sets related to endocrine therapy and resistance were identified in both survival and T47D signatures. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours prior to endocrine treatment are associated with development of endocrine resistance.

scholarly journals Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221)

2020 ◽  
Vol 38 (8) ◽  
pp. 804-814 ◽  
Author(s):  
Christine B. Ambrosone ◽  
Gary R. Zirpoli ◽  
Alan D. Hutson ◽  
William E. McCann ◽  
Susan E. McCann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Dietary Supplements ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Survival Outcomes ◽  
Therapeutic Trial ◽  
Supplement Use ◽  
Antioxidant Supplement

PURPOSE Despite reported widespread use of dietary supplements during cancer treatment, few empirical data with regard to their safety or efficacy exist. Because of concerns that some supplements, particularly antioxidants, could reduce the cytotoxicity of chemotherapy, we conducted a prospective study ancillary to a therapeutic trial to evaluate associations between supplement use and breast cancer outcomes. METHODS Patients with breast cancer randomly assigned to an intergroup metronomic trial of cyclophosphamide, doxorubicin, and paclitaxel were queried on their use of supplements at registration and during treatment (n =1,134). Cox proportional hazards regression adjusting for clinical and lifestyle variables was used. Recurrence and survival were indexed at 6 months after enrollment using a landmark approach. RESULTS There were indications that use of any antioxidant supplement (vitamins A, C, and E; carotenoids; coenzyme Q10) both before and during treatment was associated with an increased hazard of recurrence (adjusted hazard ratio [adjHR], 1.41; 95% CI, 0.98 to 2.04; P = .06) and, to a lesser extent, death (adjHR, 1.40; 95% CI, 0.90 to 2.18; P = .14). Relationships with individual antioxidants were weaker perhaps because of small numbers. For nonantioxidants, vitamin B12 use both before and during chemotherapy was significantly associated with poorer disease-free survival (adjHR, 1.83; 95% CI, 1.15 to 2.92; P < .01) and overall survival (adjHR, 2.04; 95% CI, 1.22 to 3.40; P < .01). Use of iron during chemotherapy was significantly associated with recurrence (adjHR, 1.79; 95% CI, 1.20 to 2.67; P < .01) as was use both before and during treatment (adjHR, 1.91; 95% CI, 0.98 to 3.70; P = .06). Results were similar for overall survival. Multivitamin use was not associated with survival outcomes. CONCLUSION Associations between survival outcomes and use of antioxidant and other dietary supplements both before and during chemotherapy are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.

scholarly journals Candidate methylation sites associated with endocrine therapy resistance in the TCGA ER+/HER2- breast cancer cohort

2019 ◽  
Author(s):  
Maryam Soleimani ◽  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Pernette J. Verschure ◽  
Stefan Wiemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Proportional Hazards ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Cox Proportional Hazards ◽  
Endocrine Treatment ◽  
Endocrine Therapy Resistance ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models

Abstract Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, about 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+ tumors from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AIs or TAM) that patients received (N=210 and N=172, respectively). Models were adjusted for clinical variables tumour stage, age, and AI treatment. We also identified signatures of multiple methylation loci associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Corresponding multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours and prior to any endocrine treatment are associated with development of endocrine resistance.

scholarly journals Candidate methylation sites associated with endocrine therapy resistance in the TCGA ER+/HER2- breast cancer cohort

2019 ◽  
Author(s):  
Maryam Soleimani ◽  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Pernette J. Verschure ◽  
Stefan Wiemann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Proportional Hazards ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Cox Proportional Hazards ◽  
Endocrine Treatment ◽  
Endocrine Therapy Resistance ◽  
Proportional Hazards Models ◽  
Cox Proportional Hazards Models

AbstractBackgroundEstrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, about 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance.MethodsWe used genome-wide DNA methylation profiles of primary ER+ tumors from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AIs or TAM) that patients received (N=210 and N=172, respectively). Models were adjusted for clinical variables tumour stage, age, AI treatment and luminal subtype. We also identified signatures of multiple methylation loci associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen.ResultsWe identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Corresponding multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells.ConclusionsWe identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours and prior to any endocrine treatment are associated with development of endocrine resistance.

scholarly journals Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1177
Author(s):  
In Young Choi ◽  
Sohyun Chun ◽  
Dong Wook Shin ◽  
Kyungdo Han ◽  
Keun Hye Jeon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Proportional Hazards ◽  
Screening Program ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Health Screening Program ◽  
Design And Methods

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

Advances in Adjuvant Endocrine Therapy for Postmenopausal Women

2008 ◽  
Vol 26 (5) ◽  
pp. 798-805 ◽  
Author(s):  
Nancy U. Lin ◽  
Eric P. Winer
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Diagnosis ◽  
Endocrine Treatment ◽  
Future Research ◽  
Sequential Approach ◽  
Hormone Receptor Positive

Hormone receptor-positive cancers are the most common tumor subtype among postmenopausal women with breast cancer. Despite substantial improvements in disease-free survival and overall survival with tamoxifen and chemotherapy, recurrences still occur, and may ultimately lead to death from breast cancer. Importantly, disease recurrence includes both early and late events, with over half of all recurrences detected more than 5 years from initial breast cancer diagnosis. In recent years, a number of large, randomized trials have evaluated the role of the aromatase inhibitors (AIs) in postmenopausal women with hormone receptor-positive breast cancer. These studies have tested one of three approaches: (1) an upfront AI, (2) a sequential approach after 2-3 years of tamoxifen, and (3) extended endocrine therapy beyond 5 years. Results of these studies have challenged the previous standard of a 5-year course of tamoxifen alone. While the AIs have become a standard component of treatment for most postmenopausal women, many questions remain as to how best tailor endocrine treatment to individual patients. In addition, despite the gains achieved with the AIs, many recurrences are not prevented, and novel strategies are urgently needed, particularly for those women at high risk of recurrence. In this article, we review the efficacy and toxicity data from the available trials of endocrine therapy in the postmenopausal setting. We outline controversies in choosing the optimal endocrine approach, and we discuss selected ongoing studies. Finally, we highlight future research directions, such as the need to understand host and tumor heterogeneity.

scholarly journals COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248128
Author(s):  
Mark Stewart ◽  
Carla Rodriguez-Watson ◽  
Adem Albayrak ◽  
Julius Asubonteng ◽  
Andrew Belli ◽  
...  
Keyword(s):  
Best Practices ◽  
Adverse Events ◽  
Data Science ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Parallel Analysis ◽  
Science Data ◽  
Systems Research ◽  
Cox Proportional Hazards Models ◽  
Global Threat

Background The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. Methods Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. Results Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. Conclusion Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Acute myeloid leukemia (AML) in older women after adjuvant breast cancer therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
D. A. Patt ◽  
Z. Duan ◽  
G. Hortobagyi ◽  
S. H. Giordano
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Older Women ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Significant Independent Predictor ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Adjuvant Breast Cancer ◽  
Comorbidity Scores

560 Background: Adjuvant chemotherapy for breast cancer is associated with the development of secondary AML, but this risk in an older population has not been previously quantified. Methods: We queried data from the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database for women who were diagnosed with nonmetastatic breast cancer from 1992–1999. We compared the risk of AML in patients with and without adjuvant chemotherapy (C), and by differing C regimens. The primary endpoint was a claim with an inpatient or outpatient diagnosis of AML (ICD-09 codes 205–208). Risk of AML was estimated using the method of Kaplan-Meier. Cox proportional hazards models were used to determine factors independently associated with AML. Results: 36,904 patients were included in this observational study, 4,572 who had received adjuvant C and 32,332 who had not. The median patient age was 75.3 (66.0–103.3). The median follow up was 63 months (13–132). Patients who received C were significantly younger, had more advanced stage disease, and had lower comorbidity scores (p<0.001). The unadjusted risk of developing AML at 10 years after any adjuvant C for breast cancer was 1.6% versus 1.1% for women who had not received C. The adjusted HR for AML with adjuvant C was 1.72 (1.16–2.54) compared to women who did not receive C. HR for radiation was 1.21 (0.86–1.70). HR was higher with increasing age but p>0.05. An analysis was performed among women who received C. When compared to other C regimens, anthracycline-based therapy (A) conveyed a significantly higher hazard for AML HR 2.17 (1.08–4.38), while patients who received A plus taxanes (T) did not have a significant increase in risk HR1.29 (0.44–3.82) nor did patients who received T with some other C HR 1.50 (0.34–6.67). Another significant independent predictor of AML included GCSF use HR 2.21 (1.14–4.25). In addition, increasing A dose was associated with higher risk of AML (p<0.05). Conclusions: There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. The risk appears to be highest from A-based regimens, most of which also contained cyclophosphamide, and may be dose-dependent. T do not appear to increase risk. The role of GCSF should be further explored. No significant financial relationships to disclose.

Relationship between taxane-induced neuropathy and clinical outcomes after adjuvant chemotherapy.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 270-270 ◽  
Author(s):  
B. P. Schneider ◽  
M. Wang ◽  
V. Stearns ◽  
S. Martino ◽  
V. E. Jones ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Time Dependent ◽  
Individual Treatment ◽  
Axillary Lymph ◽  
Landmark Analysis

270 Background: Neuropathy is a common and potentially enduring and disabling complication of adjuvant taxane therapy. Recent studies have identified candidate host single nucleotide polymorphisms (SNPs) associated with taxane-induced neuropathy (Schneider et al. ASCO 2011, abstr. 1000). We therefore sought to determine whether neuropathy was associated with breast cancer recurrence. Methods: This study included 4,950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer who received up to 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m2 weekly x 12 (D1). Chemotherapy doses were based on actual body weight. Cox proportional hazards model were used to determine the relationship between neuropathy and disease free survival (DFS) and overall survival (OS) treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,702 patients who received at least 1 taxane dose, grade 2-4 neuropathy developed in 20%, 27%, 16%, and 16% in the P3, P1, D3, and D1 arms, respectively. In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy- treatment interaction, there was no relationship between neuropathy and DFS and OS in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis. Baseline covariates associated with an increase rate of neuropathy included black race (25% vs. 19% grade 2-4, p=0.02) and obesity (21% vs. 19%, p=0.04), but not age. Conclusions: There was no association between taxane-induced neuropathy and DFS or OS in patients treated with contemporary AC-taxane therapy, including weekly paclitaxel. These findings show that taxane-induced neuropathy is not associated with outcome, thus suggesting that validation of SNPs predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit and thereby improve therapeutic individualization.

Missing data in breast cancer: Relationship with survival in national databases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19114-e19114
Author(s):  
Jennifer Kay Plichta ◽  
Christel N. Rushing ◽  
Holly C. Lewis ◽  
Dan G. Blazer ◽  
Terry Hyslop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Missing Data ◽  
Proportional Hazards ◽  
Cancer Registries ◽  
Cox Proportional Hazards ◽  
Future Research ◽  
Risk Of Death ◽  
Cox Proportional Hazards Models ◽  
N Stage ◽  
National Databases

e19114 Background: National cancer registries are valuable tools used to analyze patterns of care and clinical oncology outcomes; yet, patients with missing data may impact the accuracy and generalizability of these data. We sought to evaluate the association between missing data and overall survival (OS). Methods: Using the NCDB and SEER, we compared data missingness among patients diagnosed with invasive breast cancer from 2010-2014. Key variables included: demographic variables (age, race, ethnicity, insurance, education, income), tumor variables (grade, ER, PR, HER2, TNM stage), and treatment variables (surgery in both databases; chemotherapy and radiation in NCDB). OS was compared between those with and without missing data via Cox proportional hazards models. Results: Overall, 775,996 patients in the NCDB and 263,016 in SEER were identified; missingness of at least 1 key variable was 29% and 13%, respectively. Of those, the majority were missing a tumor variable (NCDB 80%; SEER 88%), while demographic and treatment variables were missing less often. When compared to patients with complete data, missingness was associated with a greater risk of death; NCDB 17% vs. 14% (HR 1.23, 99% CI 1.21-1.25) and SEER 27% vs 14% (HR 2.11, 99% CI 2.05-2.18). Rate of death was similar whether the patient was missing 1 or ≥2 variables. When stratified by the type of missing variable, differences in OS between those with and without missing data in the NCDB were small. In SEER, reductions in OS were largest for those missing tumor variables (HR 2.26, 99% CI 2.19-2.33) or surgery data (HR 3.84, 99% CI 3.32-4.45). Among the tumor variables specifically, few clinically meaningful differences in OS were noted in the NCDB, while the most significant differences in SEER were noted in T and N stage (table). Conclusions: Missingness of select variables is associated with a worse OS and is not uncommon within large national cancer registries. Therefore, researchers must use caution when choosing inclusion/exclusion criteria for outcomes studies. Future research is needed to elucidate which patients are most often missing data and why OS differences are observed. [Table: see text]

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