Competing causes of death in NCIC CTG MA.17, a placebo-controlled trial of letrozole as extended adjuvant therapy for breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 540-540
Author(s):  
J. Chapman ◽  
D. Meng ◽  
L. Shepherd ◽  
W. Parulekar ◽  
J. N. Ingle ◽  
...  

540 Background: Risk of death from other malignancies (OM) and other causes (OC) than breast cancer (BC) increases with age. Effects of baseline factors on type of death were assessed with competing risks analyses. Methods: In NCIC CTG MA.17, 5,187 women free of recurrent breast cancer after 5 years of tamoxifen were randomized to letrozole (L, 2,593 women) or placebo (P, 2,594 women). The primary endpoint was disease free survival (DFS), and secondary, overall survival (OS). Follow-up was to October 9, 2005: median 3.9 years, range <0.1 to 7.0 years. Effects of competing risks were examined for endpoints of BC, OM, and OC for 11 baseline trial factors: treatment, age, menopausal status, duration of prior tamoxifen, adjuvant radiotherapy, bone fracture, osteoporosis, cardiovascular disease, hormone receptor status, nodal status, adjuvant chemotherapy. Lagakos’ hierarchical method (Lagakos, Appl. Statist. 1978; 27:235–241) was used to test for differential effects of baseline factors on type of death (BC, OM, OC). Results: Rate of censoring was 97.8%, with 256 deaths (BC, 102; OM, 50; OC, 100; unknown, 4). Non-breast cancer deaths accounted for 60% of known deaths; 72%, for those ≥70 years; and 48%, for those <70 years. Two baseline factors differentially affected type of death. Women with cardiovascular disease were more likely to die from OC (p=0.02), while those with osteoporosis were more likely to die of OM (p=0.03). Age and nodal status had directionally similar effects. Older women had shorter survival from all 3 causes of death (p=0.01). Lymph node positivity was associated with worse survival (p=0.003). Conclusions: Extended L provides similar proportional benefit in improving DFS for all ages of women (Muss ref abstract SABCS 2006). However, the magnitude of competing non-breast cancer, and non-treatment related, causes of death needs to be considered more frequently, since with early detection and improved therapies, breast cancer patients may increasingly be expected to survive their disease to die from another cause. The novel association between baseline osteoporosis and other malignancies is being explored quantitatively. No significant financial relationships to disclose.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhangheng Huang ◽  
Xin Zhou ◽  
Yuexin Tong ◽  
Lujian Zhu ◽  
Ruhan Zhao ◽  
...  

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.


Author(s):  
Maria Koch ◽  
John Hanson ◽  
Herta Gaedke ◽  
Diane Wilson

2011 ◽  
Vol 29 (6) ◽  
pp. 419-425 ◽  
Author(s):  
Raavi Gupta ◽  
James S. Babb ◽  
Baljit Singh ◽  
Luis Chiriboga ◽  
Leonard Liebes ◽  
...  

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10083-10083 ◽  
Author(s):  
W. J. Janni ◽  
G. Wiedswang ◽  
T. Fehm ◽  
J. Jueckstock ◽  
E. Borgen ◽  
...  

10083 Background: The prognostic significance of DTC in the BM of breast cancer patients at the time of primary diagnosis has recently been confirmed by a large pooled analysis. If the persistence of DTC after adjuvant therapy confers a similar risk for relapse, there might be an indication for secondary adjuvant treatment. Methods: We analyzed BM aspirates of 697 patients from academic breast cancer units in Oslo (n=356), Munich (n=228) and Tuebingen (n=113) during recurrence-free follow-up at a median interval of 32.4 months (standard deviation [std] 19.4 mon) after primary diagnosis of breast cancer pT1–4, pN0–3 pM0. Carcinoma cells were detected using a standardized immunoassay with the monoclonal antibodies A45-B/B3 (Munich, Tuebingen), or AE1 and AE3 (Oslo), directed against cytokeratin (CK). Patients were followed for a median of 54.2 months (std 24.5 mon) after primary diagnosis. Results: Persistent DTC in the BM were detected in 15.6% of the patients (n=109). The Kaplan-Meier estimate for mean distant relapse-free survival estimate was 155.6 mon (142.4 - 168.9 95%CI) in patients with negative and 102.3 mon (93.6 - 111.0, 95% CI, p< .0001, log rank test) in patients with positive BM status. Patients without evidence of persistent DTC had a significantly longer overall survival (164.4 [155.6 - 173.3]), than patients with positive BM status (101.7 mon [89.4 - 113.9], p< .0001). In multivariate Cox regression analysis, allowing for bone marrow status, tumor size, nodal status, histopathological grading and hormone receptor status, DTC was of higher independent prognostic significance for subsequent reduced breast cancer specific survival (RR 5.9, 2.8 - 12.8, 95% CI, p< .0001), than nodal status at time of primary diagnosis (RR 1.2, 1.0 - 1.3, 95% CI, p=.014). Conclusion: Evidence of persistent DTC in breast cancer patients indicates an increased risk for subsequent relapse, and may serve for monitoring in future clinical trials. Such trials might investigate the benefit of individualized secondary adjuvant treatment or extended adjuvant therapy of patients with DTC. No significant financial relationships to disclose.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 549-549 ◽  
Author(s):  
Hadar Goldvaser ◽  
Domen Ribnikar ◽  
Tristan Alexandra Barnes ◽  
David W. Cescon ◽  
Alberto Ocana ◽  
...  

549 Background: Aromatase inhibitors (AI) are a gold standard adjuvant endocrine therapy for postmenopausal women with breast cancer. A number of randomized trials (RCTs) have reported modest improvements in breast cancer outcomes from extending treatment with AI beyond the initial 5 years after diagnosis. However, less in known about the toxicity of extended AI compared with no therapy. Methods: We conducted a systematic review of MEDLINE to identify RCTs that compared extended AI to placebo or no treatment. The search was supplemented by a review of abstracts from the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium meetings between 2013 and 2016. Odds ratios (ORs), 95% confidence intervals (CI), absolute risks, and the number needed to harm (NNH) associated with one adverse event were computed for prespecified safety and tolerability outcomes including cardiovascular disease, bone fractures, second cancers (excluding new breast cancer), treatment discontinuation due to adverse events and death without recurrence. Results: Seven trials comprising 16349 patients met the inclusion criteria. Longer treatment with AI was associated with increased odds of cardiovascular disease (OR = 1.18, 95% CI 1.00-1.40, P=0.05; NNH = 122) and bone fractures (OR = 1.34, 95% CI 1.16 - 1.55, P < 0.001; NNH = 72). Compared to control, longer AI therapy was associated with a higher odds of treatment discontinuation due to adverse events (OR = 1.45, 95% CI 1.25 - 1.68, P < 0.001; NNH = 20). Longer AI therapy did not influence the odds of second cancers (OR = 0.93, 95% CI 0.73-1.18, P = 0.56). There was a numerical excess of death without recurrence with longer AI therapy, but this was not statistically significant (OR = 1.11, 95% CI 0.9 - 1.36, P = 0.34). Conclusions: Longer durations of AI use are associated with increased cardiovascular events and bone fracture. There is a numerical, but non-statistically significant excess of deaths without breast cancer recurrence among patients receiving longer AI therapy. These data should be taken into account when considering extended adjuvant AI therapy for breast cancer patients.


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