Competing risks of death in younger and older postmenopausal breast cancer patients

查看全文 作　　者：Judy-Anne W [1]Chapman;Kathleen I [2]Pritchard;Paul E [3]Goss;James N [4]Ingle;Hyman B [5]Muss;Susan F [6]Dent;Ted A [7]Vandenberg;Brian [8]Findlay;Karen A [9]Gelmon;Carolyn F [10]Wilson;Lois E [10]Shepherd;Michael N [11]Pollak 机构地区：[1]NCIC Clinical Trials Group, Queen's University, Kingston, ON, K7L 3N6, Canada;[2]Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada;[3]Massachusetts General Hospital, Harvard University, Boston, MA 02114, United States;[4]Mayo Clinic, Rochester, MN 55902, United States;[5]Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill, Chapel Hill, NC27514, United States;[6]Ottawa Hospital Cancer Center, University of Ottawa, Ottawa, ON, K1H8L6, Canada;[7]London Health Sciences Centre, University of Western Ontario, London, ON, N6G 2V4, Canada;[8]Niagara Health System, McM aster University, St. Catharines, ON, L2R 2Z4, Canada;[9]BC Cancer Agency, University of British Columbia, Vancouver, BC, V5Z 1L3, Canada;[10]NCIC Clinical Trials Group, Queen's University, Kingston, Ontario, K7L 3N6, Canada;[11]Lady Davis Institute, Jewish General Hospital, McG ill University, Montreal, QC, H3T 1E2, Canada 出　　处：《World Journal of Clinical Oncology》索引2014年第5卷第5期,共9页 基　　金：Supported by the Canadian Cancer Society through a grant to the NCIC Clinical Trials Group from the Canadian Cancer Society Research Institute;Novartis provided the NCIC CTG MA.14 drug octreotide LAR 摘　　要：AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death. METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival(P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival(P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific(Br Ca) and other cause(OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1(IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-OH vitamin D were associated with(1) all cause mortality, and if so; and(2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models.RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447(82%) < 70 years and 120(18%) ≥ 70 years. There were 170 deaths: 106(62.3%) BrC a; 55(32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9(5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrC a and OC deaths were not significantly different by treatment arm(P = 0.40): tamoxifen patients experienced 50 BrC a and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 Br Ca and 23 OC deaths. Proportionately more deaths(P = 0.004) were from BrC a for patients< 70 years, where 70% of deaths were due to Br Ca, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index(BMI)(P = 0.02). Higher pathologic T and N were associated with more BrC a deaths(P < 0.0001 and 0.002, respectively). The cumulative hazard plot for Br Ca and OC mortality indicated the concurrent accrual of both types of death throughout followup, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality(P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC(P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrC a mortality(respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrC a mortality(P = 0.002); there was weak evidence that, lower C-peptide(P = 0.08) was associated with less BrC a mortality, while higher BMI(P = 0.01) was associated with worse OC mortality.CONCLUSION: We demonstrate here a new paradigm of simultaneous testing of therapeutics directed at multiple diseases for which postmenopausal women are concurrently at risk. Octreotide LAR did not significantly impact breast cancer or other cause mortality, although different baseline factors influenced type of death. 关 键 词：Breast cancer POSTMENOPAUSAL HORMONE receptor positive Competing risks TAMOXIFEN OCTREOTIDE LAR