Comparative Effectiveness of Chemotherapy Regimens in Prolonging Survival for Two Large Population-Based Cohorts of Elderly Adults with Breast and Colon Cancer in 1992–2009 Xianglin L. Du, MD, PhD,* † Yefei Zhang, MS,* ‡ Rohan C. Parikh, MS, † David R. Lairson, PhD, † and Yi Cai, MS* ‡ OBJECTIVES: To compare the effectiveness of chemo- therapy in prolonging survival according to age in breast and colon cancer. DESIGN: Retrospective cohort study with a matched cohort analysis based on the conditional probability of receiving chemotherapy. SETTING: The 16 Surveillance, Epidemiology, and End Results (SEER) areas from the SEER-Medicare linked data- base. PARTICIPANTS: Women diagnosed with Stage I to IIIa hormone receptor–negative breast cancer (n = 14,440) and 26,893 men and women with Stage III colon cancer (n = 26,893) aged 65 and older in 1992 to 2009. MEASUREMENTS: The main exposure was the receipt of chemotherapy, and the main outcome was mortality. RESULTS: In women with breast cancer aged 65 to 69, the risk of all-cause mortality was statistically significantly lower in those who received chemotherapy than in those who did not in the entire cohort (hazard ratio (HR) = 0.70, 95% confidence interval (CI) = 0.57–0.88) and in a pro- pensity-matched cohort (HR = 0.82, 95% CI = 0.70–0.96) after adjusting for measured confounders. These patterns were similar in participants aged 70 to 74 and 75 to 79, but in women aged 80 to 84 and 85 to 89, risk of all-cause mortality was no longer significantly lower in those receiv- ing chemotherapy in the entire and matched cohorts, except that, in a small number of women who received doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), risk of mortality was significantly lower for those aged 80 to 84. Chemotherapy appeared to be effective in all ages from 65 through 84 in participants with Stage III colon cancer. For example, in those aged 85 to 89, chemotherapy was significantly associated with lower risk of mortality in the entire cohort (HR = 0.79, 95% CI = 0.67–0.92) and the matched cohort (HR = 0.79, 95% CI = 0.66–0.95). CONCLUSION: The effectiveness of chemotherapy decreased with age in participants with breast cancer, in whom chemotherapy appears to be effective until age 79 except for the doxorubicin-cyclophosphamide combination, which was effective in participants aged 80 to 84. In individ- uals with Stage III colon cancer, chemotherapy appears to be effective to age 89. These findings were consistent with those of randomized clinical trials. J Am Geriatr Soc 63:1570–1582, 2015. Key words: chemotherapy; effectiveness; survival; breast cancer; colon cancer C hemotherapy has been documented to be efficacious in prolonging survival for individuals with various malig- nancies. 1–5 One critical finding from numerous clinical tri- als and pooled analyses 6–11 is that the efficacy of chemotherapy for breast cancer has been shown to decrease with age, from a 27% proportional reduction in 10-year mortality for women younger than 50 to 14% for women aged 50 to 59 and 8% for women aged 60 to 69, and no benefit for women aged 70 and older. These results are striking because there has been no decreasing efficacy of chemotherapy observed with advancing age for women with ovarian cancer 4,12–14 or for men or women with lung cancer 5,15–17 or colon cancer. 3,18–21 Numerous clinical tri- als have shown that chemotherapy is equally efficacious in different age groups of men and women with lung and colon cancer and in women with ovarian cancer, including populations aged 70 and older. 12–21 Therefore, evidence- based clinical guidelines on chemotherapy from the National Institutes of Health recommend chemotherapy for women with breast cancer younger than 70, 1,2 whereas there are no age-restricted recommendations for individuals From the *Departments of Epidemiology, Human Genetics, and Environmental Sciences; † Management, Policy and Community Health; and ‡ Biostatistics, School of Public Health, University of Texas Health Science Center, Houston, Texas. Address correspondence to Xianglin L. Du, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler Drive, RAS-E631, Houston, TX 77030. E-mail: Xianglin.L.Du@uth.tmc. edu DOI: 10.1111/jgs.13523 JAGS 63:1570–1582, 2015 © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society 0002-8614/15/$15.00