Background: Under-representation of women ages 65+ (“older”) in the trials may limit clinical translation of results to this growing population. We used simulation modeling to estimate chemotherapy outcomes by age and comorbidity level among older women with early stage, estrogen-receptor+/HER2- breast cancers with an Oncotype DX score of 26+. Methods: A discrete-time stochastic state-transition model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups of women based on age (65-69, 70-74, 75-79, and 80-89) and comorbidity levels (no/low, moderate, and severe). Age-, comorbidity-specific non-cancer survival was derived from a random 5% sample of women enrolled in the Medicare Part A and B program from 1992 to 2005 and included in the SEER areas. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer and other-cause mortality with chemoendocrine therapy or endocrine therapy alone. Sensitivity analysis tested the impact on outcomes of varying values of uncertain parameters. Results: Women with life expectancies of ≥ 7 years had net gains of 0.17 to 0.45 LYs (2.0-5.4 months) with chemotherapy; this group was mainly women aged 65-69 and 70-74 with no/low or moderate comorbidity. Women destined to develop distant recurrence gained between 4.2-10.4 months. LYs were reduced by chemotherapy toxicity. The majority of women died of other causes, ranging from 59% to 98% across all age groups and comorbidity levels, but chemotherapy reduced breast cancer mortality by 14.5% and 25.7% among women ages 65-69 and 70-74 with no/low comorbidity, respectively. Results were robust in sensitivity analyses, and chemotherapy improved all outcomes as treatment efficacy increased, assuming no change in toxicity. Conclusions: Older women with early stage, estrogen-receptor+/HER2- breast cancers with Oncotype DX scores of 26+ may benefit from chemotherapy, when both conditions of age <75 and comorbidity at no/low or moderate level can be met. Personalized treatment decisions for older women will ultimately depend on comorbidity-specific lifespan and individual preferences for the balance of benefits and harms of chemotherapy.