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Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I–III breast cancer: ER+/PR+, HER2- vs. triple-negative

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To investigate the impact of chemotherapy relative dose intensity (RDI) on cause-specific and overall survival for stage I–III breast cancer: estrogen receptor or progesterone receptor positive, human epidermal-growth factor receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify the optimal RDI cut-off points in these two patient populations.


Data were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women diagnosed with stage I–III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with complete information on RDI were included. Five RDI cut-off points (95, 90, 85, 80, and 75%) were evaluated on cause-specific and overall survival, adjusting for multiple demographic variables, tumor characteristics, comorbidity, use of granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens, and use of hormone therapy. Cox proportional hazards models and Kaplan–Meier survival curves were estimated and adjusted by stabilized inverse probability treatment weighting (IPTW) of propensity score.


Of 494 ER+/PR+, HER2- patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%, respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at which the low RDI was significantly associated with worse overall survival (HR = 1.93; 95% CI 1.09–3.40). Among TNBC patients, 75% was the cut-off point at which the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09, 6.38) and overall survival (HR = 2.39; 95% CI 1.04–5.51).


Higher RDI of chemotherapy is associated with better survival for ER+/PR+, HER2- patients and TNBC patients. To optimize survival benefits, RDI should be maintained ≥ 85% in ER+/PR+, HER2- patients, and ≥ 75% in TNBC patients.

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Relative dose intensity


Randomized controlled trial


Early stage breast cancer


Cyclophosphamide, methotrexate, and fluorouracil


Estrogen receptor


Progesterone receptor


Human epidermal-growth factor receptor 2


Triple-negative breast cancer


Pathologic complete response


Louisiana Tumor Registry


Enhancing Cancer Registry Data for Comparative Effectiveness Research


Patient Centered Outcomes Research


Centers for Disease Control and Prevention


American Joint Committee on Cancer


body surface area


National Comprehensive Cancer Network


Doxorubicin/cyclophosphamide followed by paclitaxel or docetaxel








Surveillance, Epidemiology, and End Results program


Charlson comorbidity index


Granulocyte-growth factors/cytokines


Inverse probability of treatment weighting


Hazard ratio


Confidence interval


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We acknowledge the Centers for Disease Control and Prevention (CDC) for funding Enhancing Cancer Registry Data for Comparative Effectiveness Research (CER) Project (Grant Number: 1eEDSK0106) and Patient Centered Outcomes Research (PCOR) project (Grant Number: 5NU58DP003915), and the Louisiana Tumor Registry for data and administrative support. We acknowledge Dr. Gary H. Lyman and Dr. Marek S. Poniewierski for clarifying variables used in the calculation of chemotherapy relative dose intensity.

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Correspondence to Tekeda Ferguson.

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Zhang, L., Yu, Q., Wu, XC. et al. Impact of chemotherapy relative dose intensity on cause-specific and overall survival for stage I–III breast cancer: ER+/PR+, HER2- vs. triple-negative. Breast Cancer Res Treat 169, 175–187 (2018).

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