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.
KeywordsBreast cancer Hormone receptor positive, Triple-negative Chemotherapy Relative dose intensity
Relative dose intensity
Randomized controlled trial
Early stage breast cancer
Cyclophosphamide, methotrexate, and fluorouracil
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
Inverse probability of treatment weighting
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
For this type of study, formal consent is not required.
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