Breast Cancer Research and Treatment

, Volume 169, Issue 1, pp 175–187 | Cite as

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

  • Lu Zhang
  • Qingzhao Yu
  • Xiao-Cheng Wu
  • Mei-Chin Hsieh
  • Michelle Loch
  • Vivien W. Chen
  • Elizabeth Fontham
  • Tekeda FergusonEmail author



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.


Breast cancer Hormone receptor positive, Triple-negative Chemotherapy Relative dose intensity 



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



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.

Ethical approval

For this type of study, formal consent is not required.

Supplementary material

10549_2017_4646_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 18 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Lu Zhang
    • 1
  • Qingzhao Yu
    • 2
  • Xiao-Cheng Wu
    • 1
  • Mei-Chin Hsieh
    • 1
  • Michelle Loch
    • 3
  • Vivien W. Chen
    • 1
  • Elizabeth Fontham
    • 1
  • Tekeda Ferguson
    • 1
    Email author
  1. 1.Epidemiology program, School of Public Health and Louisiana Tumor RegistryLouisiana State University Health Sciences CenterNew OrleansUSA
  2. 2.Biostatistics program, School of Public Health and Louisiana Tumor RegistryLouisiana State University Health Sciences CenterNew OrleansUSA
  3. 3.School of MedicineLouisiana State University Health Sciences CenterNew OrleansUSA

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