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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 Ferguson
Epidemiology

Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

Keywords

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

Abbreviations

RDI

Relative dose intensity

RCT

Randomized controlled trial

ESBC

Early stage breast cancer

CMF

Cyclophosphamide, methotrexate, and fluorouracil

ER

Estrogen receptor

PR

Progesterone receptor

HER2

Human epidermal-growth factor receptor 2

TNBC

Triple-negative breast cancer

pCR

Pathologic complete response

LTR

Louisiana Tumor Registry

CER

Enhancing Cancer Registry Data for Comparative Effectiveness Research

PCOR

Patient Centered Outcomes Research

CDC

Centers for Disease Control and Prevention

AJCC

American Joint Committee on Cancer

BSA

body surface area

NCCN

National Comprehensive Cancer Network

AC-T

Doxorubicin/cyclophosphamide followed by paclitaxel or docetaxel

TC

Docetaxel/cyclophosphamide

TAC

Docetaxel/doxorubicin/cyclophosphamide

AC

Doxorubicin/cyclophosphamide

SEER

Surveillance, Epidemiology, and End Results program

CCI

Charlson comorbidity index

G-CSF

Granulocyte-growth factors/cytokines

IPTW

Inverse probability of treatment weighting

HR

Hazard ratio

CI

Confidence interval

Notes

Acknowledgements

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
  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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