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Behavioral and health outcomes from the NRG Oncology/NSABP B-36 trial comparing two different adjuvant therapy regimens for early-stage node-negative breast cancer

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Abstract

Background

The NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in node-negative early-stage breast cancer. A sub-study within B-36, focusing on symptoms, quality of life (QOL), menstrual history (MH), and cardiac function (CF) was conducted.

Patients and methods

Patients completed the QOL questionnaire at baseline, during treatment, and every 6 months through 36 months. FACT-B Trial Outcome Index (TOI), symptom severity, and SF-36 Vitality and Physical Functioning (PF) scales scores were compared between the two groups using a mixed model for repeated measures analysis. MH was collected at baseline and subsequently assessed if menstrual bleeding occurred within 12 months prior to randomization. Post-chemotherapy amenorrhea outcome was examined at 18 months and was defined as lack of menses in the preceding year. Logistic regression was used to test for association of amenorrhea and treatment. CF assessment was done at baseline and 12 months. Correlation analysis was used to address associations between changes in baseline and 12-month PF and concurrent CF changes measured by LVEF.

Results

FEC-100 patients had statistically significantly lower TOI scores during chemotherapy (P = 0.02) and at 6 months (P < 0.001); lower Vitality score at 6 months (P < 0.01), and lower PF score during the first year than AC patients. There were no statistically significant QOL score differences between the two groups beyond 12 months. No significant differences in symptom severity between the two groups were observed. Rates of amenorrhea were significantly different between FEC-100 and AC (67.4% vs. 59.1%, P < 0.001). There was no association between changes in LVEF and PF (P = 0.38).

Conclusions

Statistically significant QOL differences between the two groups favored AC; however, the magnitude was small and unlikely to be clinically meaningful. There was a clinical and statistically significant difference in risk for amenorrhea, favoring AC.

Trial registry

NCT00087178; Date of registration: 07/08/2004.

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Data availability

Individual participant data that underlie the results reported in this article, after deidentification, will generally be available within 1 year after publication and will be accessible through the NCTN Data Archive.

Code availability

Analyses were performed using SAS standard procedures (v9.4; SAS Institute, Cary, NC.

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Acknowledgements

The authors would also like to acknowledge John Wilson, PhD (retired), who was the original Protocol Statistician for the study and was an invaluable part of the protocol team. The authors acknowledge the contributions of Barbara C. Good, PhD, Director of Scientific Publications, Christine I. Rudock, Publications and Graphics Specialist, and Wendy L. Rea, BA, Editorial Associate, all of whom are employees of NSABP. They were not compensated beyond their normal salaries for this work.

Funding

This work was supported by the National Institutes of Health grants U10CA180868, UG1CA189867, -180822, and -44066-26 (Dr. Robidoux), and Pharmacia & Upjohn Company, a subsidiary of Pfizer, Inc. The funders had no role in the design of the study; the collection, analysis, and/or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.

Author information

Author notes

  1. Deceased: André Robidoux.

Authors and Affiliations

  1. NSABP/NRG Oncology, Pittsburgh, PA, USA

    Patricia A. Ganz, Hanna Bandos, Charles E. Geyer Jr., André Robidoux, Alexander H. G. Paterson, Jonathan Polikoff, Luis Baez-Diaz, Adam M. Brufsky, Louis Fehrenbacher, Ann W. Parsons, Patrick J. Ward, Louise Provencher, John T. Hamm, Philip J. Stella, Robert L. Carolla, Richard G. Margolese, Henry R. Shibata, Edith A. Perez & Norman Wolmark

  2. Department of Health Policy and Management, UCLA Fielding School of Public Health, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, 650 Charles Young Drive South, Rm A2-125 CHS, Los Angeles, CA, 90095, USA

    Patricia A. Ganz

  3. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA

    Hanna Bandos

  4. Division of Hematology and Medical Oncology, Houston Methodist Cancer Center, Houston, TX, USA

    Charles E. Geyer Jr.

  5. Department of Surgery, Breast Cancer Research Group (GRCS), Centre Hospitalier de lʹUniversité de Montréal (CHUM), Montreal, PQ, Canada

    André Robidoux

  6. Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada

    Alexander H. G. Paterson

  7. Department of Research and Evaluation—Clinical Trials—Oncology, Kaiser Permanente—San Diego Mission, San Diego, CA, USA

    Jonathan Polikoff

  8. Department of Cancer Medicine, Puerto Rico NCORP/UPR Comprehensive Cancer Center, San Juan, Puerto Rico

    Luis Baez-Diaz

  9. UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Adam M. Brufsky & Norman Wolmark

  10. Department of Oncology, Kaiser Permanente, Northern CA Region, Vallejo, CA, USA

    Louis Fehrenbacher

  11. Department of Presbyterian Oncology, MBCCOP, University of New Mexico, Albuquerque, NM, USA

    Ann W. Parsons

  12. Department of Medical Oncology, Oncology/Hematology Care Clinical Trials, Cincinnati, OH, USA

    Patrick J. Ward

  13. Centre des Maladies du Sein Deschenes-Fabia, CHU de Québec/Université Laval, Québec City, PQ, Canada

    Louise Provencher

  14. Department of Medical Oncology, Norton Cancer Institute—a part of Norton Healthcare, Louisville, KY, USA

    John T. Hamm

  15. Department of Medical Oncology, St Joseph Mercy Hospital, Ann Arbor, MI, USA

    Philip J. Stella

  16. CCOP, Ozark Health Ventures LLC-Cancer Research for the Ozarks, Springfield, MO, USA

    Robert L. Carolla

  17. Department of Oncology, Jewish General Hospital, Montréal, PQ, Canada

    Richard G. Margolese

  18. Department of Surgery, McGill University Health Centre, Montréal, PQ, Canada

    Henry R. Shibata

  19. Department of Hematology/Oncology and Cancer Biology, Mayo Clinic Jacksonville, Jacksonville, FL, USA

    Edith A. Perez

  20. NCCTG/ALLIANCE, Rochester, MN, USA

    Edith A. Perez

Authors
  1. Patricia A. Ganz
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  2. Hanna Bandos
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  3. Charles E. Geyer Jr.
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Contributions

Conceptualization: PAG, HB, CEG, LF, JTH, RGM, and NW. Methodology: PAG, HB, CEG, and RGM. Software: HB. Validation: PAG, HB, and EPM. Formal Analysis: HB. Investigation: PAG, CEG, AR, JP, LB-D, AMB, LF, AWP, PJW, LP, JTH, PJS, RGM, HRS, EPM, and NW. Resources: AR, AHGP, JP, AMB, LF, AWP, and LP. Data curation: HB and AR. Writing—original draft: PAG, HB, CEG, and AMB. Writing—review & editing: PAG, HB, CEG, AHGP, JP, AMB, LF, PJW, LP, JTH, PJS, RLC, RGM, HRS, EPM, and NW. Visualization: HB, CEG, RGM, and EPM. Supervision: CEG, LF, LP, EPM, and NW. Project administration: CEG, AWP, and NW. Funding acquisition: NW.

Corresponding author

Correspondence to Patricia A. Ganz.

Ethics declarations

Conflict of interest

Charles E. Geyer, Jr.—Grants, non-financial support and other from Genentech/Roche, Daiichi/Sankyo, and AstraZeneca, during the conduct of the study, and personal fees from Exact Sciences and Athenex, outside the submitted work. Johnathan Polikoff—Consultant, Natera. Louis Provencher—Consulting or Advisory Role: Lilly, Pfizer, Roche, and Novartis. Research Funding: Pfizer, Roche, Novartis, Merck, GlaxoSmithKline, and Odonate Therapeutics. The remaining authors declare no conflicts of interest.

Ethical approval

The protocol was approved by institutional IRBs. All studies involving human participants are in accord with ethical standards of the institutional research board and the Helsinki declaration or comparable ethical standards.

Consent to participate

The study was approved by the local institutional review board. Written informed consent was required of all participants.

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All authors have consented for publication.

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Ganz, P.A., Bandos, H., Geyer, C.E. et al. Behavioral and health outcomes from the NRG Oncology/NSABP B-36 trial comparing two different adjuvant therapy regimens for early-stage node-negative breast cancer. Breast Cancer Res Treat 192, 153–161 (2022). https://doi.org/10.1007/s10549-021-06475-2

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