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Impact of chemotherapy on cognitive functioning in older patients with HER2-positive breast cancer: a sub-study in the RESPECT trial

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Abstract

Purpose

To investigate whether postoperative adjuvant trastuzumab plus chemotherapy negatively affected cognitive functioning during the post-chemotherapy period compared with trastuzumab monotherapy in older patients with HER2-positive breast cancer.

Methods

In the randomized RESPECT trial, women aged between 70 and 80 years with HER2-positive, stage I to IIIA invasive breast cancer who underwent curative operation were randomly assigned to receive either 1-year trastuzumab monotherapy or 1-year trastuzumab plus chemotherapy. Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) test at enrollment and 1 and 3 years after initiation of the protocol treatment. The primary outcome was change in the MMSE total score from baseline. Secondary outcomes included prevalence of suspected mild cognitive impairment (MMSE total score < 28) and suspected dementia (MMSE total score < 24).

Results

The analytical population consisted of 29 and 26 patients in the trastuzumab monotherapy and trastuzumab plus chemotherapy groups, respectively. The group differences in mean changes of the MMSE total score were 0.6 (95% confidence interval [CI] − 0.3 to 1.6) at 1 year and 0.9 (95% CI − 1.0 to 2.8) at 3 years (P = 0.136 for the group difference pooling the two visits). The prevalence of suspected mild cognitive impairment at 3 years was 41.7% in the trastuzumab monotherapy group and 28.6% in the trastuzumab plus chemotherapy group (P = 0.548).

Conclusion

This randomized sub-study did not show worse cognitive functioning during the post-chemotherapy period with trastuzumab plus chemotherapy than with trastuzumab monotherapy in older patients with HER2-positive breast cancer.

Trial registration number

NCT01104935 (first posted April 16, 2010).

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Data availability

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The codes used to analyze the datasets during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The RESPECT trial was funded by the Comprehensive Support Project for Oncology Research (CSPOR) of the Public Health Research Foundation. We thank all patients who participated in the RESPECT trial and investigators, medical staff, and data managers who were dedicated to this trial. We are grateful for support from the Comprehensive Support Project for Health Outcomes Research (CSP-HOR).

Funding

The RESPECT trial was funded by the Comprehensive Support Project for Oncology Research (CSPOR) of the Public Health Research Foundation.

Author information

Author notes

  1. Deceased March 11, 2021—Yasuo Ohashi.

Authors and Affiliations

  1. Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yasuhiro Hagiwara

  2. Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Masataka Sawaki

  3. Biostatistics Section, Department of Data Science, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan

    Yukari Uemura

  4. Biostatistics Division, Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan

    Takuya Kawahara

  5. Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, Kusatsu, Japan

    Kojiro Shimozuma

  6. Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan

    Yasuo Ohashi

  7. Department of Breast Surgery, NHO Hokkaido Cancer Center, Sapporo, Japan

    Masato Takahashi

  8. Department of Surgery, Japanese Red Cross Saitama Hospital, Saitama, Japan

    Tsuyoshi Saito

  9. Department of Surgery, Sagara Hospital, Kagoshima, Japan

    Shinichi Baba

  10. Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan

    Kokoro Kobayashi

  11. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Hirofumi Mukai

  12. Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan

    Naruto Taira

Authors
  1. Yasuhiro Hagiwara
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  2. Masataka Sawaki
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  3. Yukari Uemura
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  4. Takuya Kawahara
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  5. Kojiro Shimozuma
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  6. Yasuo Ohashi
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  7. Masato Takahashi
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  8. Tsuyoshi Saito
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  9. Shinichi Baba
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  10. Kokoro Kobayashi
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  11. Hirofumi Mukai
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  12. Naruto Taira
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Contributions

Study concept and design: MS, KS, YO, and NT. Administrative support: HM and NT. Provision of study material or patients: MS, YO, MT, SB, HM, and NT. Collection and assembly of data: MS, MT, TS, SB, KK, HM, and NT. Data analysis and interpretation: YH, MS, YU, TK, YO, MT, SB, HM, and NT. Statistical analysis: YH, YU, TK, and YO. Manuscript preparation: YH, MS, and NT. Manuscript editing: YH. Manuscript review: All authors.

Corresponding author

Correspondence to Yasuhiro Hagiwara.

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Conflict of interest

YU reports honoraria from Chugai Pharma and Teijin Pharma; consulting and advisory role for Pfizer, Ono Pharmaceutical, Zeria Pharmaceutical, and Daiichi Sankyo; speakers' bureaus for Pfizer; and travel support from Pfizer and Chugai Pharma. YO reports compensated leadership for Statcom; stock ownership of Statcom; honoraria from Chugai Pharma, Daiichi Sankyo, Sanofi, Eisai, and Shionogi; and grants from Medical Member System. MT reports honoraria from AstraZeneca, Eli Lilly, Eisai, and Pfizer; and grants paid to the institution from Eisai, Kyowa Kirin, and Taiho Pharmaceutical. HM reports honoraria from Pfizer, Daiichi Sankyo, Taiho Pharmaceutical, and Takeda; and grants paid to the institution from Daiichi Sankyo. All remaining authors have declared no conflicts of interest.

Ethical approval

The RESPECT trial protocol, including the cognitive functioning sub-study, was approved by the institutional review boards of all participating institutions.

Informed consent

All patients provided written informed consent.

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Hagiwara, Y., Sawaki, M., Uemura, Y. et al. Impact of chemotherapy on cognitive functioning in older patients with HER2-positive breast cancer: a sub-study in the RESPECT trial. Breast Cancer Res Treat 188, 675–683 (2021). https://doi.org/10.1007/s10549-021-06253-0

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  • DOI: https://doi.org/10.1007/s10549-021-06253-0

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