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NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy

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Abstract

Background

Chemotherapy-induced amenorrhea (CIA) is one of the critical side effects from the chemotherapy in premenopausal patients with breast cancer. The goals of our study are the following: (1) to investigate the factors affecting the incidence of CIA; and (2) to evaluate the prognostic role of CIA in premenopausal patients with breast cancer.

Methods

We conducted a post hoc retrospective substudy to examine the incidence of the CIA and the relationship between CIA and prognosis in NSAS-BC02 that compared taxane alone to Doxorubicin(A) Cyclophosphamide(C) followed by taxane in postoperative patients with node-positive breast cancer

Results

Of 395 premenopausal women, 287 (72.7%) had CIA due to protocol treatment. Regarding type of protocol regimen, proportion of CIA was 76.9% in AC Paclitaxel(P), 75.2% in AC Docetaxel(D), 62.8% in PTX, and 75.2% in DTX. Predictive factors of CIA were age increase by 5 years (OR 1.50), ER positivity (OR 2.08), and HER2 3 + ( OR 0.40) according to logistic regression analysis. According to the log rank test and the Cox proportional hazards model, CIA group had significantly better disease-free survival than non-CIA group (P < .0001). However, according to time-dependent Cox model that was used to reduce guarantee-time bias, CIA was not a statistically significant prognostic factor in both ER-positive and ER-negative patients.

Conclusion

Treatment with taxane alone caused high frequency of CIA in premenopausal women with breast cancer. CIA did not turn out to be an independent prognostic factor, taking guarantee-time bias into consideration. Further clinical studies are needed to validate these findings.

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Acknowledgements

We would like to thank the patients, investigators, and institutions involved in this study. We would also like to thank Editage (www.editage.jp) for English language editing.

Funding

This study was funded by the Comprehensive Support Project for Oncology Research (CSPOR) of Public Health Research Foundation.

Author information

Authors and Affiliations

  1. Departments of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Takayuki Iwamoto

  2. Breast Medical Oncology Department, Cancer Institute Hospital of JFCR, Kashiwa, Japan

    Fumikata Hara

  3. Department of Clinical Research, National Center for Global Health and Medicine, Tokyo, Japan

    Yukari Uemura

  4. Department of Breast and Medical Oncology, National Cancer Center Hospital East, Tokyo, Japan

    Hirofumi Mukai

  5. Department of Medical Oncology, Hamamatsu Oncology Center, Hamamatsu, Japan

    Toru Watanabe

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

    Yasuo Ohashi

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  1. Takayuki Iwamoto
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by FH, YU and HM. The first draft of the manuscript was written by TI and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Takayuki Iwamoto.

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Conflict of interest

FH received personal fees from Chugai, Kyowa Kirin, Eisai, Pfizer, and Eli Lilly, outside the submitted work. HM received honoraria from AstraZeneca, Pfizer, Takeda, Daiichi Sankyo and Taiho, and research grant from Japanese government, Daiichi Sankyo, Eisai, Nippon Kayaku and Pfizer, outside the submitted work. TW received advisory fee from CHUGAI PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., outside the submitted work. YO received personal fees from Statcom, Daiichi Sankyo, Chugai, Shionogi, Taiho, Sanofi and EP-Crsu and grants from Medical Member System, outside the submitted work. TI and YU declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board at National Hospital Organization Shikoku Cancer Center and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent Informed consent was not required for this retrospective analysis.

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Electronic supplementary material

Supplementary Figure 1—The Kaplan-Maier estimates of DFS for CIA and non-CIA groups. DFS was evaluated separately for (a) all, (b) ER-positive, and (c) ER-negative patients. DFS: Disease-free survival; CIA: chemotherapy induced amenorrhea; ER: Estrogen receptor. Below is the link to the electronic supplementary material.

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Iwamoto, T., Hara, F., Uemura, Y. et al. NSAS-BC02 substudy of chemotherapy-induced amenorrhea (CIA) in premenopausal patients who received either taxane alone or doxorubicin(A) cyclophosphamide(C) followed by taxane as postoperative chemotherapy. Breast Cancer Res Treat 182, 325–332 (2020). https://doi.org/10.1007/s10549-020-05692-5

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