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Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial)

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Abstract

Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. Learning how frequently paclitaxel and trastuzumab cause amenorrhea is important. Most other adjuvant breast cancer therapies induce CRA in approximately 50 % of all premenopausal recipients [1]. 410 patients enrolled on the APT Trial, a single-arm phase 2 adjuvant study of 12 weeks of paclitaxel and trastuzumab followed by nine months of trastuzumab monotherapy. Eligible patients had ≤3 cm node-negative HER2 + breast cancers. Premenopausal enrollees were asked to complete menstrual surveys every 3–12 months for 72 months. Women who responded to at least one survey at least 15 months after chemotherapy initiation (and who did not undergo hysterectomy and/or bilateral oophorectomy or receive ovarian suppressing medications prior to 15 months) were included in this analysis. A participant was defined as having amenorrhea in follow-up if her self-reported last menstrual period at last follow-up was greater than 12 months prior to the survey. Among the 64 women in the evaluable population (median age at study entry 44 years, range 27–52 years), the median time between chemotherapy initiation and last menstrual survey was 51 months (range 16–79). 18 of 64 women (28 %, 95 % CI 18–41 %) were amenorrheic at that time point. Amenorrhea rates among premenopausal women treated with adjuvant paclitaxel and trastuzumab for early stage breast cancer appear lower than those seen historically with standard alkylator-based breast cancer regimens. Future studies are needed to understand the impact of this regimen on related issues of fertility and menopausal symptoms.

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Acknowledgments

This trial was supported by Genentech. This publication was made possible by CTSA Grant Numbers UL1TR000135 and KL2TR000136-09 (KJR) from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH. Precis: Paclitaxel–trastuzumab is likely less gonadotoxic than standard chemotherapy for breast cancer. This regimen may be appealing for women who wish to preserve ovarian function.

Conflict of interest

Authors Ruddy, Guo, Barry, Moy, Marcom, Shapira, Carey, Overmoyer, Hudis, Burstein, and Partridge have no conflicts of interest to disclose. Authors Dang, Rugo, Wolff, Krop, Winer, and Tolaney have received funding from Roche/Genentech. Author Yardley discloses that she has served in a consultant/advisory role with Genentech. Author Albain also has served on ad hoc advisory boards with Roche/Genentech, unrelated to this study. Author Ellis has received remuneration from Pfiser, AstraZeneca, Novartis, and Celgene. He has also held a consultant/advisory role with Nanostring and owns Bioclassifier, LLC stock.

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Authors and Affiliations

  1. Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Kathryn J. Ruddy

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Hao Guo, William Barry, Beth A. Overmoyer, Ian E. Krop, Harold J. Burstein, Eric P. Winer, Ann H. Partridge & Sara M. Tolaney

  3. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Chau T. Dang & Clifford Hudis

  4. Sarah Cannon Research Institute and Tennessee Oncology, PLLC, Nashville, TN, USA

    Denise A. Yardley

  5. Massachusetts General Hospital, Boston, MA, USA

    Beverly Moy

  6. Duke University Medical Center, Durham, NC, USA

    P. Kelly Marcom

  7. Loyola University Medical Center, Maywood, IL, USA

    Kathy S. Albain

  8. University of California San Francisco, San Francisco, CA, USA

    Hope S. Rugo

  9. Washington University, St. Louis, MO, USA

    Matthew J. Ellis

  10. Hofstra North Shore LIJ Medical School, Hempstead, NY, USA

    Iuliana Shapira

  11. Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA

    Antonio C. Wolff

  12. University of North Carolina, Chapel Hill, NC, USA

    Lisa A. Carey

Authors
  1. Kathryn J. Ruddy
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  2. Hao Guo
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  3. William Barry
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  4. Chau T. Dang
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  6. Beverly Moy
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  7. P. Kelly Marcom
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  8. Kathy S. Albain
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  9. Hope S. Rugo
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  10. Matthew J. Ellis
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  11. Iuliana Shapira
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  12. Antonio C. Wolff
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  13. Lisa A. Carey
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  14. Beth A. Overmoyer
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  15. Clifford Hudis
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  16. Ian E. Krop
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  17. Harold J. Burstein
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  18. Eric P. Winer
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  19. Ann H. Partridge
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  20. Sara M. Tolaney
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Correspondence to Kathryn J. Ruddy.

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Ruddy, K.J., Guo, H., Barry, W. et al. Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial). Breast Cancer Res Treat 151, 589–596 (2015). https://doi.org/10.1007/s10549-015-3426-z

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  • DOI: https://doi.org/10.1007/s10549-015-3426-z

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