Abstract P3-08-05: Chemotherapy-related amenorrhea on adjuvant paclitaxel-trastuzumab (APT trial)
Authors: Ruddy KJ , Tolaney SM , Guo H , Dang CT , Yardley DA , Moy B , Marcom PK , Albain KS , Rugo HS , Ellis MJ , Shapira I , Wolff AC , Carey LA , Overmoyer BA , Hudis C , Krop IE , Burstein HJ , Winer EP , Partridge AH 
Published: August 2014

Abstract
Background: Chemotherapy-related amenorrhea (CRA) is associated with infertility and menopausal symptoms. The majority of premenopausal women experience prolonged CRA (persisting for at least a year after chemotherapy has finished) with standard adjuvant breast cancer chemotherapy regimens. Trastuzumab is not believed to cause CRA. No studies to date have evaluated the risk of CRA from a taxane in the absence of other gonadotoxic therapy. If the paclitaxel-trastuzumab regimen is adopted for treatment of women with low to moderate risk Her2+ breast cancer, understanding its impact on this important survivorship issue will be of great interest.
Methods: 410 patients enrolled on a single-arm phase 2 adjuvant chemotherapy study of 12 weeks of paclitaxel-trastuzumab followed by nine months of trastuzumab monotherapy for patients with &lt;3cm of node-negative Her2+ breast cancer (APT Trial). Participants who reported they were premenopausal at enrollment were asked to complete menstrual surveys at baseline and every 6-12 months throughout a 60 month follow-up period. Women who had follow-up menstrual survey data at least 15 months after their first dose of chemotherapy and were premenopausal at study entry (last menstrual period, LMP, &lt;6 months before enrollment) were included in this analysis. For each participant, the last available survey was reviewed. Women were defined as amenorrheic if the LMP on the most recent follow-up survey was more than 12 months prior.
Results: Seventy-seven participants in the APT trial were premenopausal at enrollment, of whom 12 (16%) did not have follow-up menstrual data at least 15 months after their first dose of chemotherapy. In the remaining 65, median age was 44 years (range 27-52), and 59 (91%) were white. Forty-two (65%) had ER+ disease. Thirty-three (51%) were taking tamoxifen and 3 (7%) were taking an aromatase inhibitor when they completed their most recent menstrual surveys. The median time between first dose of chemotherapy and the last available menstrual survey was 40 months (range 17-63 months). At the time of their last available menstrual survey, 19 (29%) were amenorrheic and 46 (71%) were not amenorrheic.
Conclusions: Amenorrhea rates among premenopausal women treated with adjuvant paclitaxel-trastuzumab for early stage breast cancer appear lower than would have been expected with standard adjuvant cytotoxic breast cancer regimens (most studies of various standard regimens have found CRA rates of at least 50%). Additional follow-up and analyses are planned to clarify how menstrual functioning changes over time after paclitaxel-trastuzumab. Future studies are also needed to understand the impact of this regimen on related issues of fertility and menopausal symptoms in young women.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-08-05.