Abstract PD7-06: MAAT: Menses after adjuvant treatment. Prediction of menses recovery after chemotherapy for early breast cancer (BC) by using a nomogram model in UNICANCER PACS04 and PACS05 trials
Authors: Pistilli B , Mazouni C , Zingarello A , Faron M , Saghatchian M , Grynberg M , Spielmann M , Kerbrat P , Roché H , Lorgis V , Bachelot T , Campone M , Levy C , Goncalves A , Lesur A , Veyrat C , Vanlemmens L , Lemonnier J , Delaloge S 
Published: February 2018

Abstract
Purpose:The likelihood of menses recovery (MR) is largely variable in premenopausal patients (pts) receiving adjuvant chemotherapy for BC. Quantifying this probability for each single patient could impact discussion of chemotherapy side effects and better individualize fertility counseling.We performed a pooled analysis from PACS04 and PACS05 randomized trials aiming to develop a nomogram to estimate the probability of menses recovery at 6 and 18 months (mos) after the end of adjuvant chemotherapy (CT) for premenopausal pts with early BC.
Patients and Methods: The analyzed population consisted of 1683 pts who were premenopausal and ≤ 50 (out of 4524 enrolled in both trials). In PACS05 node-negative BC pts were randomized to 4 or 6 cycles of FE100C (standard arm); in PACS04 node-positive pts were randomized to 6 cycles of FE100C or 6 cycles of Epirubicin 75mg/m2 and Docetaxel 75 mg/m2 (ED75). Endocrine therapy (ET) (Tamoxifen) x 5 years was mandatory for ER+ BC. Variables significantly associated with MR in the univariate analysis (P&lt;0.20) were included in the multivariate analysis. Using this data set, a logistic regression-based nomogram was developed to predict MR at 6 and 18 mos.
Results: Pts' characteristics were: median age 43 (22-50), median body mass index (BMI) at baseline 22.6 (15.6-54.7), at the end of chemotherapy 22.8 (15.8-58.6). ED75 was administrated to 517 (30.7%), while 802 (47.7%) received 6FE100C, 364 (21.6) 4FE100C. Trastuzumab was given to 122 (7.2%), ET to 1229 (73%) pts. CT-induced amenorrhea was observed in 1407 (83.6%) pts. Factors associated to MR were assessed on 1210 pts (excluding pts who recovered menses during CT or of whom date of recovery was not specified). At a median follow-up of 90 mos, 28.2% (342/1210) of pts had recovered menstrual cycles: 11% (133/1210) at 6 mos and 24.3% (294/1210) at 18 mos. Multivariate analysis showed that younger age, higher BMI at the end of CT, non-alkylating agents and absence of ET were independently associated to MR.
Table 1 Multivariate Cox regression analysis of menses recoveryVariablesHR (95%CI)P valueAge1.49 (1.16-1.93)&lt; 0.002Age2*0.99 [0.98-0.99]&lt;0.0001BMI after CT1.02 (0.99-1.04)0.07Alkylating agents0.72 (0.57-0.90)0.004Endocrine Therapy0.50 (0.40-0.62)&lt;0.001* The quadratic term in the age variable accounts for the non-linearity of the relation between the age and the probability of recovering menses. Overall this probability tend to decrease when age increase with a greater decrease for the older patients.
Nomogram concordance-index was 0.749 and 0.750 for predicting MR at 6 and 18 mos respectively. A better calibration was observed at 18 mos, comparing nomogram predictions with the actual probability of MR in the 1210 women.
Conclusion:Our analysis confirmed the possibility of developing a user-friendly nomogram for predicting menses recovery after adjuvant chemotherapy. As next step, we will externally validate our nomogram on CANTO premenopausal population, one of the biggest national cohorts aiming to assess the long-term impact of cancer treatments toxicities (UNICANCER NCT01993498 - http://etudecanto.org/).
Citation Format: Pistilli B, Mazouni C, Zingarello A, Faron M, Saghatchian M, Grynberg M, Spielmann M, Kerbrat P, Roché H, Lorgis V, Bachelot T, Campone M, Levy C, Goncalves A, Lesur A, Veyrat C, Vanlemmens L, Lemonnier J, Delaloge S. MAAT: Menses after adjuvant treatment. Prediction of menses recovery after chemotherapy for early breast cancer (BC) by using a nomogram model in UNICANCER PACS04 and PACS05 trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-06.