Abstract P6-08-16: NSAS BC02 substudy of chemo-induced amenorrhea (CIA) in premenopausal women who received either taxane alone or AC followed by taxane as a postoperative chemotherapy
Authors: Hara Fumikata , Mukai Hirofumi , Watanabe Toru , Uemura Yukari , Ohashi Yasuo 
Published: May 2015

Abstract
Background: Chemotherapy has a direct cytotoxic effect to breast cancer cells as well as ovarian suppression. In NSABP-B30 study, Swain, et al demonstrated that CIA contributed to reduce recurrence and prolong overall survival in premenopausal women with ER positive breast cancer. Thus far, incidence of CIA by anthracycline and cyclophosphamide (AC), or CMF has been reported. However, there has been no report on CIA by taxane alone therapy. Therefore, it is critically important to evaluate the incidence of the CIA in NSAS-BC02 (Watanabe T, ASCO2009) which compared taxane alone (q3w Docetaxel 75mg/m2 x8: DTX:, q3w Paclitaxel 175mg/m2 x8: PTX? to AC -&gt; taxane (q3wAC 60/600mg/m2 x4 -&gt; DTX x4: ACD, q3wAC x4 -&gt; PTX x4: ACP) in postoperative patients with node-positive breast cancer. In addition, we examined the relationship between CIA and prognosis in this substudy.
Methods: Menstrual status of all women participating in NSAS BC02 was assessed at study entry, every cycle during chemotherapy, at 2 months after protocol treatment, and then at every 6 months until 5 years. After 5 years, menstrual status was assessed annually. Women who were having regular menstrual cycles (premenopause) or irregular menstrual cycle (perimenopause) at study entry were included in this CIA substudy. We defined CIA as having no menstrual cycle for at least 6 months after chemotherapy.
Results: Of the 1049 women enrolled in NSAS BC02, 395 were analyzed, including 315 with premenopause and 80 with perimenopause. Median age was 44.2 years old (42-62). Mean body mass index was 22.7 (15.4-38.4). Tumor characteristics were pathological stage I/IIA/IIB/IIIA 12.7%/39.0%/37.0%/11.4%, ER positivity 56.0% and PgR positivity 54.4%. Of 395 women, 287 (72.7%) was CIA due to protocol treatment. Regarding the type of protocol regimen, proportion of the CIA was 76.9% in ACP, 75.2% in ACD, 62.8% in PTX and 75.2% in DTX. There was no significant difference of CIA frequency between AC followed by taxane and taxane alone ?76.0?vs 69.4%, respectively; p=0.14?. Predictive factors of CIA were ACD against PTX (odds ratio (OR): 2.15), age increase by 5 years (OR: 1.50), and ER negativity (OR: 2.08) according to logistic regression analysis. In terms of effect to prognosis, CIA was an independent prognostic factor for disease-free survival (DFS) and overall survival in overall population of substudy according to multivariate Cox analysis. To eliminate guarantee time bias (GTB) (Giobbie-Hurder et al. JCO 2013), we used time-dependent Cox model. As a result, CIA was not statistically significant prognostic factor of DFS, even in the subgroup analysis of both ER positive and ER negative patients (Table 1).
DFS in time-dependent Cox modelSubjectsHazard ratio95% Confidence intervalp valueOverall0.770.52-1.160.21ER positive0.600.31-1.160.13ER negative0.820.47-1.430.49
Conclusion: Although there has been no data on CIA by taxation alone regimen, eight cycles of taxation treatment caused a high frequency of CIA in premenopausal women with breast cancer (PTX62.8% and DTX75.2%). It would be cautious to conclude that CIA was statistically significant association with prognosis, because it might be due to GTB.
Table 1: The effect of CIA on DFS by time-dependent Cox model
Citation Format: Fumikata Hara, Hirofumi Mukai, Toru Watanabe, Yukari Uemura, Yasuo Ohashi. NSAS BC02 substudy of chemo-induced amenorrhea (CIA) in premenopausal women who received either taxane alone or AC followed by taxane as a postoperative chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-16.