Abstract P1-14-01: First report of clinicopathological analysis in neoadjuvant treatment phase in NEOS: A randomized study of adjuvant endocrine therapy with or without chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole

Background: Whether adjuvant chemotherapy is required for patients with intermediate-risk endocrine-responsive postmenopausal breast cancer remains unknown. The New primary Endocrine-therapy Origination Study (NEOS: N-SAS BC06 study: UMIN 000001090 (http://www.umin.ac.jp/) was a randomized controlled trial to verify the necessity of adjuvant chemotherapy in node-, ER+, and HER2- postmenopausal breast cancer patients who responded to neoadjuvant endocrine therapy. The primary registration and primary treatment have finished. This report evaluated clinical responses and radiological findings in the neoadjuvant LET treatment phase of 6 months. Methods: Patients meeting eligibility criteria received LET preoperatively in weeks 24-28 after primary enrollment. Patients evaluated as complete response (CR), partial response (PR) or stable disease (SD) by each investigators underwent secondary enrollment and will be divided at random into two arms, an arm given LET for 4.5-5 years after chemotherapy and another arm given only LET for 4.5-5 years. Patients evaluated as progressive disease during LET treatment will receive discretionary treatment. The primary endpoint was disease-free survival and secondary endpoints were overall survival, clinical response rate in neoadjuvant treatment phase, pathological response, breast-conserving surgery rate, DFS/OS in subgroups according to clinical response, safety, HRQOL, and cost-effectiveness. Results: Between May 2008 and June 2013, 905 patients entered primary registration. We excluded 42 patients without confirmed data. The 863 included patients’ characteristics at baseline are: median age: 63 years old, median Body Mass Index (BMI):23.90, T1c:37%, T2:63%, and PgR+:79%, and 74% of patients had planned breast-conserving surgery (BCS). The clinical responses were evaluated with calipers, ultrasound and MRI (or CT) at the baseline and end of treatment before surgery. Clinical response rates were 2, 48, 46 and 4% in CR, PR, SD and PD, respectively. Excluding those who could not enter secondary registration according to the protocol, 83 (56.1%) of 148 patients with planned total mastectomy were converted to BCS according to final radiological evaluations before surgery. The correlation between the tumor size on MRI (r=0.87) after neoadjuvant LET and the pathological invasive tumor size was stronger than with other modalities (r=0.68, 0.57, 0.33 by CT, US and calipers, respectively). On univariate analysis, a small tumor size (T1c rather than T2), PgR+, HER2:2+ and a high BMI at the baseline were significantly correlated with the clinical response. On multivariate analysis, PgR + (HR: 1.13, 95%CI: 1.01-1.27, p=0.032) and a small tumor size (HR: 1.11, 95%CI: 1.03-1.17, p=0.003) were significant independent predictors of the clinical response. Conclusion: This is the first clinical report of neoadjuvant hormone therapy for early breast cancer. Neoadjuvant LET therapy improved BCS rates. MRI was useful for predicting the residual pathological invasive tumor size. PgR + and a small tumor size at the baseline were significant independent predictors of the clinical response. Citation Format: Takehiko Sakai, Hiroji Iwata, Yoshie Hasegawa, Rikiya Nakamura, Hiromitsu Akabane, Shoichiro Ohtani, Masahiro Kashiwaba, Naruto Taira, Tatsuya Toyama, Yutaka Yamamoto, Tomomi Fujisawa, Norikazu Masuda, Takuhiro Yamaguchi, Hirofumi Mukai, Yasuo Ohashi. First report of clinicopathological analysis in neoadjuvant treatment phase in NEOS: A randomized study of adjuvant endocrine therapy with or without chemotherapy for postmenopausal breast cancer patients who responded to neoadjuvant letrozole [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 P1-14-01.