Abstract PD7-04: Association between patient derived xenograft (PDX) take rate and breast cancer recurrence in the prospective breast cancer genome guided therapy study (BEAUTY)
Authors: Boughey Judy C. , Suman Vera J. , Yu Jia , Santo Katelyn , Sinnwell Jason P. , Carter Jodi M. , Kalari Krishna R. , Tang Xiaojia , McLaughlin Sarah A. , Aspitia Alvaro Moreno , Copland John A. , Northfelt Donald W. , Gray Richard J. , Hunt Katie N. , Conners Amy Lynn , Weinshilboum Richard , Wang Liewei , Goetz Matthew P. 
Published: February 2021

Abstract
Background: Patient derived xenografts are a standard tool used to study cancer biology and evaluate drug response phenotypes. It is well known that PDX take rate is associated with more aggressive clinical features [higher grade, biologic subtype (e.g. TNBC vs luminal)]. Previous data from a small retrospective cohort of patients (pts) with no prior chemo (n=24) suggested that primary breast tumor PDX take rate was associated with reduced overall survival. (Derose Nat Med. 2011) However, whether take rate is prognostic in newly diagnosed pts receiving standard of care neoadjuvant chemotherapy (NAC) is unknown. From the prospective BEAUTY clinical trial of pts treated with NAC in which PDX was attempted from pre-NAC as well as after chemo (post-NAC), we recently reported no difference in take rate comparing pts with or without a pathologic complete response (pCR) (Yu Breast Canc Res 2018). Herein we report the association between PDX take rate and recurrence from tumor samples implanted pre-NAC as well as post-NAC (time of surgery). Methods: The BEAUTY study is a prospective NAC study which enrolled breast cancer pts (Stage I-III; n=140) treated with neoadjuvant weekly taxane +/-trastuzumab followed by anthracycline-based chemotherapy. Percutaneous tumor biopsies were obtained prior to NAC and tumor samples from residual disease at surgery were additionally used to establish PDXs. Tumor take rate was defined as percent of pts with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. Time to breast cancer recurrence was defined as the time from surgery to documentation of a local, regional, or distant recurrence. Gray’s test was used to assess whether the cumulative incidence (CI) of a breast cancer recurrence differs with respect to either pre-NAC PDX take or post-NAC PDX take. Results: Of 140 pts enrolled in the BEAUTY study, tumor tissue for PDX from the pre-NAC tumor was available for implantation in 113. As previously published, PDX take rate from pre-NAC tumor was 27.4% (31/113), and varied according to tumor clinical subtype [51.3% (20/39) in triple negative breast cancer (TNBC), 26.5% (9/34) in HER2+, 5.0% (2/40) in Luminal]. With median follow up of 5.7 years (range: 3 months to 6.75 years), 17 pts developed local, regional or distant disease relapse (4 of whom had a PDX established pre-NAC). The cumulative incidence of breast cancer relapse after surgery was not found to differ according to pre-NAC PDX take (5 yr CI rate: 13.6% no take; 13.4% take; p=0.8911). In pts with TNBC, the group with the highest take rate, there was also no significant difference in incidence of BC recurrence between those without PDX take and those with PDX take (5 yr CI rate: 21.4% vs 16.2% p=0.7314). PDXs were established from residual tissue from surgery (post-NAC) in 6 of 34 pts (17.6%), [specifically, TNBC: 5/9; Her2+: 1/8; and Luminal: 0/17]. Nine of these 34 pts developed a local, regional or distant recurrence. There was a tendency for pts who had a PDX established from their residual disease to have a higher incidence of a breast event (p=0.1092). The 5 year cumulative incidence of a breast event was 19.6% for pts whose post-NAC PDX did not take and 50.0% for pts whose post-NAC PDX took. Discussion: In pts receiving NAC for breast cancer, we observed no significant difference between establishment of a pre-NAC PDX and breast cancer relapse. In contrast, post-NAC PDX take rate (from residual tumor obtained from the breast at surgery) was associated with a tendency to have a higher incidence of a breast cancer event. PDXs remain a valuable tool for the evaluation of tumor biology and development of new therapeutics, especially those models established from pts with chemotherapy resistance.
Citation Format: Judy C. Boughey, Vera J. Suman, Jia Yu, Katelyn Santo, Jason P. Sinnwell, Jodi M. Carter, Krishna R. Kalari, Xiaojia Tang, Sarah A. McLaughlin, Alvaro Moreno Aspitia, John A. Copland, III, Donald W. Northfelt, Richard J. Gray, Katie N. Hunt, Amy Lynn Conners, Richard Weinshilboum, Liewei Wang, Matthew P. Goetz. Association between patient derived xenograft (PDX) take rate and breast cancer recurrence in the prospective breast cancer genome guided therapy study (BEAUTY) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD7-04.