Abstract P3-18-05: Impact of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) on breast tumor downsizing for patients with HER2+ breast cancer - results from a single-arm clinical trial
Authors: Anna Weiss, Tianyu Li, Neelam V. Desai, Nadine M. Tung, Nabihah Tayob, Tari A. King, Eric P. Winer, Elizabeth A. Mittendorf, Adrienne G. Waks
Journal: Cancer Research (2022)

Abstract Background: As abbreviated neoadjuvant regimens emerge for treating HER2+ breast cancer, it is important to examine the effect this may have on breast tumor downsizing. The DAPHNe trial was a single-arm prospective trial enrolling stage II-III HER2+ breast cancer patients for treatment with neoadjuvant THP. The primary outcome, feasibility of de-escalating adjuvant chemotherapy following pCR, has been previously reported. The goals of this study were 1) to report how many patients who were not initial BCT candidates because of tumor size were deemed candidates after the completion of therapy; 2) to identify characteristics associated with conversion to BCT; and 3) to report how many patients with contraindications to BCT had a pathologic complete response to THP. Methods: Surgeon assessment for BCT candidacy was prospectively recorded before and after THP. Pre- and post-treatment mammogram and breast ultrasound were required; magnetic resonance imaging (MRI) was strongly encouraged. The following variables were compared between patients who did and did not convert to BCT candidacy: gender, estrogen/progesterone receptor (ER/PR) status, intensity of HER2+ staining, tumor size by baseline physical exam/imaging, and clinical nodal status. Results: 97 patients received neoadjuvant THP. By pre-treatment surgeon assessment, 51 (52.6%) were not BCT candidates. Tumor downsizing was possible for 34/51 (66.7%) but 17/51 (33.3%) had absolute contraindications to BCT (Table 1). Among the 34 with potential for BCT, 23 (67.6%) became eligible and BCT was the final surgical procedure performed in 19/23 (82.6%). Baseline tumor size by MRI was significantly different between patients who converted to BCT candidacy vs those who did not (median tumor size 2.4cm [range 1.5-4.5] vs 5.5cm [range 2.3-6.4] respectively, p=0.002). Patients with ER-negative disease were numerically more likely to convert to BCT (10/11 [90.9%]) than ER-positive (13/23 [56.5%], p=0.06). Of 9 who could never convert to BCT due to multifocal/multicentric disease, 7 (77.8%) had ypT0 and 2 (22.2%) had ypTis disease. Of 6 who could never convert due to extensive calcifications, 1 (16.7%) had ypT0, 3 (50.0%) had ypTis, 1 (16.7%) had ypT1, and 1 (16.7%) had ypT2 disease. Of 2 with contraindications to radiation, 1 (50%) had ypT1 and 1 (50.0%) had ypT2 disease. Conclusions: Of patients with potential for BCT, 67.6% who were not upfront BCT candidates converted to BCT candidacy after THP. Smaller baseline tumor size by MRI was the only characteristic significantly related to BCT conversion in this relatively small cohort. Patients with ER-negative disease were numerically more likely to convert to BCT. There remains opportunity to improve prediction of ypT staging - several patients who had a contraindication to BCT had ypT0 disease, including most patients with multifocal/multicentric disease. Table 1.Reasons for non-BCT candidacy at baselineCharacteristicN= 51Potential for tumor downsizing and BCTN=34Tumor to breast size ratio29 (56.9%)Nipple retraction2 (3.9%)Tumor location1 (2.0%)Unknown2 (3.9%)Contraindication to BCTN=17Multifocal/multicentric disease9 (17.6%)Extensive calcifications6 (11.8%)Contraindication to radiation2 (3.9%) Citation Format: Anna Weiss, Tianyu Li, Neelam V. Desai, Nadine M. Tung, Nabihah Tayob, Tari A. King, Eric P. Winer, Elizabeth A. Mittendorf, Adrienne G. Waks. Impact of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) on breast tumor downsizing for patients with HER2+ breast cancer - results from a single-arm clinical trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-05.