Abstract P5-06-13: Second-harmonic generation imaging reveals neoadjuvant chemotherapy-induced changes in breast tumor collagen

Abstract

Abstract Breast cancer is the most common invasive cancer in women, with most deaths attributed to metastases. Neoadjuvant chemotherapy (NACT) may be prescribed prior to surgical removal of the tumor for subsets of breast cancer patients but can have diverse undesired and off-target effects including increased appearance of the ‘tumor microenvironment of metastasis’ or TMEMs, image-based multicellular signatures which are prognostic of metastasis. In this study we explored whether NACT alters other image-based prognostic/predictive signatures, specifically second-harmonic generation (SHG) directionality, which is indicative of collagen fiber internal structure, as well as the disorganization in collagen fiber alignment. This was performed in paired biopsy/excision samples from 22 patients with HER2 overexpressing invasive ductal carcinoma as well as 22 patients with triple negative breast cancer (TNBC). We found that collagen fiber internal structure, measured using the SHG forward-to-backward-scattered ratio (F/B), is altered in the bulk of the tumor in both tumor types (p = 0.015 and 0.038, respectively), but not the adjacent tumor-stroma interface (p = 0.54 and 0.92, respectively), where F/B is prognostic of metastatic outcome. Overall disorganization in collagen fiber alignment was not significantly changed by NACT in HER2 overexpressing disease (p = 0.41) but was decreased in TNBC (p = 0.0051). These results suggest that NACT alters the collagenous extracellular matrix in diverse ways, with implications for the use of F/B and collagen fiber alignment as prognostic and predictive tools. Citation Format: Edward Brown, Danielle Desa, Robert M Brown, Edward B Brown, Robert L Hill, Bradley M Turner. Second-harmonic generation imaging reveals neoadjuvant chemotherapy-induced changes in breast tumor collagen [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 P5-06-13.