Abstract PS3-11-13: Fatty Acid Profile and Its Association with HER2-Positive Breast Cancer and Response to Neoadjuvant Chemotherapy

Abstract Introduction Fatty acids (FAs), particularly omega-3 (n-3) polyunsaturated fatty acids, exhibit anti-inflammatory and antitumor properties. Preclinical models have demonstrated their ability to modulate HER2 expression and enhance the efficacy of targeted therapies. However, clinical evidence regarding the relationship between lipid profiles and the clinicopathological subtypes of breast cancer, as well as their utility as biomarkers of therapeutic response, remains limited. Methods Blood samples from 99 patients with stage I-III breast cancer treated with neoadjuvant chemotherapy (NAC) were analyzed. In a subset of 28 patients, paired plasma and erythrocyte samples were collected before and after treatment. Individual and grouped FAs (saturated FAs [SFAs], monounsaturated FAs [MUFAs], polyunsaturated FAs [PUFAs], n-3, and n-6) were quantified by gas chromatography. Associations between these profiles and HER2 status (immunohistochemistry and gene amplification) as well as pathological complete response (pCR) were evaluated. Statistical analyses included bivariate tests and linear and logistic regression models. Results Plasma MUFA levels (pMUFAs) were lower in HER2-positive patients (mean ± SD: 22.07 ± X vs. 25.00 ± Y; p = 0.0044), as were erythrocyte MUFA levels (eMUFAs; 19.95 ± X vs. 22.28 ± Y; p = 0.0107). In contrast, erythrocyte SFA levels (eSFAs) were higher in the HER2-positive group (54.89 ± X vs. 51.42 ± Y; p = 0.0069), as were plasma PUFA levels (pPUFAs; 41.10 ± X vs. 36.82 ± Y; p = 0.0166). A significant increase in plasma omega-6 fatty acids (linoleic acid + arachidonic acid) was also observed among HER2-positive patients (37.90 ± X vs. 34.21 ± Y; p = 0.0198). In the HER2 amplification analysis, higher plasma n-3 levels (ALA + DPA + EPA + DHA) were significantly associated with lower gene amplification (β = -0.73; 95% CI: -1.44 to -0.02; p = 0.045; R2 = 0.13). Among the paired pre- and post-NAC samples, an increase in plasma n-3 fatty acids was correlated with higher rates of pCR, particularly in HER2-positive patients (p = 0.0321). Conclusions Blood FA profiles differ significantly according to HER2 status, especially regarding SFAs, MUFAs, PUFAs, and omega-6 fatty acids. Moreover, plasma omega-3 levels were inversely associated with HER2 amplification, and their increase during NAC may play a beneficial role in treatment response. These findings support the hypothesis that FAs, particularly omega-3s, could serve as complementary biomarkers for stratification and monitoring of patients with HER2-positive breast cancer. Citation Format: F. Acevedo, B. Walbaum, K. Ramirez, L. Medina, F. Dominguez, M. Camus, C. Vargas, M. Abud, R. Valenzuela, C. Farias, c. G. sanchez. Fatty Acid Profile and Its Association with HER2-Positive Breast Cancer and Response to Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-11-13.