Abstract P2-12-04: Characterization of gut microbiome composition in triple negative breast cancer patients treated with neoadjuvant chemotherapy
Authors: Vernaci Grazia Maria , Massa Davide , Patuzzi Ilaria , Menichetti Alice , Giarratano Tommaso , Griguolo Gaia , Miglietta Federica , Fassan Matteo , Savarino Edoardo , Conte PierFranco , Guarneri Valentina , Dieci Maria Vittoria 
Published: March 2022

Abstract
Background: Recent evidences showed intestinal microbiota to be implicated in carcinogenesis and response to chemotherapy and immune checkpoint inhibitors in solid tumors. Furthermore, antibiotics are known to deeply influence microbiome composition in healthy people and cancer patients. The role of gut microbiome in triple negative breast cancer (TNBC) is underexplored. Methods: In this pilot prospective study, we characterized the gut microbiome of 30 TNBC patients undergoing neoadjuvant chemotherapy at two Italian Institutions. Fecal samples were collected at 2 timepoints: at the baseline (t0) and at 1 week (t1) from CT. Microbiome was analyzed by 16S rRNA sequencing. Measures of α-diversity expressed by Richness and Simpson evenness were evaluated at the species level. β-diversity was calculated using PERMANOVA test according to UniFrac measures of dissimilarity at the species level.Tumor infiltrating lymphocytes (TILs) were assessed from diagnostic core biopsy and surgical specimen. Results: From September 2017 to March 2020, 30 TNBC patients were enrolled. Median age was 53 years, 43% were premenopausal, 43% were overweight or obese (BMI&gt;25); 97% had a histologic G3 carcinoma, clinical nodal involvements was present in 57%; median TILs at diagnosis was 30%. All patients received anthracycline and taxane-based chemotherapy, including carboplatin in 23 patients (77%). A pCR was achieved in 15 (50%) patients. The overall rate of stool samples collection was 93%. With regards to t0, no differences in terms of α- and β-diversity were found.At t1, α-diversity was significantly higher in pCR group (Simpson evenness index, p=0.016). Considering clinical-pathological features, a BMI &lt;24.9 was associated with higher microbiome richness (p=0.012). Measurements of β-diversity did not differ between groups.As 73% of patients during the treatment phase received antibiotics, with consequent potential microbiome impairment, we repeated analyses at t1 considering fecal samples collected &gt;90 days after the end of antibiotic therapy (N=17). At this analysis, β-diversity evaluated with Unifrac measure was significantly correlated with pCR (p=0.035), with Haemophilus Influentiae being significantly enriched in non-pCR group. Conclusions: Fecal microbiome collection and analysis in this population is feasible and deserves further investigation with regards its association with response to chemotherapy.
Citation Format: Grazia Maria Vernaci, Davide Massa, Ilaria Patuzzi, Alice Menichetti, Tommaso Giarratano, Gaia Griguolo, Federica Miglietta, Matteo Fassan, Edoardo Savarino, PierFranco Conte, Valentina Guarneri, Maria Vittoria Dieci. Characterization of gut microbiome composition in triple negative breast cancer patients treated with neoadjuvant chemotherapy [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 P2-12-04.