Abstract PS4-05: Prospective evaluation of the gut microbiome and response to neoadjuvant therapy (NAT) in early-stage triple negative breast cancer (TNBC)
Authors: Abuhadra Nour , Chang Chia-Chi , Yam Clinton , Sun Ryan , Huo Lei , White Jason , Ravenberg Elizabeth E , Litton Jennifer , Lim Bora , Ueno Naoto T , Arun Banu , Tripathy Debu , Damodaran Senthil , Murthy Rashmi , Valero Vicente , Hortobagyi Gabriel , Ibrahim Nuhad , Thompson Alastair , Mittendorf Elizabeth , Moulder Stacy , Jenq Robert 
Published: February 2021

Abstract
Introduction: Emerging data suggest that the gut microbial composition influences responses to chemotherapy and immunotherapy. However, similar data in patients with TNBC receiving NAT remains limited. Thus, we investigated the association between the gut microbial composition in patients with newly-diagnosed, early-stage TNBC and response to NAT in a cohort of patients enrolled in the ARTEMIS trial (NCT02276443). Methods: We performed 16S sequencing on bacterial genomic DNA extracted from pre-NAT fecal samples using the 2x250 bp paired-end read protocol. Quality-filtered sequences were clustered into Operational Taxonomic Units and classified using Mothur method with the Silva database version 128. Associations between abundance and pathologic response to NAT were assessed using the Mann Whitney U Test. A cohort of 32 patients had longitudinal samples collected. Mann-Whitney U Test and Fishers exact were used to compare clinical variables as appropriate between the pCR and non-pCR groups. Results: There was no significant difference in age, race or stage between the pCR and non-pCR groups (Table 1). As expected, the pCR group was enriched for high TIL (p=0.026). There was no difference in alpha-diversity of the gut microbiome between patients with NAT-sensitive (pCR) and NAT-resistant disease (non-pCR) (p=0.5). Relative to patients with NAT-sensitive disease (pCR), the gut microbiome in patients with NAT-resistant disease was enriched for Fusobacterium (p=0.009), Intestinimonas (p=0.01) and Lachnospiraceae (p=0.003) at the genus level; the median abundances between pCR and non-pCR are provided in Table 1. Longitudinal samples collected during NAT demonstrated no substantial impact of NAT on the gut microbiome.
Conclusions: Taken together, these data suggest that response to NAT may be influenced by the gut microbial composition, which remains unaltered during NAT. Research efforts to modulate the gut microbiome should be further explored as a potential therapeutic strategy in TNBC.
Table 1: Median Microbial Abundance and Clinicopathological Variables (N=43)pCR (n=18)Non-pCR (n=25)p- valueMicrobial AbundanceFusobacterium1 x 10-61.02 x 10-50.009Intestinimonas6.4 x 10-54.8 x 10-40.01Lachnospiraceae6.2 x 10-31.0 x 10-20.003Age median, interquartile range (n=44)45 (38-59)53 (46-58)0.61n (%)Race/EthnicityWhite, non-Hispanic11 (61.1)14 (56.0)0.53White, Hispanic4 (22.2)3 (12.0)Black2 (11.1)7 (28.0)Asian1 (5.6)1 (4.0)T categoryT15 (27.8)4 (16.0)0.15T213 (72.2)17 (68.0)T304 (16.0)T400Nodal statusNegative12 (66.7)14 (56.0)0.54Positive6 (33.3)11 (44.0)StageI3 (16.7)3 (12.0)0.91II11 (61.1)15 (60.0)III4 (22.2)7 (28.0)TIL&lt;20%7 (38.9)19 (76.0)0.026&gt;20%11 (61.1)6 (24.0)
Citation Format: Nour Abuhadra, Chia-Chi Chang, Clinton Yam, Ryan Sun, Lei Huo, Jason White, Elizabeth E Ravenberg, Jennifer Litton, Bora Lim, Naoto T Ueno, Banu Arun, Debu Tripathy, Senthil Damodaran, Rashmi Murthy, Vicente Valero, Gabriel Hortobagyi, Nuhad Ibrahim, Alastair Thompson, Elizabeth Mittendorf, Stacy Moulder, Robert Jenq. Prospective evaluation of the gut microbiome and response to neoadjuvant therapy (NAT) in early-stage triple negative breast cancer (TNBC) [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 PS4-05.