1. Nalley, Catlin

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Researchers recently conducted a comprehensive literature review to gain a better understanding of where the evidence stands on the connection between the microbiome and breast cancer (Cancer Treat Rev 2022; doi: 10.1016/j.ctrv.2022.102470).

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"The role of microbiome in breast cancer is far from understood and available data is scarce and heterogeneous," noted Mafalda Oliveira, MD, PhD, Medical Oncologist at the Medical Department of the Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO) in Barcelona, and colleagues. "We launched a project awarded with an ESMO Translational Research Fellowship to investigate tumor-associated microbiome in breast cancer and, going through the available literature, we felt that a review in this area was needed to help the field move forward."


The investigators, including first author Andri Papakonstantinou, PhD, a fellow from the Karolinska Institutet, examined the "different aspects related to the microbial landscape of the breast tissue and breast tumors, as well as its relation to systemic therapy."


Literature Review Takeaways

According to the researchers, the researchers focused on the available data regarding the "composition of the breast microbiome, the factors that may influence its constitution, and the existing evidence regarding the relationship between breast cancer, breast and gut microbiome, and cancer therapy."


Oliveira and colleagues noted three key messages derived from their review. "First, there seems to be a difference in the microbiome composition between healthy breast and breast tumoral tissue. Second, the association between tumor and gut microbiome and treatment efficacy and toxicity is largely unknown but should be investigated as a potential biomarker given the biological rational behind it," she told Oncology Times. "Third, and most importantly, there is a large heterogeneity in the methodology and report of microbiome studies, and an effort in harmonization and reporting is fundamental to advance in the field."


Understanding of the relationship between the microbiome-breast or gut-and breast cancer has evolved with ongoing study and advancement; however, questions remain.


"The evolution of metagenomics has improved the possibility to perform microbiome-related studies, even in tissues with low biomass as the breast," Oliveira said. "We now know that the breast is not a sterile tissue and has a rich microbiome landscape. However, there are still large gaps, not least regarding causal relationship between specific type of microbiome composition and breast cancer development, or correlation with treatment response-for example, when treating with immune checkpoint inhibitors."


The study authors concluded that there is a critical need for the identification of novel biomarkers in breast cancer and predictors of therapy benefit and/or toxicity. "The microbiome directly influences drug metabolism and can promote or compromise efficacy and toxicity while conversely cancer therapies directly affect microbiota leading to a spiral that can be either vicious or beneficial," they wrote. "The field of microbiome in breast cancer is relatively novel and data has just begun to emerge. It is a field that undeniably deserves further review for the identification of potential preventive, diagnostic, therapeutic, or predictive strategies."


Ongoing Research

As the study authors have highlighted in their review, there are a number of avenues of research that warrant further exploration. According to Oliveira and colleagues, this includes the relationship between microbiome signatures and breast cancer development, as well as correlation of specific types of gut bacteria and breast cancer characteristics.


"There is today evidence from other types of solid tumor suggesting correlation of specific microbiome composition and risk for immunotherapy-related toxicity, but this has not been confirmed in breast cancer," they explained. "There is a number of studies investigating microbiome manipulation in breast cancer and it will be interesting to see what they demonstrate.


"A better understanding of the microbiome, both in the breast and the gut, would improve the understanding of breast cancer carcinogenesis, the impact of microbiome in breast cancer natural history, and the role of microbiome as a potential predictive biomarker for several therapies," the investigators stated.


Oliveira and colleagues are currently conducting a prospective study at VHIO. This research is investigating whether there is a specific microbiome-signature in the breast and/or gut at baseline or during the course of treatment that can predict response to immune checkpoint inhibitors. Preliminary results from this study are expected in 2023.


Catlin Nalley is a contributing writer.