
Introduction
Increasing evidence link the gut microbiome to cancer progression and response to treatment; however, its effect on breast cancer remains underexplored. The aim of our study is to highlight the differences in the gut microbiome between breast cancer patients and healthy women and asses its longitudinal changes throughout endocrine therapy.
Materials and methods
Fecal samples from 92 breast cancer patients at diagnosis were collected at Sheba Breast Oncology Center and sequenced using shotgun metagenomics. The microbiome of breast cancer patients was compared to that of a healthy, age and BMI matched, control group of 920 women, collected at the Weizmann Institute. Comprehensive longitudinal clinical data, along with stool samples, were collected and analyzed at different stages of the treatment process.
Results
The gut microbiome of women with breast cancer exhibited distinct characteristics, including lower alpha diversity compared to control. A machine learning prediction model successfully separated samples based on cancer status, and multiple species displayed significant differences in abundance between the groups. Certain species that were dominant in breast cancer samples had decreased in proportion during endocrine treatment. Additionally, shifts in clinical parameters — such as reductions in LDL and elevations in HbA1c levels — were observed during treatment, with variations depending on chemotherapy exposure and the type of endocrine therapy. Strong correlations between microbiome shifts and clinical parameter alterations were observed, suggesting a potential interaction between gut microbiota and the host`s response to treatment.
Conclusions
The results highlight the gut microbiome as a promising indicator for breast cancer detection. We explored the interplay between the microbiome and physiological response to endocrine treatment, with further research needed to establish better personalized treatment strategies.