Abstract

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

Highlights

  • Breast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million incident cases (11.7%) reported in 2020

  • Difference in diversity and taxonomy of gut microbiota between control individuals and breast cancer patients with different menopausal statuses In this study, we recruited 267 participants belonging to four groups: premenopausal female controls (Pre-C, N = 50), premenopausal breast cancer patients (Pre-BC, N = 100), postmenopausal female controls (Post-C, N = 17), and postmenopausal breast cancer patients (Post-BC, N = 100)

  • Patients in the Pre-BC and Post-BC groups had similar body mass indices (BMIs) and grades; a significant difference was found in tumor size and progesterone receptor (PR) status

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Summary

Introduction

Breast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million incident cases (11.7%) reported in 2020. Compared to the incidence of breast cancer in Western countries, the incidence of breast cancer in Asia is relatively low; the proportion of younger women diagnosed with breast cancer is increasing in Asian countries. The median onset age of breast cancer in Asia (40–50 years) is approximately 20 years younger than that in Western countries (60–70 years)[2,3]. In Taiwan, more than 30% of women with breast cancer are younger than 50 years of premenopausal breast cancer. This high proportion of premenopausal breast cancer in Taiwan differs from that in Western countries, where the proportion is usually less than 20%4,5

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