Did You Know?

The Left Breast Is Slightly More Susceptible. Breast cancer is about 5–10% more common in the left breast than the right. Researchers are still exploring why this asymmetry exists.

Breast Cancer

Researched by:

Karen Pendergrass ID

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Divine Aleru ID

Divine Aleru

I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

May 19, 2025

Traditionally linked to genetic predispositions and environmental exposures, emerging evidence highlights the microbiome as a critical and underappreciated factor influencing breast cancer progression, immune response, and treatment outcomes.

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Divine Aleru

I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

Researched by:

Karen Pendergrass ID

Karen Pendergrass

Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
Divine Aleru ID

Divine Aleru

I am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.

Last Updated: May 11, 2025

References
Identified MMAs

Overview

Breast cancer is the most prevalent cancer among women globally, accounting for over 2.3 million cases annually and representing a leading cause of cancer mortality.^[1] Traditionally linked to genetic predispositions and environmental exposures, emerging evidence highlights the microbiome as a critical and underappreciated factor influencing breast cancer progression, immune response, and treatment outcomes.[3]^[x] Central to its development are mutations in tumor suppressor genes BRCA1 and BRCA2, which impair DNA repair, promote genomic instability, and increase susceptibility, particularly to aggressive subtypes like triple-negative breast cancer.^[4] Screening strategies such as mammography and breast self-examination play critical roles in early detection, yet awareness and participation remain insufficient in many populations. Emerging evidence highlights the microbiome’s relevance in breast cancer, with dysbiosis in gut and oral microbiota implicated in modulating estrogen metabolism, inflammatory responses, and immune surveillance, thereby influencing tumorigenesis and treatment outcomes.^[5][6][7] Understanding the microbiome signatures associated with breast cancer offers unprecedented opportunities for targeted therapies, preventive strategies, and personalized treatment in breast cancer management.

Associated Conditions

Diabetes and benign breast disease (BBD) are interconnected risk factors that influence breast cancer risk. Type 2 diabetes (T2D) increases the risk of breast cancer through mechanisms like hyperinsulinemia and the activation of the insulin-like growth factor (IGF) pathway, which promotes cell growth and inhibits apoptosis, leading to a higher likelihood of cancer development, particularly in estrogen receptor-positive breast cancer.^[8]Type 1 diabetes (T1D) also elevates breast cancer risk, especially shortly after diagnosis.^[9] Meanwhile, a history of BBD, especially conditions like fibroadenoma and lobular proliferation, is a known risk factor for breast cancer. Surgical treatment for certain benign conditions, such as fibroadenoma, has been shown to reduce future cancer risk.^[10] These factors, along with potential microbiome disruptions, can worsen insulin resistance and influence immune function, further elevating breast cancer risk. The gut microbiome, in particular, has been shown to play a role in breast cancer development, with a reduction in short-chain fatty acid-producing bacteria like Faecalibacterium prausnitzii, which are associated with anti-inflammatory effects and maintaining metabolic health.[11]^[x] Dysbiosis, or an imbalance in gut bacteria, may contribute to increased systemic inflammation and other metabolic conditions that heighten breast cancer susceptibility.^[12] Thus, managing diabetes, monitoring BBD, and understanding the role of the microbiome are crucial for reducing breast cancer risk.

Causes

Breast cancer is thought to arise from a multifactorial interplay of genetic, environmental, and hormonal factors, with up to 70% of cases having unknown etiology. However, recent studies find that dysbiosis—characterized by a significant overgrowth of Proteobacteria and reduced diversity of beneficial taxa like Bacteroidetes and SCFA-producing bacteria like Faecalibacterium prausnitzii, plays a critical role by disrupting estrogen metabolism, promoting inflammation, and altering the tumor microenvironment in breast cancer.[13]^[x] Evidence suggests that frequent antibiotic use may contribute to breast cancer risk by promoting Proteobacteria blooms as well as Escherichia coli and Klebsiella sp., which are enriched in the breast cancer patient, amplifying systemic inflammation and immune suppression.[14]^[x]^[15] Microbial dysbiosis, both local and systemic, has significant implications for breast cancer progression, with some literature even proposing that antibiotics may potentially play a causal role in the condition.[16]^[x]

Diagnosis

Currently, breast cancer diagnosis relies heavily on imaging (mammography, ultrasound) and histopathological confirmation. However, advancements in microbiome research suggest that microbial signatures, including shifts in gut and breast tissue microbiota, could serve as non-invasive diagnostic biomarkers. For instance, altered ratios of Firmicutes to Bacteroidetes in the gut and specific microbial markers in breast tissue (e.g., Bacteroides fragilis, Methylobacterium radiotolerans) offer promising diagnostic potential. Integrating microbiome analyses into routine diagnostics could improve early detection, especially for aggressive subtypes like triple-negative breast cancer. ^[17]

Primer

The interplay between the microbiome, immune modulation, and hormone metabolism highlights the microbiome’s central role in breast cancer pathogenesis. Dysbiosis contributes to systemic inflammation, immune escape, and tumor growth. For example, reductions in SCFA production impair anti-inflammatory pathways, while overgrowth of specific taxa drives estrogen metabolism disruptions, fueling hormone receptor-positive cancers. Addressing these microbial imbalances through targeted interventions may enhance therapeutic outcomes. Additionally, the activity of beta-glucuronidase, an enzyme involved in estrogen conjugation, is linked to the microbial dysbiosis observed in women with a history of breast cancer. ^[18]

Metallomic Signatures

Metallomic signatures play an important role in understanding breast cancer, with recent research highlighting how heavy metals and metabolites contribute to the progression of the disease.^[19] A growing body of evidence suggests that exposure to heavy metals, including copper (Cu), cadmium (Cd), and zinc (Zn), can significantly influence breast cancer development by altering cellular pathways, including reactive oxygen species (ROS) production.^[20] These metals can induce cancer progression by mimicking or disrupting essential metabolic pathways, influencing cell growth and survival. Studies have shown that increased concentrations of Cu and Cd, combined with lower levels of Zn, are associated with breast cancer patients compared to healthy controls.^[21][22] Cadmium’s estrogenic effects are implicated in promoting breast cancer cell proliferation, suggesting a potential role in hormone-sensitive breast cancer. This is because cadmium, a heavy metal, can mimic the effects of estrogen by binding to estrogen receptors and activating them.^[23] This activation can lead to increased cell growth and proliferation, contributing to the development of hormone-sensitive breast cancer.

What are the metallomic signatures of Breast Cancer?

Copper (Cu)

Copper is an essential heavy metal in the body, playing a crucial role in several enzymatic processes and maintaining normal cellular function. However, elevated levels of Cu have been linked to breast cancer development, particularly through the induction of oxidative stress and dysregulation of various cellular processes. Studies have indicated that high copper concentrations in both serum and tumor tissue are associated with increased breast cancer risk.^[24] Copper influences angiogenesis, the process by which new blood vessels are formed, which is critical for tumor growth and metastasis.^[25] It also activates several signaling pathways, including those related to cell proliferation and survival, thus contributing to tumor progression.

Cadmium (Cd)

Cadmium is a well-known environmental toxicant and a suspected carcinogen that has been consistently associated with breast cancer. Studies have shown that cadmium mimics the action of estrogen by binding to estrogen receptors (ER), particularly in estrogen-sensitive tissues such as the mammary glands.^[26] This estrogenic effect promotes the proliferation of breast cancer cells, especially in hormone receptor-positive breast cancers.^[27] Epidemiological evidence supports the notion that chronic exposure to cadmium, particularly through smoking or polluted environments, increases the risk of developing breast cancer.^[28] Moreover, high cadmium levels have been found in breast cancer tissues, which further supports its role in disease development. The cadmium-induced carcinogenic mechanism is also believed to involve oxidative stress, DNA damage, and the disruption of DNA repair pathways, which can lead to mutations and tumorigenesis.^[29]

Zinc (Zn)

Zinc is an essential trace element that plays a critical role in immune function, DNA synthesis, and cell division. Interestingly, while low zinc levels are commonly observed in individuals with breast cancer, the relationship between zinc and breast cancer risk is complex.^[30] A meta-analysis indicated that low levels of zinc in serum and tissues were correlated with breast cancer cases.^[31] Zinc deficiency may also impair immune responses and increase oxidative stress, creating an environment conducive to cancer development. Zinc’s involvement in DNA repair and apoptosis makes it a key player in tumor suppression.^[32][33] Zinc’s role in the proper functioning of metallothioneins (MTs), proteins that regulate metal homeostasis and protect against oxidative stress, is also important in the context of breast cancer.^[34]

Manganese (Mn)

Manganese is another essential metal involved in various physiological processes, including enzyme activation and antioxidant defense. However, like other heavy metals, its dysregulated levels have been associated with breast cancer. Studies have found that elevated manganese concentrations in tissues and blood are linked to increased breast cancer risk.^[35] Manganese plays a role in the ROS pathway, which is critical in cancer biology as it contributes to cell survival, migration, and invasion. Manganese is involved in the activation of several oncogenic pathways, including those related to growth factor signaling. The imbalance of manganese metabolism may lead to increased ROS production, further driving the progression of breast cancer.^[36]

MMAs

The Major Microbial Associations (MMAs) for breast cancer can be identified as taxa that are consistently reported as being significantly altered and biologically relevant to disease pathogenesis. The MMAs for breast cancer reflect key microbial patterns that are enriched or depleted in affected patients, revealing functional dysbiosis contributing to disease progression. Enriched microbes, such as Proteobacteria and Bacteroides, drive pro-inflammatory pathways and systemic effects, exacerbating cancer-related outcomes. Conversely, depleted microbes, including Faecalibacterium prausnitzii and Clostridiales, represent a loss of anti-inflammatory and protective functions critical for maintaining gut and systemic health.[37]^[x] Additionally, microbes like Prevotella amnii and Lactobacillus vaginalis highlight specific effects on estrogen metabolism and mucosal immunity, which are especially relevant in postmenopausal breast cancer. Understanding these microbial associations offers insights into potential microbiome-targeted interventions and biomarkers for breast cancer.

What are the Major Microbial Associations (MMAs) for breast cancer

Gut Microbiome and Breast Cancer
Alterations in the gut microbiome composition have been linked to breast cancer development. In postmenopausal women, breast cancer patients exhibit a distinct gut microbiota compared to healthy controls, with an increase in microbial diversity.^[38] Specific taxa such as Escherichia coli, Klebsiella sp., Prevotella amnii, and Enterococcus gallinarum are significantly enriched in breast cancer patients, while beneficial bacteria like Lactobacillus vaginalis are reduced. These alterations may affect systemic inflammation, immunity, and metabolic processes, contributing to cancer susceptibility.^[39][40]

Premenopausal vs. Postmenopausal Breast Cancer
Studies on premenopausal breast cancer patients reveal reduced alpha diversity in the gut microbiota, with significant differences in microbial abundance between cases and controls. Notably, Bacteroides fragilis is found in higher abundance in premenopausal breast cancer patients, whereas Klebsiella pneumoniae is more prevalent in postmenopausal patients.^[41] This suggests that the gut microbiota plays a role in breast cancer across menopausal statuses, with distinct microbial signatures observed in different age groups.

Breast Tissue Microbiota
The microbiota within breast tissue itself shows significant changes in cancerous and adjacent tissues compared to healthy tissues. For example, bacteria such as Methylobacterium radiotolerans are enriched in tumor tissues, while Sphingomonas yanoikuyae is more abundant in adjacent normal tissues.^[42] This microbial dysbiosis in the breast may influence local immune responses and the progression of cancer.

Gut and Oral Microbiota Correlations
There is a strong correlation between gut and oral microbiota in breast cancer patients, which is weaker in healthy controls. The relative abundance of specific oral microbes like Porphyromonas is inversely correlated with gut bacteria such as Bacteroides in breast cancer patients, highlighting the interaction between the microbiomes of different body sites.^[43] The gut and oral microbiota’s interrelationship in breast cancer patients suggests that microbial imbalances may not be confined to one body site.

Tumor Characteristics and Gut Microbiome
Associations between the gut microbiome and tumor characteristics such as HER2 status have been observed. Specifically, HER2+ breast cancer patients show lower microbial diversity and an altered balance of gut bacteria compared to HER2− patients. Additionally, high body fat and early menarche are linked to distinct changes in the gut microbiota, which may contribute to cancer risk.^[44]

MMA	Status in Breast Cancer	Key Role/Impact

Proteobacteria

Enriched

Associated with pro-inflammatory effects and systemic immune modulation, contributing to dysbiosis.

Enterobacteriaceae (guild)

Enriched

A major family within Proteobacteria; significant pro-inflammatory effects and disease-associated dysbiosis.

Actinobacteria

Depleted

Protective role in health; reduction, especially in postmenopausal women, marks disease-associated dysbiosis.

Bacteroides (guild)

Enriched

Involved in lipid metabolism, immune modulation, and inflammation, contributing to systemic cancer effects.

Faecalibacterium prausnitzii

Depleted

Anti-inflammatory properties and role in gut homeostasis make it a marker of health.

Clostridiales (guild)

Depleted

Linked to anti-inflammatory effects; its reduction indicates loss of protective microbial functions.

Prevotella amnii

Enriched

Associated with inflammation and estrogen metabolism, particularly in postmenopausal breast cancer.

Lactobacillus vaginalis

Depleted

Supports mucosal health and immune balance; depletion is a marker of dysbiosis, especially postmenopause.

Microbiome Signature: Breast Cancer

Interventions

The validation process aligns microbiome-targeted interventions (MBTIs) with microbial dysbiosis correction and clinical improvements. Breast cancer treatments may benefit from incorporating strategies to restore microbial balance, such as dietary SCFA supplementation, probiotics, and precision microbiome therapies.

Class	Interventions	Mechanisms of Action	MBTI Status
Pharmacological	Tamoxifen	Selectively binds estrogen receptors (ER), preventing estrogen from binding to the receptor, inhibiting cancer cell proliferation. It also downregulates estrogen-dependent gene expression, preventing tumor growth in estrogen receptor-positive breast cancers.^[45][46]	Validated
Non-Pharmacological	Exercise Therapy	Increases circulation, reduces systemic inflammation, enhances immune function, and helps manage cancer-related fatigue by promoting the release of endorphins.^[47]	Promising
	Fecal Microbiota Transplantation (FMT)	FMT directly targets the gut microbiome by reintroducing a healthy microbiota, thus potentially altering microbial-related immune pathways. It has been shown to improve chemotherapy efficacy by restoring a more favorable microbial composition that supports anti-tumor immune responses.^[48][49]	Experimental
Supplements	Vitamin D	As vitamin D downregulates ERα expression via inhibition of NF-κB, it may increase the sensitivity to tamoxifen through induction of functional ERα in ER-negative cancer cells. Vitamin D combined with tamoxifen may be effective in tamoxifen-resistant tumors, and its concurrent use with aromatase inhibitors may be another suitable therapeutic option.^[50][51][52]	Validated
	Short-Chain Fatty Acid (SCFA)	SCFAs play a crucial role in maintaining gut health by promoting gut barrier integrity, regulating immune responses, and reducing systemic inflammation. SCFAs, especially butyrate, are known to inhibit histone deacetylases (HDACs), leading to changes in gene expression that promote apoptosis (programmed cell death) and inhibit tumor cell proliferation.^[53][54]	Under Investigation
	Flavonoids	Flavonoids, including apigenin, quercetin, and genistein, have been shown to inhibit estrogen receptor signaling, suppress aromatase activity, and reduce estrogen synthesis within cancer cells. They also induce apoptosis and inhibit cell proliferation.^[55]	Promising Candidate
Nutritional Therapy	Probiotics	Probiotics produce short-chain fatty acids (SCFAs) that support gut health, enhance immune function, and help in reducing systemic inflammation. These actions can influence cancer progression, as inflammation and immune dysregulation are often linked to tumor development.^[56][57]^[x]^[58]	Promising Candidate
	High-Fiber Diet	Regulates blood sugar and insulin levels, which affect breast cancer risk and prognosis. Fiber promotes the growth of beneficial gut bacteria like Bifidobacterium and Lactobacillus.[59]^[x]	Validated
Drug Repurposing	Aspirin	Inhibits COX-2, reducing inflammation and tumor growth by suppressing pro-inflammatory cytokines.^[60][61]	Promising Candidate
	Metformin	Regulates insulin levels, inhibits mTOR, and reduces cell proliferation in cancer cells.^[62]	Promising Candidate

STOPs

The STOPs initiative advocates for the careful re-evaluation of common clinical practices that could potentially disrupt the microbiome and increase breast cancer risk. It emphasizes the significant role the microbiome plays in modulating immune responses, systemic inflammation, and estrogen metabolism. Recent studies suggest that specific practices, such as the routine use of chlorhexidine mouthwash, prolonged estrogen supplementation, and increased use of antibiotics, can negatively impact the microbiome, contributing to dysbiosis (microbial imbalance) that might promote breast cancer progression, particularly hormone receptor-positive and chemoresistant breast cancers.[63]^[x]^[64] Chlorhexidine is widely used for oral hygiene but has been found to alter the oral microbiome, reducing microbial diversity and promoting the overgrowth of potentially harmful species like Proteobacteria.^[65] These shifts in the oral microbiome are linked to systemic inflammation and estrogen metabolism alterations, which could exacerbate hormone-driven breast cancer.

STOP	Microbiome Impact	Breast Cancer Risk
Chlorhexidine Mouthwash	Reduces oral microbial diversity, increases Proteobacteria, decreases beneficial microbes like Fusobacterium and Porphyromonas.	Potential causal link to breast cancer through oral and gut dysbiosis, influencing estrogen metabolism and immune function.

FAQs

How does the gut microbiota influence breast cancer subtypes?

The gut microbiota plays a critical role in shaping systemic hormone levels, inflammation, and immune responses, all of which are linked to breast cancer subtypes. For example, hormone receptor-positive (HR+) breast cancers are influenced by the gut microbiota’s role in estrogen metabolism.

Dysbiosis can increase β-glucuronidase activity, leading to elevated circulating estrogen levels, which fuel HR+ tumors. In contrast, triple-negative breast cancers (TNBC) are more dependent on immune surveillance, and gut dysbiosis can impair anti-tumor immunity. Specific microbial taxa, such as Faecalibacterium prausnitzii and Bacteroides fragilis, exhibit protective roles by producing anti-inflammatory short-chain fatty acids (SCFAs) and modulating the tumor microenvironment.

Are probiotics effective in improving treatment outcomes for breast cancer?

Probiotics have shown potential to improve breast cancer treatment outcomes by restoring gut microbiota diversity, reducing inflammation, and enhancing the efficacy of therapies. Studies suggest that probiotics can mitigate chemotherapy and radiation-induced dysbiosis, improving tolerance to treatment and reducing side effects like diarrhea and mucositis.

Additionally, probiotics may enhance immune responses, which are critical for the efficacy of therapies such as immune checkpoint inhibitors. However, the use of probiotics remains an emerging area, and their clinical efficacy in breast cancer requires further validation through large-scale trials.

Can microbiome-targeted interventions reduce chemotherapy side effects?

Yes, microbiome-targeted interventions, including probiotics, prebiotics, and dietary modifications, can help alleviate chemotherapy side effects. For instance, supplementation with SCFA-producing bacteria, like Faecalibacterium prausnitzii, has been associated with reduced inflammation and improved gut barrier function, which can mitigate chemotherapy-induced gastrointestinal toxicity. Fecal microbiota transplantation (FMT) has also shown promise in restoring microbiota diversity and reducing treatment-related side effects. Emerging research indicates that maintaining a healthy microbiome can reduce weight gain, neurotoxicity, and inflammation associated with breast cancer therapies.

Research Feed

October 27, 2021

•

What was studied?

This study investigated the gut microbiota profiles, diagnostic value, and functional pathways specific to premenopausal breast cancer patients. It aimed to identify unique gut microbial markers distinguishing premenopausal breast cancer patients from postmenopausal patients and age-matched controls. The study also explored functional pathways of gut microbiota linked to breast cancer progression and diagnostic potential.

Who was studied?

The study analyzed 267 participants divided into four groups: premenopausal controls (Pre-C, n=50), premenopausal breast cancer patients (Pre-BC, n=100), postmenopausal controls (Post-C, n=17), and postmenopausal breast cancer patients (Post-BC, n=100). All breast cancer patients were newly diagnosed with stage I–II disease and excluded if they had received treatments or medications affecting gut microbiota before fecal sample collection.

What were the most important findings?

The study highlights significant differences in gut microbial diversity, composition, and functional pathways between premenopausal and postmenopausal breast cancer patients. Premenopausal breast cancer patients showed reduced α-diversity and distinct β-diversity compared to controls, with alterations in specific bacterial taxa linked to inflammation and cancer progression. In contrast, postmenopausal patients exhibited a different microbial profile, including an increase in pathogenic bacteria. Functional pathway analyses revealed steroid-related and oncogenic pathways in premenopausal patients, while postmenopausal patients were associated with chemical carcinogenesis and aldosterone-regulated pathways. The findings emphasize the diagnostic potential of gut microbiota in differentiating breast cancer subtypes and guiding prevention strategies.

Aspect	Premenopausal Breast Cancer	Postmenopausal Breast Cancer	Universal Markers (Both Types)

α-Diversity

Significantly reduced compared to controls

No reduction observed compared to postmenopausal controls

β-Diversity

Distinct from controls

Enriched Microbes

Bacteroides fragilis, Anaerostipes (linked to inflammation and progression)

Proteobacteria, Klebsiella pneumoniae (pathogenic bacteria)

Haemophilus parainfluenzae (increased in both)

Reduced Microbes

Bifidobacterium spp. (tumor suppressor)

Akkermansia muciniphila (beneficial microbe)

Faecalibacterium prausnitzii (decreased in both)

Functional Pathways

Steroid-related pathways; Oncogenic pathways (e.g., Notch/Wnt signaling)

Chemical carcinogenesis; Aldosterone-regulated pathways

Diagnostic Potential

Strong microbial markers for distinguishing premenopausal breast cancer

Strong microbial markers for distinguishing postmenopausal breast cancer

What are the greatest implications of this study?

The findings underscore the diagnostic potential of microbial markers for early, non-invasive breast cancer detection based on menopausal status. Identifying these microbial and functional pathways expands the understanding of breast cancer pathogenesis, especially in premenopausal women. Moreover, the study highlights the gut microbiota as a modifiable factor, suggesting potential interventions like probiotics or dietary changes to mitigate breast cancer risk.

May 24, 2006

•

What was reviewed?

This study, published in the Journal of Applied Toxicology, reviewed the concept and emerging evidence of metalloestrogens mimicking estrogenic activity. The review focused on how these metals interact with estrogen receptors (ERs) like organic xenoestrogens, potentially contributing to estrogenic activity in human breast tissue and increasing the risk of hormone-related cancers such as breast cancer. The review primarily covered in vitro and in vivo studies of various metal ions, including aluminum, antimony, arsenite, barium, cadmium, chromium (Cr(II)), cobalt, copper, lead, mercury, nickel, selenite, tin, and vanadate. The review also highlights significant research contributions from multiple studies and scholars focusing on the effects of metalloestrogens on human breast cancer cell lines, such as MCF-7 and T47D, as well as their impact on gene expression and cellular proliferation.

Most Important Findings:

Estrogenic Activity of Metals: The review found that various metal ions can act as estrogen agonists by binding to estrogen receptors, particularly ERα, and mimicking the actions of physiological estrogens. This was demonstrated in studies showing that metals such as cadmium, nickel, and aluminum could displace estradiol from the ligand-binding domain of ERα, leading to altered gene expression and increased cell proliferation in breast cancer cells.

Molecular Mechanisms: Metals such as cadmium were shown to bind directly to the ligand-binding domain (LBD) of the estrogen receptor, interfering with the receptor's normal function. This binding alters the receptor’s ability to interact with estrogen response elements (EREs) on DNA, thereby affecting the transcription of estrogen-regulated genes. For instance, cadmium was found to downregulate ER levels and upregulate estrogen-regulated gene expression, driving cell proliferation.

Cooperative Action with Estrogens: The metals did not antagonize estradiol’s action; instead, they often enhanced the agonist actions of estradiol. In some cases, metals like copper and cobalt increased breast cancer cell proliferation when combined with estradiol, indicating a synergistic effect that may exacerbate estrogenic signaling in hormone-dependent cancers.

In Vivo Evidence: The review highlighted evidence of in vivo estrogenic activity in animal models, particularly for cadmium, which was shown to increase uterine weight, induce mammary gland development, and alter gene expression. The estrogenic effects of cadmium were noted at doses relevant to human exposure, raising significant concerns about environmental exposure to these metals.

Environmental and Occupational Exposure: The presence of metalloestrogens such as cadmium and aluminum in everyday consumer products (e.g., antiperspirants) and the environment (e.g., tobacco smoke, and industrial pollutants) implies widespread human exposure. These metals can accumulate in the body, especially in breast tissue, and may contribute to the burden of aberrant estrogen signaling involved in breast cancer development.

Greatest Implications:

Breast Cancer Risk: The review underscores the potential for metalloestrogens to increase the risk of breast cancer by contributing to estrogenic signaling within breast tissue. Given that breast cancer is often driven by estrogen receptor activation, the cumulative burden of environmental estrogens and metalloestrogens could enhance the likelihood of cancer development and progression.

Environmental Health and Toxicology: The widespread presence of these metals in the environment, their ability to accumulate in the body, and their newly recognized estrogenic activity suggest a need for revised regulatory guidelines and risk assessments for human exposure to metalloestrogens. This includes re-evaluating safe exposure levels, especially for metals like cadmium, which is already classified as a human carcinogen.

Endocrine Disruption: The concept of metalloestrogens extends the traditional understanding of endocrine-disrupting chemicals (EDCs) beyond organic compounds, emphasizing the need for further investigation into how inorganic metals may impact hormone-related diseases. This review calls for more research on the long-term effects of chronic exposure to metalloestrogens in both wildlife and humans.

Public Health Awareness: There is a strong implication for public health education regarding the sources of metalloestrogen exposure, such as antiperspirants, diet, cigarette smoke, and industrial pollutants. Raising awareness could lead to better personal care practices and lifestyle choices to reduce individual exposure to these potentially harmful metal ions.

November 30, 2017

•

What Was Studied?

This study investigated the microbial composition of breast tumor tissues compared to non-cancerous adjacent (NCA) tissues, focusing on identifying specific microbiota associated with different breast cancer subtypes. The research utilized RNA sequencing data from The Cancer Genome Atlas (TCGA), analyzing microbial reads and their association with host gene expression profiles to explore the role of the tumor microbiota in breast cancer pathogenesis.

Who Was Studied?

The study involved 668 breast tumor tissue samples and 72 NCA samples. The samples were filtered to exclude male patients, metastatic cases, and individuals with a history of breast cancer or neoadjuvant therapy, ensuring a robust cohort for microbial and host gene analysis.

What Were the Most Important Findings?

The study identified distinct microbial signatures between tumor and NCA tissues. Proteobacteria were significantly enriched in tumor samples, while Actinobacteria were more prevalent in NCA tissues. Specific microbial taxa, such as Haemophilus influenzae, were associated with genes involved in tumor-promoting pathways, including the G2M checkpoint, E2F transcription factors, and mitotic spindle assembly. Similarly, Listeria fleischmannii correlated with epithelial-to-mesenchymal transition pathways, a hallmark of cancer metastasis.

Twelve of the most abundant species, including Escherichia coli, Mycobacterium fortuitum, and Salmonella enterica, showed significant differential abundance between tumor and NCA tissues. These species are notable for their potential roles in DNA damage and estrogen metabolism, contributing to genomic instability and hormonal dysregulation in breast cancer. The findings also revealed that less prevalent taxa often showed the most significant differential abundance, highlighting the challenges of detecting meaningful microbial shifts in underpowered studies.

What Are the Greatest Implications of This Study?

This research underscores the complex interplay between the tumor microbiota and host gene expression in breast cancer. The enrichment of specific microbial taxa in tumor tissues and their associations with oncogenic pathways suggest that the microbiota may play an active role in breast cancer progression. These findings open avenues for microbiota-targeted interventions and diagnostic tools based on microbial markers. Furthermore, the study highlights the need for large-scale, well-controlled cohorts to accurately characterize the tumor microbiome and its clinical relevance.

June 28, 2022

•

What was studied?

This study investigated the composition and functional potential of the human mammary microbiota in healthy breast tissues and those associated with breast cancer development. The researchers focused on tissue samples collected before cancer diagnosis (prediagnostic or PD), as well as adjacent normal (AN) and tumor (T) tissues from breast cancer patients. Using 16S rRNA sequencing and functional metagenomic predictions, they aimed to identify bacterial dysbiosis and metabolic changes associated with breast cancer progression.

Who was studied?

A total of 141 women were included in the study, contributing 159 breast tissue samples. These included 49 samples from healthy individuals (H), 15 from prediagnostic cases (PD), 49 from adjacent normal tissues (AN), and 46 from tumor tissues (T). The prediagnostic samples were obtained from women who later developed breast cancer, allowing researchers to explore early microbial changes.

What were the most important findings?

The study revealed significant bacterial dysbiosis and metabolic reprogramming in PD, AN, and T tissues compared to healthy tissues. Prediagnostic tissues exhibited an intermediary bacterial composition between healthy and cancerous tissues. Shifts in specific bacterial families such as Bacillaceae, Streptococcaceae, and Corynebacteriaceae were detected in PD tissues and were more pronounced in AN and T tissues. Functional analysis revealed reduced bacterial metabolic activities, particularly pathways related to xenobiotics degradation, which could otherwise protect against carcinogenesis. Additionally, altered correlations between host gene expression and microbial functions were observed, highlighting potential early microbial responses to tumor microenvironments.

What are the greatest implications of this study?

This research highlights the mammary microbiota's potential as a critical biomarker for early breast cancer detection and risk stratification by revealing bacterial dysbiosis and metabolic reprogramming in prediagnostic tissues, suggesting microbial changes may precede clinical symptoms or histological abnormalities. The identification of an intermediary microbiota composition in prediagnostic tissues supports the microbiome's role in early cancer development, indicating microbial shifts as potential early drivers or responders to tumorigenesis. A significant reduction in metabolic functions, such as xenobiotic degradation, in cancer-associated tissues implies a diminished microbial ability to detoxify carcinogens, increasing susceptibility to tumor formation. Altered correlations between microbial taxa and host gene expression further suggest dynamic interactions influencing immune responses, inflammation, and cellular proliferation, with positive associations between microbial functions and tumor-related genes pointing to potential mechanistic links to cancer progression.

These findings not only enhance understanding of the microbiota's role in breast cancer but also offer clinical translation opportunities, including the development of non-invasive diagnostic tools based on prediagnostic microbial signatures, microbiome-modulating therapies to target dysbiosis, and therapeutic interventions aimed at restoring protective bacterial functions and reducing cancer risk.

January 11, 2023

•

What was studied?

This study investigated the gut microbiome composition in breast cancer (BC) patients from the Midwest region of the United States, focusing on its taxonomic composition and functional profiling. Using 16S ribosomal RNA sequencing, the study examined the bacterial microbiome, specifically targeting short-chain fatty acid (SCFA)-producing bacteria. It aimed to identify microbial dysbiosis and its potential role in breast cancer pathobiology, emphasizing regional differences in microbiome signatures.

Who was studied?

The study included 22 breast cancer patients and 19 healthy controls, all recruited from the University of Iowa. Participants were matched by race, body mass index (BMI), and sex. Inclusion criteria required BC patients to have invasive breast cancer, with exclusion criteria such as antibiotic use during sample collection. Healthy controls were similarly screened for factors that might impact gut microbiota, like recent antibiotic or laxative use.

What were the most important findings?

The study identified significant gut microbiome differences between breast cancer patients and healthy controls, particularly in alpha and beta diversity measures. Breast cancer (BC) patients showed evidence of gut dysbiosis, including a decrease in beneficial SCFA-producing bacteria and an enrichment of pro-inflammatory taxa. These alterations suggest a microbiome imbalance that may contribute to inflammation and disease progression. Furthermore, the study highlighted functional disruptions in microbiome pathways, with reduced production of SCFAs such as propionate and acetate, which are essential for maintaining gut health and modulating immune responses. These findings underscore the importance of microbiome-targeted interventions to restore microbial balance and support breast cancer treatment.

Finding	Breast Cancer Patients (BC)	Healthy Controls (HC)	Relevance
SCFA-Producing Bacteria	Reduced Faecalibacterium prausnitzii, Alistipes, Parabacteroides merdae, Lachnospira pectinoschiza	Higher levels	SCFA reduction contributes to inflammation and impaired gut motility.
Pro-Inflammatory Bacteria	Enriched Eggerthella lenta, Blautia species	Reduced levels	Linked to inflammation and cancer progression.
Functional Pathways	Decreased SCFA pathways (propionate, acetate)	Intact pathways	Dysbiosis may exacerbate systemic inflammation and disrupt gut homeostasis.
Beta Diversity Clustering	Significant clustering distinct from HC	No significant clustering	Indicates an altered microbiome composition in BC.

What are the greatest implications of this study?

The findings underscore the role of gut microbial dysbiosis in breast cancer, with SCFA-producing bacteria depletion linked to inflammation and cancer pathogenesis. This highlights potential avenues for microbiome-targeted therapies, such as probiotics or dietary interventions, aimed at restoring SCFA production and microbial balance. Moreover, the study emphasizes the need for region-specific microbiome research to tailor interventions effectively.

May 2, 2023

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What Was Studied?

This study examined the association between gut microbiota composition and breast cancer, focusing on the role of diet as a potential modulating factor. Researchers conducted a case-control study involving 42 newly diagnosed, treatment-naïve BCa patients and 44 age-matched cancer-free controls. The gut microbiome was analyzed through 16S rRNA sequencing, and dietary patterns were assessed using the National Cancer Institute Diet History Questionnaire.

Who Was Studied?

Participants included females aged 20–89 years from the Oregon Health & Science University. breast cancer patients were diagnosed through biopsy and had not yet undergone any treatment. Cancer-free controls were matched by age and underwent recent mammograms with non-suspicious results. The study collected fecal samples, dietary data, and comprehensive lifestyle information to ensure robust comparisons.

Most Important Findings

The study identified significant differences in the gut microbiome composition between breast cancer cases and controls, including reduced microbial diversity among breast cancer patients, indicative of dysbiosis. Specifically, the genera Acidaminococcus, Hungatella, and Tyzzerella were enriched, while controls exhibited enrichment of genera such as Christensenellaceae and Dialister. These findings were linked to dietary patterns: Acidaminococcus correlated with lower fruit intake, Hungatella with reduced dairy intake but increased vegetable consumption, and Tyzzerella was not significantly associated with dietary variables. Importantly, the reduced diversity and altered microbial profiles in breast cancer patients align with previous evidence suggesting a role for gut dysbiosis in cancer progression via immune modulation and microbial metabolite production.

Greatest Implications

This study highlights the gut microbiome's potential as a biomarker for breast cancer risk and emphasizes the role of diet in modulating microbial composition. Dysbiosis, characterized by an imbalance in gut microbiota, is linked to breast cancer, suggesting that microbiome-targeted dietary interventions could aid in prevention and management. For example, increased consumption of whole fruits may help reduce levels of Acidaminococcus, a genus enriched in breast cancer patients, while higher dairy intake could lower the abundance of Hungatella, a genus associated with TMAO production and cancer-promoting pathways. Interestingly, the study also found that greater vegetable consumption was linked to higher levels of Hungatella, which has been associated with increased risks of both breast and colorectal cancer. These findings underscore the complexity of dietary influences on the gut microbiome and their potential role in cancer prevention.

January 24, 2024

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What Was Studied?

This study investigated the relationship between gut microbiota composition and breast cancer (BC), focusing on the potential impact of menopausal status on microbiota variations. The researchers used shotgun metagenomics to compare the gut microbiota of 88 newly diagnosed BC patients (47 premenopausal and 41 postmenopausal) with 86 cancer-free controls, stratified by menopausal status.

Who Was Studied?

The participants included Polish women divided into two groups: BC patients and controls. The BC group was further divided into premenopausal and postmenopausal subgroups. Fecal samples were collected before systemic cancer treatment, and patients with prior antibiotic use, inflammatory bowel disease, or a history of cancer (for controls) were excluded.

Most Important Findings

The study showed that menopausal status had no significant impact on the overall gut microbiota composition or diversity. However, breast cancer (BC) patients exhibited gut dysbiosis compared to controls. Premenopausal BC patients demonstrated lower abundances of taxa such as Bifidobacterium and Collinsella massiliensis but higher abundances of the genus Gemmiger. In postmenopausal BC patients, taxa such as Blautia obeum, Dorea formicigenerans, and Bacteroides thetaiotaomicron were reduced, while Faecalibacterium prausnitzii showed an overrepresentation, potentially indicating a protective or prognostic role. Functional alterations were minimal, with the NAD salvage pathway downregulated in premenopausal BC patients, possibly affecting DNA repair. Enterotype analysis revealed that Bacteroides-dominated enterotypes were more common in controls, while Prevotella and Alistipes were enriched in BC patients. Additionally, bacterial diversity was notably lower in postmenopausal BC patients compared to controls, emphasizing the role of gut dysbiosis in BC pathology rather than menopausal status.

Group	Microbial Changes	Functional Changes

Premenopausal BC Patients

Lower abundances: Bifidobacterium, Collinsella massiliensis. Higher abundances: Gemmiger.

Downregulation of NAD salvage pathway, possibly affecting DNA repair.

Postmenopausal BC Patients

Reduced levels: Blautia obeum, Dorea formicigenerans, Bacteroides thetaiotaomicron. Overrepresentation: Faecalibacterium prausnitzii.

Minimal functional alterations.

Controls vs. BC Patients

Bacteroides enterotypes prevalent in controls; Prevotella and Alistipes enriched in BC patients.

N/A

Postmenopausal BC Patients (Alpha-Diversity)

Lower bacterial diversity compared to controls.

N/A

Greatest Implications

The study underscores the importance of gut microbiota in BC development, suggesting that dysbiosis may not be directly related to menopausal status but rather to BC pathology itself. These findings have potential diagnostic implications, as machine learning models using gut microbiota profiles demonstrated an ability to distinguish BC patients from controls with high accuracy (AUC > 0.8). The study highlights the need for further research to explore the mechanisms linking microbiota alterations and BC progression, particularly focusing on key taxa like Faecalibacterium prausnitzii and Bifidobacterium, as well as geographic and lifestyle factors influencing microbiota composition.

August 6, 2018

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What Was Studied?

This study investigated the differences in the composition and functional capacities of gut microbiota between postmenopausal breast cancer patients and postmenopausal healthy controls. The researchers conducted a comprehensive shotgun metagenomic analysis to assess microbial diversity, taxonomic abundance, functional gene profiles, and potential associations with clinical indices.

Who Was Studied?

The study involved 44 postmenopausal breast cancer patients and 46 postmenopausal healthy controls, as well as 18 premenopausal breast cancer patients and 25 premenopausal healthy controls. All participants were treatment-naive and free from other conditions such as diabetes or inflammatory bowel diseases, which could confound the microbiome analysis.

What Were the Most Important Findings?

The study found significant differences in gut microbial diversity and composition between postmenopausal breast cancer patients and healthy controls. Microbial diversity was higher in breast cancer patients. Forty-five microbial species exhibited significant differences in abundance; 38 species were enriched in breast cancer patients, including Escherichia coli, Klebsiella sp., and Prevotella amnii, while 7 species, such as Eubacterium eligens and Lactobacillus vaginalis, were depleted. Functionally, the gut metagenomes of patients were enriched in genes linked to lipopolysaccharide (LPS) biosynthesis, iron transport, and secretion systems, which may contribute to systemic inflammation and metabolic alterations. Importantly, butyrate-producing bacteria like Roseburia inulinivorans were reduced in patients, potentially affecting anti-inflammatory processes.

What Are the Greatest Implications of This Study?

This study highlights the potential role of gut microbiota in influencing systemic inflammation, estrogen metabolism, and immune regulation in postmenopausal breast cancer. The enrichment of LPS biosynthesis and iron transport genes points to mechanisms that may drive inflammation and tumorigenesis. The depletion of butyrate producers suggests a loss of anti-inflammatory microbiota functions, underscoring the gut microbiota’s importance in maintaining immune homeostasis. These findings suggest that gut microbiota could serve as biomarkers for breast cancer and potential therapeutic targets to mitigate disease progression.

November 19, 2024

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What was studied?

This study investigated and compared the gut and oral microbiota in three distinct groups: women with breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected and analyzed using 16S rRNA sequencing to assess microbial diversity, composition, and predicted functional potential.

Who was studied?

The study analyzed samples from 154 women, comprising 73 with BC, 32 with DCIS, and 49 healthy controls. Samples were collected before any therapy to ensure no treatment effects influenced the microbiota.

What were the most important findings?

The study found significant differences in gut microbiota composition and diversity between groups, while the oral microbiota exhibited fewer variations. Women with BC had lower gut microbial alpha diversity compared to healthy women. Beta diversity analysis revealed distinct microbial profiles for the BC and DCIS groups compared to healthy controls. Taxonomic analysis identified several major microbial associations (MMAs) in the gut: the Bacteroides and Enterobacteriaceae guilds were enriched in BC patients, while the Clostridiales guild was more prevalent in healthy women. Functionally, the gut microbiota of BC patients showed increased pathways for lipopolysaccharide (LPS) biosynthesis, glycan metabolism, and sphingolipid metabolism, which are linked to systemic inflammation and cancer progression. Conversely, the oral microbiota showed minimal variation across cohorts, with no significant differences in functional pathways or microbial guilds.

What are the greatest implications of this study?

The findings highlight the role of gut microbiota in breast cancer development and progression. The identification of distinct microbial signatures and functional pathways provides a basis for developing microbiome-targeted interventions aimed at improving treatment outcomes and prognosis. Notably, the lack of significant findings in oral microbiota suggests that gut microbiota might have a more critical role in breast cancer etiology. These results pave the way for further research on microbiome-based diagnostic tools and therapeutic strategies for breast cancer.

May 7, 2021

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What was studied?

This study examined the impact of intestinal microbiota on the clinical outcomes and side effects of early breast cancer (BC) treatments. Shotgun metagenomics was used to analyze fecal microbiota samples from 76 early BC patients, both pre- and post-chemotherapy. The study aimed to identify specific microbial species associated with BC prognosis and the side effects of chemotherapy, focusing on neurological, gastrointestinal, and metabolic complications. It also explored the functional relevance of gut microbiota in immunocompetent mouse models colonized with BC patient microbiota to establish a causal link between gut microbial composition and tumor growth or therapy efficacy.

Who was studied?

The study involved 76 female BC patients from the CANTO trial (NCT01993498), a long-term prospective cohort designed to quantify and prevent treatment-related toxicities. Patients provided fecal samples before and after chemotherapy, and their plasma was also analyzed for metabolomics. A separate analysis included healthy volunteers (54 Italian and 282 samples from public metagenomes) to contrast microbial signatures. Mouse models were humanized with fecal microbiota from patients and healthy individuals to assess the causal relationship between microbiota and BC outcomes.

What were the most important findings?

The study revealed that the gut microbiota composition significantly correlates with BC prognosis and treatment side effects. Patients with more aggressive tumors (larger size, advanced stage, lymph node involvement) had overrepresentation of species like Clostridiaceae, Veillonella, Bacteroides uniformis, and Blautia wexlerae.In contrast, patients with better prognosis had higher levels of Akkermansia muciniphila, Collinsella aerofaciens, and Eubacterium rectale. Chemotherapy shifted microbial diversity, reducing bacteria associated with poor prognosis and increasing favorable commensals like Methanobrevibacter smithii and Blautia obeum. Functionally, favorable microbiota patterns were linked to neuroprotective and immunomodulatory pathways, such as polyamine biosynthesis and ketogenesis, while unfavorable profiles were associated with inflammation and metabolic dysregulation. Humanized mouse models demonstrated that fecal microbiota from healthy volunteers enhanced tumor response to chemotherapy compared to microbiota from BC patients.

What are the greatest implications of this study?

This study underscores the gut microbiota's role as a biomarker and potential therapeutic target in BC management. The findings suggest that monitoring and modulating gut microbiota could optimize chemotherapy efficacy, mitigate side effects, and improve overall prognosis. Strategies like fecal microbiota transplantation, probiotics, or diet interventions targeting specific microbiota shifts may hold promise. The causal evidence provided by mouse models highlights the translational potential of microbiome-targeted interventions (MBTIs) to improve clinical outcomes for breast cancer patients.

January 8, 2014

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What Was Studied?

This study examined the microbiota present in breast tumor tissue compared to paired normal breast tissue from the same individuals, as well as healthy breast tissue from individuals without breast cancer. Using next-generation sequencing and quantitative PCR, the research aimed to identify differences in microbial composition, bacterial load, and their potential impact on the tumor microenvironment and breast cancer progression.

Who Was Studied?

The study included 20 breast cancer patients with estrogen receptor-positive (ER+) tumors, for whom paired tumor and normal adjacent tissue were analyzed. Additional bacterial load analysis included 23 healthy controls undergoing reduction mammoplasty. Gene expression profiling was conducted on tissue from six breast cancer patients and three healthy individuals.

Most Important Findings

The study revealed distinct microbial signatures associated with breast cancer. Methylobacterium radiotolerans was significantly enriched in tumor tissue, while Sphingomonas yanoikuyae was more abundant in paired normal tissue. A strong inverse correlation between the abundance of these two species was observed in normal tissue, but not in tumor tissue. Importantly, bacterial load in tumor tissue was markedly reduced compared to both paired normal and healthy breast tissue, with advanced-stage tumors exhibiting the lowest bacterial counts. This reduction in bacterial load correlated with decreased expression of antibacterial response genes, including Toll-like receptors (TLR2, TLR5, and TLR9) and antimicrobial effectors like IL-12A and BPI.

These findings suggest that microbial dysbiosis and a diminished antibacterial immune response in tumor tissue may contribute to breast cancer progression. Additionally, the results highlight the potential diagnostic value of bacterial load as a marker for breast cancer staging.

Greatest Implications

The association between microbial dysbiosis and breast cancer offers novel insights into the disease’s pathogenesis. The depletion of beneficial bacteria, such as Sphingomonas yanoikuyae, and a reduced immune response may create a permissive environment for tumorigenesis. This study supports the exploration of microbiota as a diagnostic tool and potentially as a therapeutic target to restore a healthy microbial balance and enhance immune surveillance. The inverse correlation between bacterial load and tumor stage underscores its potential utility in disease staging and progression monitoring.

October 15, 2023

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What was studied?

This study investigated the relationship between the oral microbiome, breast cancer, and non-malignant breast disease, as well as the correlation between the oral and fecal microbiomes in a case-control population in Ghana. Researchers analyzed microbiome samples from 881 women, including 369 breast cancer cases, 93 non-malignant cases, and 419 controls, using 16S rRNA gene sequencing.

Who was studied?

The study population included Ghanaian women aged 18–74 years who were recruited from Accra and Kumasi. Participants comprised breast cancer patients, individuals with non-malignant breast disease, and population-based controls. Oral and fecal microbiome samples were collected, and demographic, lifestyle, and medical history data were recorded.

What are the Most important findings?

The study revealed that oral microbiome alpha-diversity was significantly lower in breast cancer and non-malignant breast disease cases compared to controls. For instance, each 10-unit increase in observed amplicon sequence variants (ASVs) corresponded to a reduction in the odds of breast cancer and non-malignant breast disease by 14% and 21%, respectively. Beta-diversity analyses also showed distinct microbial community compositions between cases and controls. Key genera, including Porphyromonas and Fusobacterium, were inversely associated with breast cancer, with their relative abundances being significantly lower in cases than in controls. A notable finding was the strong inverse correlation between oral Porphyromonas and fecal Bacteroides in breast cancer cases. This relationship is particularly relevant as fecal Bacteroides has been implicated in estrogen metabolism and breast cancer risk. Breast cancer cases also exhibited stronger correlations between oral and fecal microbiomes compared to controls, suggesting a potential systemic interaction.

Shockingly, the study also found that breast cancer and non-malignant breast disease cases were more likely to have taken antibiotics within the last 30 days compared to controls. This raises critical questions about the role of antibiotics in microbiome disruption and their potential contribution to systemic microbial changes that could influence breast cancer risk.

What are the greatest implications?

This study is extraordinary in its scope and implications. It bridges the gap between two traditionally separate microbiomes—oral and fecal—and ties these microbial systems to breast cancer, a disease of immense global health importance. The findings reveal striking patterns: the inverse associations of oral microbiome diversity and specific genera, such as Porphyromonas and Fusobacterium, with breast cancer and non-malignant breast disease are compelling. These microbes, often linked to periodontal disease, emerge here as potential protective or systemic markers in a population with distinct environmental and health contexts.

The strong correlation between the oral and fecal microbiomes in breast cancer cases further underscores the interconnectedness of microbial communities and highlights systemic microbial interactions that remain underexplored in cancer research. The inverse relationship between Porphyromonas in the oral microbiome and Bacteroides in the fecal microbiome—key players in estrogen metabolism—provides intriguing clues about the mechanisms underlying breast cancer pathogenesis.

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Breast Cancer

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Overview

Associated Conditions

Causes

Diagnosis

Primer

Metallomic Signatures

MMAs

Microbiome Signature: Breast Cancer

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