Breast cancer (BC) is the most common cancer among women worldwide. BC remains a significant cause of mortality in women, despite the use of adjuvant chemotherapeutic and hormonal agents (Braden et al. 2014). Genetic and other established risk factors such as early menarche age, high body mass index (BMI), and sedentary lifestyle have been associated with the onset and progression of BC. Benign breast lesions (BBLs), including fibroadenoma, are commonly found in young women. Estrogens and their receptors are implicated in the onset and progression of BBLs. Accumulating data have indicated that alterations in the host microbiome, primarily intestinal microbiota, may contribute to the pathogenesis of both gastrointestinal and extra-intestinal tumors (Belkaid and Hand 2014; Dzutsev et al. 2017).
The number of genes in the human intestinal microbiota, regarded as an alternative genome in humans, is nearly 150 times higher than that of the human genome (Zhu et al. 2010). This intestinal ecosystem is involved in a dynamic interaction with host cells, microbes, and food. Besides, it acts as a multi-dimensional “microbial organ” by enhancing the synthesis of essential amino acids and vitamins, producing small molecules, nutritional absorption, metabolism of bile acids, activation of immune cells, and inactivation of toxins and carcinogens (Eslami-S et al. 2020). The remarkable contribution of the gut microflora to human health and disease has been extensively recognized. It has been speculated that changes in the constitution and functions of the gut microbiome might contribute to the onset and progression of BC and BBLs.
Although some studies reported higher microbial diversity in BC patients than healthy controls (Gopalakrishnan et al. 2018; Zhu et al. 2018), other investigations found less microbial diversity in post-menopausal BC subjects (Goedert et al. 2015; 2018). In addition, gut dysbiosis in individuals with BBLs is not fully understood. Therefore, 16S ribosomal RNA (16S rRNA) gene sequencing technology was utilized to explore intestinal microbiota dysbiosis in BC and BBL patients.
Materials and Methods
Patient selection. Seventy subjects, including 27 BC patients, 22 BBL patients, and 21 healthy controls, were recruited from The Affiliated Hospital of Qinghai University between November 2020 to February 2021. Pathology reports confirmed the diagnosis of all cases. Healthy controls with color Doppler ultrasound showing no breast lesions were enrolled from the physical examination center and matched with cases by age, gender, BMI, and geographic region. Exclusion criteria included diabetes, inflammatory bowel disease, autoimmune diseases, and past treatment with chemotherapy, surgery, or radiation prior to obtaining fecal samples. None of the subjects had received antibiotics or probiotics within one month of stool collection. All subjects provided written consent.
Specimen collection. Fresh stool specimens were obtained from eligible subjects and then frozen at –80°C 2 h before use.
Fecal specimen processing and analysis. Microbiota evaluations were conducted at the Wuhan Huada Medical Laboratory Co., Ltd. Four samples had remarkably low numbers of reads and were ultimately excluded from the analysis. Hence, the final analysis was based on data collected from 26 BC patients, 20 BBL patients, and 20 healthy subjects. Polymerase chain reaction (PCR) amplification was performed in a 50-μl reaction mixture containing 30 ng of genomic DNA, and specific primers were designed. Agencourt AMPure XP beads were used to purify the amplicons. RNA quality was confirmed using an Agilent 2100 Bioanalyzer (Agilent, USA). High-quality libraries were sequenced on the Illumina HiSeq 2500 sequencing platform (BGI, China). The 16S rRNA V3-V4 hypervariable region was amplified with degenerate PCR primers: 341F (5’-ACTCCTACGGGAGGCAGCAG-3’) and 806R (5’-GGACTACHVGGGTWTCTAAT-3’). Raw reads were filtered to remove adaptors and low-quality and ambiguous reads. Next, fast length adjustment of short reads (FLASH, v1.2.11) software was used to merge paired-end reads. UPARSE implemented within USEARCH (v7.0.1090) was used to cluster effective tags to obtain operational taxonomic units (OTUs) at 97% sequence similarity, and chimeras were identified and removed with UCHIME (v4.2.40). Taxonomy was assigned to each OTU with the Ribosomal Database Project (RDP, http://rdp.cme.msu.edu) database using usearch_global of USEARCH.
Statistical analysis. Statistical analyses were conducted using SPSS Statistics 25, R software (v3.2.1), and other online analysis tools. A p-value of < 0.05 was considered statistically significant. A Petaline graph was generated using R (v3.1.1). Microbial diversity was evaluated using alpha and beta diversity indices. Alpha diversity was measured using Sobs and Chao1 diversity indices to estimate community richness and was compared using the Wilcox statistical test. The alpha diversity boxplot, and the statistical tests, were performed using R (v3.2.1). Beta diversity was calculated using unweighted and weighted UniFrac distance metrics, principal coordinate analysis (PCoA), and partial least squares-based discriminant analysis (PLS-DA) models. The beta diversity boxplot was generated using the R (v3.4.1) package ggplot. PCoA plots were generated to visually display patterns of beta diversity after 100 iterations using QIIME (v1.80). PLS-DA was implemented in the R mixOmics package. The linear discriminant analysis (LDA) coupled with effect size (LEfSe) was performed using the LEfSe program to determine differentially abundant taxa in each group, and a logarithmic LDA score > 2 was considered significant.
Patient characteristics. All participants were Chinese women (healthy controls, n = 20; BC: n = 26; BBL: n = 20). There were no significant differences in age and BMI among the three groups (Table I).
Baseline characteristics of the patients enrolled.
Benign breast lesions
No. of individuals
Mean age (± SD, years)
Mean BMI (± SD, kg/m2)
Different groups showed different OTUs. Sequencing showed 3,567,593 effective sequences (average of 54,054 sequences per sample). In the three groups, 723 OTUs were detected. Among them, 517 OTUs were common to the three groups, but 64 were exclusive to BC patients, 77 were exclusive to individuals with BBLs, and 65 were exclusive to healthy controls (Fig. 1).
Microbiota composition analysis. The same four bacteria were identified at the phylum level to be dominant in all three groups, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, of which Firmicutes and Bacteroidetes were predominant in each group (Fig. 2A). In addition, 23 bacteria genera with relative abundance higher than 0.5% were identified among the three groups, including Veillonella, Dialister, Oscillibacter, Lachnospiracea_incertae_sedis, Parasutterella, Megasphaera, Prevotella, Roseburia, Bifidobacterium, Clostridium_XlVa, Barnesiella, Eubacterium, Escherichia, Faecalibacterium, Phascolarctobacterium, Bacteroides, Blautia, Megamonas, Gemmiger, Parabacteroides, Ruminococcus, Alistipes, and Succinivibrio (Fig. 2B). The patterns of microbial composition were highly variable among these three groups.
As shown in Table II, compared with the healthy control group, the relative richness of five bacterial genera was increased in the BC group (Escherichia, Peptoniphilus, Bilophila, Lactobacillus, and Porphyromonas) while the relative richness of fifteen bacterial genera was decreased (Faecalibacterium, Lachnospiracea_incertae_ sedis, Collinsella, Alistipes, Anaerofilum, Christensenella, Butyricimonas, Erysipelothrix, Acidaminococcus,
Changes in bacterial abundance at the genus level in patients with breast cancer and benign breast lesions.
Benign breast lesions
More abundant genera
Less abundant genera
More abundant genera
Less abundant genera
Victivallis, Eubacterium, Tissierella, Hydrogenoanaerobacterium, Cloacibacillus, and Oxalobacter). Also, compared with the healthy controls, the relative richness of five bacterial genera was increased in patients with BBLs (Escherichia, Peptoniphilus, Coprobacillus, Lactobacillus, and Porphyromonas), whereas the relative richness of eight bacterial genera was decreased (Collinsella, Alistipes, Megamonas, Butyricimonas, Acidaminococcus, Asaccharobacter, Tissierella, and Cloacibacillus).
Biodiversity analysis. Alpha diversity indices (Sobs and Chao1) are shown in Fig. 3. Compared with the healthy controls, BC patients had significantly lower alpha diversity indices (Sobs index, p = 0.019; Chao1 index, p = 0.033). There were no differences in Sobs and Chao1 indices between patients with BBLs and healthy individuals (p = 0.279, p = 0.314, respectively).
In addition, beta diversity assessments based on weighted UniFrac were markedly different among the three groups (both p < 0.001, Fig. 4A, B). These results suggested an altered gut microbiota composition in BC and BBL patients.
The weighted UniFrac PCoA plot showed no visible separation among the three groups (Fig. 5A), but the PLS-DA analysis separated the three groups (Fig. 5B). Collectively, this observation revealed that the structure of the gut microbiota community was different among the three groups.
Bacterial taxonomic differences. Prevotella, Porphyromonas, Peptoniphilus, and Megamonas were the major taxonomic groups in the BC group, whereas Lactobacillus, Escherichia, and Coprobacillus were the major taxonomic groups in the BBL group. Cloacibacillus, Asaccharobacter, Christensenella, Alistipes, Tissierella, Hydrogenoanaerobacterium, Butyricimonas, Acidaminococcus, Oxalobacter, Collinsella, and Eubacterium were the major taxonomic groups in the healthy controls (Fig. 6).
Previous studies showed a direct and strong association between fecal microbiota diversity and estrogen levels in women (Flores et al. 2012). Generally, estrogens and their metabolites undergo sulfation and glucuronidation in the liver. The conjugated estrogens can then be excreted via stool and urine. Intestinal bacteria can directly affect estrogen production by secreting β-glucuronidase (GUS), an enzyme that depolymerizes estrogens into their active forms, to control the concentration of estrogens reabsorbed into the enterohepatic circulation. In addition, gut microbes synthesize estrogen-like compounds or estrogen mimics from the daily diet.
Furthermore, multiple bacterial metabolites (e.g., short-chain fatty acids, acetate, butyrate, pyruvate, formate, active amines, bile acids and derivatives, indole derivatives, etc.) can be involved in cancer cell growth, apoptosis, and invasion, epithelial-to-mesenchymal transition, and antitumor immune activity (Kovács et al. 2021). Changes in microbiome composition will lead to changes in the profiles of metabolites (Kovács et al. 2021). We, therefore, speculate that the proportion of microbiota-encoded GUS enzymes changed, thus affecting the metabolism of steroid hormones, metabolite profiles, and alpha diversity of intestinal microorganisms in BC and BBL patients.
Furthermore, microbial diversity can affect the efficacy of anticancer therapy. Fecal samples from melanoma patients receiving anti-PD-1 treatment exhibited a more diverse microbiome, and patients had significantly longer progression-free survival. The microbiota of immune therapy responders may upregulate the immune response by enhancing antigen presentation or increasing T cell recruitment in the local tumor environment (Gopalakrishnan et al. 2018).
Similarly, gut microbiota conditions the metastasis and therapeutic efficacy of trastuzumab in HER2-positive BC (Ingman 2019; Di Modica et al. 2021). Probiotic administration can significantly increase the number of bacterial species and the bacterial diversity assessed with the Chao1 index in overweight BC survivors (Pellegrini et al. 2020). Therefore, we hypothesize that the reduced microbial diversity may affect the treatment efficacy of BC patients.
According to the LEfSe analysis, Prevotella, Porphyromonas, Peptoniphilus, and Megamonas were indicator bacterial species in BC patients. Prevotella and Porphyromonas were also identified as potential microbial markers for postmenopausal BC patients (Amanatullah et al. 2017; Zhu et al. 2018). The two genera are also associated with colorectal cancer and precancerous adenomas (Warren et al. 2013; Lasry et al. 2016). Notably, Prevotella has been found on breast skin and mammary tissue (Urbaniak et al. 2014; Hieken et al. 2016; Urbaniak et al. 2016). Transferring microorganisms from the intestine to the breast tissue leads to increased systemic inflammation in BC and is therefore considered a cause of BC (Rao et al. 2007). Previous studies have shown that inflammatory indicators, such as platelet/lymphocyte ratio and lymphocyte/monocyte ratio, significantly influence the prognosis of various cancers, and neutrophilia is associated with a poor prognosis of BC (Lakritz et al. 2015). Systemic inverse interactions among microbes, interleukin-6 (IL-6), and neutrophils have been noted in BC (Rutkowski et al. 2015). A high lymphocyte/neutrophil ratio increases the risk of relapse in BC patients (Margolis et al. 2007). Therefore, we hypothesize that Prevotella was involved in the inflammatory response in BC patients. In addition, Prevotella can activate Toll-like receptor 2, leading to the production of Th17-polarizing cytokines by antigen-presenting cells, including IL-23 and IL-1. Prevotella can also stimulate epithelial cells to produce IL-8, IL-6, and CCL20, which promote mucosal Th17 immune responses (Larsen 2017). Porphyromonas uenonis showed a weak positive correlation with CD19 in BC patients (Zhu et al. 2018). Peptoniphilus were abundant in endocrine receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative BC types (Banerjee et al. 2018). Megamonas decreased significantly in patients with Bechet’s disease, and this alteration may be associated with immune aberration (Shimizu et al. 2019). Thus, we infer that the bacterial abundance changes were involved in the disruption of immune homeostasis in BC patients.
Among the genera with a decreased abundance in patients with BC, Collinsella has been associated with a cancer-free status and a better prognosis in BC patients (Terrisse et al. 2021). In the present study, Alistipes was decreased in the gut of patients with BC but was increased in the nipple aspiration fluid of patients with BC in a previous study (Laborda-Illanes et al. 2020). In BC, the number of Anaerofilum in the gut appears to be associated with the number of tumor-infiltrating lymphocytes (Shi et al. 2019). A lower number of gut Butyricimonas have been reported before in BC (Bobin-Dubigeon et al. 2021), supporting the present study. Acidaminococcus and Cloacibacillus have been observed with different gut abundance among BC subtypes associated with prognoses (Wu et al. 2020; Yang et al. 2021).
Even if the association between gut dysbiosis and BC has been extensively studied (Kovács et al. 2021), the association between gut dysbiosis and BBLs has not been extensively explored before. The present study suggests that women with BBLs display changes in the gut microbiome compared with healthy women. Many BBLs are precursor lesions in a spectrum of lesions leading to BC or to be markers of increased risk of breast cancer (Hartmann et al. 2005; Worsham et al. 2009; Johansson et al. 2021). Some of the bacteria found to be increased or decreased in patients with BBLs were also observed in patients with BC (increased Escherichia, Peptoniphilus, Lactobacillus, and Porphyromonas; decreased: Collinsella, Alistipes, Butyricimonas, Acidaminococcus, Tissierella, and Cloacibacillus). It is supported by Yang et al. (2021), who showed that among 31 genera of gut microbiota, only one (Citrobacter) was different between patients with BC and BBL. Still, Meng et al. (2018) reported differences in gut microbiota between BBL and BC. The roles of the various bacteria in immunity and cancer development discussed above might also apply to BBLs. Therefore, it could be hypothesized that a gut dysbiosis is an early event in the development of BBLs and BC and that the changes in gut microbiota are an early event in the spectrum of events from normal breast tissue to BBLs to BC. Ideally, longitudinal studies should be performed to examine this point.
In this study, the populations of Escherichia and Lactobacillus were significantly upregulated in BBL patients. The impaired barrier function allows bacterial access to the intestinal epithelium, enabling the delivery of toxins. Escherichia coli can putatively induce tumorigenesis by generating DNA mutagens such as genotoxin colibactin (Arthur et al. 2012). Staphylococcus aureus is an important factor inducing mutation of the MED12 gene, which may contribute to uterine leiomyomas and breast fibroadenomas (Bullerdiek and Rommel 2018). However, no significant changes in S. aureus were detected. Surprisingly, Lactobacillus was upregulated in BBL patients. Lactobacillus is usually considered to be a beneficial bacterium. Oral consumption of Lactobacillus acidophilus can decrease in fecal enzyme activity of GUS (Kwa et al. 2016), thereby reducing the estrogen burden in the body. Lactobacillus reuteri was found to be helpful in suppressing mammary tumorigenesis in genetically susceptible Her2 mutant mice (Lakritz et al. 2014). In addition, Lactobacillus exhibited anti-inflammatory properties in E. coli-stimulated bovine mammary epithelial cells (Bouchard et al. 2015). Hence, the upregulation of Lactobacillus in BBL patients may be due to the presence of the tumor, which allows the intestine to attract more beneficial bacteria to fight it.
In conclusion, non-malignant breast diseases have been far less studied. However, the great potential of intestinal microbiota in the development and treatment of benign breast diseases cannot be overlooked. The use of probiotics to treat mastitis in breastfeeding women has been reported. Probiotics are potentially effective at eliminating chronic subclinical infections as antibiotic treatment (Arroyo et al. 2010). Therefore, more related studies are required in the future.
Herein, we performed 16S rRNA gene sequencing of fecal samples collected from BC and BBL patients and healthy controls matched by gender, age, and BMI. Compared with healthy controls, BC and BBL patients showed a decreasing trend in intestinal microbiota diversity, which may be associated with their pathogenesis. The up- or down-regulated strains may be an essential indicator of the initiation of BC and BBLs. These results may provide a valuable reference for future related studies. However, several limitations must be addressed in future studies. First, species-level differences were not captured due to the limitations of 16S rRNA sequencing. More studies with whole-genome sequencing are needed. Second, this study was a single-center study with relatively small sample size. Third, the dietary structures differed among individuals, which might have influenced the results. Additional studies should be conducted with larger samples to explore the functions of intestinal flora in BC and BBLs.
Amanatullah DF, Tamaresis JS, Chu P, Bachmann MH, Hoang NM, Collyar D, Mayer AT, West RB, Maloney WJ, Contag CH, et al. Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells. Breast Cancer Res. 2017 Dec;19(1):121. https://doi.org/10.1186/s13058-017-0910-xAmanatullahDFTamaresisJSChuPBachmannMHHoangNMCollyarDMayerATWestRBMaloneyWJContagCHet alLocal estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells2017Dec19112110.1186/s13058-017-0910-x568876129141657Open DOISearch in Google Scholar
Arroyo R, Martín V, Maldonado A, Jiménez E, Fernández L, Rodríguez JM. Treatment of infectious mastitis during lactation: antibiotics versus oral administration of lactobacilli isolated from breast milk. Clin Infect Dis. 2010 Jun 15;50(12):1551–1558. https://doi.org/10.1086/652763ArroyoRMartínVMaldonadoAJiménezEFernándezLRodríguezJMTreatment of infectious mastitis during lactation: antibiotics versus oral administration of lactobacilli isolated from breast milk2010Jun 1550121551155810.1086/65276320455694Open DOISearch in Google Scholar
Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012 Oct 05;338(6103):120–123. https://doi.org/10.1126/science.1224820ArthurJCPerez-ChanonaEMühlbauerMTomkovichSUronisJMFanTJCampbellBJAbujamelTDoganBRogersABet alIntestinal inflammation targets cancer-inducing activity of the microbiota2012Oct 05338610312012310.1126/science.1224820364530222903521Open DOISearch in Google Scholar
Banerjee S, Tian T, Wei Z, Shih N, Feldman MD, Peck KN, DeMichele AM, Alwine JC, Robertson ES. Distinct microbial signatures associated with different breast cancer types. Front Micro-biol. 2018 May 15;9:951. https://doi.org/10.3389/fmicb.2018.00951BanerjeeSTianTWeiZShihNFeldmanMDPeckKNDeMicheleAMAlwineJCRobertsonESDistinct microbial signatures associated with different breast cancer types2018May 15995110.3389/fmicb.2018.00951596270629867857Open DOISearch in Google Scholar
Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014 Mar;157(1):121–141. https://doi.org/10.1016/j.cell.2014.03.011BelkaidYHandTWRole of the microbiota in immunity and inflammation2014Mar157112114110.1016/j.cell.2014.03.011405676524679531Open DOISearch in Google Scholar
Bobin-Dubigeon C, Luu HT, Leuillet S, Lavergne SN, Carton T, Le Vacon F, Michel C, Nazih H, Bard JM. Faecal microbiota composition varies between patients with breast cancer and healthy women: a comparative case-control study. Nutrients. 2021 Aug 05; 13(8):2705. https://doi.org/10.3390/nu13082705Bobin-DubigeonCLuuHTLeuilletSLavergneSNCartonTLeVacon FMichelCNazihHBardJMFaecal microbiota composition varies between patients with breast cancer and healthy women: a comparative case-control study2021Aug 05138270510.3390/nu13082705839970034444865Open DOISearch in Google Scholar
Bouchard DS, Seridan B, Saraoui T, Rault L, Germon P, Gonzalez-Moreno C, Nader-Macias FME, Baud D, François P, Chuat V, et al. Lactic acid bacteria isolated from bovine mammary microbiota: potential allies against bovine mastitis. PLoS One. 2015 Dec 29;10(12):e0144831. https://doi.org/10.1371/journal.pone.0144831BouchardDSSeridanBSaraouiTRaultLGermonPGonzalez-MorenoCNader-MaciasFMEBaudDFrançoisPChuatVet alLactic acid bacteria isolated from bovine mammary microbiota: potential allies against bovine mastitis2015Dec 291012e014483110.1371/journal.pone.0144831469470526713450Open DOISearch in Google Scholar
Braden A, Stankowski R, Engel J, Onitilo A. Breast cancer bio-markers: risk assessment, diagnosis, prognosis, prediction of treatment efficacy and toxicity, and recurrence. Curr Pharm Des. 2014 Aug 31;20(30):4879–4898. https://doi.org/10.2174/1381612819666131125145517BradenAStankowskiREngelJOnitiloABreast cancer bio-markers: risk assessment, diagnosis, prognosis, prediction of treatment efficacy and toxicity, and recurrence2014Aug 3120304879489810.2174/138161281966613112514551724283956Open DOISearch in Google Scholar
Bullerdiek J, Rommel B. Factors targeting MED12 to drive tumorigenesis? F 1000 Res. 2018;7:359. https://doi.org/10.12688/f1000research.14227.2BullerdiekJRommelBFactors targeting MED12 to drive tumorigenesis?1000Res. 2018735910.12688/f1000research.14227.2632561830647905Open DOISearch in Google Scholar
Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack S, Harris HMB, Coakley M, Lakshminarayanan B, O’Sullivan O, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012 Aug;488(7410):178–184. https://doi.org/10.1038/nature11319ClaessonMJJefferyIBCondeSPowerSEO’ConnorEMCusackSHarrisHMBCoakleyMLakshminarayananBO’SullivanOet alGut microbiota composition correlates with diet and health in the elderly2012Aug488741017818410.1038/nature1131922797518Open DOISearch in Google Scholar
Di Modica M, Gargari G, Regondi V, Bonizzi A, Arioli S, Belmonte B, De Cecco L, Fasano E, Bianchi F, Bertolotti A, et al. Gut microbiota condition the therapeutic efficacy of trastuzumab in HER2-positive breast cancer. Cancer Res. 2021 Apr 15;81(8): 2195–2206. https://doi.org/10.1158/0008-5472.CAN-20-1659DiModica MGargariGRegondiVBonizziAArioliSBelmonteBDe CeccoLFasanoEBianchiFBertolottiAet alGut microbiota condition the therapeutic efficacy of trastuzumab in HER2-positive breast cancer2021Apr 158182195220610.1158/0008-5472.CAN-20-165933483370Open DOISearch in Google Scholar
Dzutsev A, Badger JH, Perez-Chanona E, Roy S, Salcedo R, Smith CK, Trinchieri G. Microbes and cancer. Annu Rev Immunol. 2017 Apr 26;35(1):199–228. https://doi.org/10.1146/annurev-immunol-051116-052133DzutsevABadgerJHPerez-ChanonaERoySSalcedoRSmithCKTrinchieriGMicrobes and cancer2017Apr 2635119922810.1146/annurev-immunol-051116-05213328142322Open DOISearch in Google Scholar
Eslami-SZ, Majidzadeh-AK, Halvaei S, Babapirali F, Esmaeili R. Microbiome and breast cancer: new role for an ancient population. Front Oncol. 2020 Feb 12;10:120. https://doi.org/10.3389/fonc.2020.00120Eslami-SZMajidzadeh-AKHalvaeiSBabapiraliFEsmaeiliRMicrobiome and breast cancer: new role for an ancient population2020Feb 121012010.3389/fonc.2020.00120702870132117767Open DOISearch in Google Scholar
Ferreira RM, Pereira-Marques J, Pinto-Ribeiro I, Costa JL, Carneiro F, Machado JC, Figueiredo C. Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut. 2018 Feb;67(2):226–236. https://doi.org/10.1136/gutjnl-2017-314205FerreiraRMPereira-MarquesJPinto-RibeiroICostaJLCarneiroFMachadoJCFigueiredoCGastric microbial community profiling reveals a dysbiotic cancer-associated microbiota2018Feb67222623610.1136/gutjnl-2017-314205586829329102920Open DOISearch in Google Scholar
Flores R, Shi J, Fuhrman B, Xu X, Veenstra TD, Gail MH, Gajer P, Ravel J, Goedert JJ. Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study. J Transl Med. 2012 Dec;10(1):253. https://doi.org/10.1186/1479-5876-10-253FloresRShiJFuhrmanBXuXVeenstraTDGailMHGajerPRavelJGoedertJJFecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study2012Dec10125310.1186/1479-5876-10-253355282523259758Open DOISearch in Google Scholar
García Rodríguez LA, González-Pérez A. Use of antibiotics and risk of breast cancer. Am J Epidemiol. 2005 Apr 01;161(7):616–619. https://doi.org/10.1093/aje/kwi087GarcíaRodríguez LAGonzález-PérezAUse of antibiotics and risk of breast cancer2005Apr 01161761661910.1093/aje/kwi08715781950Open DOISearch in Google Scholar
Goedert JJ, Hua X, Bielecka A, Okayasu I, Milne GL, Jones GS, Fujiwara M, Sinha R, Wan Y, Xu X, et al. Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-non-coated faecal microbiota. Br J Cancer. 2018 Feb 20;118(4):471–479. https://doi.org/10.1038/bjc.2017.435GoedertJJHuaXBieleckaAOkayasuIMilneGLJonesGSFujiwaraMSinhaRWanYXuXet alPostmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-non-coated faecal microbiota2018Feb 20118447147910.1038/bjc.2017.435583059329360814Open DOISearch in Google Scholar
Goedert JJ, Jones G, Hua X, Xu X, Yu G, Flores R, Falk RT, Gail MH, Shi J, Ravel J, et al. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study. JNCI: J Natl Cancer Inst. 2015 Aug;107(8):djv147. https://doi.org/10.1093/jnci/djv147GoedertJJJonesGHuaXXuXYuGFloresRFalkRTGailMHShiJRavelJet alInvestigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study2015Aug1078djv14710.1093/jnci/djv147455419126032724Open DOISearch in Google Scholar
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 05;359(6371):97–103. https://doi.org/10.1126/science.aan4236GopalakrishnanVSpencerCNNeziLReubenAAndrewsMCKarpinetsTVPrietoPAVicenteDHoffmanKWeiSCet alGut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients2018Jan 0535963719710310.1126/science.aan4236582796629097493Open DOISearch in Google Scholar
Goubet AG, Wheeler R, Fluckiger A, Qu B, Lemaître F, Iribarren K, Mondragón L, Tidjani Alou M, Pizzato E, Durand S, et al. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae. Cell Death Differ. 2021 Jul;28(7):2276–2295. https://doi.org/10.1038/s41418-021-00753-8GoubetAGWheelerRFluckigerAQuBLemaîtreFIribarrenKMondragónLTidjaniAlou MPizzatoEDurandSet alMultifaceted modes of action of the anticancer probiotic Enterococcus hirae2021Jul2872276229510.1038/s41418-021-00753-8825778033976389Open DOISearch in Google Scholar
Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, Vierkant RA, Maloney SD, Pankratz VS, Hillman DW, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005 Jul 21;353(3):229–237. https://doi.org/10.1056/NEJMoa044383HartmannLCSellersTAFrostMHLingleWLDegnimACGhoshKVierkantRAMaloneySDPankratzVSHillmanDWet alBenign breast disease and the risk of breast cancer2005Jul 21353322923710.1056/NEJMoa04438316034008Open DOISearch in Google Scholar
Hieken TJ, Chen J, Hoskin TL, Walther-Antonio M, Johnson S, Ramaker S, Xiao J, Radisky DC, Knutson KL, Kalari KR, et al. The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep. 2016 Nov;6(1):30751. https://doi.org/10.1038/srep30751HiekenTJChenJHoskinTLWalther-AntonioMJohnsonSRamakerSXiaoJRadiskyDCKnutsonKLKalariKRet alThe microbiome of aseptically collected human breast tissue in benign and malignant disease2016Nov613075110.1038/srep30751497151327485780Open DOISearch in Google Scholar
Ingman WV. The gut microbiome: a new player in breast cancer metastasis. Cancer Res. 2019 Jul 15;79(14):3539–3541. https://doi.org/10.1158/0008-5472.CAN-19-1698IngmanWVThe gut microbiome: a new player in breast cancer metastasis2019Jul 1579143539354110.1158/0008-5472.CAN-19-169831308136Open DOISearch in Google Scholar
Jiang Y, Fan L. The effect of Poria cocos ethanol extract on the intestinal barrier function and intestinal microbiota in mice with breast cancer. J Ethnopharmacol. 2021 Feb;266:113456. https://doi.org/10.1016/j.jep.2020.113456JiangYFanLThe effect of Poria cocos ethanol extract on the intestinal barrier function and intestinal microbiota in mice with breast cancer2021Feb26611345610.1016/j.jep.2020.11345633039631Open DOISearch in Google Scholar
Johansson A, Christakou AE, Iftimi A, Eriksson M, Tapia J, Skoog L, Benz CC, Rodriguez-Wallberg KA, Hall P, Czene K, et al. Characterization of benign breast diseases and association with age, hormonal factors, and family history of breast cancer among women in Sweden. JAMA Netw Open. 2021 Jun 01;4(6):e2114716. https://doi.org/10.1001/jamanetworkopen.2021.14716JohanssonAChristakouAEIftimiAErikssonMTapiaJSkoogLBenzCCRodriguez-WallbergKAHallPCzeneKet alCharacterization of benign breast diseases and association with age, hormonal factors, and family history of breast cancer among women in Sweden2021Jun 0146e211471610.1001/jamanetworkopen.2021.14716823370334170304Open DOISearch in Google Scholar
Katagiri S, Shiba T, Tohara H, Yamaguchi K, Hara K, Nakagawa K, Komatsu K, Watanabe K, Ohsugi Y, Maekawa S, et al. Re-initiation of oral food intake following enteral nutrition alters oral and gut microbiota communities. Front Cell Infect Microbiol. 2019 Dec 20; 9:434. https://doi.org/10.3389/fcimb.2019.00434KatagiriSShibaTToharaHYamaguchiKHaraKNakagawaKKomatsuKWatanabeKOhsugiYMaekawaSet alRe-initiation of oral food intake following enteral nutrition alters oral and gut microbiota communities2019Dec 20943410.3389/fcimb.2019.00434695143031956606Open DOISearch in Google Scholar
Kovács T, Mikó E, Ujlaki G, Yousef H, Csontos V, Uray K, Bai P. The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer. Cancer Metastasis Rev. 2021 Dec;40(4):1223–1249. https://doi.org/10.1007/s10555-021-10013-3KovácsTMikóEUjlakiGYousefHCsontosVUrayKBaiPThe involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer2021Dec4041223124910.1007/s10555-021-10013-3882538434967927Open DOISearch in Google Scholar
Kwa M, Plottel CS, Blaser MJ, Adams S. The intestinal microbiome and estrogen receptor-positive female breast cancer. J Natl Cancer Inst. 2016 Apr 22;108(8). https://doi.org/10.1093/jnci/djw029KwaMPlottelCSBlaserMJAdamsSThe intestinal microbiome and estrogen receptor-positive female breast cancer2016Apr 22108810.1093/jnci/djw029501794627107051Open DOISearch in Google Scholar
Laborda-Illanes A, Sanchez-Alcoholado L, Dominguez-Recio ME, Jimenez-Rodriguez B, Lavado R, Comino-Méndez I, Alba E, Queipo-Ortuño MI. Breast and gut microbiota action mechanisms in breast cancer pathogenesis and treatment. Cancers (Basel). 2020 Aug 31;12(9):2465. https://doi.org/10.3390/cancers12092465Laborda-IllanesASanchez-AlcoholadoLDominguez-RecioMEJimenez-RodriguezBLavadoRComino-MéndezIAlbaEQueipo-OrtuñoMIBreast and gut microbiota action mechanisms in breast cancer pathogenesis and treatment2020Aug 31129246510.3390/cancers12092465756553032878124Open DOISearch in Google Scholar
Lakritz JR, Poutahidis T, Levkovich T, Varian BJ, Ibrahim YM, Chatzigiagkos A, Mirabal S, Alm EJ, Erdman SE. Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int J Cancer. 2014 Aug; 135(3):529–540. https://doi.org/10.1002/ijc.28702LakritzJRPoutahidisTLevkovichTVarianBJIbrahimYMChatzigiagkosAMirabalSAlmEJErdmanSEBeneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice2014Aug135352954010.1002/ijc.28702413143924382758Open DOISearch in Google Scholar
Lakritz JR, Poutahidis T, Mirabal S, Varian BJ, Levkovich T, Ibrahim YM, Ward JM, Teng EC, Fisher B, Parry N, et al. Gut bacteria require neutrophils to promote mammary tumorigenesis. Oncotarget. 2015 Apr 20;6(11):9387–9396. https://doi.org/10.18632/oncotarget.3328LakritzJRPoutahidisTMirabalSVarianBJLevkovichTIbrahimYMWardJMTengECFisherBParryNet alGut bacteria require neutrophils to promote mammary tumorigenesis2015Apr 206119387939610.18632/oncotarget.3328449622425831236Open DOISearch in Google Scholar
Larsen JM. The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology. 2017 Aug; 151(4):363–374. https://doi.org/10.1111/imm.12760LarsenJMThe immune response to Prevotella bacteria in chronic inflammatory disease2017Aug151436337410.1111/imm.12760550643228542929Open DOISearch in Google Scholar
Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016 Mar;17(3):230–240. https://doi.org/10.1038/ni.3384LasryAZingerABen-NeriahYInflammatory networks underlying colorectal cancer2016Mar17323024010.1038/ni.338426882261Open DOISearch in Google Scholar
Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M, Arumugam M, Batto JM, Kennedy S, et al.; MetaHIT consortium. Richness of human gut microbiome correlates with metabolic markers. Nature. 2013 Aug 29;500(7464):541–546. https://doi.org/10.1038/nature12506Le ChatelierENielsenTQinJPriftiEHildebrandFFalonyGAlmeidaMArumugamMBattoJMKennedySet alMetaHIT consortium. Richness of human gut microbiome correlates with metabolic markers2013Aug 29500746454154610.1038/nature1250623985870Open DOISearch in Google Scholar
Margolis KL, Rodabough RJ, Thomson CA, Lopez AM, McTiernan A; Women’s Health Initiative Research Group. Prospective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women. Arch Intern Med. 2007 Sep 24;167(17):1837–1844. https://doi.org/10.1001/archinte.167.17.1837MargolisKLRodaboughRJThomsonCALopezAMMcTiernanA; Women’s Health Initiative Research GroupProspective study of leukocyte count as a predictor of incident breast, colorectal, endometrial, and lung cancer and mortality in postmenopausal women2007Sep 24167171837184410.1001/archinte.167.17.183717893304Open DOISearch in Google Scholar
Méndez Utz VE, Pérez Visñuk D, Perdigón G, de Moreno de LeBlanc A. Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy. Appl Microbiol Biotechnol. 2021 Jan; 105(1):327–340. https://doi.org/10.1007/s00253-020-11007-xMéndezUtz VEPérezVisñuk DPerdigónGdeMoreno de LeBlanc AMilk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy2021Jan105132734010.1007/s00253-020-11007-x33205285Open DOISearch in Google Scholar
Meng S, Chen B, Yang J, Wang J, Zhu D, Meng Q, Zhang L. Study of microbiomes in aseptically collected samples of human breast tissue using needle biopsy and the potential role of in situ tissue microbiomes for promoting malignancy. Front Oncol. 2018 Aug 17;8:318. https://doi.org/10.3389/fonc.2018.00318MengSChenBYangJWangJZhuDMengQZhangLStudy of microbiomes in aseptically collected samples of human breast tissue using needle biopsy and the potential role of in situ tissue microbiomes for promoting malignancy2018Aug 17831810.3389/fonc.2018.00318610783430175072Open DOISearch in Google Scholar
Newman TM, Vitolins MZ, Cook KL. From the table to the tumor: the role of mediterranean and western dietary patterns in shifting microbial-mediated signaling to impact breast cancer risk. Nutrients. 2019 Oct 24;11(11):2565. https://doi.org/10.3390/nu11112565NewmanTMVitolinsMZCookKLFrom the table to the tumor: the role of mediterranean and western dietary patterns in shifting microbial-mediated signaling to impact breast cancer risk2019Oct 241111256510.3390/nu11112565689345731652909Open DOISearch in Google Scholar
Patel SH, Vaidya YH, Patel RJ, Pandit RJ, Joshi CG, Kunjadiya AP. Culture independent assessment of human milk microbial community in lactational mastitis. Sci Rep. 2017 Dec;7(1):7804. https://doi.org/10.1038/s41598-017-08451-7PatelSHVaidyaYHPatelRJPanditRJJoshiCGKunjadiyaAPCulture independent assessment of human milk microbial community in lactational mastitis2017Dec71780410.1038/s41598-017-08451-7555281228798374Open DOISearch in Google Scholar
Pellegrini M, Ippolito M, Monge T, Violi R, Cappello P, Ferrocino I, Cocolin LS, De Francesco A, Bo S, Finocchiaro C. Gut microbiota composition after diet and probiotics in overweight breast cancer survivors: a randomized open-label pilot intervention trial. Nutrition. 2020 Jun;74:110749. https://doi.org/10.1016/j.nut.2020.110749PellegriniMIppolitoMMongeTVioliRCappelloPFerrocinoICocolinLSDeFrancesco ABoSFinocchiaroCGut microbiota composition after diet and probiotics in overweight breast cancer survivors: a randomized open-label pilot intervention trial2020Jun7411074910.1016/j.nut.2020.11074932234652Open DOISearch in Google Scholar
Pourbaferani M, Modiri S, Norouzy A, Maleki H, Heidari M, Alidoust L, Derakhshan V, Zahiri HS, Noghabi KA. A newly characterized potentially probiotic strain, Lactobacillus brevis MK05, and the toxicity effects of its secretory proteins against MCF-7 breast cancer cells. Probiotics Antimicrob Proteins. 2021 Aug;13(4):982–992. https://doi.org/10.1007/s12602-021-09766-8PourbaferaniMModiriSNorouzyAMalekiHHeidariMAlidoustLDerakhshanVZahiriHSNoghabiKAA newly characterized potentially probiotic strain, Lactobacillus brevis MK05, and the toxicity effects of its secretory proteins against MCF-7 breast cancer cells2021Aug13498299210.1007/s12602-021-09766-833687634Open DOISearch in Google Scholar
Rao VP, Poutahidis T, Fox JG, Erdman SE. Breast cancer: should gastrointestinal bacteria be on our radar screen? Cancer Res. 2007 Feb 01;67(3):847–850. https://doi.org/10.1158/0008-5472.CAN-06-3468RaoVPPoutahidisTFoxJGErdmanSEBreast cancer: should gastrointestinal bacteria be on our radar screen?2007Feb 0167384785010.1158/0008-5472.CAN-06-346817283110Open DOISearch in Google Scholar
Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, Perales-Puchalt A, Brencicova E, Escovar-Fadul X, Nguyen JM, Cadungog MG, et al. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell. 2015 Jan;27(1):27–40. https://doi.org/10.1016/j.ccell.2014.11.009RutkowskiMRStephenTLSvoronosNAllegrezzaMJTesoneAJPerales-PuchaltABrencicovaEEscovar-FadulXNguyenJMCadungogMGet alMicrobially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation2015Jan271274010.1016/j.ccell.2014.11.009429326925533336Open DOISearch in Google Scholar
Sergentanis TN, Zagouri F, Zografos GC. Is antibiotic use a risk factor for breast cancer? A meta-analysis. Pharmacoepidemiol Drug Saf. 2010 Nov;19(11):1101–1107. https://doi.org/10.1002/pds.1986SergentanisTNZagouriFZografosGCIs antibiotic use a risk factor for breast cancer? A meta-analysis2010Nov19111101110710.1002/pds.198620845408Open DOISearch in Google Scholar
Shi J, Geng C, Sang M, Gao W, Li S, Yang S, Li Z. Effect of gastrointestinal microbiome and its diversity on the expression of tumor-infiltrating lymphocytes in breast cancer. Oncol Lett. 2019 Jun;17(6):5050–5056. https://doi.org/10.3892/ol.2019.10187ShiJGengCSangMGaoWLiSYangSLiZEffect of gastrointestinal microbiome and its diversity on the expression of tumor-infiltrating lymphocytes in breast cancer2019Jun1765050505610.3892/ol.2019.10187650729831186716Open DOISearch in Google Scholar
Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, Ueda Y, Wakisaka S, Suzuki T, Suzuki N. Relative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet’s disease (210 characters). Clin Rheumatol. 2019 May;38(5):1437–1445. https://doi.org/10.1007/s10067-018-04419-8ShimizuJKubotaTTakadaETakaiKFujiwaraNArimitsuNUedaYWakisakaSSuzukiTSuzukiNRelative abundance of Megamonas hypermegale and Butyrivibrio species decreased in the intestine and its possible association with the T cell aberration by metabolite alteration in patients with Behcet’s disease (210 characters)2019May3851437144510.1007/s10067-018-04419-830628011Open DOISearch in Google Scholar
Simin J, Tamimi RM, Engstrand L, Callens S, Brusselaers N. Antibiotic use and the risk of breast cancer: a systematic review and dose-response meta-analysis. Pharmacol Res. 2020 Oct;160:105072. https://doi.org/10.1016/j.phrs.2020.105072SiminJTamimiRMEngstrandLCallensSBrusselaersNAntibiotic use and the risk of breast cancer: a systematic review and dose-response meta-analysis2020Oct16010507210.1016/j.phrs.2020.10507232679181Open DOISearch in Google Scholar
Sørensen HT, Skriver MV, Friis S, McLaughlin JK, Blot WJ, Baron JA. Use of antibiotics and risk of breast cancer: a population-based case-control study. Br J Cancer. 2005 Feb;92(3):594–596. https://doi.org/10.1038/sj.bjc.6602313SørensenHTSkriverMVFriisSMcLaughlinJKBlotWJBaronJAUse of antibiotics and risk of breast cancer: a population-based case-control study2005Feb92359459610.1038/sj.bjc.6602313236207315611791Open DOISearch in Google Scholar
Terrisse S, Derosa L, Iebba V, Ghiringhelli F, Vaz-Luis I, Kroemer G, Fidelle M, Christodoulidis S, Segata N, Thomas AM, et al. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment. Cell Death Differ. 2021 Sep; 28(9):2778–2796. https://doi.org/10.1038/s41418-021-00784-1TerrisseSDerosaLIebbaVGhiringhelliFVaz-LuisIKroemerGFidelleMChristodoulidisSSegataNThomasAMet alIntestinal microbiota influences clinical outcome and side effects of early breast cancer treatment2021Sep2892778279610.1038/s41418-021-00784-1840823033963313Open DOISearch in Google Scholar
Urbaniak C, Cummins J, Brackstone M, Macklaim JM, Gloor GB, Baban CK, Scott L, O’Hanlon DM, Burton JP, Francis KP, et al. Microbiota of human breast tissue. Appl Environ Microbiol. 2014 May 15;80(10):3007–3014. https://doi.org/10.1128/AEM.00242-14UrbaniakCCumminsJBrackstoneMMacklaimJMGloorGBBabanCKScottLO’HanlonDMBurtonJPFrancisKPet alMicrobiota of human breast tissue2014May 1580103007301410.1128/AEM.00242-14401890324610844Open DOISearch in Google Scholar
Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol. 2016 Aug 15;82(16):5039–5048. https://doi.org/10.1128/AEM.01235-16UrbaniakCGloorGBBrackstoneMScottLTangneyMReidGThe microbiota of breast tissue and its association with breast cancer2016Aug 1582165039504810.1128/AEM.01235-16496854727342554Open DOISearch in Google Scholar
Warren RL, Freeman DJ, Pleasance S, Watson P, Moore RA, Cochrane K, Allen-Vercoe E, Holt RA. Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome. 2013 Dec; 1(1):16. https://doi.org/10.1186/2049-2618-1-16WarrenRLFreemanDJPleasanceSWatsonPMooreRACochraneKAllen-VercoeEHoltRACo-occurrence of anaerobic bacteria in colorectal carcinomas2013Dec111610.1186/2049-2618-1-16397163124450771Open DOISearch in Google Scholar
Watts AM, West NP, Zhang P, Smith PK, Cripps AW, Cox AJ. The gut microbiome of adults with allergic rhinitis is characterised by reduced diversity and an altered abundance of key microbial taxa compared to controls. Int Arch Allergy Immunol. 2021;182(2):94–105. https://doi.org/10.1159/000510536WattsAMWestNPZhangPSmithPKCrippsAWCoxAJThe gut microbiome of adults with allergic rhinitis is characterised by reduced diversity and an altered abundance of key microbial taxa compared to controls202118229410510.1159/00051053632971520Open DOISearch in Google Scholar
Wirtz HS, Buist DSM, Gralow JR, Barlow WE, Gray S, Chubak J, Yu O, Bowles EJA, Fujii M, Boudreau DM. Frequent antibiotic use and second breast cancer events. Cancer Epidemiol Biomarkers Prev. 2013 Sep;22(9):1588–1599. https://doi.org/10.1158/1055-9965.EPI-13-0454WirtzHSBuistDSMGralowJRBarlowWEGraySChubakJYuOBowlesEJAFujiiMBoudreauDMFrequent antibiotic use and second breast cancer events2013Sep2291588159910.1158/1055-9965.EPI-13-0454376944223833124Open DOISearch in Google Scholar
Worsham MJ, Raju U, Lu M, Kapke A, Botttrell A, Cheng J, Shah V, Savera A, Wolman SR. Risk factors for breast cancer from benign breast disease in a diverse population. Breast Cancer Res Treat. 2009 Nov; 118(1):1–7. https://doi.org/10.1007/s10549-008-0198-8WorshamMJRajuULuMKapkeABotttrellAChengJShahVSaveraAWolmanSRRisk factors for breast cancer from benign breast disease in a diverse population2009Nov11811710.1007/s10549-008-0198-8371532218836828Open DOISearch in Google Scholar
Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, Spicer D. Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study. Breast Cancer Res Treat. 2020 Jul;182(2):451–463. https://doi.org/10.1007/s10549-020-05702-6WuAHTsengCVigenCYuYCozenWGarciaAASpicerDGut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study2020Jul182245146310.1007/s10549-020-05702-6729786932468338Open DOISearch in Google Scholar
Yang P, Wang Z, Peng Q, Lian W, Chen D. Comparison of the gut microbiota in patients with benign and malignant breast tumors: a pilot study. Evol Bioinform Online. 2021 Jan;17: 11769343211057573. https://doi.org/10.1177/11769343211057573YangPWangZPengQLianWChenDComparison of the gut microbiota in patients with benign and malignant breast tumors: a pilot study2021Jan171176934321105757310.1177/11769343211057573859328934795472Open DOISearch in Google Scholar
Zhu B, Wang X, Li L. Human gut microbiome: the second genome of human body. Protein Cell. 2010 Aug; 1(8):718–725. https://doi.org/10.1007/s13238-010-0093-zZhuBWangXLiLHuman gut microbiome: the second genome of human body2010Aug1871872510.1007/s13238-010-0093-z487519521203913Open DOISearch in Google Scholar
Zhu J, Liao M, Yao Z, Liang W, Li Q, Liu J, Yang H, Ji Y, Wei W, Tan A, et al. Breast cancer in postmenopausal women is associated with an altered gut metagenome. Microbiome. 2018 Dec;6(1):136. https://doi.org/10.1186/s40168-018-0515-3ZhuJLiaoMYaoZLiangWLiQLiuJYangHJiYWeiWTanAet alBreast cancer in postmenopausal women is associated with an altered gut metagenome2018Dec6113610.1186/s40168-018-0515-3608054030081953Open DOISearch in Google Scholar