Breast cancer develops within a complex biological context shaped by endocrine, immune, metabolic, and environmental influences

The gap

Evidence profile

Sourced from the future work of the source papers, classified as general, all from Frontiers in Medicine. Those papers have been cited 8 times in total.

Supporting evidence — 3 representative gaps

• Host–microbiome interactions in breast cancer progression and treatment response (2026) · Frontiers in Medicine · doi

  Breast cancer develops within a complex biological context shaped by endocrine, immune, metabolic, and environmental influences. Within this framework, microbial communities present in the gut, oral cavity, and mammary tissue have been linked to processes that influence inflammation, immune regulation, and hormone metabolism. Dierences in microbial composition between healthy and malignant breast tissue, together with systemic eects of gut-derived metabolites, indicate that host- microbiome interactions have been associated with variability in tumor biology and treatment response, although causality remains to be established. At present, however, most observations describe ecological associations rather than direct microbial activity within breast tumors (10, 93). Several biological pathways provide plausible connections between microbial ecosystems and BC progression. Microbial including SCFAs, bile acid derivatives, and metabolites, tryptophan-related compounds, immune signaling, influence epithelial dierentiation, and chromatin regulation. Hormone metabolism also represents a potential interface, as bacterial β-glucuronidase activity can modify enterohepatic estrogen circulation, a process relevant to hormone receptor-positive disease (54, 81). Although such mechanisms are biologically consistent with tumor-related pathways, the extent to which microbial processes actively shape human breast tumor development remains incompletely defined. Interpretation of current findings is limited by methodological variability across studies. Breast tissue represents a low-biomass microbial environment, making sequencing results vulnerable to contamination and technical artifacts. Dierences in sampling strategies, sequencing platforms, contamination filtering, and taxonomic classification pipelines further complicate comparisons across cohorts. In addition, host-related determinants, including age, diet, antibiotic exposure, metabolic status, and menopausal transition, composition, introducing additional layers of heterogeneity that must be carefully controlled in future research (13, 20, 212). influence microbial substantially these

  generalfuture work
  Keywords: microbial breast within immune tissue influence hormone tumor related biological metabolic present processes regulation metabolism
• Exploratory randomized open-label clinical trial of Triphalā Kaṣāya vaginal douche (Yoni prakṣālana) with and without Gomūtra Arka in vaginal candidiasis (2026) · Frontiers in Medicine · doi

  candidiasis: incidence, of 7. Dutta DC. D.C. Dutta’s Textbook of Gynaecology. 6th ed. Kolkata: New Central Book Agency (2013). p. 159. 8. Norton R. Women’s health: a new global agenda. Womens Health. (2016) 12:271– 3. doi: 10.2217/whe-2016-0010 9. Saraf VS, Sheikh SA, Ahmad A, Gillevet PM, Bokhari H, Vaginal microbiome: 203:3793–802. doi: 10.1007/s00203-021-02414-3 dysbiosis. Arch Microbiol. normalcy vs. Javed S. (2021) 10. Chee WJY, Chew SY, Than LTL. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. (2020) 19:203. doi: 10.1186/s12934-020-01464-4 11. Amabebe E, Anumba DOC. The vaginal microenvironment: the physiologic role of lactobacilli. Front Med. (2018) 5:181. doi: 10.3389/fmed.2018.00181 12. Dutta DC. Textbook of Gynaecology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers (2020). Chapter 13, Infections of the individual pelvic organs, p. 136. 13. Denning DW, Kneale M, Sobel JD, Rautemaa-Richardson R. Global burden of recurrent vulvovaginal candidiasis: a systematic review. Lancet Infect Dis. (2018) 18:e339–47. doi: 10.1016/S1473-3099(18)30103-8 14. Sastri HSSP, editor. Sarvanga Sundara of Arunadatta and Ayurveda Rasayana of Hemadri on Ashtanga Hridaya of Vagbhata, Uttaratantra, Chapter 34, Verse 26–27. Reprint ed. Varanasi: Chaukhamba Sanskrit Sansthan (2020). p. 899. 18. Elman S, Hynan LS, Gabriel V, Mayo MJ. The 5-D itch scale: a new measure of pruritus. Br J Dermatol. (2010) 162:587–93. doi: 10.1111/j.1365-2133.2009.09586.x 19. Panda G, Mohapatra KB. Clinical effect of Kukkutanda Twak Bhasma in the management of Swetapradara. Ayu. (2011) 32:370–4. doi: 10.4103/0974-8520.93917 20. Muskat LC, Kerkhoff Y, Humbert P, Nattkemper TW, Eilenberg J, Patel AV. Image analysis-based quantification of fungal sporulation by automatic conidia counting and grey value correlation. MethodsX. (2021) 8:101218. doi: 10.1016/j.mex.2021.101218 21. Agoni L. Old but gold: an historical perspective of wet mount microscopy and its current role for the diagnosis of vaginitis. Front Reprod Health. (2026) 8:1755906. doi: 10.3389/frph.2026.1755906 22. Amritha MR. Combined effect of Triphal¯a Kv¯atha Yoni Praks. ¯alana and Triphal¯a Guggulu Oral Administration in Three Types of Vaginitis [dissertation]. Kollam: Amrita School of Ayurveda, Amrita Vishwa Vidyapeetham (2014). ¯Ac¯arya, editor. Nibandhasamgraha commentary of

  generalfuture work
  Keywords: health vaginal dutta candidiasis textbook gynaecology global role front chapter editor ayurveda vaginitis triphal amrita
• Integrating microbiome insights into cervical cancer (2026) · Frontiers in Medicine · cited 8× · doi

  Current data indicate that the microbiome acts as a dynamic and context-dependent contributor that modulates carcinogenic trajecto- ries rather than functioning as a standalone etiological factor. Studies have consistently shown that cervicovaginal dysbiosis, marked by depletion of Lactobacillus species and enrichment of anaerobic taxa such as Gardnerella, Atopobium, and Sneathia, promotes persistent HPV infection and progression to CIN and invasive carcinoma (89, 121, 152). These microbial alterations have been individually associ- ated with chronic inflammation, oxidative stress, epithelial barrier disruption, and modulation of host immune responses. However, the sequencing, interaction strength, and causal hierarchy among these processes remain to be fully clarified (22, 30, 97). Crucially, cervico- vaginal microbiome states should not be interpreted as binary healthy or pathogenic configurations. Protective or deleterious effects emerge from context-dependent interactions among microbial composition, metabolic activity, host immunity, hormonal milieu, and population- specific factors, rather than from Lactobacillus dominance alone (137, 156). Cervicovaginal microbiome configurations therefore shape risk in a probabilistic manner. Their biological impact depends on interac- tion strength, temporal stability, and host context, rather than on fixed taxonomic dominance alone (157–159). Beyond descriptive associations, recent research has advanced toward mechanistic and translational understanding. The role of bac- terial metabolites, particularly SCFAs such as butyrate, has gained prominence. Butyrate exerts tumor-suppressive properties by inhibit- ing cervical cancer cell proliferation, inducing apoptosis, and reshaping epigenetic regulation, positioning it as a metabolite of thera- peutic interest (79). Likewise, microbiome-metabolome integration studies reveal correlations between cervicovaginal microbial profiles and altered host metabolites such as 9,10-DiHOME and glycocholic acid, which may serve as biomarkers for HPV persistence and early detection of cervical lesions. Circadian misalignment has also been linked to shifts in microbial taxa, including Lactobacillus and Bacteroides, whose rhythmic activity modulates epithelial defense and inflammatory tone, adding a temporal dimension to cervical carcino- genesis (30, 160). Leveraging microbiome-derived biomarkers enables more precise diagnostics and risk stratification. Therapeutically, the modulation of the cervicovaginal microbiota emerges as a promising strategy. Probiotic and prebiotic interventions have demonstrated potential to restore Lactobacillus dominance, enhance HPV clearance, and reduce recurrence of cervical lesions (137, 152). Probiotic formulations such as oral and intravaginal Lactobacillus rhamnosus and Lactobacillus crispatus have increased HPV clearance and decreased viral load in clinical trials (134

  generalfuture work
  Keywords: lactobacillus microbiome cervicovaginal microbial host cervical context rather dominance dependent modulates taxa epithelial modulation strength

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