The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.

Adiponectin is one of the most important adipocytokines secreted by adipocytes and is called a “guardian angel adipocytokine” owing to its unique biological functions. Adiponectin inversely correlates with body fat mass and visceral adiposity. Identified independently by four different research groups, adiponectin has multiple names; Acrp30, apM1, GBP28, and AdipoQ. Adiponectin mediates its biological functions via three known receptors, AdipoR1, AdipoR2, and T-cadherin, which are distributed throughout the body. Biological functions of adiponectin are multifold ranging from anti-diabetic, anti-atherogenic, anti-inflammatory to anti-cancer. Lower adiponectin levels have been associated with metabolic syndrome, type 2 diabetes, insulin resistance, cardiovascular diseases, and hypertension. A plethora of experimental evidence supports the role of obesity and increased adiposity in multiple cancers including breast, liver, pancreatic, prostrate, ovarian, and colorectal cancers. Obesity mediates its effect on cancer progression via dysregulation of adipocytokines including increased production of oncogenic adipokine leptin along with decreased production of adiponectin. Multiple studies have shown the protective role of adiponectin in obesity-associated diseases and cancer. Adiponectin modulates multiple signaling pathways to exert its physiological and protective functions. Many studies over the years have shown the beneficial effect of adiponectin in cancer regression and put forth various innovative ways to increase adiponectin levels.

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

Breast cancer-related mortality remains high worldwide, despite tremendous advances in diagnostics and therapeutics; hence, the quest for better strategies for disease management, as well as the identification of modifiable risk factors, continues. With recent leaps in genomic technologies, microbiota have emerged as major players in most cancers, including breast cancer. Interestingly, microbial alterations have been observed with some of the established risk factors of breast cancer, such as obesity, aging and periodontal disease. Higher levels of estrogen, a risk factor for breast cancer that cross-talks with other risk factors such as alcohol intake, obesity, parity, breastfeeding, early menarche and late menopause, are also modulated by microbial dysbiosis. In this review, we discuss the association between known breast cancer risk factors and altered microbiota. An important question related to microbial dysbiosis and cancer is the underlying mechanisms by which alterations in microbiota can support cancer progression. To this end, we review the involvement of microbial metabolites as effector molecules, the modulation of the metabolism of xenobiotics, the induction of systemic immune modulation, and altered responses to therapy owing to microbial dysbiosis. Given the association of breast cancer risk factors with microbial dysbiosis and the multitude of mechanisms altered by dysbiotic microbiota, an impaired microbiome is, in itself, an important risk factor.

Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. Different microbial signatures have been identified in the breast microbiota, which have different patterns depending on the stage and biological subgroups. The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. In this review article, we discuss the impact of the microbiota on breast cancer, with a primary focus on the gut microbiota’s regulation of the breast cancer microenvironment. Ultimately, updates on how immunotherapy can affect the breast cancer-based microbiome and further clinical trials on the breast and microbiome axis may be an important piece of the puzzle in better predicting breast cancer risk and prognosis.

Lung cancer remains the second-most-common cancer worldwide and is associated with the highest number of cancer-related mortality. While tobacco smoking is the most important risk factor for lung cancer, many other lifestyles and occupational factors significantly contribute. Obesity is a growing global health concern and contributes to ~30% cancer-related mortality, but unlike other lifestyle diseases, lung cancer is negatively associated with obesity. We meta-analyzed multiple case-control studies confirming increased survival and better outcomes in overweight and obese lung cancer patients. Tumor heterogeneity analysis showed significant enrichment of adipocytes and preadipocytes in normal lungs compared to lung cancers. Interestingly, one of the understudied adipokine, omentin, was significantly and consistently lower in lung neoplasms compared to normal lungs. Omentin has been examined in relation to osteoarthritis, inflammatory bowel disease, cardiovascular diseases, diabetes, chronic liver disease, psoriasis and some other cancers. Aberrant expression of omentin has been reported in solid tumors; however, little is known about its role in lung cancer. We found omentin to be consistently downregulated in lung cancers, and it exhibited a negative correlation with important transcription factors FOXA1, EN1, FOXC1 and ELK4. We, therefore, suggest that omentin may serve as a prognostic factor in lung cancer and explain the “obesity paradox” in lung cancer.