Breast cancer is associated with high mortality and morbidity rates. As about 20–30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine–hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics’ potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such as treatment-induced acquired resistance, which is boosted by the inflammatory phenotype of senescent cancerous cells, as well as undesired side effects resulting from the destruction of normal cells. Such a complex background of breast carcinogenesis and oncotherapy resistance opens avenues to search for new preventive approaches and adjunctive treatment regimens. Postbiotics demonstrate a variety of benefits due to their selective antineoplastic activity, as well as the cytoprotective potential associated with antioxidant, anti-inflammatory and anti-senescent properties. Pleiotropic effects of postbiotics make them a promising tool for counteracting cellular and physiological disturbances that favor breast cancer development, including age- and obesity-related factors. They are prospective adjunctive agents in oncotherapy, albeit their efficacy and safety need to be thoroughly evaluated in clinical studies prior to implementation in routine treatment modes.