The Role of Cow’s Milk Consumption in Breast Cancer Initiation and Progression

Abstract

Purpose of Review This review evaluates cow milk’s impact on breast carcinogenesis by linking recent epidemiological evidence and new insights into the molecular signaling of milk and its constituents in breast cancer (BCa) pathogenesis. Recent Findings Recent prospective cohort studies support the association between cow’s milk consumption and the risk of estrogen receptor-α-positive (ER+) BCa. Milk is a complex biological fluid that increases systemic insulin-like growth factor 1 (IGF-1), insulin and estrogen signaling, and interacting hormonal promoters of BCa. Further potential oncogenic components of commercial milk include exosomal microRNAs (miR-148a-3p, miR-21-5p), bovine meat and milk factors, aflatoxin M1, bisphenol A, pesticides, and micro- and nanoplastics. Individuals with BRCA1 loss-of-function mutations and FTO and IGF1 gain-of-function polymorphisms enhancing IGF-1/mTORC1 signaling may be at increased risk for milk-induced ER+ BCa. Summary Recent prospective epidemiological and pathobiochemical studies identify commercial milk consumption as a critical risk factor of ER+ BCa. Large meta-analyses gathering individuals of different ethnic origins with milk derived from dairy cows of varying genetic backgrounds and diverse feeding procedures as well as missing data on thermal processing of milk (pasteurization versus ultra-heat treatment) make multi-national meta-analyses unsuitable for BCa risk estimations in susceptible populations. Future studies are required that consider all vulnerable periods of breast carcinogenesis to cow’s milk exposure, beginning during the perinatal period and puberty, since these are the most critical periods of mammary gland morphogenesis. Notwithstanding the need for better studies including detailed information on milk processing and vulnerable periods of human breast carcinogenesis, the available evidence suggests that dietary guidelines on milk consumption may have to be reconsidered.

Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease

“…MiR-21 and miR-155 have been related to the most advanced stages of breast cancer progression, being involved in the development of tamoxifen resistance, metastasis formation, and worst prognosis [ 46 ]. Commercial milk consumption has been correlated to an increased risk of estrogen receptor-positive breast cancer development, due to the content of multiple oncogenic factors, as miR-148a-3p and miR-21-5p [ 47 ]. Milk-derived miRNAs have been associated with prostate cancer tumorigenesis promotion.…”

“…In addition, the biological and functional role of dietary miRNAs from different sources in human health is still controversial. Different milk-derived miRNAs have been reported to modulate oncogenic and adipogenic pathways, promoting the development of B-cell lymphoma, hormone-dependent breast and prostate cancer [ 43 , 44 , 45 , 47 ], as well as the ginger-related miRNA has been associated with colitis development [ 64 ] and the pork-derived miRNAs to the development of metabolic disorders in mice [ 22 ]. The evaluation of food-derived xenomiRNA effects cannot refrain from considering the co-existence of a great variety of dietary bioactive compounds.…”

Role of Exosomes in Cancer and Aptamer-Modified Exosomes as a Promising Platform for Cancer Targeted Therapy

“…The cow’s milk consumption was also demonstrated to correlate with increased risk of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive breast cancer by epidemiological evidence [ 56 , 57 ]. Although the explanation to these findings is complicate, it is worth to note that the miRNAs in MDEs may play an important part via functioning as oncogenic factors in recipient cells in ER + breast cancer [ 50 , 58 ].…”