Soy isoflavone exposure through all life stages accelerates 17β-estradiol-induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats

Abstract

There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17β-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened.

New Evaluation of Isoflavone Exposure in the French Population

“…The effect of soy isoflavones in food supplements was also shown on triple-negative breast tumours of women with family risks of breast cancer, probably due to the activation of tumour cell proliferation by phytoestrogens via the GPR30 receptor [66]. Hence, the available data indicate a protective effect of isoflavones at the initiation step of estrogen-dependent breast cancers and, on the opposite, a deleterious effect of the same compounds at proliferation stage of the corresponding tumours [67]. Therefore, it is not surprising to see a difference of phytoestrogen effect on breast cancer during the first year of phytoestrogen-based food-supplements intake and after [68].…”

State of the evidence 2017: an update on the connection between breast cancer and the environment

“…In several studies, exposures to phytoestrogens have led to increases in mammary tumor proliferation and growth. In ACI rats, dietary exposure to total soy isoflavone content from conception through adulthood decreased incidence of mammary tumors in adult animals by 20% and multiplicity by 56%, while also decreasing the latency to tumor onset by 20% and almost tripling tumor volumes [ 605 ]. Exposure of Wistar rats to genistein from conception through weaning led to decreases in DMBA-induced tumor number, multiplicity and incidence at postnatal day 50 [ 606 ].…”

Impact of Physical Exercise on Growth and Progression of Cancer in Rodents—A Systematic Review and Meta-Analysis

“…Especially dietary estrogens can profoundly influence molecular and cellular event actions on estrogen receptors androgen receptors and estrogen-sensitive genes (64). This is of major importance in tumor models for estrogen or androgen sensitive tumors like breast (65, 66) or prostate cancer (67). However also in non-steroid hormone dependent tumor models effects of such substances in the diet have been described (68).…”