Epidemiological, clinical, and experimental data indicate that the risk of developing breast cancer is strongly dependent on the ovary and on endocrine conditions modulated by ovarian function, such as early menarche, late menopause, and parity. Women who gave birth to a child when they were younger than 24 years of age exhibit a decrease in their lifetime risk of developing breast cancer, and additional pregnancies increase the protection. The breast tissue of normally cycling women contains three identifiable types of lobules, the undifferentiated Lobules type 1 (Lob 1) and the more developed Lobules type 2 and Lobules type 3. The breast attains its maximum development during pregnancy and lactation (Lobules type 4). After menopause the breast regresses in both nulliparous and parous women containing only Lob 1. Despite the similarity in the lobular composition of the breast at menopause, the fact that nulliparous women are at higher risk of developing breast cancer than parous women indicates that Lob 1 in these two groups of women might be biologically different, or might exhibit different susceptibility to carcinogenesis. Based on these observations it was postulated that Lob 1 found in the breast of nulliparous women and of parous women with breast cancer never went through the process of differentiation, retaining a high concentration of epithelial cells that are targets for carcinogens and are therefore susceptible to undergo neoplastic transformation. These epithelial cells are called Stem cells 1, whereas Lob 1 structures found in the breast of early parous postmenopausal women free of mammary pathology, on the contrary, are composed of an epithelial cell population that is refractory to transformation, called Stem cells 2. It was further postulated that the degree of differentiation acquired through early pregnancy has changed the 'genomic signature' that differentiates Lob 1 of the early parous women from that of the nulliparous women by shifting the Stem cells 1 to Stem cells 2 that are refractory to carcinogenesis, making this the postulated mechanism of protection conferred by early full-term pregnancy. The identification of a putative breast stem cell (Stem cells 1) has, in the past decade, reached a significant impulse, and several markers also reported for other tissues have been found in the mammary epithelial cells of both rodents and humans. Although further work needs to be carried out in order to better understand the role of the Stem cells 2 and their interaction with the genes that confer them a specific signature, collectively the data presently available provide evidence that pregnancy, through the process of cell differentiation, shifts Stem cells 1 to Stem cells 2 – cells that exhibit a specific genomic signature that could be responsible for the refractoriness of the mammary gland to carcinogenesis.

Bisphenol A (BPA), known as an environmental endocrine disruptor, is widely used as a plasticizer. This study aims to investigate whether exposure in utero to BPA alters the architecture, proliferative index, and genomic signature of the rat mammary gland during critical stages of development. Pregnant rats were gavaged with 25 μg BPA/kg body weight (BW; low-dose group) or 250 μg BPA/kg BW (high-dose group) from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50, and 100 days, and mammary glands were collected. Analysis of gland morphology was performed from whole-mounted mammary tissue, while proliferative index was determined by detection of bromodeoxyuridine incorporation in the epithelial cells. Genomic profiles were obtained by microarray analysis, and some genes were validated by real-time RT-PCR. BPA exposure induced changes in the mammary gland that were time and dose specific. High-dose exposure resulted in architectural modifications, mainly in the number of undifferentiated epithelial structures of the breast tissue. Proliferative index did not show remarkable differences by the effect of BPA. Low and high doses of BPA changed the gene expression signature of the mammary gland following a different fashion: low dose had the highest effect by 50 days, while high dose had a highest influence on gene expression by 100 days. Both doses presented a significant cluster of up-modulated genes related to the immune system at the age of maximal changes. Moreover, high-dose exposure induced changes in genes related to differentiation suggesting alterations in the normal development of the gland. The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation.

Breast cancer is the most frequent malignant neoplasia and a leading cause of mortality in women worldwide. The Mediterranean diet has been proposed as a healthy dietary pattern with protective effects in several chronic diseases, including breast cancer. This diet is characterized by the consumption of abundant plant foods and olive oil as the principal source of fat, which is considered one of the main components with potential antioxidant, anti-inflammatory and anticancer effects. Extra-virgin olive oil (EVOO) has several bioactive compounds, mainly including monounsaturated fatty acids, triterpenes and polyphenols, such as phenolic alcohols (e.g., hydroxytyrosol), secoiridoids (e.g., oleuropein and oleocanthal), lignans (e.g., pinoresinol) or flavonoids (e.g., luteolin). While epidemiological evidence is still limited, experimental in vivo and in vitro data have shown a protective effect of this oil and its compounds on mammary carcinogenesis. Such effects account through complex and multiple mechanisms, including changes in epigenetics, transcriptome and protein expression that modulate several signaling pathways. Molecular targets of EVOO compounds have a role in the acquisition of cancer hallmarks. Although further research is needed to elucidate their beneficial effects on human prevention and progression of the disease, evidence points to EVOO in the context of the Mediterranean diet as a heathy choice, while EVOO components may be promising adjuvants in anticancer strategies.

Objective: The Mediterranean diet has been related to a lower risk of some chronic diseases, including cancer. We aim to gain insight into the effects of the main source of fat of this diet on breast cancer, the most common type of malignancy in women.Design: Data from sixteen experimental series analysing the effects of dietary lipids on mammary carcinogenesis in an animal model, in the context of the international literature on the Mediterranean diet, olive oil and breast cancer risk.Setting: Experimental and human data on the effects of olive oil and Mediterranean diet on breast cancer.Subjects: An animal model of induced breast cancer and other human and experimental studies in the literature.Results: Diets rich in extra virgin olive oil (EVOO) exert a negative modulatory effect on experimental breast cancer to a weak promoting effect, much lower than that obtained with a high-corn oil diet. EVOO confers to the mammary adenocarcinomas a clinical behaviour and morphological features compatible with low tumour aggressiveness. This differential effect, in relation to other dietary lipids, may be related to a lower effect on body weight and sexual maturation. In addition, EVOO induced different molecular changes in tumours, such as in the composition of cell membranes, activity of signalling proteins and gene expression. All these modifications could induce lower proliferation, higher apoptosis and lower DNA damage. These results, together with the favourable effect of olive oil reported in the literature when it is consumed in moderate quantities, suggest a beneficial influence of EVOO on breast cancer risk.Conclusions: Consumption of EVOO in moderate quantities and throughout the lifetime appears to be a healthy choice and may favourably influence breast cancer risk.