Multifocal breast cancer (MFBC), defined as multiple synchronous unilateral lesions of invasive breast cancer, is relatively frequent and has been associated with more aggressive features than unifocal cancer. Here, we aimed to investigate the genomic heterogeneity between MFBC lesions sharing similar histopathological parameters. Characterization of different lesions from 36 patients with ductal MFBC involved the identification of non‐silent coding mutations in 360 protein‐coding genes (171 tumour and 36 matched normal samples). We selected only patients with lesions presenting the same grade, ER, and HER2 status. Mutations were classified as ‘oncogenic’ in the case of recurrent substitutions reported in COSMIC or truncating mutations affecting tumour suppressor genes. All mutations identified in a given patient were further interrogated in all samples from that patient through deep resequencing using an orthogonal platform. Whole‐genome rearrangement screen was further conducted in 8/36 patients. Twenty‐four patients (67%) had substitutions/indels shared by all their lesions, of which 11 carried the same mutations in all lesions, and 13 had lesions with both common and private mutations. Three‐quarters of those 24 patients shared oncogenic variants. The remaining 12 patients (33%) did not share any substitution/indels, with inter‐lesion heterogeneity observed for oncogenic mutation(s) in genes such as PIK3CA, TP53, GATA3, and PTEN. Genomically heterogeneous lesions tended to be further apart in the mammary gland than homogeneous lesions. Genome‐wide analyses of a limited number of patients identified a common somatic background in all studied MFBCs, including those with no mutation in common between the lesions. To conclude, as the number of molecular targeted therapies increases and trials driven by genomic screening are ongoing, our findings highlight the presence of genomic inter‐lesion heterogeneity in one‐third, despite similar pathological features. This implies that deeper molecular characterization of all MFBC lesions is warranted for the adequate management of those cancers. © 2015 The Authors. Pathological Society of Great Britain and Ireland.

The androgen receptor (AR) is a ligand-dependent transcription factor, and its effects on breast range from physiological pubertal development and age-related modifications to cancer onset and proliferation. The prevalence of AR in early breast cancer is around 60%, and AR is more frequently expressed in ER-positive than in ER-negative tumors. We offer an overview of AR signaling pathways in different breast cancer subtypes, providing evidence that its oncogenic role is likely to be different in distinct biological and clinical scenarios. In particular, in ER-positive breast cancer, AR signaling often antagonizes the growth stimulatory effect of ER signaling; in triple-negative breast cancer (TNBC), AR seems to drive tumor progression (at least in luminal AR subtype of TNBC with a gene expression profile mimicking luminal subtypes despite being negative to ER and enriched in AR expression); in HER2-positive breast cancer, in the absence of ER expression, AR signaling has a proliferative role. These data represent the rationale for AR-targeting treatment as a potentially new target therapy in breast cancer subset using androgen agonists in some AR-positive/ER-positive tumors, AR antagonists in triple-negative/ AR-positive tumors and in combination with anti-HER2 agents or with other signaling pathways inhibitors (including PI3K/MYC/ERK) in HER2-positive/AR-positive tumors. Only the ongoing and future prospective clinical trials will allow us to establish which agents are the best option in every specific condition, keeping in mind that there is evidence of opposite androgens and AR agonist/antagonist drug effects on cell proliferation particularly in AR-positive/ER-positive tumors.

The proportion of colorectal cancer attributed to dietary habits is high, but several inconsistencies remain, especially with respect to the influence of some food groups. To further elucidate the role of dietary habits, 1,225 subjects with cancer of the colon, 728 with cancer of the rectum and 4,154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in 6 different Italian areas. The validated food-frequency questionnaire included 79 questions on food items and recipes, categorised into 16 food groups. After allowance for non-dietary confounding factors and total energy intake, significant trends of increasing risk of colorectal cancer with increasing intake emerged for bread and cereal dishes (odds ratio [OR] in highest vs. lowest quintile 5 1.7), potatoes (OR 5 1.2), cakes and desserts (OR 5 1.1), and refined sugar (OR 5 1.4). Intakes of fish (OR 5 0.7), raw and cooked vegetables (OR 5 0.6 for both) and fruit other than citrus fruit (OR 5 0.7) showed a negative association with risk. Consumption of eggs and meat (white, red or processed meats) seemed uninfluential. Most findings were similar for colon and rectum, but some negative associations (i.e., coffee and tea, and fish) appeared stronger for colon cancer. The proportion of colorectal cancer avoidable by changes in diet is thought to be high, probably one of the highest among cancer sites. It was estimated to be in the order of 90% by Doll and Peto in 1981 and 70%, with a lower limit of 50%, by Willett in 1994(Nelson, 1996. Research on diet and colon cancer has concentrated, with respect to food groups, on vegetables and fruit (Potter, 1996), red meat (Willett et al., 1990;Giovannucci et al., 1994;Goldbohm et al., 1994) and dairy products (Kampman et al., 1994;Kearney et al., 1996). In the search for the mechanism(s) responsible of inter-country and inter-individual variations in risk, some food constituents (e.g., fiber and animal fat, Giovannucci, 1995), micronutrients and minerals (e.g., calcium and vitamin D, Kampman et al., 1994;Kearney et al., 1996; folate, Giovannucci, 1995; ascorbate and carotenoids, Ferraroni et al., 1994) were particularly investigated.The present multicentre case-control study was undertaken in Italy to elucidate the role of recent diet in the development of cancer of the colon and rectum. This approach provides original information on a southern European population where dietary and life-style habits and awareness of diet-related health issues are different from those in North America and northern Europe, where most other investigations have been conducted.Our analysis concerns the evaluation of individual food items or food groups and, therefore, avoids some problems inherent to analyses of nutrient intake (e.g., inaccuracy and incompleteness of food-composition tables). It does not preclude, however, adjustment for total energy intake in order to assess the issue of dietary composition rather than absolute intake and to allow for over-or under-reporting. Furthermore, it offers ...

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