Vitamin D plays a key role in immune modulation, cell proliferation, and hormone regulation. Dysregulated testosterone may contribute to breast cancer progression. We investigated whether long-term vitamin D supplementation affects serum testosterone levels in breast cancer survivors. Complete data at baseline, 12, and 24 months were derived from 253 women with early-stage breast cancer participating in the DEDiCa trial and randomized to receive either a high-dose vitamin D to maintain serum 25(OH)D at 60 ng/mL (group A) or a standard dose to maintain serum levels at 30 ng/mL (group B). Serum 25(OH)D levels significantly increased in both groups (p < 0.001). No significant changes in testosterone concentrations were observed between treatment groups over the 24 month treatment period (A: 0.125 to 0.140 ng/mL; B: 0.162 to 0.193 ng/mL; p = 0.682). Baseline serum testosterone levels emerged as the most significant predictor of testosterone trajectories, possibly modulated by hormone-suppressive therapy. These results are reassuring that vitamin D supplementation did not adversely affect testosterone levels in this population of breast cancer survivors and may partially concur with a healthy lifestyle to equilibrate testosterone levels.

Background: Plant-based diets are recommended in guidelines for the prevention of cancer and cardiometabolic diseases, which remain major causes of death in breast cancer survivors (BCS). Since not all plant foods are healthy, we calculated the plant-based dietary index (PDI), healthy (hPDI) and unhealthy (uPDI), and their associations with cardiometabolic targets in BCS. Methods: Baseline dietary and cardiometabolic data were derived from 492 (median age 51, IQR 46–59) female BCS participating in a multicentric lifestyle trial conducted in Italy. Dietary data were collected with 7-day food records. PDI, hPDI, and uPDI were calculated by assigning positive scores to all plant foods, healthy plant foods or less healthy plant foods, respectively, as defined by the literature (scores ranged from 18 to 90). Using logistic or multinomial regression models, we estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) between PDIs and cardiometabolic risk factors. Results: The OR of being obese (BMI ≥ 30 Kg/m2) was 0.47 (95%CI: 0.29–0.77), 0.37 (95%CI: 0.22–0.61) and 1.38 (95%CI: 0.83–2.28) with higher PDI, hPDI and uPDI, respectively. The OR of having a large waist circumference (≥88 cm) was 0.64 (95%CI: 0.42–1.00) with higher hPDI. The OR for hypercholesterolemia (≥200 mg/dL) was 1.80 (95%CI: 1.16–2.78) with higher uPDI. The ORs of hypertriglyceridemia (≥150 mg/dL) and metabolic syndrome were 0.38 (95%CI: 0.20–0.71) and 0.59 (95%CI: 0.35–0.97), respectively, with higher PDI. No other significant association was observed. Conclusions: Maintaining cardiometabolic risk factors within normal ranges is clinically relevant in BCS, and this may be more likely when a plant-based diet is consumed, especially if low in unhealthy plant foods.

Objective. To report cross-sectionally serum levels of 25-hydroxyvitamin D [25(OH)D] in women living in Italy within 12 months from breast cancer (BC) diagnosis. Methods. Baseline data were obtained from 394 women diagnosed with primary BC, enrolled from 2016 to 2019 in a lifestyle trial conducted in Italy. Subjects’ characteristics were compared between two 25(OH)D concentrations (hypovitaminosis D<20 and ≥20 ng/mL) with the Chi-squared test or Fisher’s exact test for small-expected counts. Using multiple logistic regression-adjusted models, we estimated odds ratios (ORs) of hypovitaminosis D with 95% confidence intervals (CIs) in the total sample and in the unsupplemented subgroup. Results. Hypovitaminosis D was found in 39% of all subjects, 60% in unsupplemented subjects, and 10% in supplemented subjects. Increasing ORs of hypovitaminosis D were found with increasing body mass index, 25-30, >30, and ≥35 versus <25 kg/m2 (ORs: 2.50, 4.64, and 5.81, respectively, in the total cohort and ORs: 2.68, 5.38, and 7.08 in the unsupplemented); living in the most southern Italian region (OR 2.50, 95%CI 1.22-5.13); and with hypertriglyceridemia (OR 2.46; 95%CI 1.16-5.22), chemotherapy history (OR 1.86, 95%CI 1.03-3.38), and inversely with anti-estrogenic therapy (OR 0.43, 95%CI 0.24-0.75) in the total sample. Conclusions. Hypovitaminosis D in women recently diagnosed with BC and participating in a lifestyle trial in Italy was widespread and highest with obesity, hypertriglyceridemia, and chemotherapy use. Considering that hypovitaminosis D is a risk factor for lower efficacy of bone density treatments and possibly BC mortality, our results suggest the need to promptly address and treat vitamin D deficiency.

Health-related quality of life (HRQoL) represents one of the most concerning aspects for cancer patients. The Healthy Eating Index (HEI) is an a priori diet quality index directly associated with health outcomes and HRQoL in cancer survivors in North American populations. We evaluated, in a Mediterranean population, the baseline associations between HEI-2015 and HRQoL in 492 women with breast cancer recruited in a DEDiCa lifestyle trial. Dietary data were obtained from 7-day food records; HRQoL was assessed through the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30) and the C30 Summary Score (SumSc). Analysis of variance and multivariable linear and log-gamma regression models were performed. Mean and standard deviation for HEI-2015 score was 68.8 ± 11.2; SumSc was 81.5 ± 12.9. Women with lower HEI-2015 score had higher BMI, were more frequently exposed to tobacco smoke and had fewer years of education. Patients with a HEI-2015 score greater than 68.7 (median value) showed a significant increase in SumSc of 4% (p = 0.02). HEI-2015 components also associated with SumSc were beans and greens (β = 1.04; p = 0.02). Weak associations were found for total vegetables and saturated fats. Higher diet quality in breast cancer survivors was associated with higher overall HRQoL in this cross-sectional analysis.

Background: the Mediterranean diet, the low dietary glycemic index (GI) and the dietary inflammation index (DII®) have been associated with lower risk of breast cancer (BC) incidence and mortality. Objective: to investigate whether one-year nutrition counselling in the context of a Mediterranean diet, with or without low-GI carbohydrates counselling, may influence the DII in women with BC. Methods: data were obtained from participants of DEDiCa trial randomized to a Mediterranean diet (MD, n = 112) or a Mediterranean diet with low-GI carbohydrates (MDLGI, n = 111). The diet-derived DII and GI were calculated from 7-day food records while Mediterranean diet adherence from PREDIMED questionnaire. Differences between study arms were evaluated through Fisher's exact test or Mann-Whitney test and associations with multivariable regression analyses. Results: Mediterranean diet adherence significantly increased by 15% in MD and 20% in MDLGI with no difference between arms (p < 0.326). Dietary GI significantly decreased from 55.5 to 52.4 in MD and 55.1 to 47.6 in MDLGI with significant difference between arms (p < 0.001). DII significantly decreased by 28% in MD and 49% in MDLGI with no difference between arms (p < 0.360). Adjusting for energy intake (E-DII) did not change the results. Higher Mediterranean diet adherence and lower dietary GI independently contributed to DII lowering (β-coefficient -0.203, p < 0.001; 0.046, p = 0.003, respectively). Conclusions: DII and E-DII scores decreased significantly after one-year with 4 nutrition counselling sessions on the Mediterranean diet and low GI. Increased adherence to the Mediterranean diet and low GI independently contributed to the DII changes. These results are relevant given that lowering the inflammatory potential of the diet may have implications in cancer prognosis and overall survival.

Background We retrospectively evaluated safety and performance of magnetic seed localisation of nonpalpable breast lesions. Methods We reviewed records of patients with nonpalpable breast lesions preoperative localised by placing magnetic Magseed® marker between February 2019 and December 2020. During surgery, Sentimag® magnetic probe was used to localise the marker and guide surgery. Safety, lesion identification and excision with tumour with free margins and re-excision rate were assessed. Results A total of 77 Magseed® devices were placed into the breasts of 73 patients, 44 under ultrasound and 33 under stereotactic guidance (4 bilateral). All devices were retrieved as were the target lesions. Magnetic marker placement was successful in all cases without any adverse event. Intraoperative identification and excision of the localised lesion were successful in 77 of 77 of cases (100%). In three cases (all of them calcifications with the seed placed under stereotactic guidance), the seed did not reach the exact target position of the biopsy clip; thus, larger excision was needed, with localisation failure attributed to incorrect clip insertion ( n = 1) or to clip dislocation ( n = 2). Migration of the marker was negligible in all patients. Complete excision after the initial procedure with at least 1-mm disease-free margins was obtained in 74 out of 77 (96.1%) lesions. The re-excision rate was 3 out of 77 (4%). Conclusions Magnetic marker localisation for nonpalpable breast lesions was safe, reliable, and effective in terms of lesion identification, excision with tumour-free margins and re-excision rate.

Immune cell components are able to infiltrate tumor tissues, and different reports described the presence of infiltrating immune cells (TILs) in several types of solid tumors, including breast cancer. The primary immune cell component cells are reported as a lymphocyte population mainly comprising the cytotoxic (CD8+) T cells, with varying proportions of helper (CD4+) T cells and CD19+ B cells, and rarely NK cells. In clinical practice, an expert pathologist commonly detects TILs areas in hematoxylin and eosin (H&E)-stained histological slides via light microscopy. Moreover, other more in-depth approaches could be used to better define the immunological component associated with tumor tissues. Using a multiparametric flow cytometry approach, we have studied the immune cells obtained from breast tumor tissues compared to benign breast pathologies. A detailed evaluation of immune cell components was performed on 15 and 14 biopsies obtained from breast cancer and fibroadenoma subjects, respectively. The percentage of tumor-infiltrating T lymphocytes was significantly higher in breast cancer patients compared to patients with fibroadenoma. Infiltrating helper T lymphocytes were increased in the case of malignant breast lesions, while cytotoxic T lymphocytes disclosed an opposite trend. In addition, our data suggest that the synergistic effect of the presence/activation of NK cells and NKT cells, in line with the data in the literature, determines the dampening of the immune response. Moreover, the lymphocyte-to-monocyte ratio was calculated and was completely altered in patients with breast cancer. Our approach could be a potent prognostic factor to be used in diagnostic/therapeutic purposes for the improvement of breast cancer patients’ management.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

[This corrects the article DOI: 10.1371/journal.pone.0239803.].

Angiosarcoma of the breast is one of the rarest malignancies. Breast angiosarcoma can be classified into primary when arising de novo and secondary to chronic lymphoedema or breast irradiation. Molecular pathways involved in angiosarcoma development have not been described clearly, yet some gene point mutations and protein altered expression levels have been detected. So far, their management is based above all on surgery. Hence, further studies starting from the few known key points may help to develop more effective strategies based both on target therapies, together with surgery.

INTRODUCTION:Psychosocial suffering involves diverse human, social and economic costs. Some 34.4% of workers in Switzerland report chronic stress related to their jobs. Medical consultations for suffering at work aim to maintain-or renew-patients' abilities to make decisions and act following a diagnosis of psychological suffering related to their work; they also aim to help workers return to their workstations or remain there. Workplace interventions by consulting occupational physicians can go beyond the subjective issues: they can be offered to employees, in anticipation of a return to work when this appears feasible from the outset.OBJECTIVE:To qualitatively evaluate perceptions of workplace interventions and identify their effects by collecting the verbatim statements of employees and their employers.MATERIALS AND METHODS:Qualitative single-centre study of workplace interventions conducted by the Consultation Service for Suffering at Work's occupational physicians for patients seen between January 2015 to December 2017. Nineteen workplace interventions took place, out of 184 different consultations. The verbatim statements of employees and their employers will be collected over a variable timeframe, using semi-structured face-to-face interviews. These will then be recorded, transcribed and analysed. Fourteen patients refused the workplace intervention. Their professional path will be collected for comparison and exploratory purposes.CONCLUSION:This exploratory research project will provide a better understanding of the issues surrounding work-related psychological suffering and of which strategies support patients most effectively.

Here we report a case of 50-mm lump within the left breast in a 56-year-old man. The patient underwent left total mastectomy and sentinel node biopsy. The pathology report showed low-grade intracystic papillary breast carcinoma surrounded by ductal carcinoma in situ. Sentinel node biopsy was negative. The patient was prescribed five years tamoxifen.

Introduction: Life expectancy in women with breast cancer (BC) is 80% at 5 years. Age, medications, obesity, metabolic syndrome and diabetes increase cardiovascular risk. The Mediterranean diet (MeD) and low glycemic index (GI) diets, nevertheless, are protective. Therefore, we evaluated the effect of low-GI Mediterranean diet on cardiovascular risk factors in women treated for BC.

Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting.

En Suisse, la thématique des risques psychosociaux est en essor. Trente-quatre pour cent des salariés se disent stressés avec des répercussions sur leur santé. Mise en place en 2009 à l’IST, la consultation travail et souffrance vise à faire émerger les déterminants du processus de déstabilisation, dans une perspective d’élargissement des scénarios de lecture, d’optimisation des soins, d’aide à la décision et restauration de la capacité d’action. Pluridisciplinaire, collaborative, elle permet d’entrevoir la dynamique psychique du collaborateur, en particulier à travers son rapport au travail. L’objectif est de préciser ses besoins et apports. Une évaluation de sa phase pilote, un recul clinique de 5 ans a permis à la consultation de progressivement s’enrichir et s’adapter au contexte sociétal. De nouveaux indicateurs relatifs à son fonctionnement et contenu ont été progressivement inclus. La tendance évolue vers une sollicitation plus précoce de cette consultation lors des parcours de soins. Ceci en réponse aux besoins des soignants d’aborder rapidement et précisément le champ du travail pour l’intégrer dans la prise en charge globale du patient. Cette approche systémique précoce permet une orientation ciblée et optimisée des soins favorisant une dynamique vers le changement. Pour les entreprises, l’implémentation du travail comme dimension d’une approche globale et intégrée aux soins, semble également favoriser leur ouverture à la collaboration avec les médecins du travail, ressentie comme une garantie de moyens et de compétence. Les attentes concernant la consultation travail et souffrance de l’IST augmentent et devront être approfondies. L’évolution de la demande vers des interventions précoces axées sur le milieu de travail est à confirmer.

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non‐metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin‐related non‐malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32–2.87 and OR = 2.46, 95% CI 1.38–4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11–5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24–7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53–17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144–1150, 2017. © 2016 Wiley Periodicals, Inc.

INTRODUCTION:The purpose of this study was to evaluate the added value of breast magnetic resonance imaging (MRI) in preoperative diagnosis of ductal carcinoma in situ (DCIS). We reviewed our institution database of 3499 consecutive patients treated for breast cancer.PATIENTS AND METHODS:A total of 362 patients with histologically proven DCIS were selected from the institutional database. Of these, 245 (67.7%) preoperatively underwent conventional imaging (CI) (mammography/ultrasonography) (CI group), and 117 (32.3%) underwent CI and dynamic MRI (CI + MRI group). The pathology of surgical specimens served as a reference standard. The Mann-Whitney U, χ2 test, and Spearman correlation coefficient were performed.RESULTS:The CI + MRI group showed a sensitivity of 98.5% with an increase of 10.1% compared with the CI group to detect pure DCIS. Dynamic MRI identified 19.7% (n = 13) additional pure DCIS compared with CI. In the CI + MRI group, a single (1.5%) false negative was reported, whereas in the CI group, 11 (11.6%) false negatives were reported. Moreover, the CI + MRI group showed a sensitivity of 98.0% to detect DCIS + small invasive component. In this group, dynamic MRI identified 21.6% (n = 11) additional DCIS and a single (2.0%) false negative compared with the CI group, whereas in the CI group, 7 (4.7%) false negatives were reported. MRI and histopathologically measured lesion sizes, Breast Imaging Reporting and Data System MRI assessment categories, and enhancement signal intensity curve types showed a significant correlation. The MRI detection rate of DCIS increased significantly with increasing nuclear grade.CONCLUSIONS:Preoperative breast MRI showed a better accuracy then CI in preoperative diagnosis for both pure DCIS and DCIS + small invasive component with a precise assessment of lesion size. This can provide a more appropriate management of DCIS patients.

1 Unit of Epidemiology, National Cancer Institute, G. Pascale Foundation, Via Mariano Semmola, 1 – 80131 Naples, Italy; 2 Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Queen St. East, 61 – M5c 2T2 Toronto, Canada; 3 Department of Diagnostic Pathology and Laboratory, National Cancer Institute, G. Pascale Foundation, Via Mariano Semmola, 1 – 80131 Naples, Italy; 4 Department of Breast Surgery, National Cancer Institute G. Pascale Foundation, Via Mariano Semmola, 1 – 80131 Naples, Italy; 5 Department of Surgery, National Cancer Institute G. Pascale Foundation, Via Mariano Semmola, 1 – 80131 Naples, Italy; 6 Section of Clinical & General Pathology & Oncology, Department of Biomedical & Biotechnological Sciences, University of Catania, Via Androne, 83 – 95124 Catania, Italy; 7 Scientific Direction, National Cancer Institute, G. Pascale Foundation, Via Mariano Semmola, 1 – 80131 Naples, Italy; 8 Department of Clinical Medicine and Surgery, Federico II University, Via Sergio Pansini, 5 – 80131 Naples, Italy.