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Trento, Italy

Veit-Rubin N.,Unit of Senology | Rapiti E.,University of Geneva | Usel M.,University of Geneva | Benhamou S.,University of Geneva | And 5 more authors.
Oncologist | Year: 2012

Purpose. To assess breast cancer (BC) risk after Hodgkin's lymphoma (HL) and compare characteristics, risk of second BC, and prognosis of patients with these BCs with patients with first primary BC. Patients and Methods. We considered all 9,620 women with HL recorded in the Surveillance, Epidemiology and End Results dataset in 1973-2007. We calculated age-period standardized incidence ratios of BC. We compared patient, tumor, and treatment characteristics, risk of second BC, and prognosis between patients with BC after HL (n=316) and patients with other BCs occurring during the same period (n = 450,413) using logistic regression and Cox models adjusted for confounders. Results. HLpatients had a 2.4-fold higher risk for developing BC (95% confidence interval [CI], 2.2-2.7) than the general population. Age at HL diagnosis and radiation therapy influenced this risk. Compared with first primary BCs, BCs afterHLwere diagnosed at a younger age, at an earlier stage, were less frequently hormone receptor positive, were located more frequently in external quadrants, and were less frequently treated using radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85; 95% CI, 1.79- 4.53) for developing a second BC and had a higher BC mortality risk (adjusted HR, 1.36;95%CI, 1.05-1.76). The higher mortality risk was only partly explained by the higher occurrence rate of a second BC. Conclusion. HL survivors have a higher risk for developing BC, their BCs are more aggressive, they have a higher risk for a second BC occurrence, and they have a poorer prognosis. Guidelines of care should be adapted to decrease the impact of BC in these high-risk patients. © AlphaMed Press. Source

Villarini A.,Fondazione Istituto Nazionale Dei Tumori | Pasanisi P.,Fondazione Istituto Nazionale Dei Tumori | Traina A.,A.R.N.A.S Ospedali Civico e Benfratelli G. di Cristina e M. Ascoli | Mano M.P.,Centro Of Riferimento Per Lepidemiologia E La Prevenzione Oncologica In Piemonte Cpo | And 18 more authors.
Tumori | Year: 2012

Aims and background. The DIANA (Diet and Androgens)-5 study is a multi-institutional randomized controlled trial of the effectiveness of a diet based on Mediterranean and macrobiotic recipes and principles, associated with moderate physical activity, in reducing additional breast cancer events in women with early stage invasive breast cancer at high risk of recurrence because of metabolic or endocrine milieu. The intervention is expected to reduce serum insulin and sex hormones, which were associated with breast prognosis in previous studies. Methods. Between 2008 and 2010, the study randomly assigned 1208 patients to an intensive diet and exercise intervention or to a comparison group, to be followed-up through 2015. General lifestyle recommendations for the prevention of cancer are given to both groups, and the intervention group is being offered a comprehensive lifestyle intervention, including cooking classes, conferences, common meals and exercise sessions. Adherence assessments occurred at baseline and at 12 months and are planned at 36 and 60 months. They include food frequency diaries, anthropometric measures, body fat distribution assessed with impedance scale, one week registration of physical activity with a multisensor arm-band monitor, metabolic and endocrine blood parameters. Outcome breast cancer events are assessed through self report at semi annual meetings or telephone interview and are validated through medical record verification. Results. The randomized groups were comparable for age (51.8 years), proportion of ER-negative tumors (22%), axillary node metastasis (42%), reproductive variables, tobacco smoking, blood pressure, anthropometric measurements and hormonal and metabolic parameters. Conclusions. DIANA-5 has the potential to establish whether a Mediterranean-macrobiotic lifestyle may reduce breast cancer recurrences. We will assess evidence of effectiveness, first by comparing the incidence of additional breast cancer events (local or distant recurrence, second ipsilateral or contralateral cancer) in the intervention and in the control group, by an intention-to-treat analysis, and second by analyzing the incidence of breast cancer events in the total study population by compliance assessment score. © Il Pensiero Scientifico Editore. Source

Mello-Grand M.,Cancer Genomics Laboratory | Singh V.,Cancer Genomics Laboratory | Ghimenti C.,Cancer Genomics Laboratory | Scatolini M.,Cancer Genomics Laboratory | And 11 more authors.
Breast Cancer Research and Treatment | Year: 2010

Aromatase inhibition (AI) is the most effective endocrine treatment for breast cancer in post-menopausal patients, but a percentage of hormone receptor-positive cancers do not benefit from such therapy: for example, about 20% of patients treated with anastrozole do not respond and it is still impossible to accurately predict sensitivity. Our main goal was to identify a robust expression signature predictive of response to neoadjuvant treatment with anastrozole in patients with ER+ breast cancer. At the same time, we addressed the question of delineating treatment effects and possible mechanisms of intrinsic resistance occurring in non-responder patients. We analyzed the transcriptome of 17 tru-cut biopsies before treatment and 13 matched surgical samples after 3 months treatment with anastrozole taken from ER+ breast tumors. Molecular profiles were related to clinical response data. Treatment with anastrozole was associated with a decreased expression of genes relating to cell proliferation and an increased expression of genes relating to inflammatory processes. There was also an enrichment of induction of T-cell anergy, positive regulation of androgen signalling, synaptic transmission and vesicle trafficking in non-responders, and of cell cycle inhibition and induction of immune response in responders. We identified an expression signature of 77 probes (54 genes) that predicted response in 100% of our cases. Five of them were able to accurately predict response on an independent dataset (P = 0.0056) of 52 ER+ breast cancers treated with letrozole. Ten fixed independent samples from the anastrozole study were also used for RT-qPCR validations. This study suggests that a relative small number of genes analysed in a pre-treatment biopsy may identify patients likely to respond to AI neoadjuvant treatment. This may have practical utility translatable to the clinics. Furthermore, it delineates novel mechanisms of intrinsic resistance to AI therapy that could be further investigated in order to explore circumventing treatments. © Springer Science+Business Media, LLC. 2010. Source

Giuliani S.,Unit of Surgical Pathology | Ciniselli C.M.,Unit of Medical Statistics | Leonardi E.,Unit of Surgical Pathology | Polla E.,Unit of Surgical Pathology | And 12 more authors.
Virchows Archiv | Year: 2016

Human epithelial growth factor receptor 2 (HER2) overexpression and/or amplification is of predictive and prognostic value in infiltrating breast carcinoma (IBC). We evaluated the proportion of HER2-positive cases (score 3 overexpression/score 2 plus fluorescence in situ hybridization (FISH) amplification) in a consecutive series of 2163 patients. According to immunohistochemical analysis of HER2 expression, using Herceptest and FDA criteria, 839 cases had score 0, 476 score 1+, 699 score 2+, and 149 score 3+. Of the 699 scoring 2+ cases, 160 (22.88 %) showed Her2 gene amplification by FISH analysis, making a total of 309 (14.28 %) HER2-positive cases. Grade 1 ductal and special type IBC were never HER2 positive, while only three infiltrating lobular carcinomas but a relevant percentage of small IBC were HER2 positive. Of HER2-positive cases, 52.1 % was pT1 and of these, 38.5 % was pT1b or smaller. Logistic regression analysis revealed that estrogen receptor (ER), progesterone receptor (PgR), grade, and pT were significantly associated with HER2 positivity and that HER2 3+ cases were more frequently of higher grade and pT than HER2 2+/Her2 amplified cases. In addition, HER2 3+ cases were more frequently in ER and PgR negative than HER2 2+/Her2 amplified cases. We conclude that the proportion of HER2 positive cases is lower than that reported in older literature and that pathological characteristics differ between HER2 3+ and HER2 2+/Her2 amplified cases. © 2016 Springer-Verlag Berlin Heidelberg Source

Giuliani S.,Laboratory of Molecular Pathology | Leonardi E.,Laboratory of Molecular Pathology | Aldovini D.,Laboratory of Molecular Pathology | Bernardi D.,Unit of Senology | And 6 more authors.
Pathologica | Year: 2012

Objective. Triple negative breast carcinomas (TNT) are infiltrating breast carcinomas (BC) with negative oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER-2) expression, and are associated with frequent BRCA1/BRCA2 mutations. The aim of the present study is to analyze the frequency and distribution of TNT in our population where a breast cancer screening program for women aged between 50 and 69 years is effective since 2001 with 85% accrual. Methods. We investigated the records of 2112 consecutive BC and 153 interval BC (i.e. BC detected in the screened negative women in the interval between screening rounds). Tumours with complete negative expression of ER, PgR and Her2 were considered TNT; tumours with negative ER and PgR status and faint Her2 expression (score 1) were considered as possible TNT (pTNT). Results. We identified 82 (3.8%) TNT and 20 (0.9%) pTNT in the series of 2112 consecutive BC and 7 TNT and 1 pTNT (5.2%) in the series of 153 interval BC. In the consecutive series, TNT/pTNT were observed in 6.5% patients below 50 years and in 4.3% of patients above 50 years. A high proliferation rate (Ki-67 labelling > 36%) was observed in 87.8% of TNT (median labelling 56.3%) and in 60% of pTNT (median labelling 48.4%). Conclusions. Since TNT/pTNT occurring in women < 50 years is a criterion for selecting patients whom genetic counselling and BRCA1 testing should be offered, our study is of help in foreseeing the workload of the Unit of Medical Genetics and the Laboratory of Molecular Pathology. Source

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