Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Massimiliano Cazzaniga is active.

Publication


Featured researches published by Massimiliano Cazzaniga.


Cancer Prevention Research | 2010

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

Andrea Decensi; Matteo Puntoni; Pamela J. Goodwin; Massimiliano Cazzaniga; Alessandra Gennari; Bernardo Bonanni; Sara Gandini

Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched. Cancer Prev Res; 3(11); 1451–61. ©2010 AACR.


Journal of Clinical Oncology | 2012

Dual Effect of Metformin on Breast Cancer Proliferation in a Randomized Presurgical Trial

Bernardo Bonanni; Matteo Puntoni; Massimiliano Cazzaniga; Giancarlo Pruneri; Davide Serrano; Aliana Guerrieri-Gonzaga; Alessandra Gennari; Maria Stella Trabacca; Viviana Galimberti; Paolo Veronesi; Harriet Johansson; Valentina Aristarco; Fabio Bassi; Alberto Luini; Matteo Lazzeroni; Clara Varricchio; Giuseppe Viale; Paolo Bruzzi; Andrea Decensi

PURPOSE Metformin is associated with reduced breast cancer risk in observational studies in patients with diabetes, but clinical evidence for antitumor activity is unclear. The change in Ki-67 between pretreatment biopsy and post-treatment surgical specimen has prognostic value and may predict antitumor activity in breast cancer. PATIENTS AND METHODS After tumor biopsy, we randomly allocated 200 nondiabetic women with operable breast cancer to either metformin 850 mg/twice per day (n = 100) or placebo (n = 100). The primary outcome measure was the difference between arms in Ki-67 after 4 weeks adjusted for baseline values. RESULTS Overall, the metformin effect on Ki-67 change relative to placebo was not statistically significant, with a mean proportional increase of 4.0% (95% CI, -5.6% to 14.4%) 4 weeks apart. However, there was a different drug effect depending on insulin resistance (homeostasis model assessment [HOMA] index > 2.8, fasting glucose [mmol/L] × insulin [mU/L]/22.5; P(interaction) = .045), with a nonsignificant mean proportional decrease in Ki-67 of 10.5% (95% CI, -26.1% to 8.4%) in women with HOMA more than 2.8 and a nonsignificant increase of 11.1% (95% CI, -0.6% to 24.2%) with HOMA less than or equal to 2.8. A different effect of metformin according to HOMA index was noted also in luminal B tumors (P(interaction) = .05). Similar trends to drug effect modifications were observed according to body mass index (P = .143), waist/hip girth-ratio (P = .058), moderate alcohol consumption (P = .005), and C-reactive protein (P = .080). CONCLUSION Metformin before surgery did not significantly affect Ki-67 overall, but showed significantly different effects according to insulin resistance, particularly in luminal B tumors. Our findings warrant further studies of metformin in breast cancer with careful consideration to the metabolic characteristics of the study population.


Circulation | 2002

Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women

Andrea Decensi; Umberto Omodei; Chris Robertson; Bernardo Bonanni; Aliana Guerrieri-Gonzaga; Francesca Ramazzotto; Harriet Johansson; Serena Mora; Maria Teresa Sandri; Massimiliano Cazzaniga; Massimo Franchi; Sergio Pecorelli

Background—The increase in C-reactive protein (CRP) during oral conjugated equine estrogen (CEE) may explain the initial excess of cardiovascular disease observed in clinical studies. Because the effect of transdermal estradiol (E2) on CRP is unclear, we compared CRP changes after 6 and 12 months of transdermal E2 and oral CEE in a randomized 2×2 retinoid-placebo trial. Methods and Results—A total of 189 postmenopausal women were randomized to 50 &mgr;g/d transdermal E2 and 100 mg BID of the retinoid fenretinide (n=45), 50 &mgr;g/d transdermal E2 and placebo (n=49), 0.625 mg/d oral CEE and 100 mg BID fenretinide (n=46), or 0.625 mg/d oral CEE and placebo (n=49) for 1 year. Sequential medroxyprogesterone acetate was added in each group. Relative to baseline, CRP increased by 10% (95% CI −9% to 33%) and by 48% (95% CI 22% to 78%) after 6 months of transdermal E2 and oral CEE, respectively. The corresponding figures at 12 months were 3% (95% CI −14% to 23%) for transdermal E2 and 64% (95% CI 38% to 96%) for oral CEE. Fenretinide did not change CRP levels at 6 and 12 months relative to placebo. Relative to oral CEE, the mean change in CRP after 12 months of transdermal E2 was −48% (95% CI −85% to −7%, P =0.012), whereas fenretinide was associated with a mean change of −1% (95% CI −34% to 40%, P =0.79) compared with placebo. Conclusions—In contrast to oral CEE, transdermal E2 does not elevate CRP levels up to 12 months of treatment. The implications for early risk of coronary heart disease require further studies.


Cancer Epidemiology, Biomarkers & Prevention | 2009

Is it Time to Test Metformin in Breast Cancer Clinical Trials

Massimiliano Cazzaniga; Bernardo Bonanni; Aliana Guerrieri-Gonzaga; Andrea Decensi

Several studies have identified an increased risk of cancer in type 2 diabetic patients and this is in accordance with the hypothesis that increased insulin levels might promote cancer. Thus, there is a great interest in exploring the possibility that antidiabetic therapies lowering insulin levels could decrease cancer incidence or cancer-related mortality. Recent observational studies have shown that metformin, an oral safe and well-tolerated insulin-sensitizer antidiabetic drug, has been associated with reduced cancer risk. Recently, several preclinical studies have evaluated the effect of metformin in vivo on nude mice and showed a significant reduction of both breast epithelial cell proliferation and protein synthesis. Further investigations in the clinical setting are well-supported by the promising results obtained thus far. At the European Institute of Oncology, the Division of Cancer Prevention and Genetics is planning to conduct a clinical trial to evaluate the activity of metformin on tumor cell proliferation in breast cancer patients undergoing surgery. It will be a presurgical randomized, double blind, placebo-controlled phase II biomarker trial: 100 histologically confirmed breast cancer patients will be randomly assigned to metformin (850 mg twice/daily) or placebo for 28 + 7 days till surgery to assess drug activity on tumor proliferation, as measured by Ki-67. The confirmation of the efficacy of metformin on cancer cell proliferation may lead the way to larger chemoprevention clinical trials. (Cancer Epidemiol Biomarkers Prev 2009;18(3):701–5)


Journal of Clinical Oncology | 2008

Randomized double-blind 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in high-risk premenopausal women.

Andrea Decensi; Chris Robertson; Aliana Guerrieri-Gonzaga; Davide Serrano; Massimiliano Cazzaniga; Serena Mora; Marcella Gulisano; Harriet Johansson; Viviana Galimberti; Enrico Cassano; Simona Moroni; Franca Formelli; Ernst A. Lien; Giuseppe Pelosi; Bernardo Bonanni

PURPOSE Tamoxifen and fenretinide are active in reducing premenopausal breast cancer risk and work synergistically in preclinical models. The authors assessed their combination in a two-by-two biomarker trial. PATIENTS AND METHODS A total of 235 premenopausal women with pT1mic/pT1a breast cancer (n = 21), or intraepithelial neoplasia (IEN, n = 160), or 5-year Gail risk > or = 1.3% (n = 54) were randomly allocated to either tamoxifen 5 mg/d, fenretinide 200 mg/d, their combination, or placebo. We report data for plasma insulin-like growth factor I (IGF-I), mammographic density, uterine effects, and breast neoplastic events after 5.5 years. RESULTS During the 2-year intervention, tamoxifen significantly lowered IGF-I and mammographic density by 12% and 20%, respectively, fenretinide by 4% and 10% (not significantly), their combination by 20% and 22%, with no evidence for a synergistic interaction. Tamoxifen increased endometrial thickness principally in women becoming postmenopausal, whereas fenretinide decreased endometrial thickness significantly. The annual rate of breast neoplasms (n = 48) was 3.5% +/- 1.0%, 2.1% +/- 0.8%, 4.7% +/- 1.3%, and 5.2% +/- 1.3% in the tamoxifen, fenretinide, combination, and placebo arms, respectively, with hazard ratios (HRs) of 0.70 (95% CI, 0.32 to 1.52), 0.38 (95% CI, 0.15 to 0.90), and 0.96 (95% CI, 0.46 to 1.99) relative to placebo (tamoxifen x fenretinide adverse interaction P = .03). There was no clear association with tumor receptor type. Baseline IGF-I and mammographic density did not predict breast neoplastic events, nor did change in mammographic density. CONCLUSION Despite favorable effects on plasma IGF-I levels and mammographic density, the combination of low-dose tamoxifen plus fenretinide did not reduce breast neoplastic events compared to placebo, whereas both single agents, particularly fenretinide, showed numerical reduction in annual odds of breast neoplasms. Further follow-up is indicated.


Annals of Oncology | 2011

Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer

Andrea Decensi; Aliana Guerrieri-Gonzaga; Sara Gandini; Davide Serrano; Massimiliano Cazzaniga; Serena Mora; Harriet Johansson; Ernst A. Lien; Giancarlo Pruneri; Giuseppe Viale; Bernardo Bonanni

BACKGROUND Studies have shown that Ki-67 response after short-term neoadjuvant aromatase inhibitors may predict recurrence in postmenopausal breast cancer, whereas its prognostic effect in premenopausal women is unknown. PATIENTS AND METHODS We compared the prognostic and predictive value of baseline and post-treatment Ki-67 in 120 pre- and postmenopausal women with early-stage estrogen receptor-positive breast cancer who participated in a 4-week presurgical trial of tamoxifen. RESULTS After 7.2 years of follow-up, women with post-treatment Ki-67 in the second (14%-19%), third (20%-29%) and top (≥30%) quartiles had a recurrence hazard ratio of 2.92 [95% confidence interval (CI) 0.95-8.96], 4.37 (1.56-12.25) and 6.05 (2.07-17.65), respectively, as compared with those in the bottom quartile (<14%) (P-trend = 0.001). The risk of invasive disease recurrence was 2.2% (95% CI 0.9-5.0) per point increase in baseline Ki-67 (P-trend = 0.076) and 5.0% (95% CI 2.3-7.7) per point increase in post-tamoxifen Ki-67 (P-trend < 0.001). The risk of death was 5.5 (95% CI 1.26-23.16) times higher in patients with post-drug Ki-67 ≥20% than in those with Ki-67 <20% (P-trend = 0.006). CONCLUSIONS Ki-67 response after short-term neoadjuvant tamoxifen is a good predictor of recurrence-free survival and overall survival, further supporting its use as surrogate biomarker to personalize adjuvant treatment and to screen novel drugs cost-effectively.


Journal of Clinical Oncology | 2007

Randomized Dose-Ranging Trial of Tamoxifen at Low Doses in Hormone Replacement Therapy Users

Andrea Decensi; Sara Gandini; Davide Serrano; Massimiliano Cazzaniga; Maria Pizzamiglio; Fausto Maffini; Giuseppe Pelosi; Cristina Daldoss; Umberto Omodei; Harriet Johansson; Debora Macis; Matteo Lazzeroni; Mauro Penotti; Laura Sironi; Simona Moroni; Vanda Bianco; Gabriella Rondanina; Jennifer Gjerde; Aliana Guerrieri-Gonzaga; Bernardo Bonanni

PURPOSE The combination of hormone replacement therapy (HRT) and low-dose tamoxifen may retain the benefits while reducing the risks of either agent. We assessed the optimal biologic dose and schedule of tamoxifen in HRT users using surrogate end point biomarkers and menopausal symptoms. SUBJECTS AND METHODS Two hundred ten current or de novo HRT users were randomly assigned to one of the following four arms: tamoxifen 1 mg/day and placebo/week, placebo/day and tamoxifen 10 mg/week, tamoxifen 5 mg/day and placebo/week, or both placebos for 12 months. The primary end point was the change of plasma insulinlike growth factor 1 (IGF-I) through 12 months, and secondary end points were IGF-I/IGF binding protein-3 (IGFBP-3) ratio, fibrinogen, antithrombin III, C reactive protein, C-telopeptide, mammographic percent density, and endometrial thickness. Endometrial proliferation was assessed by Pipelle biopsy in superficial, deep glandular, and stromal compartments after 12 months. RESULTS Compared with placebo, IGF-I declined in all tamoxifen arms (P = .005), with a greater change on 5 mg/day (P = .019 v 10 mg/week or 1 mg/day). Tamoxifen increased IGFBP-3 and lowered antithrombin-III, C reactive protein, and mammographic density, with greater effects of 5 mg/day. Tamoxifen increased endometrial thickness but not Ki-67 expression, which was lower on 5 mg/day among the three doses. Menopausal symptoms were not significantly worsened by tamoxifen. CONCLUSION Doses of tamoxifen < or = 5 mg/day modulate favorably biomarkers of breast carcinogenesis and cardiovascular risk in HRT users with no increase of endometrial proliferation and menopausal symptoms. A dose of 5 mg/day was the most effective and has been selected for a phase III trial in HRT users.


BioMed Research International | 2012

Breast Cancer Chemoprevention: Old and New Approaches

Massimiliano Cazzaniga; Bernardo Bonanni

In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.


Journal of Clinical Oncology | 2006

Preliminary results on safety and activity of a randomized, double-blind, 2 x 2 trial of low-dose tamoxifen and fenretinide for breast cancer prevention in premenopausal women

Aliana Guerrieri-Gonzaga; Chris Robertson; Bernardo Bonanni; Davide Serrano; Massimiliano Cazzaniga; Serena Mora; Marcella Gulisano; Harriet Johansson; Franca Formelli; Mattia Intra; Antuono Latronico; D. Franchi; Giuseppe Pelosi; Andrea Decensi

PURPOSE To determine whether low-dose tamoxifen and fenretinide have a synergistic effect on surrogate biomarkers, including circulating insulin-like growth factor I (IGF-I) and mammographic density, in premenopausal women at risk for breast cancer and to study drug safety. PATIENTS AND METHODS Premenopausal women (n = 235) were randomly assigned in a double-blind four-arm trial to receive tamoxifen 5 mg/d, fenretinide 200 mg/d, both agents, or placebo for 2 years. The present analysis refers to preliminary data on safety, IGF-I, and breast cancer events. RESULTS Patients were included if they had an excised ductal carcinoma-in-situ (57%), lobular carcinoma-in-situ (13%), minimal invasive breast cancer (7%), or a 5-year Gail risk > or = 1.3% (23%). After a median follow-up of 40 months, there was a reduction of 13%, 2%, 20%, and 1% in IGF-I levels for patients on tamoxifen, fenretinide, tamoxifen plus fenretinide, and placebo, respectively. Recruitment was stopped based on the lack of an interaction on IGF-I levels, which was a primary end point for the study. Thirty-six patients have dropped out of the study, 17 because of adverse events and 19 for various other reasons. One stage I endometrial cancer occurred in a patient on fenretinide, and one optic nerve ischemia and one deep venous thrombosis occurred on tamoxifen. There was no difference in menopausal symptoms, endometrial thickness, polyps, or ovarian cysts among treatment arms. To date, 24 breast cancers have been observed, without differences among arms. CONCLUSION The combination of low-dose tamoxifen and fenretinide is safe but not synergistic in lowering IGF-I levels in premenopausal women. The clinical implications require further follow-up.


Cancer | 2002

Ductal lavage and the clinical management of women at high risk for breast carcinoma: A commentary

Joyce A. O'Shaughnessy; Britt Marie Ljung; William C. Dooley; Jenny Chang; Henry M. Kuerer; David T. Hung; Michael D. Grant; Seema A. Khan; Rogsbert F. Phillips; Karen Duvall; David M. Euhus; Bonnie L. King; Benjamin O. Anderson; Susan L. Troyan; Julian Kim; Umberto Veronesi; Massimiliano Cazzaniga

Received June 28, 2001; revision received September 24, 2001; accepted October 1, 2001. Breast carcinoma arises in the epithelial cells lining the milk ducts and lobules that comprise the ductal system of the breast. Ductal lavage is a minimally invasive office procedure performed on women who are considered to be at high risk for breast carcinoma to collect breast ductal epithelial cells for cytologic analysis to provide further risk stratification. The procedure involves the insertion of a microcatheter approximately 1.5 cm into a nipple orifice after topical anesthesia; lavaging the cannulated ductal system with normal saline; and analyzing the collected lavage effluent for the presence of normal, atypical, or malignant breast ductal cells. The purpose of this commentary is to review the data supporting breast ductal cytology as a tool to provide high-risk women with individualized information regarding their risk of developing breast carcinoma, and to provide a discussion of clinical management options based on the results of ductal lavage cytology.

Collaboration


Dive into the Massimiliano Cazzaniga's collaboration.

Top Co-Authors

Avatar

Bernardo Bonanni

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Andrea Decensi

Queen Mary University of London

View shared research outputs
Top Co-Authors

Avatar

Davide Serrano

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar

Matteo Lazzeroni

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar

Harriet Johansson

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar

Serena Mora

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar

Sara Gandini

European Institute of Oncology

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Debora Macis

European Institute of Oncology

View shared research outputs
Researchain Logo
Decentralizing Knowledge