Fabio Falcini’s research while affiliated with Local Health Authority of Ravenna and other places

Tamoxifen 5 mg/d (Babytam) decreases the incidence of new breast cancer events by 42% in women with breast intraepithelial neoplasia with limited toxicity, providing a new treatment option in these disorders. However, predictive biomarkers of Babytam efficacy are lacking. We studied whether baseline IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), estradiol, sex hormone-binding globulin (SHBG), and their ratios predict Babytam efficacy on breast cancer events in a pre-planned secondary analysis.Within a 1:1 placebo-controlled, randomized trial of Babytam or placebo given for 3 years after surgery in women with ADH or LCIS or DCIS, 406/500 participants consented to blood sampling at baseline, at 1 and 3 years. Serum IGF-I, IGFBP-3, estradiol, SHBG levels and their ratios were measured by chemiluminescent immune assays. Biomarker changes were estimated using mixed-effects models, and Incidence Rate Ratios (IRR) were calculated after 10 years of follow-up with Poisson regression. Subgroup analyses were performed using an interaction test and subpopulation treatment effect pattern plot.Baseline levels of IGFBP-3 in the three top quartiles (≥3.44 ug/mL), but not in the lower quartile, predicted greater Babytam efficacy compared to placebo (p-interaction=0.006, Table 1). Baseline IGF-I, estradiol, or SHBG were not predictive of Babytam efficacy, whereas the IGF-I/IGFBP-3 ratio was borderline significant (p-interaction=0.067).High baseline levels of IGFBP-3 (≥3.44 ug/mL) predicted Babytam efficacy and may help differentiate which women benefit most from this treatment. Table 1. Mean event rate (x1000 person-years) by treatment arm and baseline IGF-I, IGFBP-3, E2, SHBG, and IGF-I/IGFBP-3 and E2/SHBG ratio at 10 year follow-up. 10y follow-up BabyTam Placebo IRR (95% CI) IGF-I†, ng/mL ≤median (127.3) 11.8 (6.3-21.9) 20.9 (13.2-33.2) 0.49 (0.22-1.11) >median 11.0 (5.9-20.5) 21.5 (13.5-34.0) 0.52 (0.23-1.15) IRR (95% CI) 0.90 (0.35-2.31) 1.09 (0.53-2.22) Pinteraction=0.967 IGFBP-3†, ug/mL Q1 (≤3.43) 10.6 (4.0-28.3) 8.8 (3.3-23.4) 1.24 (0.33-4.66) Q2 (3.44 to 4.21) 21.4 (11.5-39.8) 25.5 (13.3-49.0) 0.75 (0.30-1.85) Q3 (4.22 to 4.91) 11.6 (4.8-27.8) 20.6 (10.3-41.3) 0.59 (0.18-1.98) Q4 (≥4.92) 2.2 (0.3-15.9) 30.7 (18.2-51.8) 0.07 (0.01-0.52)** IRR (95% CI) 0.71 (0.50-1.01) 1.36 (1.02-1.82)* Pinteraction=0.006 IGF-I/IGFBP-3† ≤median (0.167) 7.7 (3.7-16.2) 26.3 (17.2-40.4) 0.29 (0.13-0.69)** >median 15.9 (9.2-27.4) 16.4 (9.7-27.7) 0.89 (0.41-1.94) IRR (95% CI) 1.72 (0.67-4.40) 0.60 (0.30-1.20) Pinteraction=0.067 E2†, pg/mL ≤median (15.8) 7.9 (3.7-16.5) 21.1 (13.3-33.5) 0.38 (0.16-0.91)* >median 15.0 (8.7-25.8) 21.3 (13.4-33.8) 0.62 (0.29-1.34) IRR (95% CI) 1.47 (0.54-3.96) 0.90 (0.39-2.11) Pinteraction=0.390 SHBG†, nMol/L ≤median (60.2) 13.2 (7.3-23.8) 25.2 (16.4-36.8) 0.50 (0.24-1.05) >median 9.7 (5.1-18.7) 17.3 (10.5-28.8) 0.54 (0.23-1.30) IRR (95%CI) 0.67 (0.24-1.90) 0.77 (0.32-1.85) Pinteraction=0.801 E2/SHBG† ≤median (1.37) 9.4 (4.7-18.9) 19.3 (12.0-31.1) 0.49 (0.21-1.16) >median 13.2 (7.5-23.2) 23.2 (14.8-36.4) 0.52 (0.24-1.10) IRR (95% CI) 0.91 (0.33-2.50) 1.09 (0.51-2.35) Pinteraction=0.977 Citation Format Harriet Johansson, Debora Macis, Martino Oliva, Matteo Puntoni, Eva Blondeaux, Aliana Guerrieri-Gonzaga, Valentina Aristarco, Irene Maria Briata, Tania Buttiron-Webber, Alessio Carbone, Luca Boni, Matteo Lazzeroni, Davide Serrano, Livia Giordano, Maria Digennaro, Laura Cortesi, Francesco Millo, Katia Cagossi, Giuseppe Aprile, Fabio Falcini, Elisa Gallerani, Bernardo Bonanni, Andrea De Censi. Predictive effect of IGFBP-3 on low-dose tamoxifen efficacy in non-invasive breast cancer in the phase III Tam-01 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2328.

Introduction We report a population-based, competing risk-adjusted analysis of the risk and timing of true recurrences and second primaries in women with breast cancer (BC), that are still ill-defined. Methods We performed a manual review of medical charts of 1988 BC patients from a cancer registry in northern Italy (2000–2013). The occurrence and timing of true recurrences (TRs, including local, regional and distant recurrences) and second BCs (SBCs, including ipsilateral and contralateral SBC) during 10 years of follow-up were evaluated. The prognostic factors for TRs and SBCs were identified using the Fine and Gray model. Results The cumulative incidence was 13.7 % (95 % confidence interval (CI), 12.2–15.3 %) for TRs and 4.6 % (95 % CI, 3.7–5.7 %) for SBCs. The median time to detection varied between 3.4 (TRs) and 5.1 (SBCs) years. The risk of TRs had two peaks, one between the 2nd and the 3rd year of follow-up and another between the 7th and the 8th year. The subhazard of SBCs fluctuated for five years, had a drop between the 6th and the 7th year and a marked peak between the 8th and the 9th year. Prognostic factors for TRs (tumour stage and grade, lymph node status and residual disease) and SBCs (patient age and –inverse association– hormone therapy) were different. In the 9th-10th year of follow-up, the excess incidence of total BC episodes as compared with the expected incidence of BC was no longer significant (standardised incidence ratio, 1.15; 95 % CI, 0.86–1.53). Conclusions The multifaceted results of this study warrant further research into the risk and timing of all types of BC recurrence.

Purpose To present the prevalence screening results of the RIsk-Based Breast Screening (RIBBS) study (ClinicalTrials.gov NCT05675085), a quasi-experimental population-based study evaluating a personalized screening model for women aged 45–49. This model uses digital breast tomosynthesis (DBT) and stratifies participants by risk and breast density, incorporating tailored screening intervals with or without supplemental imaging (ultrasound, US, and breast MRI), with the goal of reducing advanced breast cancer (BC) incidence compared to annual digital mammography (DM). Materials and methods An interventional cohort of 10,269 women aged 45 was enrolled (January 2020–December 2021. Participants underwent DBT and completed a BC risk questionnaire. Volumetric breast density and lifetime risk were used to assign five subgroups to tailored screening regimens: low-risk low-density (LR–LD), low-risk high-density (LR–HD), intermediate-risk low-density (IR–LD), intermediate-risk high-density (IR–HD), and high-risk (HR). Screening performance was compared with an observational control cohort of 43,838 women undergoing annual DM. Results Compared to LR–LD, intermediate-risk groups showed a 4.9- (IR–LD) and 4.6-fold (IR–HD) higher prevalence of BC, driven by a 7.1- and 7.1-fold higher prevalence of pT1c tumors. The interventional cohort had lower recall rate (rate ratio, 0.5), higher surgery rate (1.9) and increased prevalence of DCIS (2.9), pT1c (2.3) and grade 3 tumors (2.4), compared to controls. Conclusion The prevalence screening demonstrated the feasibility of using DBT and —in high-density subgroups— supplemental US. The stratification criteria effectively identified subpopulations with different BC prevalence. Increasing the detection rate of pT1c tumors is not sufficient but necessary to achieve a reduction in advanced BC incidence.

Objective The epidemiologic scenario of prostate cancer (PC) is changing rapidly. The present study updates to 2024 the estimates of PC in Italy, including incident and prevalent cases, deaths, and metastatic PC (mPC), which is further subdivided into de novo mPC (metastasis detected at diagnosis) and recurrent mPC (metachronous metastasis). Methods The study was based on updated data from the Italian Network of Cancer Registries and the National Institute of Statistics and the age-specific short-term PC projections made available by the International Agency for Cancer Research. For mPC, we applied the age-specific ratios between deaths and estimated de novo and recurrent mPCs for the USA to the Italian age-specific deaths. Results In Italy, in 2024, we expect 8400 PC deaths, approximately 39 000 new diagnoses, 4900 of whom are diagnoses of mPC, and almost 670 000 prevalent cases, about 36 000 of whom are mPCs. Conclusion These estimates provide updated and realistic information to policy makers, clinicians, and the community to properly address the needs of patients with PC in Italy from diagnosis to end-of-life care.

BaCKgrouND: the epidemiology of skin melanoma (Sm) is rapidly changing. therefore, we aimed at updating up to 2024 the Italian estimates on Sm providing the number of incident and prevalent cases, the deaths and the distribution by stage at diagnosis. METHODS: Incidence was extrapolated from age- and sex-specific International Agency for Research on Cancer (IARC) estimates from 2022 to 2025. For mortality, we applied to the most recent observed deaths, the average sex- and age-specific annual percent change estimated by the IARC from 2022 to 2025. Regarding SM prevalence, we assumed the age- and sex-specific annual change in the number of prevalent cases observed from 2010 to 2020 to be stable until 2024. finally, we applied the average distribution by tNm-8 stages of four population-based Sm series to provide a possible stage distribution at diagnosis. reSultS: We estimated almost 13,800 newly diagnosed Sms (54% men and 82% people older than 44 years), 2240 deaths (60% men and 49% people older than 74 years) and about 216,000 prevalent cases (51% women). at diagnosis, around 10,240 cases are expected to be stage I, 2120 stage II, 1100 stage III and 327 stage IV. as regards stage I 79% will be Ia. among stage II we expect 44% IIa, 33% IIB and 22% IIC. among stage III, 49% case are expected to be IIIC. CoNCluSIoNS: these estimates allow clinicians and policymakers to quantify and properly address the burden of Sm patients’ diagnostic, therapeutic and supportive needs.

Importance Studies on the epidemiology of retinoblastoma (RB) could lead to improvement in management. Objective To estimate the incidence and survival of RB in European children and the occurrence of second primary tumors (other than RB) in these patients. Design, Setting, and Participants This cohort study used population-based data from 81 cancer registries in 31 European countries adhering to the European Cancer Registries (EUROCARE-6) project. Data collection took place between January 2000 and December 2013. European children aged 0 to 14 years diagnosed with RB were included. Data were analyzed from May to November 2023. Exposures Diagnosis of RB with International Classification of Diseases for Oncology , Third Edition ( ICD-O-3 ), morphology coded 9510-9514 (retinoblastoma) and malignant behavior (fifth digit of morphology code, 3). Main Outcome and Measures Annual incidence (per million children aged 0-14 years), 5-year survival (%), and the standardized incidence ratio (SIR) of subsequent malignant neoplasms. Results The study included 3262 patients (mean [SD] age, 1.27 [1.63] years; 1706 [52%] male and 1556 [48%] female) from 81 registries. Of these, 3098 patients were considered in trend analysis after excluding registries with incomplete time coverage: 940 in 2000 to 2003, 703 in 2004 to 2006, 744 in 2007 to 2009, and 856 in 2010 to 2013. The estimated overall European incidence rate was 4.0 (95% CI, 3.9-4.1). Rates among countries varied from less than 2 million to greater than 6 million per year. No time trend of incidence was observed in any area. The overall European 5-year survival was 97.8% (95% CI, 95.5-98.9; 3180 cases). Five-year survival was lower in Estonia and Bulgaria (<80%) and 100% in several countries. Twenty-five subsequent malignant neoplasms were recorded during follow-up (up to 14 years), with an SIR of 8.2 and with cases occurring at mean ages between 1.3 and 8.9 years across different sites. An increased risk was found for hematological tumors (SIR, 5) and bone and soft tissue sarcomas (SIR, 29). Conclusions and Relevance This study showed RB incidence remained stable at 4.0 per 1 000 000 European children aged 0 to 14 years from 2000 to 2013, but estimates varied among countries and differences in survival across countries persist. These data might be used to monitor RB management and occurrences of second tumors. The findings suggest future registry studies should aim to collect standardized RB stage at diagnosis and treatment to interpret disparities and potentially improve surveillance.