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Breast lesions of uncertain malignant potential (B3) are frequently diagnosed in the era of breast cancer (BC) screening and their management is controversial. They are generally removed surgically, but some international organizations and guidelines for breast research suggest follow-up care alone or, more recently, propose vacuum-assisted excision (VAE). The risk of upgrade to BC is known, but very little data exist on its role as risk factor for future BC development. We analyzed 966 B3 lesions diagnosed at our institution, 731 of which had long-term follow-up available. Surgical removal was performed in 91%, VAE in 3.8%, and follow-up in 5.2% of cases. The B3 lesions included flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), lobular intraepithelial neoplasia (LIN), atypical papillary lesions (PLs), radial scars (RSs), and others. Overall, immediate upgrade to BC (invasive or in situ) was 22.7%. After long-term follow-up, 9.2% of the patients were diagnosed with BC in the same or contralateral breast. The highest risk was associated with ADH diagnosis, with 39.8% of patients upgraded and 13.6% with a future BC diagnosis (p < 0.0001). These data support the idea that B3 lesions should be removed and provide evidence to suggest annual screening mammography for women after a B3 diagnosis because their BC risk is considerably increased.

Breast cancer (BC) has overtaken lung cancer as the most common cancer in the world and the projected incidence rates show a further increase. Early detection through population screening remains the cornerstone of BC control, but a progressive change from early diagnosis only-based to a personalized preventive and risk-reducing approach is widely debated. Risk-stratification models, which also include personal lifestyle risk factors, are under evaluation, although the documentation burden to gather population-based data is relevant and traditional data collection methods show some limitations. This paper provides the preliminary results from the analysis of clinical data provided by radiologists and lifestyle data collected using self-administered questionnaires from 5601 post-menopausal women. The weight of the combinations of women’s personal features and lifestyle habits on the BC risk were estimated by combining a model-driven and a data-driven approach to analysis. The weight of each factor on cancer occurrence was assessed using a logistic model. Additionally, communities of women sharing common features were identified and combined in risk profiles using social network analysis techniques. Our results suggest that preventive programs focused on increasing physical activity should be widely promoted, in particular among the oldest women. Additionally, current findings suggest that pregnancy, breast-feeding, salt limitation, and oral contraception use could have different effects on cancer risk, based on the overall woman’s risk profile. To overcome the limitations of our data, this work also introduces a mobile health tool, the Dress-PINK, designed to collect real patients’ data in an innovative way for improving women’s response rate, data accuracy, and completeness as well as the timeliness of data availability. Finally, the tool provides tailored prevention messages to promote critical consciousness, critical thinking, and increased health literacy among the general population.

Introduction. Breast-conserving surgery (BCS) followed by postoperative radiotherapy (RT) still represents the standard of care for early breast cancer (BC) patients. Hypofractionated schedules in maximum 15 fractions are currently accepted as the gold standard for external beam whole and partial breast irradiation (PBI). PBI for selected early BC patients allowed a shorter overall treatment duration and an improved patient compliance as compared to old-fashioned RT schedules. Preoperative PBI, due to the advantage of treating a well-defined volume, has been gaining attention in this multidisciplinary scenario. It avoids local treatment delay and might allow tumour downstaging with increased rates of BCS and improved cosmetic outcomes. Since local recurrence might be driven by biological mechanisms of radioresistance rather than geographical miss, higher dose per fraction may overcome repair mechanisms allowing tumoral cells to escape from conventional RT damage. We report the results of the phase II ROCK trial (NCT03520894), enrolling early BC patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods. The study recruited between August 2018 and September 2021 at the Radiation Oncology Unit of the University of Florence (Florence, Italy). Eligible patients were women aged 50+ years, with histologically proven invasive early BC, HR+/HER2- disease, without lymph vascular invasion, tumour size up to 25 mm suitable for BCS. Exclusion criteria were clinical node positive disease, multiple foci tumours, and patients with breast lesion limiting within 5 mm from the skin surface. The study aimed to prospectively assess the safety and feasibility of a single Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) 21Gy-fraction prRS in preoperative setting, and to identify predictive factors for outcomes based on biologic and clinical features. The primary endpoint was the acute skin toxicity (from the end of prRS to surgery) according to the RTOG and the EORTC scales. Secondary endpoints were the rate of early late skin and non-skin toxicity as measured 90 days from the end of prRS, the rate of pathological complete response (pCR) according to Chevalier score. Cosmetic outcomes were prospectively scored every 6-month using the BCCT.core software. Results. From August 2018 to September 2021, a total of 70 patients were recruited and enrolled. Of those, 41 were excluded due to tumour biology exclusion criteria and 7 due to multiple foci breast disease evidenced at basal MRI. Therefore, 22 patients were successfully treated with pRS. Median age at diagnosis was 68 years (range 50-86), median tumour size was 14 mm (range 7.5-25). Required target dosimetric parameters were met in all patients, as well as normal tissue constraints. Patients received surgery after a median time of 29 days from biopsy, without any delay or postoperative complication. Overall, three G1 adverse events (13.6%) were recorded within 7 days from prRS (1 erythema, 2 breast pain). Three events (13.6%) were recorded between 7 and 30 days from prRS, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity (1 breast pain, 4 breast induration). One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Overall, pCR after surgery was reported in 2 patients (9%). Two patients received postoperative whole breast irradiation, according to histopathological results. Conclusions. ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing a good safety profile and a promising effectiveness. Citation Format: Icro Meattini, Giulio Francolini, Vanessa Di Cataldo, Luca Visani, Carlotta Becherini, Erika Scoccimarro, Monica Mangoni, Viola Salvestrini, Laura Masi, Chiara Bellini, Raffaela Doro, Federica Di Naro, Marco Bernini, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Lorenzo Livi. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-03.

Introduction. Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. Angiotensin-converting enzyme inhibitors and β-blockers are recommended first-line agents for heart failure. However, the optimal approach still represents a controversial issue. We hypothesized whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with an anthracycline-based chemotherapy. Patients and methods. The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at eight oncology departments in Italy. The study recruitment was conducted between July 2015 and June 2020. A prespecified interim analysis on 174 women at 12 months was reported in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded. Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for one year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5mg, once daily), ramipril (5mg, once daily), and placebo, if tolerated. The primary end point was defined as detection of any subclinical impairment (worsening 10%) in myocardial function and deformation measured at 24 months using 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS). ClinicalTrials.gov identifier: NCT2236806. Results. 262 women (median age, 48 years; range, 24-75 years) were enrolled and treated in the study. We analyzed patients who had completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between groups. All patients received an anthracycline-based chemotherapy, 215 patients received at least three cycles of anthracyclines (range 1-6), 223 patients received also a taxanes-based chemotherapy, and 84 cases were treated with adjuvant trastuzumab. Sixty patients were treated with neoadjuvant chemotherapy, 157 cases received adjuvant endocrine therapy, and 128 patients had postoperative radiation therapy. GLS worsened 10% or greater in 68% of patients enrolled in the placebo arm, 15%, 13%, and 13% in the ramipril, bisoprolol, and ramipril plus bisoprolol arms, respectively (P < 0.05). A reduction of 10% or greater in 3D-LVEF was observed in 19% in the placebo arm, 11% in the ramipril arm, 11% in the bisoprolol arm, and 7% in the ramipril plus bisoprolol arm (P < 0.05). Study drugs were well tolerated with no serious adverse events, the ramipril plus bisoprolol arm showed significantly more toxic effects and had a significantly higher rate of allocated treatment discontinuation as compared to the other arms. Conclusions. Cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and protect against cancer therapy–related LVEF decline and heart remodeling. Citation Format: Icro Meattini, Carlotta Becherini, Luca Visani, Calogero Saieva, Viola Salvestrini, Francesca Martella, Carlotta Bacci, Elena Molinara, Mario Airoldi, Maria Riccarda Del Bene, Domenico Amoroso, Luigi Coltelli, Isacco Desideri, Vieri Scotti, Marco Bernini, Lorenzo Orzalesi, Jacopo Nori, Simonetta Bianchi, Giuseppe Barletta, Lorenzo Livi. Beta blockers and/or ACE inhibitors as cardioprotective strategy for patients affected by nonmetastatic breast cancer who are receiving an anthracycline-based chemotherapy (SAFE - NCT02236806): final results of a randomized trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-03.

PURPOSE To report the long-term results of external-beam accelerated partial-breast irradiation (APBI) intensity-modulated radiation therapy (IMRT) Florence phase III trial comparing whole-breast irradiation (WBI) to APBI in early-stage breast cancer. PATIENTS AND METHODS The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence (IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed boost (WBI arm) after breast-conserving surgery. RESULTS Five hundred twenty patients, more than 90% of whom had characteristics associated with low recurrence risk, were randomly assigned (WBI, n = 260; APBI, n = 260) between 2005 and 2013. Median follow-up was 10.7 years. The 10-year cumulative incidence of IBTR was 2.5% (n = 6) in the WBI and 3.7% (n = 9) in the APBI arm (hazard ratio [HR], 1.56; 95% CI, 0.55 to 4.37; P = .40). Overall survival at 10 years was 91.9% in both arms (HR, 0.95; 95% CI, 0.50 to 1.79; P = .86). Breast cancer–specific survival at 10 years was 96.7% in the WBI and 97.8% in the APBI arm (HR, 0.65; 95% CI, 0.21 to 1.99; P = .45). The APBI arm showed significantly less acute toxicity ( P = .0001) and late toxicity ( P = .0001) and improved cosmetic outcome as evaluated by both physician ( P = .0001) and patient ( P = .0001). CONCLUSION The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late treatment-related toxicity and cosmesis outcomes were significantly in favor of APBI.

Background CEDM has demonstrated a diagnostic performance similar to MRI and could have similar limitations in breast cancer (BC) detection. Purpose The aim of our study was to systematically analyze the characteristics of the lesions with the absence of enhancement with CEDMs, called false-negatives (FNs), in order to identify which clinical, radiological, histological and molecular parameters are associated with the absence of enhancement of known BCs with CEDMs, and which types of BC are most likely to cause FNs in CEDMs. We also tried to evaluate which parameters instead increased the probability of showing enhancement in the same context. Materials and methods Included in our study group were 348 women with 348 diagnosed BCs performing CEDM as preoperative staging. Two breast-imaging radiologists reviewed the CEDM exams. The absence of perceptible contrast enhancement at the index cancer site was indicative of an FN CEDM, whereas cases with appreciable enhancement were considered true positives (TPs). Dichotomic variables were analyzed with Fisher’s exact probability test or, when applicable, the chi-square test. Binary logistic regression was performed on variables shown to be significant by the univariate analysis in order to assess the relationship between predictors (independent variables) and TFNs (outcome). Results Enhancement was observed in 317 (91.1%) of the 348 BCs. From the 31 (8.9%) lesions which were FNs, we excluded 12 (38.7%) which showed an artifact generated by the post biopsy hematoma and 6 (19.4%) which were outside the CEDM field of vision. We thus obtained 13 (41.9%) BCs considered “True False Negatives” (TFNs), i.e. BCs which showed no enhancement despite being within the CEDM field of vision and failed to show post biopsy hematoma artifacts. We found that the TFNs frequently have a unifocal disease extension, diameter, Highlights • The variables associated with an increased risk of no enhancement were unifocal disease extension, non-classifiable molecular subtype, DCIS histotype, lesion dimensions

Objectives: To compare second-look ultrasound (SL-ultrasound) with second-look digital breast tomosynthesis (SL-DBT) in the detection of additional lesions (ALs) with presurgical contrast-enhanced spectral mammography (CESM). Methods: We retrospectively included 121 women with 128 ALs from patients who underwent CESM for presurgical staging at our centre from September 2016 to December 2018. These ALs underwent SL-ultrasound and a retrospective review of DBT (SL-DBT) performed 1–3 weeks prior to CESM to evaluate the performance of each technique individually and in combination. ALs in CESM images were evaluated according to enhancement type (focus, mass, or non-mass), size (10 mm) and level of suspicion (BI-RADS 2, 3, 4 or 5). Our gold-standard was post-biopsy histology, post-surgical specimen or >24 month negative follow-up. McNemar’s test was used for the statistical analysis. Results: Out of the 128 ALs, an imaging correlate was found for 71 (55.5 %) with ultrasound, 79 (61.7%) with DBT, 53 (41.4 %) with DBT and ultrasound, and 97 (75.8%) with ultrasound and/or DBT. SL-DBT demonstrated a higher detection rate vs SL-ultrasound in non-mass enhancement (NME) pattern (p: 0.0325) and ductal carcinoma in situ histological type (p: 0.0081). Adding SL-DBT improved the performance vs SL-ultrasound alone in the overall sample (p: Conclusion: Combined second-look imaging (SL-DBT+ SL-ultrasound) for CESM ALs is superior to SL-DBT alone and SL-ultrasound alone. In B3 lesions, NME, and foci, the analysis of a larger sample could determine whether adding SL-ultrasound to SL-DBT is necessary or not. Advances in knowledge: Thanks to its high sensitivity, CESM is a useful tool in presurgical staging to detect the extent of the disease burden and identify ALs not detected with conventional imaging. Since CESM-guided biopsy systems are still scarcely available in clinical practice, it is necessary to look for other approaches to histologically characterize ALs detected with CESM. In our study, combined second-look imaging (SL-DBT + SL-ultrasound) showed better performance in terms of detectability of ALs, than either SL-DBT or SL-ultrasound alone, and allowed us to identify 91.2% of ALs that turned out to be malignant at final histology; for the remaining 8.8% it was still necessary to perform MRI or MRI-guided biopsy. However, this issue could be solved once CESM-guided biopsies spread in clinical practice. SL-DBT demonstrated a higher detection rate than SL-ultrasound in NME and ductal carcinoma in situ histology.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting.From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate.We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3-78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55).Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction.

Background/aim We evaluated the efficacy of neoadjuvant chemotherapy (NACT) in reducing locally-advanced breast cancer (LABC) size, thus improving breast-conserving surgery (BCS) rates, as well as its long-term outcome. Patients and methods We analyzed 59 patients treated between 1999-2017 with NACT and subsequent surgery for LABC. Results We observed a tumor size reduction in 95% of cases, resulting in downstaging in 62.7%. The average tumor shrinkage was 49%. Women with a reduction in tumor size >50% after NACT had better 10-year OS rates than women with a reduction ≤50% (p=0.025). NACT allowed to perform BCS in 44% cases, whereas the remaining 56% cases underwent mastectomy. Overall, we observed recurrences in 37.2% patients. Recurrence rates after BCS and mastectomy were 30.7% (6 loco-regional and 2 distant cases) and 42.4% (5 loco-regional and 9 distant cases), respectively (p=0.07). Conclusion NACT confirmed its effectiveness in reducing mastectomy rates by approximately 50%, without increasing the risk of local or distant recurrences.

Background Radiology is an essential tool in the management of a patient. The aim of this manuscript was to build structured report (SR) Mammography based in Breast Cancer. Methods A working team of 16 experts (group A) was composed to create a SR for Mammography Breast Cancer. A further working group of 4 experts (group B), blinded to the activities of the group A, was composed to assess the quality and clinical usefulness of the SR final draft. Modified Delphi process was used to assess level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency and to measure quality analysis according to the average inter-item correlation. Results The final SR version was built by including n = 2 items in Personal Data, n = 4 items in Setting, n = 2 items in Comparison with previous breast examination, n = 19 items in Anamnesis and clinical context; n = 10 items in Technique; n = 1 item in Radiation dose; n = 5 items Parenchymal pattern; n = 28 items in Description of the finding; n = 12 items in Diagnostic categories and Report and n = 1 item in Conclusions. The overall mean score of the experts and the sum of score for structured report were 4.9 and 807 in the second round. The Cronbach’s alpha (Cα) correlation coefficient was 0.82 in the second round. About the quality evaluation, the overall mean score of the experts was 3.3. The Cronbach’s alpha (Cα) correlation coefficient was 0.90. Conclusions Structured reporting improves the quality, clarity and reproducibility of reports across departments, cities, countries and internationally and will assist patient management and improve breast health care and facilitate research.

The aim of this retrospective study is to compare the radiation dose received during CEDM, short and long protocol (CEDM SP and CEDM LP), with dose received during DM and DBT on patients with varying breast thickness, age and density.Between January 2019 and December 2019, patients having 6214 DM, 3662 DBT and 173 CEDM examinations in our department were analyzed. Protocol total single breast AGD has been evaluated for all clinical imaging protocols, extracting AGD values and exposure data from the dose DICOM Structured Report (SR) information stored in the hospital PACS system. Protocol AGD was calculated as the sum of single projection AGDs carried out in every exam for each clinical protocol. A total amount of 23,383 exams for each breast were analyzed. Protocol AGDs, stratified as a function of patient breast compression thickness, age, and breast density were assessed.The total protocol AGD median values for each protocol are: 2.8 mGy for DM, 3.2 mGy for DBT, 6.0 mGy for DM+DBT, 4.5 mGy for CEDM SP, 7.4 mGy for CEDM SP_DBT (CEDM SP protocol with DBT), 8.4 mGy for CEDM LP and 11.6 mGy for CEDM LP_DBT (CEDM LP protocol with DBT). CEDM SP AGD median value is 59% higher than DM AGD median value and 40% lesser than DM+DBT AGD median; this last difference was statistically confirmed with a p-value0.001. AGD value for each standard breast CEDM SP projection results to be below 3-mGy limit. AGD value for each standard breast CEDM SP projection results to be below 3 mGy, as required by international legislation. For dense breasts, the AGD median value is 4.2 mGy, with the first and third quartile of 3.3 mGy and 6.0 mGy respectively; for non-dense breasts, the AGD median value is 4.7 mGy, with first and third quartile of 3.5 mGy and 6.3 mGy respectively. The difference between the two groups was statistically tested and confirmed, with a p-value of 0.039.CEDM SP results in higher radiation exposure compared with conventional DM and DBT but lower than the Combo mode. The dose administered during the CEDM SP is lower in patients with dense breasts regardless of their size. An interesting outcome, considering the ongoing studies on CEDM screening in patients with dense breasts.

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p &lt, 0.001) and overall survival (OS) (p &lt, 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p &lt, 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

Background. Partial breast irradiation (PBI) is a reasonable alternative for a whole breast irradiation (WBI) in selected early stage breast cancer patients. The 5-year analysis of the APBI IMRT Florence phase 3 trial showed no significant difference in terms of ipsilateral tumor recurrence (IBTR) and survival rates between the two arms. We present the 10-year follow up data. Methods. From March 2005 to June 2013, women aged more than 40 years affected by early BC, with a maximum pathological tumor size of 25 mm, were randomly assigned in a 1:1 ratio to receive either WBI using three-dimensional conformal radiotherapy (3DCRT) or accelerated PBI (APBI) using intensity-modulated radiotherapy (IMRT) technique. Patients in the APBI arm received a total dose of 30 Gy to the tumor bed in five daily fractions. The WBI arm received 50 Gy in 25 fractions, followed by a boost on the tumor bed of 10 Gy in five fractions. The primary end-point, IBTR rate is now assessed at 10 years in the ITT population, as well as secondary endpoints: overall survival (OS), breast cancer specific survival (BCSS), distant metastasis free survival (DMFS), contralateral breast cancer (CBC), and locoregional recurrences (LRR). This trial is registered with ClinicalTrials.gov, number NCT02104895. Results. Of the 520 patients, 260 were enrolled in the APBI-arm and 260 in the WBI-arm; median age was 62.8 years (63.6 in the APBI and 61.6 in the WBI arm, p=0.20). Both treatment-arms achieved a median 10-year follow-up (10.1 in APBI-arm and 10.4 in WBI-arm, p=0.39) and were comparable regarding age, tumor size, grade, tumor type, and adjuvant endocrine treatment. No significant difference in terms of IBTR rates between treatment arms was shown (log rank test p=0.58). In the group who received APBI, the 5-year IBTR was 1.96% (5 events; 95% CI: 0.3;3.7) and the 10-year IBTR was 3.74% (9 events; 95% CI: 1.5;6.3). In the group who received WBI, the 5-year IBTR rate was 1.2% (3 events; 95% CI: 0;2.5) and the 10-year IBTR was 2.5% (6 events; 95% CI: 0.7;4.5). HR for APBI patients compared with WBI patients was 1.33 (p=0.58; 95% CI: 0.49;3.56). There were no significant differences between treatment arms regarding survival outcomes. OS (log rank test p=0.33): APBI 95.4% (95% CI: 93.6;97.2) versus WBI 94.3% (95% CI: 92.3;96.3); HR for APBI patients 0.66 (p=0.33; 95% CI: 0.29;1.53). BCSS (log rank test p=0.55): APBI 98% (95% CI: 96.8;99.2) versus WBI 97.5% (95% CI: 96.2;98.8); HR for APBI patients 0.68 (P=0.55; 95% CI: 0.19;2.42). DMFS (log rank test p=0.45): APBI 97.4% (95% CI: 96.0;98.8) versus WBI 96.1% (95% CI: 94.4;97.8); HR for APBI patients 0.67 (p=0.45; 95% CI: 0.24;1.89). Cumulative incidence estimates of 10-year LRR were 3.9% (95% CI: 2.24;5.56) for APBI versus 3.0% (95% CI: 1.53;4.47) for WBI (log rank test p=0.59). CBC observed after APBI were 5 (1.9%) as compared to 9 (3.5%) after WBI (p=0.42). Conclusion. IBTR rate after 10 years in patients with early breast cancer who were treated with APBI using IMRT technique in 5 fractions is rare and not significantly different from patients treated with WBI. OS, BCSS, DMFS, and LRR control are also comparable. Thus, APBI should be considered a reasonable alternative for a WBI in early breast cancer patients. Citation Format: Icro Meattini, Calogero Saieva, Sara Lucidi, Monica lo Russo, Vieri Scotti, Isacco Desideri, Livia Marrazzo, Gabriele Simontacchi, Monica Mangoni, Carlotta Becherini, Luca Visani, Lisa Paoletti, Erica Moretti, Luca Triggiani, Marco Bernini, Lorenzo Orzalesi, Luis Sanchez, Jacopo Nori, Stefania Pallotta, Simonetta Bianchi, Lorenzo Livi. Accelerated partial breast or whole breast irradiation after breast conservation surgery for patients with early breast cancer: 10-year follow up results of the APBI IMRT Florence randomized phase 3 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS4-06.

The FGD3 gene works as a cell migration inhibitor and seems to be a promising indicator of outcome in some human cancers including breast. In this study, we analysed for the first time the prognostic role of FGD3 in young breast cancer patients. We studied the relationship between traditional prognostic factors, FGD3 expression and outcome in ≤40 years breast cancer patients. We found that lower FGD3 expression decreased the probability of disease-free survival (p = 0.042) and overall survival (p = 0.007). In a multivariate analysis for overall survival AJCC stage (p = 0.005) and FGD3 expression (p = 0.03) resulted independent prognostic factors. Low FGD3 expression increased the risk of death from disease (HR 5.73, p = 0.03). Moreover, low FGD3 expression was associated with more widespread lymph node involvement (p = 0.04) and a lower FGD3 staining intensity was found in positive-lymph-node patients vs negative (p = 0.003) and in patients with ≥10 involved lymph nodes vs p = 0.05). Our results suggest FGD3 to be a significant independent prognostic factor in young breast cancer patients in terms of disease-free survival and overall survival. A lower expression increased the risk of recurrence and death from disease and was associated with widespread lymph node metastases.

Imaging-guided Core Needle Biopsy (CNB) is a procedure for tissue sampling in case of suspicious findings, such as breast masses and abnormal lymph nodes. It provides definitive diagnosis with a high accuracy rate and generally with no significant complications. To our knowledge, this is the first case report to document a pseudoaneurysm of the axilla after CNB. An illustrative case and a diagnostic and therapeutic literature review are presented.

Background/aim Breast cancer treatment represents a substantial amount of health-care costs and has a negative impact on womens' psychological health. Day-Surgery managment (DS) is a favorable alternative to a classic inpatient setting. In our prospective study we evaluated DS-treatment feasibility in terms of patient satisfaction, same-day-discharge rate, surgical-reintervention rate, psychological impact and costs. Patients and methods We operated on 131 early breast cancer patients in DS. Surgical outcomes were evaluated. In 64 DS-treated breast cancer patients, psychological outcomes were analyzed using validated psychometric questionnaires and comparison was made with a corresponding group of women treated as inpatients. Results The same-day-discharge rate was 95.4%. No patient required readmission. The surgical-reintervention rate was 6.2%. DS-treatment significantly reduced anxiety (p=0.05) and depression (p=0.01) and afforded cost savings of 49%. Conclusion DS-treatment of early breast cancer was feasible, with low reintervention rate, reduced anxiety and depression, high patients' satisfaction and substantial financial savings.

Background. Several randomized trials demonstrated aromatase inhibitors (AI) superiority in terms of disease-free survival (DFS) compared to tamoxifen treatment for postmenopausal hormone receptor-positive breast cancer (BC) patients. Anyway, AI toxicity profile is a concern due to estrogen suppression. Pivotal trials demonstrated a significant bone mineral density (BMD) loss due to AI, with a consistent 5-year risk of bone fractures, thus impacting on patients' quality of life. Bisphosphonates represent an effective treatment in postmenopausal osteoporosis fractures prevention. However, an adequate patient's selection for adjuvant bisphosphonates treatment during AI endocrine therapy is still a challenge. Final results of BONADIUV trial presented at San Antonio Breast cancer Symposium in 2016 showed that treatment with ibandronate, as compared to placebo, significantly improved BMD change in osteopenic women treated with adjuvant AI, and consistently protected patients' bone loss. We present the secondary 5-year analysis on survival outcomes of the trial. Patients and methods. The BONADIUV trial is a single-blind, randomized, placebo-controlled phase 2 study designed to evaluate the impact of ibandronate treatment on BMD in osteopenic women taking AI. Between January 2011 and May 2014, 171 osteopenic patients (lumbar spine [LS] and/or trochanter -1< T-score Results. At the database cutoff time for the present analysis on May 4, 2018, median follow up was 63.3 months (mean 61.2; range 2.7-87.3) for whole series, 64.9 months (range 33.8-84.0) for the placebo arm, and 62.2 months (range 24.2-87.3) for the ibandronate arm. Ten patients in the placebo group and 17 patients in the ibandronate group withdrew the allocated arm before any follow up data collection, and so were excluded from the analysis, performed on 144 patients (72 patients per arm). At the database cutoff time, the OS rate was 97.2% in the placebo group and 100% in the ibandronate arm. We observed four loco-regional relapse (three in the placebo arm, one in the ibandronate arm; p=0.33), three distant metastases (none in the placebo arm, three in the ibandronate arm; p=0.075), and three contralateral BC (one in the placebo arm, two in the ibandronate arm; p=0.65). The number of iDFS events did not differ between groups: four in the placebo group and six in the ibandronate group (p=0.56). Up to data cutoff, two deaths have occurred; none in the placebo arm and two in the ibandronate arm (p=0.15). The OS rate did not differ between arms. Conclusions. The secondary analysis of survival outcomes showed no difference between arms in terms of OS and iDFS rates. Further large investigations and mature follow-up from the published ones are awaited. Citation Format: Meattini I, Scotti V, Desideri I, Saieva C, Visani L, Salvestrini V, Cecchini S, De Feo ML, Mariotti M, Olmetto E, Delli Paoli C, Francolini G, Bernini M, Orzalesi L, Sanchez L, Nori J, Bianchi S, Livi L. Oral ibandronate for osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: secondary 5-year survival outcomes analysis of the single-center phase 2 BONADIUV trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-04.

Aims. To evaluate acute and late toxicity-related factors among breast cancer (BC) patients who underwent prepectoral breast reconstruction (BR). Methods. We performed a retrospective analysis of BC patients who underwent therapeutic or prophylactic mastectomy from October 2012 to May 2016 at our Center. We recorded individual patient-related features (i.e. age, body mass index [BMI], smoke-history, comorbidity, BRCA-carrier), BC-related treatments characteristics (i.e. axillary surgery, adjuvant radiotherapy [RT], adjuvant chemotherapy, primary systemic therapy [PST], endocrine therapy, and use of trastuzumab). Toxicity profile was evaluated in terms of complications related to BR; we recorded acute and late toxicity data and prosthesis/implant explant rate. Results. We analyzed 146 consecutive BC patients treated with subcutaneous BR, 117 therapeutic and 29 prophylactic mastectomies. Thirty-seven patients received postmastectomy RT. Significant factors related to acute toxicity were: previous RT (34.5% [RT] vs 8.5% [no RT]; p=0.001), BMI (31.3% [BMI ≥25] vs 8.8% [ Conclusions. In our experience prepectoral subcutaneous implant-based BR is a safe and effective approach, with low rates of acute toxicity. Major risk factors were evidenced for patients previously treated with RT or surgery, and in case of diabetes or BMI ≥25; postmastectomy RT seems not to be related to higher rate of toxicity. ALND seems to be the only factor significantly related to late toxicity. PST, and smoking exposition were significantly associated with higher rate of implant/prosthesis explant. However, further investigations and mature follow-up are warranted to confirm these encouraging results. Citation Format: Meattini I, Bernini M, Saieva C, Desideri I, Scotti V, Salvestrini V, Visani L, Mariotti M, Delli Paoli C, Olmetto E, Maragna V, Orzalesi L, Sanchez L, Nori J, Bianchi S, Livi L. Conservative breast reconstruction: Outcomes of 146 consecutive cases of prepectoral, subcutaneous implant-based breast reconstruction in a single-Institution series [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-07.

Breast cancer (BC) is the cancer with the highest incidence in women in the world. In this last period, the COVID-19 pandemic has caused in many cases a drastic reduction of routine breast imaging activity due to the combination of various factors. The survival of BC is directly proportional to the earliness of diagnosis, and especially during this period, it is at least fundamental to remember that a diagnostic delay of even just three months could affect BC outcomes. In this article we will review the state of the art of breast imaging, starting from morphological imaging, i.e., mammography, tomosynthesis, ultrasound and magnetic resonance imaging and contrast-enhanced mammography, and their most recent evolutions, and ending with functional images, i.e., magnetic resonance imaging and contrast enhanced mammography.

We re-evaluated acute and early-late toxicity-related factors among pre-pectoral immediate tissue expander/implant (TE/I) breast reconstruction (BR) unselected, first-era, cases, including previous breast radiation treatment and post-mastectomy radiation therapy (PMRT). A retrospective analysis of 146 (117 therapeutic and 29 prophylactic) pre-pectoral reconstructions, between 2012 and 2016, considered patient-related (age, body mass index [BMI], smoke-history, comorbidity, BRCA mutation), and treatment-related characteristics (previous irradiation, axillary surgery, PMRT, pre- and postoperative chemotherapy, endocrine therapy, and target-therapy). Safety was evaluated as acute and early-late complications, and TE/I failures. At multivariate analysis of the 146 cases (117 patients submitted to BR) a significant factor related to acute toxicity was: BMI ≥ 25 (31.3% [≥ 25] vs 8.8% [

Background Selective pectoralis major muscle (PMM) denervation has been described in retro-pectoral reconstructions to obtain the advantages of the pre-pectoral approach. Present study compared subjective evaluations between retro-pectoral implant based breast reconstructions (IBBRs) with denervation to traditional techniques without denervation. Methods. In 2020, two 2 groups of patients submitted to retro-pectoral IBBR, minimum 12-month follow-up, were compared through BREAST-Q post-operative questionnaire. Group-1 included direct-to-implant or two2-stage tissue expanderTE cases with selective PMM denervation, while Group-2 similar procedures, in the same time span 2017-2019, without denervation. BREAST-Q was divided into five 5 independent scales and for each scale item responses were summed up and transformed into a score, ranging from 0 to 100, to analyze and compare the results. Results. 50 patients were included both in Group1 and Group-2. Group-1 patients reported significantly higher scores in “satisfaction with the reconstructed breast” scale compared to Group-2, means-medians of 56-58 and 47-50, respectively. A trend in favor of Group-1 was recorded in the scales of “psycho-social well-being”, 64-65 vs. 58-53, and “sexual well-being”, 53-47 vs. 48-47, albeit not significant. Substantial equivalence was found in “satisfaction with the result overall” and “physical well-being”. Conclusion. PMM denervation can improve cosmetic results in retro-pec IBBRs, thus leading to better QoL. Possible pain and physical discomfort weren't caused by denervation with scores similar to non-denervated controls.

Breast cancer is a clear example of excellent survival when it is detected and properly treated in the early stage. Currently, screening of this cancer relies on mammography, which may be integrated by new imaging techniques for more exhaustive evaluation. The Personalized, Integrated, Network, Knowledge (P.I.N.K.) study is a longitudinal multicentric study involving several diagnostic centres across Italy, co-ordinated by the Italian National Research Council and co-funded by the Umberto Veronesi Foundation. Aim of the study is to evaluate the increased diagnostic accuracy in detecting cancers obtained with different combinations of imaging technologies, and find the most effective diagnostic pathway matching the characteristics of an individual patient. The study foresees the enrolment of 50,000 women over the age of 40 years presenting for breast examination and providing informed consent to data handling. So far, the 15 participating centres across Italy have recruited a total of 22,848 patients. Based on the analyses of the first 175 histopathological-proven breast cancers, mammographic sensitivity was estimated to be 61.7% (n = 108 cancers), whereas diagnostic accuracy increased by 35.5% (n = 44 cancers) when mammography was integrated with other imaging modalities (ultrasound and/or digital breast tomosynthesis). Increase was mainly determined by ultrasound alone. Given the ongoing data collection and recruitment, the number of cancers detected is too low to allow any further in-depth analysis to explore links to patient characteristics. Past studies show that the uniform approach of population screening guidelines should be revised in favour of more personalised regimens, where known standards are integrated by imaging techniques most suitable for the individual’s characteristics. With the ultimate goal of identifying early breast cancer detection strategies, our preliminary results suggest that integrated diagnostic approach could lead to a paradigm shift from an age-based regimen toward more specific and effective risk-based personalised screening regimens, in order to reduce mortality from breast cancer.

Lesions of uncertain malignant potential represent a group of diverse histopathological entities, with a variable degree of associated malignancy. The lesions in this group include atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), classical lobular neoplasia (LN), papillary lesions (PL), benign phyllodes tumours and radial scars (RS). They are found in the 4–9% of all core needle biopsies (CNB) and this value increases with other techniques such as vacuum-assisted biopsy (VAB).

The aim of our work is to illustrate a new technique for the histological diagnosis of Paget’s disease (PD) using a core needle biopsy with a semiautomated 14-gauge needle called nipple-core needle biopsy (N-CNB). We report 3 years’ experience in our senology unit. Twenty-six women with 26 clinical of nipple–areola complex (NAC) changes with suspected PD and subjected to core needle biopsy using our new 14G semiautomated needle technique were included in our study group. Institutional review board approval was obtained for this retrospective analysis. A semiautomated biopsy gun with a 14-gauge, 15-cm-long needle was used for this new procedure. After a subcutaneous injection of anesthetic and spray-ice application to the NAC, the 14G needle was opened with the cradle exposed and positioned on the NAC with considerable pressure exerted on the same. The cradle was then closed by triggering the needle spring, and 2–4 core samples were withdrawn by moving the needle position each time. Clinical, instrumental and histological differences between the lesions that gave benign results after N-CNB and those that resulted PD were analyzed by applying the Fisher's exact test. After N-CNB, 13/26 lesions were found to be PD (50%) while 13/26 alterations were benign (50%). No malignant lesions were detected during the follow-up in patients with benign N-CNB results. The diagnosis of PD obtained with N-CNB was confirmed in all 13 cases by means of a histological analysis of the surgical specimens. No significant post-biopsy complications were recorded. Patients with PD more frequently presented nipple retraction (ρ = 0.0407) and associated suspicious (i.e., BI-RADS 4 and 5) mammographic (ρ = 0.0006) findings compared to patients whose N-CNB had given benign results and the difference was statistically significant. In conclusion, with this novel technique, we were able to obtain an easy, painless, major complication-free and accurate diagnosis of PD of the NAC using a semiautomated core needle biopsy with a 14-gauge needle.

The process of subtraction requires two images. Therefore, in CEM, paired mammograms are acquired in rapid succession after the administration of the iodinated contrast agent. They are then subtracted in order to cancel the appearance of normal breast tissue and permit the visualization of lesions with neoangiogenesis. Combining images acquired with different X-ray energy spectra would result in artefacts.

Contrast-enhanced digital mammography (CEDM) is a diagnostic tool for breast cancer detection. Artefacts are observed in about 10% of CEDM examinations. Understanding CEDM artefacts is important to prevent diagnostic misinterpretation. In this article, we have described the artefacts that we have commonly encountered in clinical practice; we hope to ease the recognition and help troubleshoot solutions to prevent or minimise them.