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Background: In women undergoing breast surgery, Measurement of Patient Related Outcome Measures (PROMs) is important for improving the process of care, focusing on the patient's perspective. BREASTQ is a validated patient-reported outcome measure used increasingly in aesthetic and recostructive surgery. Only recently a breast conserving therapy module (BREASTQ-BCT) has been available. The aim of this study was to assess patient satisfaction and quality of life using BREAST-Q questionnaire in patients undergoing breast conserving surgery (BCS) plus IORT.Methods: Women undergoing BCS plus IORT for an early-stage breast cancer for at least a year were invited by telephone to partecipate. We scheduled dedicated outpatient visits to our center. The medical interviewer collected medical history information and administered the BREASTQ-BCT in paper format. Data were inserted in a de-identified database. Univariate regression analysis was used to identify clinicopathological variables associated with "satisfaction with breast" domain score.Results: Overall, 38 women completed the questionnaire. The domains of the questionnaire that obtained the lowest scores were ‘satisfaction with IORT information’ and ‘satisfaction with breasts’ (median score 59, IQR 55-73 and 51-69.5). Weight of specimen and vascular invasion were risk factors for lower ‘Satisfaction with breasts’ at univariate analysis. There was a moderate-strong correlation between 'satisfaction with the breasts' and 'psychosocial wellbeing' and 'Sexual wellbeing'.Conclusions: In this retrospective study, without a pre-operative questionnaire, changes in individuals’ satisfaction and quality of life could not be identified. A prospective study comparing BCS plus external RT group and BCS plus IORT group could be informative.

Highlights • There is no uniformly accepted indication to perform the correct management of hibernoma. • Only the complete surgical resection of the known axillary lesion, could be diagnostic and, in most case, curative. • A full multidisciplinary team is essential to focus on all aspects for the management of hibernoma and MEN-1 syndrome., Introduction The present study reports the case of an axillary hibernoma in a patient with lobular homolateral breast cancer and multiple endocrine neoplasia type1 (MEN-1). Hibernoma is a rare benign adipose tissue tumor, and usually manifests as a slowly growing and painless rubbery mass. These tumors can arise in various sites, but mammary hibernomas remain extraordinarily uncommon. Although hibernomas are metabolically active and therefore “glucose-avid” on fluorodeoxyglucose CT-positron emission tomography (FDG CT-PET), imaging alone is inadequate in providing a reliable diagnosis and definitive differential diagnosis from other malignancy. Only complete surgical excision is diagnostic and, in most cases, curative. Presentation of case A 42-years-old woman was followed for MEN-1 syndrome associating with hyperparathyroidism, insulinoma, non-secretory adrenal adenoma and thyroid lump. A FDG CT-PET found high glucid hypermetabolism in thickened elongated area on the front axillary line. Hibernoma was diagnosed after realization of prophylactic left mastectomy, homolateral sentinel lymph node biopsy and exeresis of the known axillary lesion. Discussion Clinical importance lies in distinguishing hibernoma from other benign and malignant breast neoplasms, as well as inflammatory conditions that come into the histologic or radiologic differential. Hibernoma is not currently classified as a non-endocrine tumor related to MEN1, but this association could be not fortuitous for the linkage between modification of Menin protein function and pathogenesis of hibernomas. Conclusion Our case deserves extraordinary attention because, not only it’s a case of MEN1 syndrome associated with hibernoma, but in the context of this lesion there are multiple micro-foci of infiltrating lobular carcinoma.

Sentinel lymph node biopsy (SLNB) is now considered the "gold standard" for axillary staging in the treatment of breast cancer. Most of the lymph node mapping experiences have been performed with a radioisotope (albumin-Tc99m) associated or not with the intraoperative injection of a dye, such as Patent-Blue V. Recent studies have shown how the use of indocyanine green (ICG; a drug used for diagnostic use for many years in other sectors) as a fluorescent tracer, allows to obtain alone detection rate of the sentinel lymph node similar or even better, without the risks related to radioactivity and with better use of resources.From March 2020 to February 2021, 184 patients with breast cancer cN0, candidate for SLNB were enrolled at the Complex Operative Unit (UOC) of Breast Surgery, Breast Unit of the Hospital of Verona. The ICG was injected into the periareolar site and was used the NOVADAQ SPY Elite system (StrykerThe sentinel lymph node was detected and removed in 98.3%. The average number of sentinel lymph nodes extracted is 1.527, while the average number of total lymph nodes (TLNs) extracted is 3.375. The sensitivity of the sentinel lymph node detection technique with ICG, turns out to be 100%. Finally, in the literature, lymphatic function decreases with increasing age, reducing the identification rate of the SLN; this is not confirmed in our study.Our study confirms the use of the only ICG tracer for SLNB in cN0 breast cancer, demonstrating that it is a safe, effective and sensitive technique, which also allows to reduce costs, risks and organizational efforts.

Background To define the possibility of Intraoperative Radiation Therapy (IORT)'s application on clinical practice and point out the problems observed by Verona Breast Unit. Methods Among AOUI ( Azienda Ospedaliera Universitaria Integrata ) Verona Breast Unit's patients, treated between July 2015 and June 2017, were identified 459 patients undergoing breast conserving surgery for a carcinoma, followed by IORT in 77 cases or by Whole Breast Radiotherapy (WBRT) in 382 cases. The data of WBRT group were analysed considering IORT' eligibility criteria to identify a sub-group of candidable patients, for whom we evaluated the diagnostic process that had lead to exclusion from IORT. Results In WBRT group 184 patients (48%) had a ductal NOS infiltrating carcinoma, of which 64 cases (16.8%) were eligible for IORT. Other 79 patients of WBRT group (21%) presented DCIS, of which only 27 were in ASTRO (American Society for Radation Oncology) "suitable" group for IORT. Considering the results of the pre-operative exams, or rather agobiopsy and MRI scan, 55 patients of 64 (85.9%) resulted unsuitable for IORT, while 9 patients (14.1%) could be eligible. Conclusions IORT' major limits are: the restricted eligibility criteria, especially on histology; the need of a complete execution of preoperative exams and the tecnical limits of these exams. ASTRO suitable group, including small diameter, low-grade DCIS, might be used to extend the candidability criteria. A multidisciplinary approach might improve the pre-operative study, so the use of IORT in clinical practice.

Highlights • Currently, there is no indication to perform prophylactic mastectomy in CDH1 mutation carriers: breast surveillance is recommended. • To reduce the psychological impact due to bilateral prophylactic mastectomy, that is followed by immediate breast reconstruction. • A full multidisciplinary team is crucial for the management of patients with CDH1 mutation., Introduction Germline CDH1 mutations, classically associated with hereditary diffuse gastric cancer (HDGC), also imply an increased lifetime risk of developing lobular breast cancer (LBC) in a highly penetrant autosomal dominant manner. Presentation of case We report a 44-year-old woman CDH1 mutation carrier with a strong family history of cancer, who previously had prophylactic total gastrectomy. We registered normal findings at the breast and axilla assessment. Mammography, ultrasonography and breast MRI scans were negative for cancer. In our Institute a bilateral prophylactic mastectomy followed by breast reconstruction was performed. Foci of atypical lobular hyperplasia(ALH) and lobular carcinoma in situ (LCIS) were histologically shown. Discussion The current consensus guidelines for women with pathogenic CDH1 mutations recommend annual mammography, ultrasound, breast MRI scans and clinical breast examination starting at the age of 35. Due to the well-documented aggressive behavior of this particular type of cancer, bilateral mastectomy and reconstruction would be more beneficial for this kind of high-risk patients. Conclusion Conflicting evidences and lacking data about the benefits in terms of overall survival, disease-free survival and the long-term outcomes related to prophylactic bilateral mastectomy for CDH1 mutation carriers restrict the instruction for this type of procedure to selected cases, which should always be managed by a multidisciplinary team.

Introduction: The advent of the COVID-19 pandemic has led to the sudden disruption of routine medical care, and the subsequent reorganization of hospital structures and therapeutic algorithms, aiming at protecting patients and health professionals. This was inevitably bound to affect our Breast Unit, dilating both pre- and post-operative times. The aim of this study was to evaluate the effect on patients' flow of organizational and logistic changes (key interventions) based on lean thinking implemented after the COVID-19 outbreak.Materials and Methods: Clinical and demographic data were retrospectively collected from patients undergoing sentinel lymph node biopsy for breast cancer at the Verona University Hospital from January 2018 to June 2020. Patients enrolled (n = 341) were divided into two groups according to date of admission: before (Group A; n = 294) and after (Group B; n = 47) the implementation of key interventions. Each case in Group B was subsequently matched 1:1 by means of case-control matching with cases from Group A for age, comorbidities, and type of surgery (Subgroup A1; N = 47). Pre-admission time (T0) and length of stay (T1) were compared between the three groups.Results: Median T0 was 312 h, whereas median T1 was 24 h. Patients in Group B had a higher frequency of comorbidities (57.4 vs. 25.2%, p = 0.001) and underwent mastectomy more often than patients in Group A (61.7 vs. 36.7%, p = 0.001). Both median T0 and T1 were higher in group B than in group A (384 vs. 300 h, p = 0.001, 48 vs. 24 h, p = 0.001, respectively). Median T0 and T1 did not significantly differ between Group B and Subgroup A1 (all p > 0.05).Conclusions: Lean thinking and new technologies could prove useful to the optimization of preoperative and postoperative times during the current pandemic, minimizing healthcare personnel and patients' exposure to SARS-CoV-2, and promoting a rational use of limited resources, while complying with oncological principles.

Abstarct Methods and Materials From July 2006 to December 2015, 295 patients suitable for breast-conserving therapy entered a single-arm phase II study and were treated with IOERT as radical treatment. Inclusion criteria were age >50, postmenopausal status, cT1N0M0 stage, grade G1-G2, positive estrogen receptor status; unicentric and unifocal disease, histologically proven invasive ductal carcinoma no previous breast irradiation, good performance status. Results With a median follow-up of 7.1 years (95% CI, 6.5;7.4) 6 women (2.0%) experienced a true local recurrence (reappearance of the tumour in the same quadrant). Five-year overall survival and local recurrence-free survival were 96% (95% CI, 92.9;97.8) and 94.9% (95% CI, 91.6;97.0) respectively. Conclusion Our trial suggests that, in highly selected early stage breast cancers, a single-dose IOERT can be safely delivered with excellent results and very low long-term recurrence rates.

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role. Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants’ electronic clinical records were reviewed. Patients’ data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives. Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers. Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.

Neoadjuvant therapy for triple negative breast cancer (TNBC) has recently generated growing interest given the more aggressive biologic characteristics of such subtype and the lack of approved targeted therapies. Systemic chemotherapy represents the mainstay of treatment for TNBC. Although neoadjuvant chemotherapy has consistently demonstrated higher response rates for TNBC compared to non-TNBC, and the pathological complete response predicts long-term outcome, most patient display residual disease with a higher risk of relapse. In order to improve the outcome of TNBC new chemotherapic combinations, including platinum agents, and different targeted agents such as antiangiogenetics, poly-ADP ribose polymerase (PARP) inhibitors and other small molecule inhibitors are being evaluated in neoadjuvant setting. Currently, the research is ongoing to further characterize TNBC from a phenotypical and molecular perspective, in order to identify potential new target agents and to individualize the treatment. In this regard, the neoadjuvant setting may represent the best potential scenario to assess the activity and the sensitivity of novel agents.

Angiogenesis plays a fundamental role in breast cancer (BC) growth, progression and metastatic spread. After the promising introduction of bevacizumab for the treatment of advanced BC, the initial enthusiasm decreased when the FDA withdrew its approval in 2011. Nevertheless, several clinical studies exploring the role of bevacizumab have been subsequently published. Areas covered: The aim of this study is to review the available clinical trials exploring the potential effectiveness of bevacizumab in BC, regardless of the disease setting. Expert opinion: Even if the evidence suggests that bevacizumab must be ruled out from the HER2-positive and adjuvant setting, bevacizumab's benefit remains uncertain in the neoadjuvant setting and in the advanced treatment of HER2-negative patients. In the first setting, the addition of bevacizumab to chemotherapy increased the pathological complete response (pCR) rate in most clinical trials. However, the current absence of evidence that pCR is a trial-level surrogate for survival requires waiting for long-term results. In the advanced setting, all trials showed a benefit in progression-free survival, but not in overall survival, highlighting an increase of adverse events. The lack of predictors of response represents the main unmet need in which future clinical research will undoubtedly invest.

Introduction The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage ‘pure’ invasive lobular carcinoma (ILC). Methods Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well. Results Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap. Conclusions Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.

Objectives: Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a marker of aggressiveness in invasive breast carcinoma (BC). Methods: We explored the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI-BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control group (CG-BC) were recruited. Results: Patients affected by ePVI-BC were younger, had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu overexpressed, and more lymph node metastases compared with CG-BC (P < .001). Interestingly, only younger mean age at diagnosis differentiated patients with ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome intermediate between the prognoses of IBC and CG-BC. Conclusions: Results suggest that ePVI-BC and IBC may share some pathologic processes, providing a novel perspective on the heterogeneity of BC. Epidemiologic data and molecular studies on gene expression features are needed to rationally classify these tumors into their identified subtypes.

Background The aim of this analysis was to investigate the potential impact of Ki67 assay in a series of patients affected by early stage invasive lobular carcinoma (ILC) undergone surgery. Methods Clinical-pathological data were correlated with disease-free and overall survival (DFS/OS). The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate appropriate cut-offs. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed to assess the interaction between ‘pure’ or ‘mixed’ histology ILC and Ki67. Results At a median follow-up of 67 months, 10-years DFS and OS of 405 patients were 67.8 and 79.8 %, respectively. Standardized Log-Rank statistics identified 2 optimal cut-offs (6 and 21 %); 10-years DFS and OS were 75.1, 66.5, and 30.2 % (p = 0.01) and 84.3, 76.4 and 59 % (p = 0.003), for patients with a Ki67 21 %, respectively. Ki67 and lymph-node status were independent predictor for longer DFS and OS at the multivariate analysis, with radiotherapy (for DFS) and age (for OS). Ki67 highly replicated at the internal cross-validation analysis (DFS 85 %, OS 100 %). The STEPP analysis showed that DFS rate decreases as Ki67 increases and those patients with ‘pure’ ILC performed worse than ‘mixed’ histology. Conclusions Despite the retrospective and exploratory nature of the study, Ki67 was able to significantly discriminate the prognosis of patients with ILC, and the effect was more pronounced for patients with ‘pure’ ILC. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0325-z) contains supplementary material, which is available to authorized users.

Paclitaxel and docetaxel represent the most adopted taxanes in the neoadjuvant treatment of HER2-positive breast cancer. Questions still remain with regard to their difference in terms of activity and tolerability. Events for pathological complete response (pCR), severe and febrile neutropenia (FN), and severe neurotoxicity were pooled by adopting a fixed- and random-effect model. A sensitivity analysis to test for the interaction between paclitaxel and docetaxel was accomplished. Absolute differences with 95% confidence intervals (CIs) and the number of patients needed to treat/harm (NNT/NNH) were calculated to derive the Likelihood of being Helped or Harmed (LHH). Data from 15 trials (3601 patients) were included. Paclitaxel significantly increases pCR rate by 6.8% in comparison with docetaxel (43.4%, 95% CI 41.1-45.7% versus 36.6%, 95% CI 34.3-39.0%, p=0.0001), regardless of the chemotherapy backbone, with an absolute difference of 9% and 9.2% for anthracycline-based or free-regimens. Paclitaxel significantly improves pCR versus docetaxel with a single HER2-inhibition by 6.7% (p=0.0012), with no difference if combined with a dual HER2-inhibition. Severe neutropenia and FN are significantly lower with paclitaxel, with an absolute difference of 32.4% (p

539 Background: Patients (pts) resected for early breast cancer are assigned to receive aCT according to international guidelines based upon immunophenotype and clinical/pathological features, regardless of the histotype, given the lack of prospective data for ILC. Thus, the magnitude of the benefit of aCT for ILC is still not sizable. The aim of this analysis was to investigate the effect of aCT in a multi-center series of early stage pure ILC. Methods: Clinical-pathological data of consecutive pts affected by pure ILC, undergone surgery at 3 Italian institutes, were correlated with disease-free and overall survival (DFS/OS) using a Cox model. A propensity score analysis was performed to evaluate the prognostic impact of aCT. Kaplan-Meier curves were compared with Log-Rank analysis. Results: Data from 739 pts were gathered (median age 57 years (yrs); Luminal/Triple-Negative/HER2 pos.: 98%/1.6%/0.4%). At median follow-up of 78 months, 5-/10-yrs DFS and OS were 79.4%/66.0% and 91.4%/76.5%, respectively. Tumor-size according to TNM (T, HR 1.34, 95% CI 1.04-1.72, p=0.025) and lymph-node (N) status (HR 2.39, 95% CI 1.47-3.89, p1, with an absolute difference of 17%/35% and 15%/13% at 5 and 10 yrs, respectively ( p=0.003 and p=0.04). OS was longer for pts with positive N ( p=0.02), Ki67 >4% ( p=0.01) and grading >1 ( p=0.01). Conclusions: Despite the retrospective nature of this analysis, the propensity score analysis indicates that pts with ILC may significantly benefit from aCT in terms of long-term survival, particularly for larger and more aggressive tumors. [Table: see text]

The role of the dual HER2 inhibition, and the best chemotherapy backbone for neoadjuvant chemotherapy still represent an issue for clinical practice. A literature-based meta-analysis exploring single versus dual HER2 inhibition in terms of pathological complete response (pCR, breast plus axilla) rate and testing the interaction according to the chemotherapy (anthracyclines-taxanes or taxanes) was conducted. In addition, an event-based pooled analysis by extracting activity and safety events and deriving 95% confidence intervals (CI) was accomplished. Fourteen trials (4149 patients) were identified, with 6 trials (1820 patients) included in the meta-analysis and 31 arms (14 trials, 3580 patients) in the event-based pooled analysis. The dual HER2 inhibition significantly improves pCR rate, in the range of 16-19%, regardless of the chemotherapy backbone (relative risk 1.37, 95% CI 1.23-1.53, p0.0001); pCR was significantly higher in the hormonal receptor negative population, regardless of the HER2 inhibition and type of chemotherapy. pCR and the rate of breast conserving surgery was higher when anthracyclines were added to taxanes, regardless of the HER2 inhibition. Severe neutropenia was higher with the addition of anthracyclines to taxanes, with an absolute difference of 19.7%, despite no differences in febrile neutropenia. While no significant differences according to the HER2 inhibition were found in terms of cardiotoxicity, a slightly difference for grade 3-4 (1.2%) against the addition of anthracyclines was calculated. The dual HER2 inhibition for the neoadjuvant treatment of HER2-positive breast cancer significantly increases pCR; the combination of anthracyclines, taxanes and anti-Her2 agents should be currently considered the standard of care.

Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a marker of aggressiveness in invasive breast carcinoma (BC).We explored the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI-BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control group (CG-BC) were recruited.Patients affected by ePVI-BC were younger, had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu overexpressed, and more lymph node metastases compared with CG-BC (P.001). Interestingly, only younger mean age at diagnosis differentiated patients with ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome intermediate between the prognoses of IBC and CG-BC.Results suggest that ePVI-BC and IBC may share some pathologic processes, providing a novel perspective on the heterogeneity of BC. Epidemiologic data and molecular studies on gene expression features are needed to rationally classify these tumors into their identified subtypes.

544Background: In clinical practice, the prognostic potential (and best cut-off) of Ki67 for pure ILC is usually borrowed from the ductal histotype, though a formal validation has not yet been full...