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Purpose Accurate evaluation of breast cancer on bioptic samples is of fundamental importance to guide therapeutic decisions, especially in the neoadjuvant or metastatic setting. We aimed to assess concordance for oestrogen receptor (ER), progesterone receptor (PR), c-erbB2/HER2 and Ki-67. We also reviewed the current literature to evaluate our results in the context of the data available at present. Methods We included patients who underwent both biopsy and surgical resection for breast cancer at San Matteo Hospital, Pavia, Italy, between January 2014 and December 2020. ER, PR, c-erbB2, and Ki-67 immunohistochemistry concordance between biopsy and surgical specimen was evaluated. ER was further analysed to include the recently defined ER-low-positive in our analysis. Results We evaluated 923 patients. Concordance between biopsy and surgical specimen for ER, ER-low-positive, PR, c-erbB2 and Ki-67 was, respectively, 97.83, 47.8, 94.26, 68 and 86.13%. Cohen’s κ for interobserver agreement was very good for ER and good for PR, c-erbB2 and Ki-67. Concordance was especially low (37%) in the c-erbB2 1 + category. Conclusion Oestrogen and progesterone receptor status can be safely assessed on preoperative samples. The results of this study advise caution in interpreting biopsy results regarding ER-low-positive, c-erbB2/HER and Ki-67 results due to a still suboptimal concordance. The low concordance for c-erbB2 1 + cases underlines the importance of further training in this area, in the light of the future therapeutic perspectives.

Purpose: To describe the feasibility of a new one-step approach to aspirate the aqueous and apply melphalan in a single-go without repeated entries into the anterior chamber. Methods: This retrospective non-comparative study was conducted at a referral center and included 12 patients. The one-step approach is described in a step-wise manner. No complications were observed among the patients. Results: One single injection of intracameral melphalan proved to be a successful treatment in nine cases. Two patients required a second injection, which was administered two weeks after the first one following the same technique. Conclusions: This proved to be a reasonable technique for the smooth application of melphalan in the anterior chamber studded with retinoblastoma seeds. Our outcomes revealed that it is an effective, quick, and cost-effective technique. Longer-term data collection is underway, though initial findings are encouraging.

Aim of the studyThe study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies. MethodsPatients’ data were provided by the Senonetwork data warehouse Senonet. In order to examine changes in the surgical and oncological management of BC patients during different phases of COVID-19 pandemic, we took advantage of a selection quality indicators (QIs). We performed the analyses in two time-frames, from July to September (Jul-Sep) (2019 versus 2020) and from October to December (Oct-Dec) (2019 versus 2020). ResultsOur analysis did not show any statistically significant difference in terms of diagnosis, surgical, oncological and radiation therapy procedures between the two trimesters 2019 and 2020. Nevertheless, we observed statistically significant differences, favoring 2020, when analyzing time-to surgery and time-to radiotherapy. On the other hand, we observed a significant reduction of neoadjuvant chemotherapy and we did not recollect any data on a major use of neoadjuvant endocrine therapy. ConclusionsIn Italian Breast Centers, partners of Senonetwork, we could not observe any treatment-delay or change in standard clinical practice for BC care during the 2020 pandemic year, compared to 2019 pre-pandemic year. This finding is in contrast with the globally reported decrease in the performance of the Italian Breast Centers due to the COVID-19 pandemic, and has to be linked to the sharp selection of Senonetwork Breast Centers.

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group. We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology ( www.sign.ac.uk ). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered. Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation). Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Background Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. Methods Data on muscle strength by handgrip (HG) dynamometry and total‐body SMM estimated by bioelectrical impedance analysis (BIA) of Italian and German patients with cancer observed prospectively until death or censoring were analysed (N = 1076). Patients were stratified in four risk categories based on low HG (60 months for both). After adjusting for sex, age, body mass index and percentage of weight loss, disease's stage, performance status and type of cancer, compared to reference category (normal HG and SMM; N = 210) the hazard ratios were: low SMM/normal HG (N = 342), 0.83 [95% confidence interval, CI, 0.67–1.02] (p = 0.073); normal SMM/low HG (N = 158), 1.19 [95% CI, 1.07–1.32] (p = 0.002); low SMM/low HG (N = 366), 1.39 [95% CI, 1.27–1.53] (p, Low muscle strength has been pointed out as a key characteristic of sarcopenia, but the prognostic significance of muscle function next to reduced skeletal muscle mass (SMM) in patients with cancer has been scantily investigated. Muscle weakness was found to be a more powerful predictor of survival than SMM and should be considered as additional key feature of sarcopenia in patients with cancer.

IMPORTANCE To promptly recognize and manage cardiovascular (CV) risk factors before, during, and after cancer treatment, decreasing the risk of cancer therapy-related cardiac dysfunction is crucial. After recent advances in breast cancer treatment, mortality rates from cancer have decreased, and the prevalence of survivors with a potentially higher CV disease risk has increased. Cardiovascular risks might be associated with the multimodal approach, including systemic therapies and breast radiotherapy (RT). OBSERVATIONS The heart disease risk seems to be higher in patients with tumors in the left breast, when other classic CV risk factors are present, and when adjunctive anthracycline-based chemotherapy is administered, suggesting a synergistic association. Respiratory control as well as modern RT techniques and their possible further refinement may decrease the prevalence and severity of radiation-induced heart disease. Several pharmacological cardioprevention strategies for decreasing cardiac toxic effects have been identified in several guidelines. However, further research is needed to ascertain the feasibility of these strategies in routine practice. CONCLUSIONS AND RELEVANCE This review found that evidence-based recommendations are lacking on the modalities for and intensity of heart disease screening, surveillance of patients after RT, and treatment of these patients. A multidisciplinary and multimodal approach is crucial to guide optimal management.

AIM To test whether a reduced total single dose of 18 Gy of intraoperative radiotherapy with electrons (IORT) may be tailored to safely treat patients in comparison with the standard dose of 21 Gy. (NCT01276938). PATIENTS AND METHODS From October 2009 to December 2011, 199 females affected by breast cancer were treated with conservative surgery and IORT with two different exclusive doses, 18 or 21 Gy. RESULTS The median follow-up was 91 months (16-104 months). Sixty-five patients (pT1a\b, pN0\mic, pMx, G1-G3) received 18 Gy and 134 patients (pT1c\2, pN0\mic, pMx, G1-G3) received 21 Gy. No significant difference in local recurrence-free survival or overall survival was detected in the 18 Gy-treated arm versus that treated with 21 Gy: 96.9% vs. 96.3%, p=0.72, and 96.9% vs. 95.5%, p=0.82, respectively at 5 years. CONCLUSION The lower dose of 18 Gy achieved excellent results in terms of local toxicity and local control in early breast cancer.

Background The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. Materials and methods From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3–50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). Results With a median follow up of 47 months (range 10–78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. Conclusion Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Background/aim A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR). Materials and methods The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm. Results At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243). Conclusion The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins.

Aim: To develop a method capable of identifying human corneal limbal stem cells (LSCs) and follow their proliferation and migration in the epithelium. Materials and Methods: Ten fresh matched pairs of cadaveric normal human corneas were obtained from donors. Carboxyfluorescein diacetate succinimidyl ester (CFSE) was used to target LSCs. The distribution of CFSE-positive cell clusters was analyzed by fluorescence microscopy by counterstaining with 4’,6-diamidino-2-phenylindole (DAPI). Fluorescence was digitally recorded for seven days, and the rate of cell movement was determined. Results: CFSE-labeled cells were tracked in corneas. Analysis of time sequences revealed that they moved centripetally. Daily average CFSE-labeled LSC movement was 0.073±0.01 cm (±SD). Conclusion: CFSE allowed us to identify LSCs and to track their centripetal migration from the limbal basal layer to the anterior ocular surface. This experimental system appears to be a valuable tool for further studies on corneal epithelial cell migration and proliferation.

Aim To evaluate once-weekly hypofractionated radiotherapy in elderly patients affected by early breast cancer, reporting acute and late toxicity profiles, and treatment feasibility. Patients and methods Fifty patients were treated with a hypofractionated regimen: 28.5±2.5 Gy in five fractions at one fraction weekly. Simultaneous integrated boost (SIB) to the tumor bed in high-risk cases. Inclusion criteria patients over 70 years old, pT1-2, N0-1a. Acute and late toxicities were assessed based on Radiation Therapy Oncology Group. Results The median follow-up was 20 months and the median patient age was 79 years. SIB was added for 22 patients (44%). Grade 3-4 acute cutaneous toxicities were not observed; grade 2 toxicity occurred only in four patients (8%). Late subcutaneous tissue toxicity consisted of grade 2 fibrosis in two patients (4%), grade 1 in five (10%) and grade 0 in 41(85%). Conclusion Limiting fraction numbers with a safer profile may improve the management of breast cancer for the elderly.

A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR).The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm.At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243).The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins.

To test whether a reduced total single dose of 18 Gy of intraoperative radiotherapy with electrons (IORT) may be tailored to safely treat patients in comparison with the standard dose of 21 Gy. (NCT01276938).From October 2009 to December 2011, 199 females affected by breast cancer were treated with conservative surgery and IORT with two different exclusive doses, 18 or 21 Gy.The median follow-up was 91 months (16-104 months). Sixty-five patients (pT1a\b, pN0\mic, pMx, G1-G3) received 18 Gy and 134 patients (pT1c\2, pN0\mic, pMx, G1-G3) received 21 Gy. No significant difference in local recurrence-free survival or overall survival was detected in the 18 Gy-treated arm versus that treated with 21 Gy: 96.9% vs. 96.3%, p=0.72, and 96.9% vs. 95.5%, p=0.82, respectively at 5 years.The lower dose of 18 Gy achieved excellent results in terms of local toxicity and local control in early breast cancer.

Aim To evaluate cardiotoxicity in patients with human epidermal growth factor receptor 2+ (HER2+) breast cancer (29 left-sided, 23 right-sided) treated with adjuvant whole-breast hypofractionated radiotherapy (HRT) concurrently administered with the humanized monoclonal antibody to HER2, trastuzumab. Patients and methods From February 2008 to June 2017, 52 patients received three-dimensional conformal RT, with different HRT schemes. Echocardiogram monitoring was used to evaluate the decrease in left ventricular ejection fraction (LVEF). Results At a median follow-up of 5 years, cardiotoxicity was as follows: among the 15 patients treated with 46 Gy: grade (G) 2 in two (13%), G1 in three (20%), and G0 in 10 (67%);in those treated with 39 Gy (16 patients): G1 in five (31%), and G0 in 11 (69%);among the 21 patients treated with 35 Gy: G2 in one (5%), G1 in five (24%), and G0 in 15 (71%). Conclusion Trastuzumab was shown to be a safe adjuvant treatment when administered with concomitant HRT since it did not increase cardiotoxicity in those with left-sided breast cancer. No differences in LVEF were observed between the HRT schemes.

We report a case of a 63-year-old Caucasian female referred to the cornea service of Clinica Oculistica with a neurotrophic corneal ulcer, decreased corneal sensitivity, absent corneal reflex, and decreased lacrimation. The medical record review was relevant for mastectomy and adjuvant therapy for breast cancer complicated by pontocerebellar angle metastasis. Eye patching and application of antibiotic and vitamin ointments were prescribed at first, without a significant improvement. Thus, treatment with autologous serum was started. In about two weeks, the cornea recovered and visual acuity improved with a residual corneal scarring. Finally, we should mention that, in our case, the main cause of the neurotrophic corneal ulcer could be identified in the previous trigeminal damage at the pontocerebellar angle and trigeminal ganglion. Sensory nerves play an important regulatory role via neuro-mediators on corneal wound healing, as denervation may interfere with cellular metabolism and inhibit mitosis, leading to an epithelial defect even with no direct damage.

We report a case of a long-term local control and survival achieved in a patient affected by radiation-induced angiosarcoma (RIA). A 57-year-old woman had a history of breast-conserving surgery and radiation therapy for primary breast cancer. Eight years after the mastectomy, multiple nodal progression was diagnosed as RIA and subsequentially treated by salvage lymph node dissection followed by adjuvant intensified radiotherapy to control the residual disease. Two and a half years later, the patient is alive and cancer-free. This experience shows that radiotherapy may have the potential to be a feasible and effective treatment to control RIA progression, and it may also play a role in the management of RIA as adjuvant.

After standard treatment of primary breast cancer, local relapse can develop in a previously irradiated region. The decision to refer a patient for a second radiotherapy must be thoroughly evaluated due to the increased risk of side effects. We report a case of a 43-year-old Caucasian female with a history of left breast lumpectomy and radiation treatment in 1990 for an invasive ductal carcinoma who presented with a locoregional recurrence 19 years later. After careful evaluation, the patient has undergone a second breast-conserving surgery and successful reirradiation with 18 Gy single dose of intraoperative radiation therapy (IORT).