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Background: Adoption of neoadjuvant chemotherapy (NACT) in the "real world" has been poorly investigated. Aim of this study was to examine the rate of NACT in Italy, trends over time and determinants of therapeutic choices., Methods: Senonetwork, the recognized network of Breast Centers in Italy, has developed a voluntary national data warehouse with the aim to monitor and improve treatments quality. A retrospective analysis was conducted among 58,661 breast cancer (BC) patients treated between 2017 and 2022 by 24 high-volume Breast Centers participating in the project., Results: After subset exclusion, 37,215 primary BC patients were analysed, 32,933 underwent primary-breast-surgery and 4,282 underwent NACT. From 2017 to 2022, the overall NACT incidence increased particularly for HR-/HER2+, Triple-Negative, and HR+/HER2+ BC (p < 0.001). In cN + patients the recommendation to axillary lymph-node dissection after NACT decreased over time along with an increase of <4 lymph-nodes removed (p < 0.001). Immediate breast reconstruction and indication for nipple sparing mastectomy increased significantly over time (OR = 1.10, p = 0.011 and OR 1.14, p < 0.001, respectively). On multivariate analysis, there was a trend towards an increased adoption of conservative treatment for HR-/HER2+ (p = 0.01) and Triple Negative tumors (p = 0.06). Implementation of NACT varied significantly among Breast-Centers from 3.8 to 17.7 % (p < 0.001)., Conclusion: The impact of NACT on the subsequent surgical management is substantial and continues to evolve over time, resulting in less-extensive surgery. Even among high-volume Centers NACT implementation rate is still highly variable. Although we registered a significant increase in its use during the study period, these results need to be further improved., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This research received no specific grants or funding., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Non palpable breast tumors are increasingly diagnosed because of screening programs, and their localization during surgery is essential to ensure an adequate resection. Little is known regarding which techniques are used in "real world"., Materials and Methods: A national web-based survey, with a 21-items questionnaire, was conducted among Breast Centers (BCs) in Italy in 2023., Results: Among 153 BCs, 110 (72 %) participated. Wire-guided localization was reported to be the most used technique, regardless of the volume of malignant tumors treated by each Center (N = 36, 33 %). However, newer techniques such as Radioactive occult lesion localization and magnetic seeds, were reported to be employed in 34 (31 %) BCs, and more often among high-volume BCs (>300 cases/year) (N = 32, 29 % vs. N = 13, 12 %; p = 0.02). Logistic problems of localization were reported to cause delays to the scheduled surgery at least once or in multiple occasions in 26 (24 %) and in 4 (3.5 %) BCs, respectively. Although the majority of BCs declared they were satisfied (N = 48, 44 %) or somewhat satisfied (N = 41, 37 %) with the procedure used in their center, responders stated that they would change their technique, or that they were strongly considering this possibility in 24 (22 %) and in 38 (35 %) cases, respectively. The main barrier to introducing a new technique was associated with procedure costs (90 BCs, 82 %)., Conclusions: There are several critical issues regarding localization techniques at a national level. This should be recognized as a priority because of its impact on both patients and clinical practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Neoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists., Materials and Methods: The Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system., Results: A total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy., Conclusion: There is still a wide variability in surgical approaches after NAC in the "real world". As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field., Competing Interests: Declaration of competing interest None., (© 2024 Elsevier Ltd, BASO ∼ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies. However, the integration of BRCA testing in Italian BUs faces multiple challenges. This study, by Senonetwork Italia, aimed to evaluate genetic testing practices and identify obstacles within Italian BUs., Methods: Senonetwork Italia conducted a 16-question web-based survey involving 153 BUs. The survey assessed aspects of BRCA testing, including timing, urgency, counseling, patient selection, and multi-gene panels., Results: Of the 153 BUs, 109 (71.2%) responded. Testing before surgery was performed by 70.6% of centers, with urgent cases acknowledged by 87.2%. Most centers (56.0%) arranged urgent pre-test counseling within a week. BRCA mutation status influenced treatment decisions in 99.1% of cases. Multi-gene panels were used by 33.0% of centers for all genetic counseling cases, while 56.0% followed standard referral criteria. The main challenges included cost, reimbursement, and reporting timelines., Conclusions: This survey highlights significant variations in BRCA testing practices across Italian BUs and identifies key logistical and financial challenges. There is a need for standardized practices of genetic testing to ensure personalized and effective BC management in Italy.

Background: Sentinel lymph node (SLN) biopsy for cN+ breast cancer patients after neoadjuvant chemotherapy (NAC) is controversial because the false-negative rate (FNR) is high. Identification of three or more SLNs with a dual tracer improves these results, and inclusion of a clipped lymph node (CLN) (targeted axillary dissection [TAD]) may be even more effective., Methods: A retrospective, single-institution analysis of consecutive cN+ patients undergoing NAC from 2019 to 2021 was performed. Patients routinely underwent placement of a clip in the positive lymph node before NAC, and TAD was performed after completion of therapy., Results: The study analyzed 73 patients, and the identification rate for CLN was 98.6% (72/73). A complete response in the lymph nodes was achieved for 43 (59%) of the 73 patients. Overall, the CLN was not a SLN in 18 (25%) of 73 cases, and for women who had one or two and those who had three or more SLNs identified, this occurred in 11 (32%) and 7 (21%) of 34 cases, respectively. Failure of SLN or TAD to identify a positive residual lymph node status after NAC occurred in 10 (15%) of 69 and 2 (3%) of 73 cases, respectively (p = 0.01). In four cases, a SLN was not retrieved (5.5%), and two of these cases had a positive CLN. In three cases, the CLN was the only positive node and did not match with a SLN, directing lymphadenectomy and oncologic management change in two cases. Therefore, 7 (10%) of 73 cases had a change in surgical or oncologic management with TAD., Conclusions: For a conservative axillary treatment in this setting, TAD is an effective method. It is more accurate than SLN alone and allows management changes. Further studies are warranted., (© 2024. Society of Surgical Oncology.)

Background: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice., Material and Methods: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients., Results: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women., Conclusions: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials., (© 2024 Published by Elsevier Ltd.)

Background: Intraoperative examination of retro-areolar margin (IERM) often is used during nipple-sparing mastectomy (NSM) for cancer, but there is no robust data regarding its real advantage., Methods: Consecutive patients undergoing NSM for cancer with omission of IERM according to institutional protocols from 2016 to 2021 were retrospectively analyzed. The decision to maintain or remove the Nipple-Areola Complex (NAC) after definitive pathology was taken at the multidisciplinary meeting., Results: Among 162 women operated in the study period, the presence of neoplastic cells within 2 mm from the inked retroareolar margin (RAM) was detected at permanent pathology in 17 cases (10.5%). Nipple-Areola-Complex (NAC) was removed postoperatively in five patients (3%) for margins <1 mm, the other 12 were observed, whereas postoperative NAC necrosis required surgical removal in additional five cases (3%). The NAC was thus preserved in 152 of 162 patients (94%). At multivariate analysis, RAM ≤2 mm was associated with radiological tumor-to-nipple distance less than or equal to 1 cm (p = 0.04) and Ki67 label index ≥ 20 (p = 0.04), whereas multifocality/multicentricity showed a trend towards significance (p = 0.07). At a median follow-up of 46 months, five locoregional relapses occurred (3%), only one of them involving the NAC (0, 6%). Locoregional relapse and overall survival for patients with RAM > or < 2 mm were not different., Conclusions: IERM is not routinely necessary during NSM for cancer, because its omission is associated with a very low return to the operating room, it is oncologically safe, and associated pitfalls are avoided. Further studies are necessary to confirm these findings., (© 2023. Society of Surgical Oncology.)

This article aims to present the results of a national, cross-sectional, voluntary, online survey on the presence and roles of associations of breast cancer patients and volunteers in Italian specialist breast centres. The survey was developed according to standard methods. The questionnaire was pre-tested by a random sample of three breast centres, loaded onto the SurveyMonkey platform, and piloted by one volunteer breast centre. The breast centre clinical leads were invited to participate via email. A link to the online instrument was provided. No financial incentives were offered. The results were reported using standard descriptive statistics. The response rate was 82/128 (65%). Members of associations were routinely present in 70% Italian breast centres. Breast centres most often reporting their presence were those certified by the European Society of Breast Cancer Specialists. Patient support (reception and information, listening, identification of needs, and psychological support) was the primary area where associations were reported to offer services. The magnitude of this phenomenon warrants a study to investigate the impact of the activities of associations on the quality of life of patients and on the cost-benefit ratio of the service, and the modes of their interactions with the nursing staff and the medical staff.

Purpose: In modern breast cancer treatment, a growing role has been observed for breast reconstruction together with an increase in clinical indications for postmastectomy radiotherapy (PMRT). Choosing the optimum type of reconstructive technique is a clinical challenge. We therefore conducted a national multicenter study to analyze the impact of PMRT on breast reconstruction., Methods: We conducted a retrospective case-control multicenter study on women undergoing breast reconstruction. Data were collected from 18 Italian Breast Centres and stored in a cumulative database which included the following: autologous reconstruction, direct-to-implant (DTI), and tissue expander/immediate (TE/I). For all patients, we described complications and surgical endpoints to complications such as reconstruction failure, explant, change in type of reconstruction, and reintervention., Results: From 2001 to April 2020, 3116 patients were evaluated. The risk for any complication was significantly increased in patients receiving PMRT (aOR, 1.73; 95% CI, 1.33-2.24; p < 0.001). PMRT was associated with a significant increase in the risk of capsular contracture in the DTI and TE/I groups (aOR, 2.24; 95% CI, 1.57-3.20; p < 0.001). Comparing type of procedures, the risk of failure (aOR, 1.82; 95% CI, 1.06-3.12, p =0.030), explant (aOR, 3.34; 95% CI, 3.85-7.83, p < 0.001), and severe complications (aOR, 2.54; 95% CI, 1.88-3.43, p < 0.001) were significantly higher in the group undergoing DTI reconstruction as compared to TE/I reconstruction., Conclusion: Our study confirms that autologous reconstruction is the procedure least impacted by PMRT, while DTI appears to be the most impacted by PMRT, when compared with TE/I which shows a lower rate of explant and reconstruction failure. The trial is registered with NCT04783818, and the date of registration is 1 March, 2021, retrospectively registered., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Andrea Vittorio Emanuele Lisa et al.)

Background: Surgical delay (SD) techniques, performed before the nipple sparing mastectomy (NSM), are procedures conceived to improve the blood supply to the nipple-areola complex (NAC) in order to overcome the ischemic risk. The aim of the study is reporting our experience with SD of the NAC in the setting of NSM, identify the rate of nipple and skin necrosis and other complications and to evaluate patient satisfaction with cosmetic outcome., Patients and Methods: A retrospective review of female patients, who underwent NSM and breast reconstruction between the July 2014 and the July 2019, was performed at the Breast Unit of San Giovanni-Addolorata Hospital in Rome. Eighty-nine NSM after SD procedure were performed in 66 patients. In all cases immediate breast reconstruction was performed with a direct to implant technique and polyurethane implants in prepectoral plan were used in all reconstructions., Results: We registered only 1 case of total NAC necrosis and 3 skin flap necrosis. Furthermore, patient satisfaction with breast reconstruction resulted excellent or good in 23 cases and good in 36 cases; the external plastic surgeon considered the breast reconstruction excellent or good in 63 cases., Conclusion: We support the thesis that SD techniques may expand indications for NAC sparing mastectomy and immediate breast reconstruction in women with known risk factors for local complications. Microabstract This is the largest single center series on surgical delay of nipple areola complex providing interesting data on follow-up and complication rates and we support the thesis that surgical delay techniques may expand indications for nipple-areola complex sparing mastectomy and immediate breast reconstruction in women with known risk factors for local complications., (Copyright © 2023. Published by Elsevier Inc.)

Background: Nipple-sparing mastectomy (NSM) is increasingly used for women with breast cancer who are not candidates for conservative surgery. The authors previously reported satisfying results with NSM after neoadjuvant chemotherapy (NACT)., Methods: From 2010 to 2020, 1072 women underwent mastectomy at the authors' institution. In this group, 433 NSMs were performed (40%). The only contraindications to NSM were close proximity to the nipple-areola complex (NAC), bloody discharge, and Paget disease., Results: In 112 cases involving 111 women, NSM followed NACT (group 1), whereas it was performed as primary surgery in 321 instances involving 306 women (group 2). At 5 years, local relapse was 7% in group 1 and 2% in group 2, although in the multivariate analysis, locoregional relapses (LRRs) did not differ between the two groups. An increased incidence of local relapse was associated with higher tumor stage (stage III; p = 0.046) and age younger than 51 years (p = 0.038). For 34 (30.3%) of the 111 women in group 1 with a pathologic complete response (pCR), no LRRs were recorded. Only one NAC recurrence was observed. Overall survival with each tumor stage did not differ between the two groups. No differences in complications were observed. Cosmetic results were satisfying in 83.8% of the cases and did not get worse after NACT., Conclusions: The study data definitively confirm that NSM is safe even after NACT, with good cosmetic results and complications comparable with those in the primary surgery setting. Tumor stage and age were the only independent factors for local relapse. Patients with pCR enjoyed optimal locoregional control., (© 2023. Society of Surgical Oncology.)

Background: Approximately 5-10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials., Methods: The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC., Results: Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration., Conclusions: The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology., Competing Interests: Declaration of competing interest FM personal fee from Roche, Novartis and Gilead outside the submitted work. MVD: personal fees from Eli Lilly, MSD, Exact Sciences, Novartis, Pfizer, Seagen, outside the submitted work; CC: consultan-cy/advisory role/speaker bureau: Pfizer, Novartis, Lilly, Roche, Gilead, MSD, Seagen, outside the submitted work; FM: Fees for advisory board participation; Novartis, Astra Zeneca, Daiichi Sankyo, SeaGen, MSD, Pfizer, Roche, PUMA, outside the submitted work; LDM: grants from Eli Lilly, personal fees from Eli Lilly, personal fees from Novartis, personal fees and non-financial support from Roche, personal fees from MSD, personal fees and non-financial support from Pfiz-er, personal fees from Genomic health, personal fees from Pierre Fabre, personal fees from Daiichi Sankyo, personal fees from Astrazeneca, personal fees from Seagen, personal fees and non-financial support from Eisai, personal fees from Ipsen, personal fees from Gilead, outside the submitted work; AZ: fees for advisory board; Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, SeaGen, MSD, Pfizer, Roche, ExactSciences; LB: honoraria, consulting or advisory role Astra-Zeneca, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Seattle Genetics; research Funding Celgene, Genomic Health, Novartis, all outside the submitted work; CM: personal consultancy fees from Bayer, Roche, Astrazeneca, Daiichi Sankyo, outside the submitted work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim of the Study: The 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., Methods: Patients' 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)., Results: Our 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., Conclusions: In 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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Despite recommendations, mammography screening is often insufficiently integrated into specialist breast centres. A national, cross-sectional, voluntary, online survey on this issue was carried out among the Italian breast centres associated with Senonetwork, the Italian network of breast cancer services., Methods: A 73-item questionnaire was created, pre-tested and piloted. Centres integrating and not integrating a screening programme were compared using the unified theory of acceptance and use of technology (UTAUT) model. Centres' clustering was performed using the Gower's distance metric. Groups and clusters were compared with the equality-of-means test., Results: The response rate was 82/128 (65%). Overall, 84% (69/82) breast centres reported a collaboration with a screening programme in performing and/or reading mammograms and in the diagnostic work-up of women with abnormal screening results. The same proportion was observed among those centres responding to all questions (62/74). Performance expectancies (or the perceived usefulness of integration in terms of clinical quality, patient convenience, ease of job, and professional growth), satisfaction and motivation were higher in those centres collaborating with the screening programme. Effort expectancy indicators (or the degree to which the respondents believe that the integration is easy to implement) and those concerning the existence of facilitating conditions were lower both in centres collaborating and not collaborating with the screening programme. Among the former, six clusters of centres, distributed from 'no integration' to 'high', were identified. In cluster analysis, the highest level of integration was associated with higher agreement that integration eases the job, offers better opportunities for professional growth, and makes the working environment more satisfactory. The least integrated cluster assigned the lowest score to the statement that local health authority made available the resources needed., Conclusions: While confirming the positive effects of integrating screening programmes into breast centres, this survey has brought to light specific difficulties that must be faced. The results provide insights into the importance of integration focusing on the perspectives of professional career and motivation. The deficiency of facilitating conditions to integration is modifiable. Screening professionals' societies may have a role as initiators of the integration. Other supporting actions may be included in health laws at the national and regional level., (© 2022. The Author(s).)

Background: Autologous fat grafting (AFG), defined as the re-implant to the breast of fat tissue from different body areas, has been firstly applied to esthetic plastic surgery and then has moved to reconstructive surgery, mainly used for scar correction and opposite breast altering. Nevertheless, due to the potentially unsafe stem-like properties of adipocytes at the tumoral bed level, no clear evidence of the procedure's oncological safety has been clearly documented at present., Patients and Methods: We retrospectively collected data of early breast cancer (BC) patients from 17 Italian Breast Units and assessed differences in terms of locoregional recurrence rate (LRR) and locoregional recurrence-free survival (LRFS) between patients who underwent AFG and patients who did not. Differences were analyzed in the entire cohort of invasive tumors and in different subgroups, according to prognostic biological subtypes., Results: With a median follow-up time of 60 months, LRR was 5.3% (n = 71) in the matched population, 3.9% (n = 18) in the AFG group, and 6.1% (n = 53) in the non-AFG group, suggesting non-inferiority of AFG (p = 0.084). Building Kaplan-Meier curves confirmed non-inferiority of the AFG procedure for LRFS (aHR 0.73, 95% CI 0.41-1.30, p = 0.291). The same effect, in terms of LRFS, was also documented among different biological subtypes (luminal-like group, aHR 0.76, 95% CI 0.34-1.68, p = 0.493; HER2 enriched-like, aHR 0.89, 95% CI 0.19-4.22, p = 0.882; and TNBC, aHR 0.61, 95% CI 0.12-2.98, p = 0.543)., Conclusions: Our study confirms in a very large, multicenter cohort of early BC patients that, aside the well-known benefits on the esthetic result, AFG do not interfere negatively with cancer prognosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Mastectomy represents a deep burden for women with breast cancer. Very little is known about the psychological consequences over time and the quality of life (QoL) of women so treated, with or without breast reconstruction (BR)., Patients and Methods: A total of 709 patients underwent mastectomy with or without BR between 2002 and 2012 at one institution. Among 468 surviving patients, a 60-query QoL questionnaire on personal issues including some European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire items was presented either by email, letter, or telephone interview., Results: Of those questioned, 328 patients participated, whereas 140 (30%) declined the invitation or were unavailable. The median age was 63 years (range, 30-93 years). Stage I or II of disease was recorded in 73% of patients. Immediate BR was performed in 168 (51%) of 328 patients. Of the remaining patients, only 7 (4%) of 160 proceeded to delayed BR. Younger women had significantly worse Emotional Functioning and Social Functioning (SF) scores (P < .001), independently of tumor stage, and immediate BR improved that (P = .02). SF score was also worsened by chemotherapy (P = .03). Cognitive Functioning score was independent of age, BR, stage, or adjuvant therapies. Body Image and Sexual Functioning scores improved with BR (P < .03), and age was a strong co-variable (P < .001). On multivariate analysis, immediate BR was correlated with age and preoperative plastic surgery consultation. Some 68 (21%) of 328 patients regretted their decision or were disappointed with their choice regarding BR., Conclusions: Younger patients with breast cancer report a worse impact on their Emotional Functioning and SF scores after mastectomy, both of which are improved by BR. Reconstructing the breast at the time of mastectomy has a significant impact on Body Image and Sexual Functioning scores. A preoperative plastic surgeon consultation improves the rate of immediate BR, whereas delayed reconstruction is rarely adopted. Some 20% of patients are disappointed in or regret their decision regarding BR. We need to improve our management in consideration of these findings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: We report long-term outcomes of phase 2 trial on patients with invasive breast cancer treated with accelerated partial-breast irradiation (APBI) using tomotherapy after breast conservative surgery., Methods and Materials: From December 2010 to December 2018, we treated 338 women with APBI-tomotherapy: 38.5 Gy in 10 once-daily fractions. Patients selected were age ≥50 years old, with ≤3 cm in size unifocal tumor and at least 2 mm of clear margins. Disease outcomes were analyzed by clinicopathologic characteristics, molecular phenotypes, and American Society for Radiation Oncology (ASTRO) 2017 updated consensus groupings., Results: The median age was 65 years (range, 50-86). The invasive ductal (87.5%) and the luminal A-like molecular phenotype (70%) were the most common tumors. Overall 242 patients (71.6%) were considered "suitable" for enrollment in APBI according to the eligibility criteria of the ASTRO-2017 consensus statement. With a median follow-up of 76 months (range, 17-113), 2 patients (0.6%) had an invasive ipsilateral breast tumor recurrence (IBTR), and 2 patients (0.6%) had an axillary ipsilateral failure. The rate of local control in terms of free of IBTR was 99.4% and locoregional control (no recurrence in ipsilateral breast as well as in regional nodes) was 98.8%. Progression-free survival was 98.4% and 92% at 5 and 10 years, respectively. Acute and late skin toxicity, graded according to the Common Terminology Criteria for Adverse Events, were 7.7% (G1) and 0.6% (G2) and 4.4% (G1) and 1.1% (G2), respectively. There were no grade 3/4 toxicities, however. Very few patients (2%) or physicians (2%) assessed cosmetic outcome as fair or poor at the 2-year follow-up., Conclusions: This phase 2 trial on APBI-tomotherapy shows excellent long-term results. Once-daily fractionation schedule was well tolerated with a low rate of adverse events and worse cosmetic outcome. In this series, even among those deemed cautionary or unsuitable for APBI by ASTRO criteria, we demonstrated a low rate of IBTR., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Pre-analytics involves handling and processing of microbiopsy and surgical specimen. It is critical for the preservation of morphology and the integrity of molecular markers, which are paramount as prognostic and predictive factors in breast cancer. Although pre-analytical variables in breast cancer are codified by national and international guidelines, there is currently no data on their actual endorsement in clinical practice among Breast Units (BU)., Materials and Methods: An anonymous questionnaire was sent by e-mail by Senonetwork Italia, a no-profit organization representing the multidisciplinary network of BU in Italy. The questionnaire involved twenty-four questions concerning critical issues related to the average time and transport temperature of the samples, monitoring of warm and cold ischemia, average fixation time for biopsies and surgical specimens, inking of the margins, and radiography of the operating sample., Results: Forty-nine of 113 affiliated BU (43%), involved in the management of 44% of all breast cancer treated every year in Italy, answered the questionnaire. More than 90% of the BU reported a biopsy/VABB fixation time between 6 and 24 h. Only 41% of the Centers received the fresh operative sample to be sectioned immediately, 20% used the vacuum method and the sample arrived in the laboratory within 24-72 h. Delay in sectioning the sample was reported in as many as 40% of BU, while hot and cold ischemia time was monitored in only 4.2% and 6.2% of BU, respectively., Conclusion: Critical issues on pre-analytics are reported by the majority of dedicated BU in Italy. This represents a major challenge regarding quality of care, and improvements are needed in order to obtain valid and reproducible results of prognostic and predictive factors., Competing Interests: Declaration of competing interest The authors have no conflicts of interest in regard to the content of this manuscript., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Capsular contracture (CC) is the most common complication following Immediate Breast Reconstruction (IBR) with breast implants. Different implant surfaces were developed aiming to reduce the incidence of CC. We evaluated the incidence and degree of CC after Direct-to-Implant (DTI) IBR with insertion of textured (TE) or polyurethane (PU) covered implants., Methods: A retrospective review of consecutive patients treated at our Institution with mastectomy and one-stage IBR and implant reconstruction between 2013 and 2018, with or without post mastectomy radiation therapy (PMRT), was conducted. Immediate breast reconstruction was performed by implanting 186 PU covered implants and 172 TE implants., Results: Three-hundred-twelve women underwent 358 DTI IBR with PU or TE implants, were analyzed with a median follow-up time of 2.3 years (range 1.0-3.0). The overall rate of CC Baker grade III and IV was 11.8% (95%CI: 8.4-16.3), while, after PU and TE implant placement it was 8.1% (95% CI: 4.1-15.7) and 15.8% (95% CI: 4.1-15.7) [p = 0.009]), respectively. Irradiated breasts developed CC more frequently rather than non-irradiated breasts (HR = 12.5, p < 0.001), and the relative risk was higher in the TE group compared with the PU group (HR = 0.3, p = 0.003)., Conclusions: After mastectomy and one-stage IBR, the use of PU covered implants is associated with a lower incidence of CC compared to TE implants. This advantage is amplified several folds for patients who necessitate PMRT. Footnote: Capsular contracture (CC); Immediate Breast Reconstruction (IBR); Directto- Implant (DTI); Textured (TE); Polyurethane (PU); Post mastectomy radiation therapy (PMRT); Nipple Sparing mastectomy (NSM)., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breast cancer treatment has deeply changed in the last decades, since clinical and oncological cure cannot be achieved without patient's satisfaction in term of aesthetic outcomes. Several methods have been proposed to objectively assess these results. However, Italian breast centers have not yet agreed on measurable, reproducible and validated aesthetic outcome indicators to monitor their performance., Methods: The study was designed and conducted by Senonetwork, a not-for-profit association of Italian breast centers. Ten breast centers were selected based on specific eligibility criteria. This multicentre observational prospective study recruited 6515 patients with diagnosis of in situ or invasive breast cancer who underwent breast surgery in the years 2013-2016. Thirteen indicators of aesthetic results and of related quality of care were analyzed. Data collection and analysis were conducted using a common study database., Results: On average, seven out of ten centers were able to collect data on the proposed indicators with a proportion of missing values < 25%. By expert consensus based on study results, some seven indicators have been defined as "mandatory" while the remaining six have been defined as "recommended" because they require further refinement before they can be proposed for monitoring aesthetic outcomes or because there are doubts on the feasibility of data collection. The minimum standard is reached for 5 of 13 indicators. This finding and the wide range between centers reveal that there is ample room for improvement., Conclusions: From the present study useful measurable aesthetic parameters have emerged, leading to the definition of target objectives that breast centers can use for benchmarking and improvement of quality of care., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Breast reconstruction after nipple sparing mastectomy (NSM) plays, nowadays, a fundamental role in breast cancer management. There is no consensus on the best implant-based reconstruction technique, considering 2 stages (expander-prosthesis) or direct-to-implant (DTI). A retrospective review of consecutive adult female patients who underwent NSM with breast reconstruction over a 3-year period (January 2013 to December 2015) was performed. Patients were divided into 2 groups according to the type of reconstruction: expander/prosthesis (group A) and DTI (group B). Anamnestic data were collected. Number and type of procedures, complications and esthetic satisfaction were registered and compared. Fifty-six patients were included in group A (34.6%) and 106 in group B (65.4%). Complications associated with the 2 types of breast reconstruction were not different (P = 0.2). Patients in group A received a higher number of total surgical procedures (considering revisions, lipostructures and contralateral symmetrizations) than those in group B (2.5 ± 0.69 and 1.88 ± 1.02, P = 0.0001). Satisfaction with breast reconstruction resulted higher in group A (7.5 ± 2.6 and 6 ± 1.9, P = 0.0004). At the multivariate analysis, chemotherapy and radiotherapy were not correlated with complications, regardless of the group (odds ratio, 0.91 and 2.74, respectively). Radiotherapy and chemotherapy did not even influence the esthetic result, regardless of the group (P = 0.816 and P = 0.521, respectively). Prosthetic breast reconstructions, both in a single and in 2 stages, are welcomed by patients and have relatively low and almost equivalent complication rates, independent of other factors such as chemotherapy, radiotherapy, lymphadenectomy, smoking and age. In our experience, 2-stage breast reconstruction, although requiring more operations, is associated with a higher esthetic satisfaction. Patients who perform a DTI breast reconstruction after NSM should be informed of the high probability of surgical revision.

Introduction: Nipple-sparing mastectomy (NSM) is considered an oncologically sound procedure but necrosis of the nipple-areola complex (NAC) or skin flaps is a concern, particularly in the presence of risk factors. To increase the indications for NSM and decrease such complications, different procedures of "surgical delay" (SD) have been described., Materials and Methods: A retrospective analysis of patients who underwent SD for NSM at four Italian Breast Centers from 2014 to 2017 was performed. SD generally consisted of a periareolar or "hemi-batwing" incision, dissecting the skin and the NAC from the underlying breast tissue. NSM was scheduled after 2-3 weeks., Results: Eighty-eight procedures were analyzed. Mild complications of SD were registered in 7.9% of cases. NSM was performed in 85 cases, whereas in three cases (3.4%) a "skin-sparing" mastectomy was necessary due to positivity of the retroareolar biopsy for cancer at SD. A direct-to- implant (DTI) reconstruction was performed in 42 cases (49.4%), while in 43 (50.6%) a tissue-expander (TE) was inserted. After NSM, eight complications (9.4%) were recorded: one total necrosis (1.2%), one partial necrosis (1.2%) and four minimal ischemia (4.7%) of NAC, one skin flap necrosis (1.2%), one haematoma (1.2%). In only two cases (2.3%) prosthesis removal was needed. Aesthetic outcome was evaluated excellent or good in 92.9% of cases. At a median follow-up of 24 months no local recurrences were seen., Conclusion: This is the largest series of SD with NSM presented so far in the literature. In our experience, SD extends indications for NSM in high-risk women., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB-Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND., (© 2019 Wiley Periodicals, Inc.)

Background and Objectives: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined., Methods: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies., Results: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001)., Conclusions: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background/aim: To investigate whether neutrophil-to-lymphocyte ratio (NLR) might represent an additional biological criterion able to identify patients with worse prognosis within the 8th edition TNM prognostic staging system for breast cancer (BC)., Patients and Methods: Pre-treatment NLR was retrospectively analyzed in 475 BC women prospectively followed for a mean time of 3.8 years. The optimal NLR cutoff, identified by ROC analysis, was set at 2., Results: Elevated pre-treatment NLR was associated with worse disease-free survival (DFS) (HR=2.28) and overall survival (OS) (HR=3.39). The prognostic value of NLR was mostly evident in stage I BC (HR for DFS=2.89; HR for OS=1.30), in whom NLR significantly stratified patients who developed distant metastasis (HR= 4.62), but not local recurrence., Conclusion: NLR might provide important information in risk stratification, especially in stage I BC patients in whom the presence of a high NLR might raise the question as to whether they should be more aggressively managed., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Accelerated partial breast irradiation (APBI) is becoming an option for patients with low-risk breast cancer. The current practice is 38.5 Gy in 10 fractions b.i.d. over 5 days. This fractionation has a higher bioequivalent dose compared to the standard schedule. We report on preliminary results of once-daily APBI in patients treated with TomoTherapy®., Patients and Methods: Patients with unifocal-breast disease who underwent breast-conserving surgery were enrolled in the study. Treatment was administered with TomoTherapy, by contouring in accordance with the NSABP B-39/RTOG 0413 APBI protocol. Treatment schedule was 38.5 Gy in 10 once-daily fractions. EORTC Cosmetic Rating System was adopted for cosmetic outcome., Results: From 2010 to 2013, 111 patients were treated. With a median follow-up of 34 months, no ipsilateral breast recurrence was observed. Very few patients (1-4%) assessed their cosmetic outcome as fair or poor during follow-up., Conclusion: Once-daily APBI with TomoTherapy yielded good cosmetic results without compromising local control efficacy., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Nipple-sparing mastectomy (NSM) has been recently implemented to improve cosmetic outcome after mastectomy, but it is rarely considered today after neoadjuvant chemotherapy (NCH)., Patients and Methods: Among 275 NSMs performed from January 2007 to January 2015, 186 cases, with a minimum follow-up of 12 months, were carried out for invasive or intraductal carcinoma. Patients were considered for NSM if there were no clinical and radiological evidence of invasion or close proximity (<1 cm) to the nipple-areola complex (NAC). We compared patients operated with NSM after NCH (Group I N = 51) with those who underwent primary surgery (Group II, N = 135)., Results: At a median follow-up of 35 months, 166/186 patients were alive and disease-free (89.7%). Three local relapses (1.6%) were observed, all in the skin flap outside the NAC in Group I: (6%; p < 0.01). No NAC recurrences have been recorded, in either group. Nipple loss due to full thickness necrosis or resection for insufficient margins was recorded in 31 cases (17%); 12 in Group I (24%) and 19 in Group II (14%) (P = 0.1). This event decreased by half in the second part of the study (21/93 vs 10/93) (P = 0.03)., Conclusions: NSM after NCH is not associated with a statistically significant difference in terms of post-operative complications, total nipple loss for necrosis or margins, and results improve with experience. The loco-regional relapse rate was higher after NCH, yet it was consistent with traditional mastectomy in the high-risk setting. There is no need to avoid NSM after NCH for locally advanced cancers, if the retro-areolar margins of resection are clear at the time of surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Objectives: Nipple-sparing mastectomy (NSM) improves cosmetic results after mastectomy. As most consider advanced tumors, or tumors near the nipple-areola complex (NAC), as a contraindication for this type of surgery, we challenged this hypothesis., Methods: One hundred thirty-eight NSM were performed in 121 consecutive patients. In 122 procedures for cancer, patients were included if there was no evidence of NAC proximity (<1 cm), and if the retro-areolar margin was negative, even for locally advanced tumors or after neoadjuvant chemotherapy., Results: Total NAC necrosis occurred in six cases (4.3%). Additionally, NAC was removed after histological exam of the retro-areolar tissue in 19 cases (16% of cancer patients). Among 93 cases whose tumor-to-NAC distance was recorded, NAC was removed in 11/31 cases (35%) if the distance was 1 cm, and in 8/62 cases (12.9%) if it was more than 1 cm (P = 0.01). NAC was removed more frequently in the first half of the study (17/69 vs. 8/69: P = 0.05). At a median follow-up of 26 months for the cancer patient group, there was only one local recurrence (outside the NAC)., Conclusions: Our experience adds evidence that NSM is safe, if the retro-areolar resection margin is clear and maximal surgical clearance is performed., (© 2013 Wiley Periodicals, Inc.)

Background: Invasive lobular carcinoma (ILC) is believed to be more often multicentric and bilateral compared with invasive ductal cancer (IDC), leading clinicians to pursue a more aggressive local and contralateral approach., Methods: Retrospective review of a consecutive cohort of breast cancer patients operated at one institution from January 2000 to January 2010 was performed. Median follow-up was 4 years., Results: There were 171 ILC (14.5%) and 1,011 IDC patients in the study period. Median age (63 vs. 65 years) and tumor diameter (1.7 cm) were similar in the two groups. Diagnoses of ILC were more frequent in the second half of the study period (55/465 vs. 116/662, p<0.01). Multicentricity was reported in 108/1,011 (10.6%) IDC and in 31/171 (18.1%) ILC patients (p<0.01). A positive margin of resection at initial surgery was documented in 71/1,011 (7%) IDC and in 21/171 (12.3%) ILC patients (p<0.001). Although the rate of mastectomy decreased over time in both groups, this was more pronounced for ILC patients (p<0.001). Locoregional control, contralateral cancer, overall survival, disease-free survival, and survival according to diameter, nodal status, and type of surgical intervention did not differ between IDC and ILC. On multivariate analysis, stage of disease and hormone receptor status were associated with disease-free survival, but histology was not., Conclusions: Although ILC is more often multicentric, bilateral, and associated with a positive margin of resection, local control and survival are similar to IDC. ILC can be treated similarly to IDC with good results.

A tremendous improvement in every aspect of breast cancer management has occurred in the last two decades. Surgeons, once solely interested in the extipartion of the primary tumor, are now faced with the need to incorporate a great deal of information, and to manage increasingly complex tasks. As a comprehensive assessment of all aspects of breast cancer care is beyond the scope of the present paper, the current review will point out some of these innovations, evidence some controversies, and stress the need for the surgeon to specialize in the various aspects of treatment and to be integrated into the multidisciplinary breast unit team.

Background: Bone marrow (BM) biopsy has been suggested as an independent prognostic factor in patients with breast cancer., Methods: Patients operated for breast cancer from June 2000 to April 2008 were enrolled in this protocol after signing an informed consent. After primary surgery, BM aspirate from the iliac crest was obtained and 5-10 cc of blood collected. Since 2002 a peripheral blood (PB) sample was also obtained. Both carcinoembryonic antigen (CEA) and Mammaglobin-specific nested reverse-transcription polymerase chain reaction (RT-PCR) were used to examine BM and PB samples. Physicians and patients were blinded to results., Results: Two hundred seventy-three patients underwent BM and/or PB test. The median age of the patients was 63 years (31-80 years), and the median tumor diameter was 1.5 cm (0.1-6 cm). BM aspirates were unsuccessful in nine patients, and RT-PCR was not technically feasible in 18 women, leaving 246 patients available for analysis of results and follow-up. Among them, 110 patients (45%) had either a BM or a PB test positive for CEA or Mammaglobin (Test+). At median follow-up of 60 months, 31 events (deaths or relapse) occurred (13%). Disease-free survival (DFS) was significantly lower in the Test+ group (BP and/or PB) (P<0.001). This effect was independent of nodal status. At 5 years, event-free survival for Node-/Test- patients was 46/49 (94%) and for Node+/Test+ patients was 21/33 (64%), while patients with only one status positive (Node-/Test+ or Node+/Test-) had an intermediate disease-free survival (35/43, 81%) (P=0.005). In a subgroup analysis, RT-PCR results for BM and Mammaglobin retained statistical significance on DFS (P<0.001), while those for PB and CEA did not., Conclusions: This study confirms that RT-PCR of the BM is an independent prognostic factor for disease-free survival of breast cancer patients, and may improve their staging, allowing better strategies for therapy and follow-up.

The most common surgical approach in case of local tumor recurrence after quadrantectomy and radiotherapy is salvage mastectomy. Breast reconstruction is the subsequent phase of the treatment and the plastic surgeon has to operate on previously irradiated and manipulated tissues. The medical literature highlights that breast reconstruction with tissue expanders is not a pursuable option, considering previous radiotherapy a contraindication. The purpose of this retrospective study is to evaluate the influence of previous radiotherapy on 2-stage breast reconstruction (tissue expander/implant). Only patients with analogous timing of radiation therapy and the same demolitive and reconstructive procedures were recruited. The results of this study prove that, after salvage mastectomy in previously irradiated patients, implant reconstruction is still possible. Further comparative studies are, of course, advisable to draw any conclusion on the possibility to perform implant reconstruction in previously irradiated patients.

Introduction: Non-palpable breast tumors represent an increasing management problem in modern Breast Units. Therefore, a simple and accurate procedure to localize these lesions is needed. To date, the most commonly used technique is wire localization, but there are some disadvantages., Methods: We conducted a prospective study on patients with malignant or benign non-palpable breast tumors who were surgically treated and underwent intraoperative ultrasound (IOUS) from May 2006 to June 2007. Margins of excision were inked and specifically assessed by the pathologist, and were considered positive if

The role of sentinel lymph node biopsy (SLNB) in pT1a and "microinvasive" breast cancer has not been extensively studied. We report our experience with SLNB in patients with "minimal" breast cancer to determine the incidence and type of SLN metastases, and to study the potential impact on their surgical or oncological management. Among some 3387 women operated upon for primary breast cancer who underwent sentinel lymph node biopsy at nine institutions participating in the Rome Breast Cancer Study Group, 251 were staged pT1a or pT1mic (7.4%). There were 13 cases of sentinel lymph node metastases identified in this group of patients (5.2%), seven macrometastases and six micrometastases. Additionally, ITC were diagnosed by immunohistochemistry in four cases (1.6%). The incidence of SLN metastases was 7/174 (4%) and 6/77 (7.8%) in patients with pT1a and pT1mic tumors, respectively (p=0.2). Age and histological grade were predictive factors for SLN metastases. Chemotherapy was seldom directed by axillary node status (8/38 patients). As the incidence of SLN metastases in these patients is very small, particularly in the pT1a group, the indications for even a minimally invasive procedure, such as sentinel lymph node biopsy, should be probably individualized.

The clinical management of breast cancer has improved tremendously in the last 2 decades. Sentinel lymph node biopsy (SNB) allows conservation of the axillary lymph nodes in most patients who have breast cancer. Furthermore, it allows identification of occult nodal disease after step sectioning and more detailed staging. Although large breast tumors, multicentric disease, recurrent cancers, and use of neoadjuvant therapy were previously considered contraindications to SNB, a large body of evidence is accumulating to support its use in these cases. The prognostic significance of micrometastases and isolated tumor cells needs clarification in prospective, randomized trials.

Background and Objectives: Sentinel lymph node (SLN) biopsy allows enhanced pathology with serial sections and immunohistochemical analysis of the retrieved node. We present our experience with a simple, practical, pathology protocol., Methods: We analysed 416 consecutive breast cancer patient who underwent SLN biopsy. These were studied with six couples of sections at three different levels, each stained with hematoxylin-eosin (H/E) and immunohistochemistry (IHC) (MNF 116)., Results: With conventional analysis the SLN was positive in 106/416 cases (25%). The addition of serial sections, according to the protocol, allowed diagnoses of micrometastases (MICRO) (n = 22) or isolated tumor cells (ITC) (n = 38) or MICRO (n = 1) in 51/416 patients (14.6%). Specifically, the diagnosis was undertaken at level I (8.9%), level II (4%), or level III (1,6%). The incidence of MICRO or ITC was not different in T1 and T2 cases (13% vs. 15%, P = 0.7). The addition of the third level of analysis added very little both in T1 and T2 cancers (1.3% vs. 3.8%, P = 0.1)., Conclusions: Serial sectioning of the SLN allows diagnosis of MICRO and ITC in a significant percentage of cases. Adoption of our protocol seems practical, as the incidence of level III positivity is extremely low, particularly in T1 cancers, and additional sections would be, therefore, unlikely useful.

Bone marrow (BM) biopsy has been suggested as an independent prognostic tool to improve staging in patients with breast cancer. Two hundred and ten consecutive patients operated for breast cancer from June 2000 to June 2005 who signed an informed consent were enrolled in this protocol. Patients underwent SLN biopsy, and lymph nodes were analysed with serial sections and stained with hematossilin-eosin and immunohistochemistry. At the end of the procedure a BM aspirate from the iliac crest was obtained and 5-10 cc of blood collected. A CEA specific nested reverse transcriptase (RT) polymerase chain reaction (PCR) assay was used to examine BM samples. Results were blinded to both patients and clinicians. The median age of the patients was 56 years (range 34-80), and the median tumor diameter 1,5 cm (range 0.2-4.5). BM aspirates were unsuccessful in ten patients, and RT-PCR was not technically feasible in seventeen women, leaving 183 patients available for analysis of results and follow up. SLN biopsy allowed diagnoses of occult metastases (micrometastases and isolated tumor cells) in 16% of patients (29/183). 25% of T1N0 patients (23/92), 35% of T2N0 patients (6/17), and 44% of N1-2 patients (32/72) were BM+ (p = 0.03). At a median follow up of 35 months 5/122 in the BM- group and 6/61 in the BM+ group have relapsed (p = 0.2), while 1/122 and 4/61 have died of disease (p = 0.04) In conclusion, ultrastaging of breast cancer patients may identify a substantial subgroup of patients N-/BM- who may not require adjuvant chemotherapy, as well as a subgroup N-/BM+ with a decreased survival who may need more aggressive therapies. Further follow-up is needed to confirm this hypothesis, and several studies are under way.

We report our multicentric experience with sentinel lymph node biopsy for breast cancer patients. Patients with breast cancer operated on from January 1999 to March 2005 in 6 different institutions in the Rome area were retrospectively reviewed. All patients gave written informed consent. 1440 consecutive patients were analysed, with a median age of 59 years (range: 33-81) and a median tumour diameter of 1.3 cm (range: 0.1-5). Patients underwent lymphatic mapping with Tc99 nanocolloid (N = 701; 49%), with Evans Blue (N = 70; 5%), or with a combined injection (N = 669, 46%). The majority of patients were mapped with an intradermal or subdermal injection (N = 1193; 84%), while an intraparenchymal or peritumoral injection was used in 41 (3%) and 206 patients (13%), respectively. Sentinel lymph nodes were identified in 1374/1440 cases (95.4%), and 2075 sentinel lymph nodes were analysed (average 1.5/patient). A total of 9305 additional non-sentinel lymph-nodes were removed (median 6/patient). Correlations between sentinel lymph nodes and final lymph node status were found in 1355/1374 cases (98.6%). There were 19 false-negative cases (5%). Lymph node metastases were diagnosed in 325 patients (24%). In this group, micrometastases (< 2 mm in diameter) were diagnosed in 103 cases (7.6%). Additionally, isolated tumour cells were reported in 61 patients (4,5%). In positive cases, additional metastases in non-sentinel lymph-nodes were identified in 117/325 cases after axillary dissection (36%). Axillary dissection was avoided in 745/1440 patients (52%). At a median follow-up of 36 months, only 1 axillary recurrence has been reported. Sentinel lymph node biopsy improves staging in women with breast cancer because it is accurate and reproducible, and allows detection of micrometastases and isolated tumour cells that would otherwise be missed. Our multicentric study confirms that this is the preferred axillary staging procedure in women with breast cancer.

We reviewed 1491 consecutive cases of operated breast cancer between 1999-2004, and found that hormone-dependence, particularly if evaluated with functional markers of the estrogen receptor (estrogen regulated proteins, ERP), is inversely proportional to antigen neu expression. Our data confirms that ERP can give additional information on the probability of response to hormonal therapy.

503 patients were retrospectively evaluated to assess whether a previous needle or core biopsy, or surgical surgical excision of the primary tumor are associated with passive dislodgment of tumor cells in the sentinel lymph node, as reported in recent publications. We could not identify any increased incidence of sentinel lymph node micrometastases or isolated tumor cells after diagnostic manipulation of the primary tumor.

Breast reconstruction can be accomplished with implants, autologous tissue or both. Thanks to the widespread of microsurgical techniques autologous tissue reconstruction has become a frequent option in many departments although it is mostly considered a second choice. The aim of this study was to review our experience covering the past five years in immediate breast reconstruction with tissue expanders. From January 2000 to January 2005 279 patients underwent immediate breast reconstruction with submuscular tissue expanders. Tissue expander was chosen according to dimension, shape and volume of the healthy breast. Operating time, early and late complications, interference with neo-adjuvant therapies as well as timing and surgical techniques of second-step reconstruction were also considered. No major complications occurred. Tissue expander, beyond proving itself a valid and safe option in immediate breast reconstruction, also decreased the psychological distress following a mastectomy.

Chest wall reconstruction following extensive resection due to advanced breast cancer or radionecrosis still represents a challenge for both oncologic and reconstructive surgeons. A multitude of techniques including pedicle muscle transposition, free muscle flaps and omental flaps have always been considered, despite the morbidity of donor site. The authors describe a new cutaneous thoraco-abdominal flap to cover full thickness defects up to 600 cm2. 16 patients underwent chest wall reconstruction with the aforementioned technique. No major complications occurred. This technique proved to be a very good options to cover large chest wall defects in patients with advanced or recurred breast cancer or radionecrosis.

The axillary lymph node status of patients with newly diagnosed breast cancer remains the most important prognostic information available at the moment. However, only a minority of patients presents with such node metastases at diagnoses. We reviewed our database and studied 500 consecutive patients with early breast cancer, and found that age inferior to 50 years, high grade, diameter superior to 1 cm, elevated Ki-67, and expression of oncogene p-53 are all factors associated with lymph node metastases.

Sentinel lymph node biopsy allows enhanced pathology through serial sections and immunohistochemical analysis of the retrieved node, with detection of micrometastases and isolated tumor cells not otherwise recognized. We present our experience with a simple, effective, pathology protocol requiring six couples of sections at three different sentinel lymph node levels. Additional micrometastases or ITC were diagnosed in 51/416 patients (14.6%).

Background: Intraoperative identification of positive sentinel lymph nodes in patients with breast cancer may avoid a return to the operating room., Methods: In a group of 402 consecutive patients with primary breast cancer who underwent sentinel lymph node biopsy, an intraoperative examination (IE) was obtained in 236 cases either by frozen section (FS; n = 68) or by touch preparation cytology (TP; n = 168)., Results: IE had an accuracy of 89% (209 of 236), but it identified only 52 of 77 positive cases (sensitivity, 68%). There were 25 false-negative cases (13.7%), of which 7 were macrometastases and 18 by micrometastases (P < .001). Six macrometastases were missed by TP and one by FS (P = .9). There were two false-positive cases (3.7%). Overall, 48 (20%) of 236 patients avoided a delayed return to the operating room for a completion lymphadenectomy because of IE findings. This occurred in 10% of patients with tumors <1 cm in diameter, in 20% of those with tumors between 1 and 2 cm, and in 34% of those with tumors >2 cm in diameter (P = .05). The cost savings for the Italian Health System amounted to 198,040 (US$223,794) in these patients., Conclusions: IE has acceptable sensitivity for lymph node macrometastases, but it is a weak tool for diagnosing micrometastases. FS and TP are roughly equivalent. IE allows management changes, because approximately 20% of all patients are expected to undergo synchronous axillary dissection, and it is particularly helpful in T2 patients. This may allow substantial cost savings for the health-care system.

The aim of the study was to describe our experience with sentinel lymph node biopsy in patients with breast cancer. 326 consecutive patients with breast cancer operated on from December 1998 to December 2002 were studied. All patients gave their informed consent. Patients were mapped with an intradermal injection of Tc-99 (median dose: 0.5 mCi) and/or Patent Blue. Sentinel lymph nodes were analyzed with serial sections. 333 procedures were performed in the 326 patients. A median of two sentinel lymph nodes were identified in 322 cases (97%). 3165 additional non-sentinel lymph nodes were removed and analyzed to assess the accuracy of the technique. The correlation between sentinel lymph nodes and final pathological status was 97% (314/322). In 66/133 cases with axillary metastases (50%) the sentinel lymph node was the only site of metastasis. Micrometastases were diagnosed in 35/66 cases (26%), while isolated tumour cells were found in 15 cases (11%). At a median follow-up of 21 months one patient presented an axillary relapse (0.3%). Our experience confirms that sentinel lymph node biopsy is accurate and reproducible. Routine axillary dissection is no longer the gold standard in patients with early breast cancer. Prospective studies are under way in an attempt to provide, definitive answers.