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Salvage mastectomy is regarded as the treatment of first choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast conserving surgery (BCS) is feasible. The purpose of this study was to compare the long-term oncological outcomes of IBCR patients who had undergone either mastectomy or second BCS, performing a propensity score matching (PSM) analysis to reduce the selection bias. All the consecutive patients with IBCR were retrospectively reviewed and divided into two different groups of treatment: repeat BCS versus salvage mastectomy. The propensity score predicting the probability of surgical treatment was determined for each patient and a 1:1 matching was performed. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. A total of 309 patients underwent surgical treatment for IBCR. After PSM, 108 patients treated with repeat BCS and 108 patients treated with salvage mastectomy were included in the analysis. There was no significant difference in terms of DFS between patients with IBCR receiving repeat BCS or salvage mastectomy (p = 0.167). However, patients with IBCR undergoing second BCS had significantly better DDFS, OS, and BCSS compared to salvage mastectomy (p

Background A small proportion of patients with primary breast cancer who receive breast conserving surgery (BCS) will develop an ipsilateral breast cancer recurrence (IBCR). In these patients, mastectomy is still considered the treatment of first choice, even if a second conservative surgical approach is technically feasible. The aims of our study are to analyze the characteristics of patients with IBCR after BCS, evaluate and compare the different treatment modalities (repeat BCS vs. mastectomy) in terms of patients and tumor characteristics, disease-free interval (DFI), disease-free survival (DFS), and overall survival (OS).MethodsOur prospectively maintained institutional database was queried, and 309 patients with IBCR after BCS who underwent either repeat BCS or mastectomy, between January 2008 and December 2018, were identified. Ipsilateral breast cancer recurrence was defined as a local tumor reappearance in the same breast or in the surgical scar. Exclusion criteria were: age Citation Format: Damiano Gentile, Andrea Sagona, Chiara Annunziata Pasqualina Anghelone, Erika Barbieri, Emilia Marrazzo, Wolfgang Gatzemeier, Giuseppe Canavese, Valentina Errico, Alberto Testori, Corrado Tinterri. Ipsilateral breast cancer recurrence: Treatment and long-term oncological results at a high volume center [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-16.

Introduction: Neuroendocrine neoplasm of the breast (bNENs) are considered a rare disease, even if in WHO data they represent about 2-5 % of all breast cancer. The last WHO classification includes: welldifferentiated neuroendocrine tumor (bNET), neuroendocrine carcinoma (NEC) and invasive carcinoma with neuroendocrine differentiation. The current knowledge on clinical management of bNENs is poor and patients are usually treated according to non-endocrine tumor components guidelines. Materials and Methods: We presented our experience of six cases of bNENs. Moreover, we conducted a systematic review of published data on diagnosis, treatment and outcome of this kind of tumors. Results: bNENS usually presented as palpable breast masses, classically appearing as irregular hypoechoic lesions at US examination and as hyperdense masses at mammography. Usually pre-operative tumor biopsy is not able to recognize the neuroendocrine components and the final diagnosis is performed only on definitive histopathological assessment. The most frequent subtype seems to be neuroendocrine carcinoma and synaptophysin is positive in most specimens. Treatment strategies, including surgical treatment, radiotherapy and medical treatment are nowadays based on current non-endocrine breast cancer guidelines, independently from neuroendocrine components, even if some studies have proposed the use of somatostatin analogues for bNET and cisplatin-etoposide for NEC. Prognosis of all bNENs, especially of poorly differentiated neoplasia, seems worse compared to non-neuroendocrine breast cancer and stage and morphology seem the best predictor of tumor outcome. Conclusions: We provide an algorithm for clinical management of bNETs, basing on available data. More studies are necessary for confirming the best treatment strategy for these patients, in order to improve clinical outcome

Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and mixed (MMC). We conducted a retrospective MC analysis in our prospective maintained database, calculating disease-free survival (DFS) and 5-year overall survival (OS). We found a global 92.1% OS (higher in MMC group and statistically significative) and a DFS of 95.3% (higher in MMC group but not statistically significative)., Highlights • Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. • We conducted a literature review and conducted a retrospective analysis in our database, finding 157 cases of MC. • Our findings are consistent with those published in literature, showing fundamental differences between PMC and MMC management and outcomes., We reviewed literature and our data to find out mucinous breast cancer's overall survival (OS), disease free survival (DFS) and if there are differences between pure mucinous breast cancer and mixed mucinous breast cancer in terms of OS and DFS.

To assess the role of radiomics parameters in predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer. Seventy-nine patients who had undergone pretreatment staging 18F-FDG PET/CT and treatment with NAC between January 2010 and January 2018 were included in the study. Primary lesions on PET images were delineated, and extraction of first-, second-, and higher-order imaging features was performed using LIFEx software. The relationship between these parameters and pCR to NAC was analyzed by multiple logistic regression models. Nineteen patients (24%) had pCR to NAC. Different models were generated on complete information and imputed datasets, using univariable and multivariable logistic regression and least absolute shrinkage and selection operator (lasso) regression. All models could predict pCR to NAC, with area under the curve values ranging from 0.70 to 0.73. All models agreed that tumor molecular subtype is the primary predictor of the primary endpoint. Our models predicted that patients with subtype 2 and subtype 3 (HER2+ and triple negative, respectively) are more likely to have a pCR to NAC than those with subtype 1 (luminal). The association between PET imaging features and pCR suggested that PET imaging features could be considered as potential predictors of pCR in locally advanced breast cancer patients.

OBJECTIVE: Neo-adjuvant chemotherapy (NAC) is the treatment of choice for patients with locally advanced breast cancer (BC). In luminal-like BC, the decision to administer NAC remains controversial. The purpose of this study was to describe the clinical characteristics, treatment, and oncological outcomes of luminal-like, node positive, BC patients treated with NAC, and to identify independent predictive factors for treatment. MATERIALS AND METHODS: All consecutive patients with luminal-like, node positive BC who underwent NAC were retrospectively reviewed. Pathologic complete response (pCR) was defined as no invasive or in situ residual tumor in both breast and axillary nodes (ypT0N0). RESULTS: A total of 205 luminal-like, node positive BC patients underwent NAC. Overall, 34 (16.6%) patients showed pCR, 86 (42.0%) patients underwent breast-conserving surgery (BCS), 119 (58.0%) patients underwent mastectomy, 130 (63.4%) patients underwent axillary lymph node dissection (ALND) without prior sentinel lymph node biopsy (SLNB), and 75 (36.6%) patients underwent breast surgery plus SLNB. Pathologic CR to NAC (29.1% vs 7.6% if no pCR, odds ratio = 2.866, 95% confidence interval = 1.296-6.341, p = 0.009) was found to significantly increase the probability to receive BCS. There was no significant difference in terms of disease-free and overall survival between patients with luminal-like, node positive BC receiving BCS or mastectomy (p = 0.596, p = 0.134, respectively), and ALND or SLNB only (p = 0.661, p = 0.856, respectively). CONCLUSION: Luminal-like, node positive BC presents low pCR rates after NAC. Pre-operative chemotherapy increases the rate of BCS. Pathologic CR has emerged as an independent predictive factor for BCS. In patients with axillary pCR, SLNB is an acceptable procedure not associated with worse oncological outcomes.

Salvage mastectomy is regarded as the treatment of first choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast conserving surgery (BCS) is feasible. The purpose of this study was to compare the long-term oncological outcomes of IBCR patients who had undergone either mastectomy or second BCS, performing a propensity score matching (PSM) analysis to reduce the selection bias. All the consecutive patients with IBCR were retrospectively reviewed and divided into two different groups of treatment: repeat BCS versus salvage mastectomy. The propensity score predicting the probability of surgical treatment was determined for each patient and a 1:1 matching was performed. Disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS) were analyzed and compared between the two groups. A total of 309 patients underwent surgical treatment for IBCR. After PSM, 108 patients treated with repeat BCS and 108 patients treated with salvage mastectomy were included in the analysis. There was no significant difference in terms of DFS between patients with IBCR receiving repeat BCS or salvage mastectomy (p = 0.167). However, patients with IBCR undergoing second BCS had significantly better DDFS, OS, and BCSS compared to salvage mastectomy (p

Salvage mastectomy is considered the treatment of choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast-conserving surgery (BCS) is feasible. The purpose of this study was to describe the characteristics of IBCR patients, to compare the 2 therapeutic options in terms of long-term outcomes, and to identify independent factors that may predict the type of treatment.A total of 309 IBCR patients who underwent either repeat BCS or mastectomy were identified. All the analyzed patients with IBCR had true recurrence.Repeat BCS and salvage mastectomy were performed in 143 and 166 patients, respectively. Age 65 years (59.6% vs 37.1% if age ≥ 65 years; odds ratio, 2.374; 95% confidence interval, 0.92-5.24; P = .018) and disease-free interval 24 months (15.7% vs 10.5% if disease-free interval ≥ 24 months; odds ratio, 2.705; 95% confidence interval, 1.42-5.97; P = .007) were found to significantly increase the probability of receipt of mastectomy. Disease-free survival rates at 3, 5, and 10 years were 79.2%, 68.2%, and 36.9%; and 77.2%, 65.9%, and 55.3% in patients receiving repeat BCS or mastectomy, respectively (P = .842). Overall survival rates at 3, 5, and 10 years were 95.4%, 91.4%, and 68.5%; and 87.3%, 69.3%, and 57.9%, respectively, in patients receiving repeat BCS or mastectomy (P = .018).Salvage mastectomy should not be considered the only treatment option for IBCR. A second BCS can still be evaluated and proposed to IBCR patients, with acceptable locoregional control and survival. The risk of poor long-term prognosis after mastectomy should be shared with the patient.

Nipple Sparing Mastectomy (NSM) requires the entire breast tissue to be removed, maintaining the nipple-areola complex, and represents nowadays the gold standard of the demolitive breast surgery. Although it represents the evolution of conservative breast surgery, NSM presents some limitations in the selection of women candidates for treatment, and still there are no real guidelines regarding its indications, but simply objective data to address the choice. How the breast surgery approach to demolitive and conservative surgery has changed over time? We evaluated throughout the years (from 2009 up to 2018) the time trend of NSM at our institution and analysed the main differences between patients undergone NSM and other mastectomies and/or breast conserving surgery in terms of cancer size, multicentricity and biological profile. We found 781 NSMs, 1261 other mastectomies and 5621 breast conservative surgeries. Among NSMs, 39.6% were reconstructed with tissue expander and 58.1% with definitive prosthesis. From 2009 to 2018 we found a general increase of NSM rate (from 21.3% of all mastectomies in 2009 to 67.3% in 2018) and a decrease of total mastectomies (from 78.7% of all mastectomies in 2009 to 32.7% in 2018). In line with the literature data, our data confirm that in the recent years NSM represents the gold standard for radical breast surgery. Undisputed in prophylaxis, NSM is continuously acquiring more support in being used as first line treatment for locally advanced disease.

OBJECTIVE: Hypofractionated radiotherapy in early stage breast cancer is an effective adjuvant treatment, but there is a lack of randomized data for patients with ductal carcinoma in situ (DCIS). The aim of this study is the evaluation of skin toxicity and cosmesis, and early clinical outcome of DCIS patients enrolled in an institutional Phase II trial of hypofractionated breast irradiation. METHODS: 137 DCIS patients were enrolled in the trial. All patients underwent volumetric modulated arc therapy (VMAT) to the whole breast with a total dose of 40.5 Gy in 15 fractions over 3 weeks, without tumour bed boost. Acute and late skin toxicities were recorded. Cosmetic outcomes were assessed as excellent/good or fair/poor. Early clinical outcome was reported. RESULTS: Median age was 58 y.o. (range 30–86). The median follow-up time was 22 months (range 6–45). At the end of the radiotherapy, skin toxicity was grade G1 in 56% of the patients, G2 in 15%, no patients presented G3 toxicity. In the range of 3–9 months of follow-up, the skin toxicity was G1 in 28% of patients, no G2–G3 cases; cosmetic outcome was good/excellent in 95% of patients. In the follow-up interval of 9–24 months, the skin toxicity was G1 in 12% of patients, no G2-G3 toxicity; cosmetic outcome was good/excellent in 96% of patients. After an early evaluation of clinical outcomes, 5 patients (3.6%) presented an in-breast recurrence. CONCLUSION: Hypofractionated radiotherapy using VMAT is a viable option for DCIS. A longer follow-up is needed to assess clinical outcomes and late toxicity. ADVANCES IN KNOWLEDGE: The use of hypofractionated VMAT is dosimetrically feasible for treating breast DCIS.

Introduction Sentinel lymph node (SLN) staging is currently used to avoid complete axillary lymph node dissection (ALND) in breast cancer (BC) patients with negative SLNs without jeopardizing survival or regional control. International guidelines keep recommending ALND in the presence of positive (+) SLNs. However SLN is the only site of axillary metastasis (MTS) in many cases (60%). Retrospective studies have also shown a low risk of locoregional relapse in patients with SLNs+ not receiving ALND.This latter finding was recently confirmed in a randomized trial comparing SLN biopsy (SLNB) alone with SLNB followed by ALND in patients with 1-2 SLNs+. However the observation of both similar relapse rate and survival in the 2 arms and the conclusion of a non-inferiority of SLNB compared to ALND require cautiousness because of some study limitations: premature enrollment cessation due to death rate lower than expected, short follow-up (6 years), small tumor size (≤2cm in 70% of cases), frequent presence of only microMTS in SLN (40%), prevalent use of “whole breast” adjuvant radiotherapy (>90%) which irradiates the breast but also the I° axillary level, thereby contributing to the low rate of regional relapse in the SLNB arm due to lymph node sterilization. Consequently further randomized trials with more precise selection criteria based on homogeneous clinico-pathological features and with longer follow-up are needed to confirm that performing only SLNB does not affect survival or relapse risk in patients with 1-2 SLNs+. Materials and Methods Primary and secondary aims of the present 2-arm randomized trial are to assess whether ALND omission in BC patients with 1-2 SLNs+ is associated with worse survival and/or increased rate of regional/distant relapse, respectively, thus evaluating whether SLNB is or is not inferior to ALND. Patients receive either conservative surgery or mastectomy and radiotherapy. They all undergo intraoperative SLNB and SLN evaluation, and are randomly assigned to either further dissection of level I-II axillary lymph nodes (standard ALND arm) or absence of any axillary surgery (experimental SLNB arm). According to International Guidelines post-surgery treatments. Eligibility criteria are: age 40-75 years; primary invasive T1-T2 tumor; axillary nodes clinically N0; no more than 2 SLNs presenting macroMTS at intraoperative or definitive histological evaluation; no distant MTS; no neoadjuvant therapy; no previous invasive BC, signed informed consent. Exclusion criteria are: in situ, inflammatory, contralateral BC; presence of only microMTS in the SLN+; pregnancy or breast feeding; comorbidity impeding adjuvant therapy. Follow-up controls foresee: clinical examination every 6 months for 5 years and yearly thereafter; annual mammography and breast echography; annual axillary echography for patients in the SLNB arm; additional laboratory and instrumental surveys in case of suspected onset of distant MTS. The primary endpoint is overall survival (OS). Secondary endpoints are disease-free survival (DFS) referring to distant MTS and to locoregional (ipsilateral breast or axillary, internal mammary or sopraclaveolar lymph nodes) disease recurrence. All analyses are performed both on all patients according to the Intention-To-Treat principle and excluding those patients who did not receive the axillary treatment randomly assigned. Citation Format: Corrado Tinterri, Emilia Marrazzo, Federico Frusone, Wolfgang Gatzemeier, Erika Barbieri, Andrea Sagona, Alberto Bottini, Valentina Errico, Alberto Testori, Giuseppe Canavese. Preservation of axillary lymph nodes compared to complete dissection in T1-T2 breast cancer patients presenting 1-2 metastatic sentinel lymph nodes: A multicenter randomized clinical trial. Sinodar One Study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-01-02.

Background Despite the well-known association between extensive lymphocytic infiltration in breast cancer (BC), good prognosis, and high response rates to neoadjuvant chemotherapy (CT), pathologic evaluation of tumor infiltrating lymphocytes (TILs) is currently not routine and a deep understanding of the properties of TILs, remain largely unfilled. So far, only in triple-negative (TN), PD-L1 positive BCs it has been possible to demonstrate a survival benefit with immunotherapy plus CT, thereby making the definition of possible immunotherapeutic targets across all biological subtypes a fundamental requirement. Material and methods Single-cell RNA-sequencing (scRNAseq) data from 8 BCs were downloaded from Gene Expression Omnibus dataset (GSE114725), obtaining CD45+ single cells only from the tumoral compartment. scRNAseq-guided high-dimensional profiling by 27-parameter FACS was then applied to a large cohort (n=54, including luminal-like, TN and HER2+ BCs) of early BC patients surgically treated at our Institution. We simultaneously profiled the peripheral blood, the normal and tumoral tissue from each patient and acquired using FACS Symphony A5 flow cytometer (BD Biosciences). Flow Cytometry Standard (FCS) 3.0 files were imported into FlowJo software v9, and analyzed by standard gating to remove aggregates and dead cells, and subsequently imported in FlowJo v10, biexponentially transformed, and exported for further analysis in R by a custom-made script, using an ad-hoc pipeline. Data were analyzed using the Phenograph unbiased algorithm coded in the cytofkit package. Data were further analyzed in FlowJo to determine the frequency of positive cells for each marker and the corresponding median fluorescence intensity (MFI). These values were multiplied to derive the integrated MFI; hierarchical metaclustering of all samples, based on the frequency of Phenograph clusters, was performed in R based on the Euclidean distance and Ward-linkage. Pearson correlation analysis was used to investigate the relationship between CD8+ and CD4+ clusters. Results Our scRNA-guided informative 27-colors flow cytometry panel included antibodies to define not only different lymphocyte subpopulations, but also different stages of T lymphocytes: differentiation and memory maturation (CCR7, CD45RA), activation status (HLA-DR), cytotoxicity (GZMK, GZMB), exhaustion (PD-1, TIGIT) and tissue residency (CD69, CD103). Focusing on CD8+ T cells, we observed, as expected, bona fide naïve T cells to be virtually absent at the tumor site and enriched in peripheral blood, while cytotoxic and effector memory cells were enriched in the tumor compartment. Of note, we identified a population of tissue resident memory T cells (Trm) CD69+ CD103+, CD39+, specifically enriched in the tumor, that could be further subdivided into a HLA-DR+ CD127- and a HLA-DR- CD127+ subpopulation. Interestingly, the HLA-DR+ subset exhibited more exhaustion markers (PD-1hi, TIGIT+, NKG2A+) and was significantly positively correlated with CD4+ regulatory T cells. We speculated, and deeply investigated by bulk RNA-seq, that these two subsets of Trm might represent different maturation states and that they could be reinvigorated targeting highly expressed inhibitory molecules using approved (e.g., PD-1) together with newly identified (e.g., NKG2A) immunotherapeutics. Moreover, as no difference was observed in the relative distribution of Phenograph clusters, our data may be applied to revert acquired immune escape mechanisms in all different BC biological subtypes. Conclusions We identified, among Trm CD69+ CD103+, tumor-specific CD39+, PD1+ exhausted population, novel dysfunctional NKG2A+ T cells previously not characterized in BC. This population is of extreme interest to characterize a novel potential immunotherapeutic target. Citation Format: Agnese Losurdo, Caterina Scirgolea, Emilia Mazza, Valentina Errico, Bethania Fernandes, Luca Di Tommaso, Andrea Sagona, Karolina Pilipow, Rosalba Torrisi, Giovanna Masci, Rita De Sanctis, Elisa Agostinetto, Alberto Testori, Corrado Tinterri, Massimo Roncalli, Armando Santoro, Enrico Lugli. Defining T cell dysfunctionality in breast cancer by single cell analysis: Implications for immunotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-07.

PURPOSE: The aim of this study was to evaluate the role of imaging features derived from [18F]FDG-PET/CT to provide in vivo characterization of breast cancer (BC). METHODS: Images from 43 patients with a first diagnosis of BC were reviewed. Images were acquired before any treatment. Histological data were derived from pretreatment biopsy or surgical histological specimen; these included tumor type, grade, ER and PgR receptor status, lymphovascular invasion, Ki67 index, HER2 status, and molecular subtype. Standard parameters (SUVmean, TLG, MTV) and advanced imaging features (histogram-based and shape and size features) were evaluated. Univariate analysis, hierarchical clustering analysis, and exact Fisher's test were used for statistical analysis of data. Imaging-derived metrics were reduced evaluating the mutual correlation within group of features as well as the mutual correlation between groups of features to form a signature. RESULTS: A significant correlation was found between some advanced imaging features and the histological type. Different molecular subtypes were characterized by different values of two histogram-based features (median and energy). A significant association was observed between the imaging signature and luminal A and luminal B HER2 negative molecular subtype and also when considering luminal A, luminal B HER2-negative and HER2-positive groups. Similar results were found between the signature and all five molecular subtypes and also when considering the histological types of BC. CONCLUSIONS: Our results suggest a complementary role of standard PET imaging parameters and advanced imaging features for the in vivo biological characterization of BC lesions.

e12580Background: TILs have been proposed as a prognostic biomarker in many tumor types both in the adjuvant and neoadjuvant setting. In TNBC, TILs are present at the highest level and have been de...

The 'regional nodal mapping', is a fundamental step to stage breast carcinoma. In addition to the axillary nodes status, the involvement of internal mammary nodes is an important prognostic factor. Six hundred and sixty-three patients with breast carcinoma, mainly in the inner quadrants, underwent a biopsy of internal mammary nodes. Positive internal mammary nodes were found in 68 out of 663 cases (10.3%) representing 27.2% of all cases with regional node metastases (250). When histologically proven metastases were detected, radiotherapy was administered to the internal mammary nodes chain. In 254 cases, the surgeon's exploration was guided by a gamma probe. Out of these cases, 28 (11.0%) showed metastatic involvement. Out of the other 409 cases, not radioguided, 40 showed positive nodes (9.8%). Patients with internal mammary metastases treated with radiotherapy and appropriate systemic treatment showed an excellent survival (95% at 5 years), a result which is in opposition to the previous experience, which stated that invasion of internal mammary nodes is an ominous prognostic sign. We assume that this excellent result is due to radiotherapy to internal mammary nodes and we propose that exploration of internal mammary nodes should be part of the staging process of carcinomas of the medial part of the breast.

Sentinel lymph node biopsy is an accepted standard of care for staging the axilla in patients with early-stage breast cancer. Little attention has been placed to the presence of intramammary sentinel lymph nodes (intraMSLNs) on preoperative lymphoscintigraphy. Between December 2001 and September 2006, in 9632 breast cancer patients with clinically uninvolved axillary nodes, lymphoscintigraphy was performed at the European Institute of Oncology (EIO). An axillary SLN (axSLN) was identified in 99.4% of cases. An intraMSLN was identified in association with the axillary sentinel lymph node in 22 patients (0.2%). In 15 cases both the axSLN and the intraMSLN were excised. The intraMSLN was positive in six patients (micrometastatic in three cases). The axSLNs were negative in all 15 cases. Two patients with positive intraMSLNs and one patient with a negative intraMSLN underwent axillary dissection; all three cases had negative axillary nodes. At a median follow-up of 24 months, no locoregional or systemic recurrences were observed. Positive intraMSLNs can improve disease staging but do not necessarily portend axillary lymph node metastasis. When intraMSLNs and axSLNs are present, we advocate biopsy of both sites and that management of the axilla should rely on axSLN status. In cases with intraMSLNs as the only draining site on lymphoscintigraphy, decisions on axillary management should be made on individualized basis.

11562Background: Mammography is the standard for breast cancer (BC) screening and diagnosis. However, its limited accuracy and false-positive results necessitate the identification of novel complem...

Background To report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. Methods Between September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor. Results The median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up. Conclusions The 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.

Approximately 10% of patients with breast cancer who are treated with breast-conserving surgery (BCS) develop an ipsilateral-breast tumor recurrence (IBTR). The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial. We report the outcome of BCS in BRCA mutation carriers followed at a single institution.A total of 54 women with BRCA1/2-associated breast cancer treated with BCS and whole breast radiotherapy were matched for age, tumor size, and time of surgery with 162 patients with sporadic breast cancer who had the same treatment between February 1994 and October 2007. Primary end points were cumulative incidence of IBTR and contralateral breast cancer (CBC). Median follow-up was 4 years for both groups.Median age was 36 and 37 years for mutation carriers and controls, respectively; mean tumor size was 1.8 cm in carriers and 1.9 cm in controls. Ten-year cumulative incidence of IBTR was 27% for mutation carriers and 4% for sporadic controls (hazard ratio 3.9; 95% confidence interval 1.1-13.8; P = 0.03). Ten-year cumulative incidence of CBC was 25% for mutation carriers and 1% for sporadic controls (P = 0.03).Our data suggest that IBTR risk after BCS in BRCA1/2 mutation carriers is increased compared with patients who have sporadic breast cancer. Likewise, the risk of CBC seems to be increased in this group. These risks and the likelihood of developing new primary tumors should be discussed with carriers interested in breast conservation as well as when choosing risk-reducing strategies.

Background: In the case of ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS), a second conservative surgical approach maybe considered in some motivated patients whereas in others mastectomy is unavoidable. Patients and methods: From 1997 to 2004, 282 patients presented at the European Institute of Oncology with an operable invasive IBTR after BCS. One hundred and sixty-one (57%) underwent a second conservative surgery, whereas 121 patients (43%) were given a mastectomy and represent the study population. We investigated the prognosis and determined predictive factors of outcome. Results: Median time from primary breast cancer to IBTR was 41 months (range 5–213). Recurrences were T2–T4 and/or multifocal in 83 cases (68.6%). With a median follow-up of 5 years after mastectomy, 5-year overall survival (OS) and disease-free survival (DFS) were 73.3% [95% confidence interval (CI) 65.0% to 81.6%] and 50.4% (95% CI 40.9% to 59.8%), respectively. At the multivariate analysis, early onset of IBTR, presence of vascular invasion and Ki67 ≥20 of the recurrent tumour were found to significantly affect both DFS and OS. Conclusions: In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors.

Aims and background Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular nodes if 4 or more axillary nodes are involved, the current practice at our Institute is not to irradiate the axilla but to perform complete axillary dissection in which all 3 Berg levels are removed. We performed a retrospective analysis of patients with 4 or more axillary nodes involved and sufficient follow-up to provide indications as to whether our current treatment is adequate. Methods We retrospectively analyzed 287 T1–T3 patients with a median follow-up of 5 years and 4 or more involved nodes treated by quadrantectomy and breast RT but no axillary RT; supraclavicular RT was given only when prognostic factors were unfavorable. Results A total of 170 (59.2%) patients did not receive supraclavicular RT, while 117 (40.8%) patients received supraclavicular irradiation. No patient received axillary RT. After a median follow-up of 5 years (range, 4–105 months), 4.7% had died and 13.5% had developed distant metastases in the no supraclavicular RT group, compared to 12.0% dead (P = 0.028 log rank) and 24.8% (P = 0.201 log rank) in the supraclavicular RT group. No patients with supraclavicular RT developed supraclavicular metastases compared to 4 in the no supraclavicular RT group. There were no axillary recurrences. Conclusions Complete axillary dissection appears adequate treatment in patients with 4 or more involved nodes. The low breast recurrence rate also suggests that breast conservation is adequate treatment in such patients. Supraclavicular RT appears to reduce the number of supraclavicular metastases but confers no survival advantage. Although a small number of cases were examined in this retrospective single-center series, all received highly uniform treatment.