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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

Carcinoma of unknown primary (CUP) syndrome occurs when metastases from an unknown primary site spread to multiple organs. Occult breast cancer (OBC) is defined as a clinically recognizable metastatic carcinoma from an undetectable primary breast tumor. It accounts for 0.3–1% of all breast cancers, often presenting with lymph node, bone, and skin metastases. Clinical and radiological examinations represent the first steps in the diagnostic algorithm for CUP syndrome from OBC. However, histological and immunohistochemical analyses, multidisciplinary team evaluation, and a multidisciplinary therapy are essential in the diagnosis and treatment of CUP syndrome from OBC. We report the case of a 52-year-old woman who underwent the removal of a parietal skin lesion. The histological and immunohistochemical analyses suggested a breast cancer origin. Clinical assessment and laboratory and radiological examinations did not locate the primary tumor. Hormone therapy was offered to the patient; however, she refused it. After 28 months, the patient reported a right cervical lump, and a total-body positron emission tomography showed dissemination of the disease to the lymph nodes and bone. A CUP syndrome from OBC was diagnosed. A multimodality approach with radiotherapy and hormone and biological therapy was started. At present, 5 years from the first presentation, the patient is asymptomatic despite the disseminated disease.

Background: Sentinel lymph node biopsy (SLNB) has emerged as the standard procedure to replace axillary lymph node dissection (ALND) in breast cancer (BC) patients undergoing neo-adjuvant chemotherapy (NAC). SLNB is accepted in clinically node-negative (cN0) patients; however, its role in clinically node-positive (cN+) patients is debatable. Methods: We performed a retrospective analysis of BC patients undergoing NAC and SLNB. Our aim was to evaluate the clinical significance of SLNB in the setting of NAC. This was accomplished by comparing the characteristics and oncological outcomes between cN0 and cN+ patients prior to NAC and type of axillary surgery. Results: A total of 291 patients were included in the analysis: 131 were cN0 and 160 were cN+ who became ycN0 after NAC. At a median follow-up of 43 months, axillary recurrence occurred in three cN0 (2.3%) and two cN+ (1.3%) patients. However, there were no statistically significant differences in oncological outcomes (disease-free survival, distant disease-free survival, overall survival, and breast-cancer-specific survival) between cN0 and cN+ patients nor between patients treated with SLNB only or ALND. Conclusions: SLNB in the setting of NAC is an acceptable procedure with a general good prognosis and low axillary failure rates for both cN0 and cN+ patients.

Background: Loco-regional therapy (LRT) in de novo metastatic breast cancer (MBC) has been investigated in several clinical trials, with heterogeneous and conflicting results. Methods: We conducted a retrospective study of de novo MBC patients treated with front-line chemotherapy (FLC) followed by LRT of the primary tumor. Our aims were to evaluate the characteristics, treatment, and oncological outcomes in terms of progression-free survival (PFS), distant progression-free survival (DPFS), and overall survival (OS) of de novo MBC. We also investigated possible subgroups of patients with better outcomes according to menopausal status, biological sub-type, location, number of metastases, and radiologic complete response after FLC. Results: We included 61 patients in the study. After a median follow-up of 55 months, disease progression occurred in 60.7% of patients and 49.2% died. There were no significant differences in PFS, DPFS, and OS between different subgroups of de novo MBC patients. A trend toward better PFS and DPFS was observed in triple-positive tumors, without a statistically significant difference in OS. Conclusions: No specific subgroup of de novo MBC patients showed a statistically significant survival advantage after FLC followed by LRT of the primary tumor.

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.

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.

Background Whether the extent of residual disease in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC) influences the prognosis in clinically node-positive breast cancer (BC) patients remains to be ascertained. Methods One hundred and thirty-four consecutive cN+/BC-patients received NAC followed by SLN biopsy and axillary lymph node dissection. Cumulative incidence of overall (OS) and disease-free (DFS) survival, BC-related recurrences and death from BC were assessed using the Kaplan-Meier method both in the whole patient population and according to the SLN status. The log rank test was used for comparisons between groups. Results The SLN was identified in 123/134 (91.8%) patients and was positive in 98/123 (79.7%) patients. Sixty-five of them (66.3%) had other axillary nodes involved. SLN sensitivity and false-negative rate were 88.0% and 2.0%, Median follow-up was 10.2 years. Ten-year cumulative incidence of axillary, breast and distant recurrences, and death from BC were 6.5%, 11.9%, 33.4% and 31.3%, respectively. Ten-year OS and DFS were 67.3% and 55.9%. When stratified by SLN status, 10-year cumulative incidence of BC-related and loco-regional events, and death from BC were similar between disease-free SLN and micrometastatic SLN subgroups (28.9% vs 30.2%, p = 0.954; 21.6% vs 13.4%, p = 0.840; 12.9 vs 24.5%, p=0.494). Likewise, 10-year OS and DFS were comparable (80.0% vs 75.5%, p=0.975 and 68.0% vs 69.8, p=0.836). Both OS and DFS were lower in patients presenting a macrometastatic SLN (60.2% and 47.5%). Conclusion Outcome of patients with micrometastatic SLN was similar to that of patients with disease-free SLN, which was more favorable as compared to that of patients with macrometastatic SLN.

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.

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.

Purpose We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint ® , MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. Results Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. Conclusions Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Purpose: Studies have shown that the 70-gene signature (MammaPrint®) (MP) may outperform clinicopathological risk assessment and may predict the benefit from chemotherapy (CT) in patients (pts) with early-stage breast cancer. However, the need of fresh tissue and the high cost of the assay limit its use in daily clinical practice. We investigated whether 1) tumor clinicopathologic features can predict MP risk (high vs. low); 2) MP results could help to make decisions for the use of CT in pts with ER positive (ER+ve) breast cancer beyond recommendations of known international guidelines (NCCN, St. Gallen). Patients and methods: Women with operable invasive breast cancer without evidence of distant disease undergoing surgery at the Breast Surgery Department were enrolled into the study. A 3 mm punch biopsy of the tumor was obtained from the specimen within the first hour after surgery. Samples were shipped to the laboratory in an RNA-stabilizing solution and were studied to ensure the presence of at least 30% of tumor cells and a customized microarray containing 70 genes was analyzed as described by the manufacturer. Results: 124 consecutive pts were enrolled into the study; 106 tumor samples were adequate for the microarray. Median age was 53 yrs (range 28–83), mean tumor size was 2.3 cm (SD ±1.34), 52.4% pts had pN0, 55% of tumors had Ki-67 ≥20% and 36% were poorly differentiated. ER were detected in ≥50% of cells in 82% and As expected, poorly differentiated, ER and PgR negative, HER2 positive and highly proliferating tumors were more likely to be classified as high-MP. We then focused our analysis on ER and PgR +ve, HER2 negative tumors and assessed features correlated with MP results in this subgroup. Unexpectedly, 31/80 (39%) of these tumors were classified as high-MP vs. 49 (61%) low-MP. We found that tumor size (T1 vs. T2-T4), poor differentiation (G3 vs G1-2) and high proliferation (Ki-67 ≥20%) were significantly associated with a high-MP result. In an exploratory multivariate analysis tumor size and Ki-67 remained as independent predictors of high-MP result. At last, when we compared MP risk with recommendations for AT from international guidelines we found that in the subgroup of candidates for endocrine therapy (ET) in whom the benefit from the addition of CT is undetermined, 25/68 pts (37%) were high-MP and 43 pts (63%) low-MP. When we considered recommendations for AT proposed by our multidisciplinary team according to international guidelines, 11/25 pts (44%) with high-MP received ET only and 14 pts (56%) CT + ET, while among 43 pts with low-MP only 9 received both CT and ET. Conclusions: Our study shows that the 70-gene signature was feasible in the clinical setting, as 85% of tumor samples were adequate. A substantial proportion of ER/PgR+ve, HER2 negative tumors was classified as high-MP; within this subgroup, proliferation and tumor size independently predicted high-MP results. In 20 pts, MP risk would have resulted in discordant recommendations for AT compared to those based on standard clinicopathologic features. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-27.

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...

Parallel to its life-threatening nature, breast cancer can affect physical integrity, having a psychosocial impact on patients. Determining the optimal proportion of patients who should undergo breast reconstruction after cancer surgery represents a complex task. What seems to be unquestionable is that the ability to offer reconstruction and a wide range of surgical options plays an important role in current breast cancer management. The multidisciplinary approach is a paramount aspect not only for a successful oncologic treatment, but also for improving patient quality of life.