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Introduction Autologous fat transfer (AFT) is widely adopted for breast reconstruction, but its long-term oncologic safety is still not clearly established. The aim of the present study was to compare the 10-year loco-regional recurrence (LRR)-free and distant metastases (DM)-free survival probabilities in AFT vs. control patients, also evaluating the impact of AFT in different intrinsic molecular subtypes of breast cancer. Materials and methods 464 AFT patients were exactly matched with a cohort of 3100 control patients treated between 2007 and 2017. A multivariate survival analysis was performed accounting for all variables related to LRR and DM, including adjuvant/neoadjuvant treatments. End-points were analyzed both overall and in each molecular subtype. Results LRR occurred in 6.4% of AFT and in 5.0% of control patients (p = 0.42), while DM were observed respectively in 7.7% and 5.4% of cases (p = 0.20). AFT showed no effect on the 10-year LRR-free survival probability (adjusted HR 0.87, 95%CI 0.43–1.76, p = 0.69) or the 10-year DM-free survival probability (adjusted HR 0.82, 95%CI 0.43–1.57, p = 0.55). Luminal A patients treated by AFT showed a decreased LRR-free survival probability (HR 2.38, 95%CI 0.91–6.17, Log-Rank p = 0.07), which was significantly lower than controls after 80 months (Log-Rank p = 0.02). No differences in the 10-year event-free survival probability were found in Luminal B, HER2-positive or triple-negative patients. Conclusion AFT does not increase breast cancer recurrence, with the possible exception of late LRRs for Luminal A patients, but further clinical and preclinical data are required to better clarify this data. The use of AFT should not be discouraged.

Background and objectives An accurate localization is mandatory to tailor breast lumpectomy in nonpalpable cancers. The aim of this study was to compare radio-guided localization (ROLL) vs ultrasound localization of a titanium clip with collagen (TCC) in nonpalpable mass-like breast cancers. Methods Two hundred seventy-three consecutive patients were reviewed: 64 patients were localized by TCC and 209 patients by ROLL. Propensity score-matched analysis was performed. Margin status and reintervention rates were compared. Adequacy of resection was expressed as the calculated resection ratio (CRR) considering lesion size. Loco-regional and distant recurrence rates were assessed with ROLL vs TCC. Results No differences were found with ROLL vs TCC in clear margins (90.6% vs 89.1%; odds ratio, 0.74; P = 0.64) or reoperations (6.7% vs 1.6%; P = 0.529). ROLL allowed more tailored resections compared with TCC (adjusted CRR, 1.7 vs 2.7; P = 0.0008), particularly in lesions with associated extensive intraductal component (CRR, 3.0 vs 4.5; P = 0.017). Loco-regional recurrence occurred in 1.9% of ROLL patients vs 3.2% of TCC cases (P = 0.628). Conclusions ROLL and TCC are equally effective to excise nonpalpable mass-like breast cancers with clear margins, providing similar loco-regional control. However, ROLL allows more tailored breast resections, particularly in lesions with the associated extensive intraductal component.

Aim of the study: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006-2015. Materials and methods: Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006-2015. Results: On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor-negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015. Conclusion: The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time. (C) 2017 Elsevier Ltd. All rights reserved.

Aromatase inhibitors (AIs), such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, ∼20% of patients with hormone receptor-positive breast tumors treated with anastrozole do not respond and it remains impossible to accurately predict sensitivity. Since polymorphisms in the aromatase gene may influence the response to inhibitory drugs, we evaluated the presence of rs6493497 and rs7176005 polymorphisms (mapping in the 5′-flanking region of the CYP19A1 gene coding for the aromatase protein) in a cohort of 37 patients with postmenopausal breast cancer who received three-month neoadjuvant treatment with anastrozole. We then investigated any association of the polymorphisms with changes in aromatase mRNA expression change and/or response to treatment. We also analyzed five miRNAs computationally predicted to target aromatase, to observe any association between their expression and sensitivity to anastrozole. Three samples carried the two polymorphisms and the remaining samples were wild-type for both, however, no association with response or with aromatase mRNA basal expression level or expression difference after therapy was observed. Polymorphic samples that were resistant to anastrozole showed no change or decrease in aromatase expression following AI treatment, whereas an increase in expression was observed for the polymorphic responsive samples. No statistically significant correlation was observed between miRNA and aromatase mRNA expression, or with response to anastrozole neoadjuvant treatment. These data indicate that the polymorphisms analyzed are not involved in aromatase activity and that other epigenetic mechanisms may regulate aromatase protein expression.

Reconstruction options following nipple-sparing mastectomy (NSM) are diverse and not yet investigated with level IA evidence. The analysis of surgical and oncological outcomes of NSM from the Italian National Registry shows its safety and wide acceptance both for prophylactic and therapeutic cases. A further in-depth analysis of the reconstructive approaches with their trend over time and their failures is the aim of this study. Data extraction from the National Database was performed restricting cases to the 2009–2014 period. Different reconstruction procedures were analyzed in terms of their distribution over time and with respect to specific indications. A 1-year minimum follow-up was conducted to assess reconstructive unsuccessful events. Univariate and multivariate analyses were performed to investigate the causes of both prosthetic and autologous failures. 913 patients, for a total of 1006 procedures, are included in the analysis. A prosthetic only reconstruction is accomplished in 92.2 % of cases, while pure autologous tissues are employed in 4.2 % and a hybrid (prosthetic plus autologous) in 3.6 %. Direct-to-implant (DTI) reaches 48.7 % of all reconstructions in the year 2014. Prophylactic NSMs have a DTI reconstruction in 35.6 % of cases and an autologous tissue flap in 12.9 % of cases. Failures are 2.7 % overall: 0 % in pure autologous flaps and 9.1 % in hybrid cases. Significant risk factors for failures are diabetes and the previous radiation therapy on the operated breast. Reconstruction following NSM is mostly prosthetic in Italy, with DTI gaining large acceptance over time. Failures are low and occurring in diabetic and irradiated patients at the multivariate analysis.

Background Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. Methods In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. Results 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. Conclusions More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy.

Choice of the most appropriate surgical treatment for breast cancer patients can also be a technical issue. Cosmetic results after conservative surgery can be poor in certain instances and, at the same time, total mastectomy can appear as an over-treatment. For some selected patients, the “nipple sparing mastectomy” (NSM) is an alternative surgical treatment and more and more papers on this technique are appearing in the literature. One hundred and two NSMs have been performed in our department between June 2003 and October 2006, initially via periareolar skin incision, now through a skin incision on the lateral aspect of the breast to reduce the necrotic risk for the nipple. The lateral skin incision saves the integrity of skin blood supply, allows for a complete breast gland removal and saves the integrity of the body image of women who show no scars when seen upfront.

Aim of the study: The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast units to establish minimum standards and ensure specialist multidisciplinary care. In the present study we assess the impact of EUSOMA certification for all breast units for which sufficient information was available before and after certification. Materials and methods: For 22 EUSOMA certified breast units data of 30,444 patients could be extracted from the EUSOMA database on the evolution of QI's before and after certification. Results: On the average of all units, the minimum standard of care was achieved for 12/13 QI's before and after EUSOMA certification (not met for DCIS receiving just one operation). There was a significant improvement of 5 QI's after certification. The proportion of patients with invasive cancer undergoing an axillary clearance containing >9 lymph nodes (91.5% vs 89.4%, p 0.003) and patients with invasive cancer having just 1 operation (83.1% vs 80.4%, p < 0.001) dropped, but remained above the minimum standard. The targeted standard of breast care was reached for the same 4/13 QI's before and after EUSOMA certification. Conclusion: Although the absolute effect of EUSOMA certification was modest it further increases standards of care and should be regarded as part of a process aiming for excellence. Dedicated units already provide a high level of care before certification, but continuous monitoring and audit remains of paramount importance as complete adherence to guidelines is difficult to achieve. (C) 2015 Elsevier Ltd. All rights reserved.

Breast conserving therapy (BCT) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer. The question is whether there is a necessity for irradiating all patients. Between 2001 and 2005, 749 women aged 55-75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery, with or without radiotherapy (RT), to evaluate the incidence of in-breast recurrence (IBR). After 5 years of median follow-up, the cumulative incidence of IBR was 2.5% in the surgery-only arm and 0.7% in the surgery plus RT arm. There are no differences in terms of overall survival and distant disease-free survival. The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence. Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT.

Breast-conserving therapy (BCT), including postoperative whole breast irradiation (WBI), is generally accepted as the treatment of choice for most patients with early-stage breast cancer. The question whether WBI is mandatory in all patients remains one of the most controversial issues in BCT. To answer this question, a randomized, prospective, multicentre study was launched in January 2001. Primary endpoints of the study were to assess the cumulative incidence of in-breast-recurrences (IBR) and overall survival (OAS) after conservative surgery (BCS) with or without WBI.From January 2001 until December 2005, 749 patients with unifocal infiltrating breast cancer up to 25 mm, 0-3 positive axillary lymph nodes, no extensive intraductal component or lymphvascular invasion from 11 centres in Italy, were randomly assigned to BCS+WBI (arm 1:373 patients) or BCS alone (arm 2:376 patients). Treatment arms were well balanced in terms of baseline characteristics. Systemic adjuvant therapy was administered according to the institutional policies. Kaplan-Meier method was used for survival analysis and log-rank test to evaluate the difference between the two arms. RESULTS (Last analysis 31.12.2012): After median follow-up of 108 months, 12 (3.4%) IBR were observed in arm 1 and 16 (4.4%) in arm 2. OAS was 81.4% in arm 1 and 83.7% in arm 2. There was no statistically significant difference regarding IBR and death in the two treatment groups.These data are promising and suggest that WBI after BCS can be omitted in selected patients with early stage breast cancer without exposing them to an increased risk of local recurrence and death. Longer follow-up is needed to further consolidate these results.

Background SEMA6B is a member of the semaphorins axon-guidance family. A growing body of evidence has been accumulated describing the role of semaphorin molecules in cancer development and the involvement of SEMA6B in cancer progression has recently been proposed. Methods Our analysis, based on real-time PCR, focused on the expression of SEMA6B in a panel of breast cancer tissues, compared to the normal counterpart. Results In cancer tissues we found a significantly strong down-modulation of this transcript. Moreover we identified and characterized a novel SEMA6B isoform, named SEMA6B a. This isoform has a novel splice junction, created by the usage of alternative donor and acceptor splice sites internal to the exon 17. By in silico analysis we found that the new transcript 3′ UTR lacks some highly-conserved miRNA binding sites, suggesting possible consequences on both spatial and temporal expression of SEMA6Ba. The translated sequence of SEMA6Ba lacks the cytoplasmic tail, crucial for triggering the reverse signaling described for the transmembrane semaphorins. We also demonstrated, by immunofluorescence analysis of endogenous and overexpressed SEMA6Ba , that the protein clearly localized to the endoplasmic reticulum and plasma membrane. In conclusion, SEMA6B gene products are strongly down modulated in breast cancer tissues and a new isoform named SEMA6Ba has been described and characterized. General significance Our work states a clear relation among breast cancer and SEMA6B expression; moreover we describe for the first time the SEMA6Ba protein and report here the analysis of SEMA6Ba RNA messenger, the protein expression and the cellular localization.

Aromatase inhibitors, such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, approximately 20% of patients treated with anastrozole do not respond, and it remains impossible to accurately predict sensitivity. Thus, novel markers to predict response are required. The K303R estrogen receptor (ER)α mutation confers resistance to tamoxifen treatment. Moreover, K303R-expressing MCF-7 cells, transfected with an aromatase expression vector and stimulated with androstenedione (an aromatase substrate), were found to be resistant to the inhibitory effect of anastrozole. The aim of this study was to verify whether the presence of the K303R ERα mutation is associated with response to 3-month neoadjuvant treatment with anastrozole (Arimidex) in a cohort of post-menopausal breast cancer patients. Of 37 patients with ER(+) tumors, 19 showed a clinical response to anastrozole and 18 were resistant. Biopsies were obtained from tumors responding to the therapy or from non-responding tumors. None carried the K303R ERα mutation. To our knowledge, this is the first study to search for K303R ERα mutations in tumors clinically responsive or resistant to an aromatase inhibitor. Lack of the mutation leads us to believe that this mutation has in vivo biological significance in only a subset of breast cancers.

Udgivelsesdato: 2007-Oct Twelve expert observers from nine different countries convened in a workshop to evaluate the validity of the Breast Cancer Conservative Treatment. Cosmetic results (BCCT.core) software, an objective method for the aesthetic evaluation of breast cancer conservative treatment. Experts were initially asked to subjectively classify the aesthetic results of 30 photographed cases submitted to breast cancer conservative treatment according to the four-point Harris scale. It was pre-established that if at least two-thirds [Cardoso MJ, Cardoso J, Santos AC, Barros H, Oliveira MC. Interobserver agreement and consensus over the esthetic evaluation of conservative treatment for breast cancer. Breast 2005] of participants provided the same classification this would be considered a consensual evaluation for that case. For cases where such agreement was not reached, consensus was obtained using a nominal group technique. Experts then individually performed objective evaluation of the same set of photographs using the BCCT.core software. This provides an automatic rating of aesthetic results, once scale and reference points in the photograph have been chosen. Agreement between observers, between each observer and the consensus, for computer evaluation obtained by the different participants and between software and consensus was calculated using multiple kappa (k) and weighted kappa (wk) statistics. In the subjective assessment, first-round consensus was achieved in 17 (57%) cases. Overall interobserver agreement was fair to moderate (k=0.40, wk=0.57). In the objective assessment there was a higher level of concordance between participants (k=0.86, wk=0.90). Agreement between software and consensus classification was fair (k=0.34, wk=0.53), but was higher in the 17 cases that reached first-round consensus (k=0.60, wk=0.73). Merging the two middle classes of the Harris scale, to form a three-point scale, led to an improvement of all non-weighted measures of agreement. These results show that the BCCT.core software provides consistent evaluation of cosmesis. It has the potential to become a gold standard method for assessment of breast cosmesis in clinical trials, as it can be used simultaneously by a panel of observers from different parts of the world to provide more reliable assessments than has been possible previously

PURPOSE OF REVIEW: Conserving the breast is one of the main objectives in treating patients affected by carcinoma. This objective should be compatible with good local control to keep the risk of local failures low. The progressive reduction of the extension of surgery in the breast and in the axilla is now accompanied by a reduction of the radiation field. This article provides an update on conservative therapy for breast cancer. RECENT FINDINGS: After the development of quadrantectomy, the effectiveness of sentinel node biopsy was demonstrated in the axillary staging of breast carcinoma. The situation took another step forward with partial breast irradiation. The highest incidence of local relapse after breast-conserving surgery is observed in the same area as the primary tumor. This factor provides the rationale for reducing the radiation field to a limited area of the breast primarily affected by carcinoma. SUMMARY: The Milan I trial on breast conservative surgery provided definitive confirmation of the equivalence of quadrantectomy, followed by radiotherapy, to mastectomy in terms of local control of disease. The randomized trial on sentinel node biopsy demonstrated the effectiveness of this procedure in axillary staging of breast carcinoma. Radiotherapy is currently under investigation in terms of limiting the radiation field to the affected quadrant of the breast by means of various techniques.

Lipofilling is becoming part of the breast reshaping after quadrantectomy or mastectomy in breast cancer patients, but there are open questions of its safety.

Plastic and oncological breast surgery have to be considered as two aspects of the same treatment. The term "oncoplastic surgery" refers to the use of plastic surgery techniques in breast cancer surgery, in order to avoid and to correct the adverse aesthetic findings. The care of cosmetic sequelae of breast cancer surgery has reached an important therapeutic role for psychological consequences of disease and because of the higher patients expectations of a good aesthetic result. Considering the concept of oncoplastic surgery, since 1999 the authors began to use a periareolar approach in the breast conserving therapy (BCT), associated to axillary dissection performed through the same periareolar incision. This technique is not different from the traditional quadrantectomy in the extension of the glandular resection, while the skin may be preserved in according to the conventional protocols of BCT. Oncological and aesthetic results have proved to be safe and satisfactory.

Plastic and oncological breast surgery are becoming more and more closer as one surgical treatment. The term "oncoplastic surgery" refers to the use of plastic surgery techniques in breast cancer surgery, in order to avoid and to correct the adverse aesthetic findings. The care of cosmetic sequelae of breast cancer surgery has reached an important therapeutic role for psychological consequences of disease and because of the higher patients expectations of a good aesthetic result. Considering the concept of oncoplastic surgery, since 1999 the Authors began to use a periareloar approach in the breast conserving therapy (BCT), associated to axillary dissection performed through the same periareolar incision. This technique, original from the oncological point of view, is not different from the traditional quadrantectomy in the extension of the glandular resection, while the skin may be preserved in according to the conventional protocols of BCT. Oncological and aesthetic results have proved to be safe and satisfactory.

The reconstruction of the female breast after mastectomy has become a crucial part of primary breast cancer therapy. Setting of an implant is possible only in case of locally abounding soft tissue coverage and when no radiation has before performed. It is necessary a complete integrity of the submuscolar pocket and good blood supply of the skin to avoid failure of the procedure. In Author's experience, started since 1994, an immediate breast reconstruction after mastectomy is performed using gel-silicon implants directly when it was possible or setting first an expander. In six cases the condition of major pectoralis muscle after mastectomy was so foul that an immediate breast reconstruction with prosthesis was not realizable. However, the Authors tried a new technique using polypropylene mesh sutured on the major pectoralis muscle to cover the muscle partially destroyed. Preliminary data from the 6 pts seems to be encouraging.

Axillary seroma is absolutely the most frequent complication of breast cancer surgery. The Authors have accrued 100 consecutive breast cancer patients in a randomized study in order to compare seroma incidence by removing drains on 2nd postoperative day (1st arm) versus 3rd postoperative day (2nd arm); 48 patients were accrued in the first arm and 52 in the second. All patients received a standard axillary dissection. Two suction drains were placed. A compressive medication was applied after surgery. Patients started physiotherapy on the 1st postoperative day. The overall seroma prevalence was 21%. We have 8/48 (16%) seromas in the 1st group and 13/52 (25%) in the 2nd. No significant differences were registered between two arms. Clinical seroma was treated by needle aspiration and medication with a steroid. Conclusions coming out from this study are: 1) early drains removal doesn't increase seroma rate; 2) axillary clearance has to be performed removing en bloc the fatty tissue respecting surgical plains; 3) apply a compressive bandaging; 4) early arm physiotherapy; 5) medication with steroid may reduce the fluid formation.

The Authors report a case of great desmoid tumor of the abdominal wall with intestinal adhesions and enterocutaneous fistula, in a patient with Gardner's syndrome, who underwent total colectomy with ileorectal anastomosis. The patient was treated at first with non steroidal antiinflammatory drugs, then with local chemotherapy. The Authors performed a second surgical procedure resecting the tumor and opening a temporary ileostomy. Despite of these treatment patient showed a local recurrence. Desmoid tumor is a neoplastic benign lesion arising from aponeurotic muscle tissue. Local infiltration and post-operative recurrence are very common. Several surgical and medical treatments are proposed, but they are not totally effective. Surgical treatment might be radical, with wide resection to reduce local recurrences. Radiotherapy and chemotherapy are second choice treatments.

Still unexplored is the correlation betweenplasmaD-dimer levels and axillary node involvement, as detected following SNB investigation, in operable breast cancer.1 This prospective study attempts to verify the correlation between D dimer level and lymph node involvement, including patients with positive Sentinel Node. Between January 2007 and October 2010, preoperative D-dimer levels were evaluated in 142 consecutive operable breast cancer, receiving axillary lymph node dissection, either preoperatively planned (41) or after sentinel node biopsy (SNB) (101). Forty-one (41) patients were candidate to quadrantectomy or mastectomy plus axillary dissection, not satisfying eligibility criteria for SNB procedure. In second group,101 patients were candidate for conservative treatment following SNB procedure. Patientswith positive SN (22) received standard axillary dissection. In order to determine a threshold in D dimer levels distinguishing between subjects with involved lymph-nodes and subjects with no lymph-nodal involvement, a ROC curve analysis was performed on both the whole sample and subgroups identified according to surgical procedure. No difference was found between patients with negative or positive lymph nodes, either in case of axillary dissection or after SNB procedure. The hypothesis that D-dimer level might be related to breast cancer clinical stage is not supported.