New techniques versus standard mapping for sentinel lymph node biopsy in breast cancer: a systematic review and meta-analysis.

New tracers for sentinel lymph node biopsy (SLNB), as indocyanine green (ICG), superparamagnetic iron oxide (SPIO) and micro bubbles, have been recently introduced in clinical practice showing promising but variable results. We reviewed the available evidence comparing these new techniques with the standard tracers to evaluate their safety. To identify all available studies, a systematic search was performed in all electronic databases. Data regarding sample size, mean number of SLN harvested for patient, number of metastatic SLN and SLN identification rate of all studies were extracted. No significant differences were found in terms of SLNs identification rates between SPIO, RI and BD but with a higher identification rate with the use of ICG. No significant differences were also found for the number of metastatic lymph nodes identified between SPIO, RI and BD and the mean number of SLNs identified between SPIO and ICG versus conventional tracers. A statistically significant differences in favor of ICG was reported for the comparison between ICG and conventional tracers for the number of metastatic lymph nodes identified. Our meta-analysis demonstrates that the use of both ICG and SPIO for the pre-operative mapping of sentinel lymph nodes in breast cancer treatment is adequately effective.

Generation and Characterization of a Tumor Stromal Microenvironment and Analysis of Its Interplay with Breast Cancer Cells: An In Vitro Model to Study Breast Cancer-Associated Fibroblast Inactivation.

Breast cancer-associated fibroblasts (BCAFs), the most abundant non-cancer stromal cells of the breast tumor microenvironment (TME), dramatically sustain breast cancer (BC) progression by interacting with BC cells. BCAFs, as well as myofibroblasts, display an up regulation of activation and inflammation markers represented by α-smooth muscle actin (α-SMA) and cyclooxygenase 2 (COX-2). BCAF aggregates have been identified in the peripheral blood of metastatic BC patients. We generated an in vitro stromal model consisting of human primary BCAFs grown as monolayers or 3D cell aggregates, namely spheroids and reverted BCAFs, obtained from BCAF spheroids reverted to 2D cell adhesion growth after 216 h of 3D culture. We firstly evaluated the state of activation and inflammation and the mesenchymal status of the BCAF monolayers, BCAF spheroids and reverted BCAFs. Then, we analyzed the MCF-7 cell viability and migration following treatment with conditioned media from the different BCAF cultures. After 216 h of 3D culture, the BCAFs acquired an inactivated phenotype, associated with a significant reduction in α-SMA and COX-2 protein expression. The deactivation of the BCAF spheroids at 216 h was further confirmed by the cytostatic effect exerted by their conditioned medium on MCF-7 cells. Interestingly, the reverted BCAFs also retained a less activated phenotype as indicated by α-SMA protein expression reduction. Furthermore, the reverted BCAFs exhibited a reduced pro-tumor phenotype as indicated by the anti-migratory effect exerted by their conditioned medium on MCF-7 cells. The deactivation of BCAFs without drug treatment is possible and leads to a reduced capability of BCAFs to sustain BC progression in vitro. Consequently, this study could be a starting point to develop new therapeutic strategies targeting BCAFs and their interactions with cancer cells.

Clinical value of radiomics and machine learning in breast ultrasound: a multicenter study for differential diagnosis of benign and malignant lesions.

OBJECTIVES: We aimed to assess the performance of radiomics and machine learning (ML) for classification of non-cystic benign and malignant breast lesions on ultrasound images, compare ML's accuracy with that of a breast radiologist, and verify if the radiologist's performance is improved by using ML. METHODS: Our retrospective study included patients from two institutions. A total of 135 lesions from Institution 1 were used to train and test the ML model with cross-validation. Radiomic features were extracted from manually annotated images and underwent a multistep feature selection process. Not reproducible, low variance, and highly intercorrelated features were removed from the dataset. Then, 66 lesions from Institution 2 were used as an external test set for ML and to assess the performance of a radiologist without and with the aid of ML, using McNemar's test. RESULTS: After feature selection, 10 of the 520 features extracted were employed to train a random forest algorithm. Its accuracy in the training set was 82% (standard deviation, SD, ± 6%), with an AUC of 0.90 (SD ± 0.06), while the performance on the test set was 82% (95% confidence intervals (CI) = 70-90%) with an AUC of 0.82 (95% CI = 0.70-0.93). It resulted in being significantly better than the baseline reference (p = 0.0098), but not different from the radiologist (79.4%, p = 0.815). The radiologist's performance improved when using ML (80.2%), but not significantly (p = 0.508). CONCLUSIONS: A radiomic analysis combined with ML showed promising results to differentiate benign from malignant breast lesions on ultrasound images. KEY POINTS: • Machine learning showed good accuracy in discriminating benign from malignant breast lesions • The machine learning classifier's performance was comparable to that of a breast radiologist • The radiologist's accuracy improved with machine learning, but not significantly.

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL): a challenging cytological diagnosis with hybrid PET/MRI staging and follow-up.

We report a case of a 55-year-old woman with left breast cosmetic augmentation performed 5 years earlier, showing at ultrasound a left small amount of peri-implant effusion suspicious for an anaplastic large cell lymphoma localization. The final diagnosis was obtained by cytology using a small amount of fluid (6 ml). Subsequently, hybrid 18F-FDG PET/MRI was used for pre-operative staging and follow-up. An appropriate management of BIA-ALCL could be obtained even in cases of a small amount of peri-implant effusion, using a comprehensive approach of clinical and imaging evaluation, including PET/MRI as useful and innovative staging imaging technique.

The continuing role of breast fine-needle aspiration biopsy after the introduction of the IAC Yokohama System For Reporting Breast Fine Needle Aspiration Biopsy Cytopathology.

BACKGROUND: Ultrasound-guided fine-needle aspiration biopsy (FNAB) (US-guided FNAB) is a rapid and cost-effective procedure for the diagnosis of breast lesions. Our Institution has a long tradition in breast FNAB performed by cytopathologists; recently we adopted both US guidance and a five-tiered classification system similar to that proposed by the International Academy of Cytology (IAC). The aim of this study was to demonstrate the continuing role of US-guided FNAB in the diagnosis of breast lesions, despite the growing adoption of core-needle biopsy (CNB). METHODS: The laboratory information database system was searched to obtain the breast FNAB diagnostic reports recorded from 2010 to 2017 and classified using a five-tiered Classification System; each entry was matched with the available histology. RESULTS: A total of 4624 breast FNAB samples were retrieved. Of these, 1745/4624 cases (37.7%) had histological follow-ups. The risk of malignancy (ROM) was 4.9% for benign, 20.7% for atypical, 78.7% for suspicious of malignancy, and 98.8% for malignant. When the atypical category was evaluated as a negative index, the positive predictive value was 93.73%, and the negative predictive value was 90.78%, reaching an overall diagnostic accuracy of 92.82%. CONCLUSIONS: The IAC Yokohama System for Reporting Breast FNAB Cytopathology clearly identifies different diagnostic categories with increasing ROM. Most of the FNAB samples were classified as benign or malignant (65.3%), warranting prompt management for these patients. Moreover, the inclusion of the atypical category as a low-risk indeterminate category avoided overtreatment of benign lesions. Thus, despite the well-established merits of CNB, US-guided FNAB still represents a cost-effective and rapid nonoperative diagnostic approach.

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination.

The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) remodeling and cancer growth. The BCM comprises a very heterogeneous tissue containing non-cancer stromal cells, namely, breast cancer-associated fibroblasts (BCAFs), which represent most of the tumor mass. Moreover, the different components of the BCM highly interact with cancer cells, thereby generating a tightly intertwined network. In particular, BC cells activate recruited normal fibroblasts in BCAFs, which, in turn, promote BCM remodeling and metastasis. Thus, comparing the roles of normal fibroblasts and BCAFs in the physiological and metastatic processes, could provide a deeper understanding of the signaling pathways regulating BC dissemination. Here, we review the latest literature describing the structure of the mammary gland and the BCM and summarize the influence of epithelial-mesenchymal transition (EpMT) and autophagy in BC dissemination. Finally, we discuss the roles of fibroblasts and BCAFs in mammary gland development and BCM remodeling, respectively.

Palbociclib added to ongoing endocrine therapy for hormone receptor-positive HER2-negative metastatic breast cancer: A case report series.

Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR)+, human epidermal growth factor receptor (HER)2- metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone. The median progression-free survival was not reached during a median follow-up of 25 months, and the most frequent best response was stable disease. Three patients remained under treatment on the last re-evaluation. All patients had highly endocrine-sensitive disease and had previously received fulvestrant for ≥12 months. The hypothesis that a selected subpopulation of patients with HR+/HER2- metastatic breast cancer may benefit from the addition of palbociclib to ongoing endocrine therapy beyond disease progression merits further investigation.

Tumor segmentation analysis at different post-contrast time points: A possible source of variability of quantitative DCE-MRI parameters in locally advanced breast cancer.

PURPOSE: to assess if tumor segmentation analysis performed at different post-contrast time points (TPs) on dynamic images could influence the extraction of dynamic contrast enhanced (DCE)-MRI parameters in locally advanced breast cancer (LABC), and potentially represent a source of variability. METHOD: forty patients with forty-two LABC lesions were prospectively enrolled and underwent breast DCE-MRI examination at 3 T. On post-processed dynamic images, enhancing tumor lesions were manually segmented at four different TPs: at the first post-contrast dynamic image in which the lesion was appreciable (TP 1) and at 1, 5 and 10 min after contrast-agent administration (TPs 2, 3 and 4, respectively) and corresponding DCE-MRI parameters were extracted. Friedman's test followed by Bonferroni-adjusted Wilcoxon signed rank test for post-hoc analysis was used to compare DCE-MRI parameters. Intra- and inter-observer reliability of DCE-MRI parameters measurements was assessed using the Intraclass Correlation Coefficient (ICC) analysis. RESULTS: Ktrans, Kep and iAUC were significantly higher when extracted from ROIs placed at TP1 and progressively decreased from TP 2-4. The intra-observer reliability ranged from good to excellent (ICC's: 0.894 to 0.990). The inter-observer reliability varied from moderate to excellent (0.770 to 0.942). The inter-observer reliability was significantly higher for Ktrans and Kep extracted at TPs1 and 2 as compared to TPs 3 and 4. CONCLUSIONS: A significant variability of DCE-MRI quantitative parameters occurs when tumor segmentation is performed at different TPs. We suggest to performing tumor delineation at an established TP, preferably the earliest, in order to extract reliable and comparable DCE-MRI data.

Influence of different post-contrast time points on dynamic contrast-enhanced (DCE) MRI T staging in breast cancer.

PURPOSE: to assess whether MRI T stage of breast cancer lesions (BCLs) is affected by maximum diameter (MD) measured at different post-contrast time points (TPs) on different acquisition planes on dynamic contrast-enhanced (DCE) MRI sequence. METHODS: 53 DCE-MRI examinations of patients with BCLs were retrospectively selected. MD of BCLs was measured on axial, coronal and sagittal planes on DCE images at five different post-contrast TPs. Friedman test followed by Bonferroni-adjusted Wilcoxon-signed rank test for post-hoc analysis was performed to evaluate differences among the five measurements. Reliability of the measurements was evaluated with the intraclass correlation coefficient analysis. Differences between pathological and MRI T stage assessed at each TP on each acquisition plane were assessed using the Wilcoxon-sign rank test; p values <0.05 were considered statistically significant. RESULTS: on axial, coronal and sagittal planes, MD measured at TP1 was significantly different (p < 0.0001) compared to those obtained at the subsequent TPs. No significant differences were found between MD measured at TPs 3, 4 and 5. Intra and inter-observer reliability resulted as very good, with ICC ranging between 0.915-0.992 and 0.845-0.911, respectively. MRI T stage assessed at TP1 on axial and sagittal plane as well as at all TPs on coronal plane was significantly different from pathological T stage. CONCLUSION: MRI T stage definition of BCLs is significantly affected by the TP used for lesions' MD measurement. TPs 3, 4 and 5 are the preferred TPs for the assessment of MRI T stage of BCLs on both axial and sagittal planes.

Mitochondrial Flexibility of Breast Cancers: A Growth Advantage and a Therapeutic Opportunity.

Breast cancers are very heterogeneous tissues with several cell types and metabolic pathways together sustaining the initiation and progression of disease and contributing to evasion from cancer therapies. Furthermore, breast cancer cells have an impressive metabolic plasticity that is regulated by the heterogeneous tumour microenvironment through bidirectional interactions. The structure and accessibility of nutrients within this unstable microenvironment influence the metabolism of cancer cells that shift between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) to produce adenosine triphosphate (ATP). In this scenario, the mitochondrial energetic pathways of cancer cells can be reprogrammed to modulate breast cancer's progression and aggressiveness. Moreover, mitochondrial alterations can lead to crosstalk between the mitochondria and the nucleus, and subsequently affect cancer tissue properties. This article reviewed the metabolic plasticity of breast cancer cells, focussing mainly on breast cancer mitochondrial metabolic reprogramming and the mitochondrial alterations influencing nuclear pathways. Finally, the therapeutic strategies targeting molecules and pathways regulating cancer mitochondrial alterations are highlighted.

The axillary flap in oncoplastic resection of breast cancers located in the upper-outer quadrants: a new surgical technique.

BACKGROUND: The combination of breast conserving surgery (BCS) with plastic surgery techniques has provided a useful surgical tool matching the radicality of the oncological excision with the preservation of breast cosmesis. Even though BCS represents a good option for surgical treatment of tumors located in these quadrants, wide excisions often necessitate breast reshaping in order to avoid nipple areola complex (NAC) displacement and skin retraction. We present a new surgical technique to repair upper-outer quadrants' defects following breast cancer excision using dermo-glandular flaps and an axillary adipo-fascial flap. METHODS: During the period from January 2014 to December 2015, 168 patients with an upper-outer quadrant's breast cancer have been treated in our Department. 83 women have been treated with the described oncoplastic technique and immediate contra-lateral symmetrisation and 85 women underwent standard BCS. We present surgical, oncological and cosmetic outcomes comparing our results with standard BCS. RESULTS: At a mean follow-up of 27 months loco-regional recurrences in the two groups were comparable. Short-term complication rates were comparable between the two groups. Re-intervention rates for positive margins were significantly higher in the standard BCS group. The overall satisfaction with cosmetic outcome both assessed by the patient and the surgeon was significantly higher in the oncoplastic group. CONCLUSIONS: The proposed oncoplastic technique represents a safe and effective solution for reshaping that follows upper-outer breast cancer wide excision, achieving comparable complication rates, lower re-intervention rates for positive margins and better cosmetic results when compared with standard BCS.

Preliminary Results of a Simplified Breast MRI Protocol to Characterize Breast Lesions: Comparison with a Full Diagnostic Protocol and a Review of the Current Literature.

RATIONALE AND OBJECTIVES: This study aimed to investigate whether a simplified breast magnetic resonance imaging (MRI) protocol consisting of a localizer, one precontrast sequence, and three time-point postcontrast sequences (at 28 seconds, 84 seconds and 252 seconds after the contrast agent administration) is suitable for the characterization of breast lesions as compared to a full diagnostic protocol (FDP). This study also aimed to review the current literature concerning abbreviated breast MRI protocols and offer an alternative protocol. MATERIALS AND METHODS: Breast magnetic resonance (MR) examinations with detected breast lesions of 98 patients were retrospectively evaluated. Two expert radiologists in consensus reviewed the simplified breast protocol (SBP) first and only thereafter the regular FDP, recording a diagnosis for each detected lesion for both protocols. Receiver operating characteristic curve analysis was performed to determine the diagnostic performance of the SBP compared to the standard FDP. A revision of the previously reported abbreviated breast magnetic resonance protocols was also carried out. RESULTS: A total of 180 lesions were identified; of these, 110 (61%) were malignant and 70 (39%) were benign. Of the 110 malignant lesions, 86 (78%) were invasive ductal carcinoma, 18 (16%) were invasive lobular carcinoma, and 6 (6%) were ductal carcinoma in situ. Areas under the curve for the receiver operating characteristic curves for the SBP vs the FDP were equivalent (0.98 vs 0.99, respectively; P = 0.76). The SBP could be performed in approximately 6 minutes and 58 seconds, compared to 14 minutes and 48 seconds for the FDP. CONCLUSIONS: An SBP protocol including a late postcontrast time point is accurate for the characterization of breast lesions and was comparable to the standard FDP protocol, allowing a potential reduction of the total acquisition and interpretation times.

Combined effect of obesity and diabetes on early breast cancer outcome: a prospective observational study.

BACKGROUND: Previous studies suggested that obesity and diabetes were correlated with breast cancer outcome. The aim of the present study was to investigate the prognostic effect of obesity and diabetes on the outcome of early breast cancer patients. MATERIALS AND METHODS: Overall, 841 early breast cancer patients were prospectively enrolled between January 2009 and December 2013. Study population was divided into four groups: (1) patients without obesity or diabetes; (2) patients with only diabetes; (3) patients with only obesity; and (4) patients with both diabetes and obesity. Categorical variables were analyzed by the chi-square test and survival data by the log-rank test. RESULTS: At diagnosis, obese and diabetic patients were more likely to be older (p < 0.0001) and post-menopausal (p < 0.0001) and to have a tumor larger than 2 cm (p < 0.0001) than patients in groups 1-3. At univariate analyses, obese and diabetic patients had a worse disease-free survival (p = 0.01) and overall survival (p = 0.001) than did patients without obesity and diabetes. At multivariate analyses, the co-presence of obesity and diabetes was an independent prognostic factor for disease-free survival (hazard ratio=2.62, 95% CI 1.23-5.60) but not for overall survival. CONCLUSIONS: At diagnosis, patients with obesity and diabetes were older, had larger tumors and a worse outcome compared to patients without obesity or diabetes. These data suggest that metabolic health influences the prognosis of patients affected by early breast cancer.

Innovative Management of Implant Exposure in ADM/Implant-Based Breast Reconstruction with Negative Pressure Wound Therapy.

INTRODUCTION: One-stage implant-based breast reconstruction has been recently improved by the introduction of biological [acellular dermal matrix (ADM)] and synthetic meshes. Advantages of ADMs in implant-based breast reconstruction derive from the expansion of the space available for the direct positioning of an implant, but their use could be associated with several complications. Although the majority of complications can be easily managed, mistakes in dealing with the first clinical signs of a potential adverse event can lead to implant loss. CASE PRESENTATION: We report a case of ADM/implant exposure following NAC-sparing mastectomy and immediate implant-based reconstruction, successfully managed with an innovative staged treatment using negative pressure wound therapy, which allowed a rapid re-positioning of the prosthesis after complete clearance of bacteria from the implant pocket. DISCUSSION: The safest strategy to manage implant exposure and concomitant bacterial growth is reported to be implant removal and delayed re-positioning after several months, following prolonged targeted antibiotic therapy. Our case shows how a short-time implant re-positioning following implant removal for implant exposure could be successfully pursued thanks to the shrewd use of negative pressure wound therapy with great advantages in terms of patient satisfaction and post-operative quality of life, offering women experiencing this complication the option of not delaying reconstruction for months after resolution of the complication, potentially avoiding major surgical procedures such as autologous tissue reconstructions. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Different types of implants for reconstructive breast surgery.

BACKGROUND: Breast cancer is the most common cancer in women worldwide, and is a leading cause of cancer death among women. Prophylactic or curative mastectomy is often followed by breast reconstruction for which there are several surgical approaches that use breast implants with which surgeons can restore the natural feel, size and shape of the breast. OBJECTIVES: To assess the effects of different types of breast implants on capsular contracture, surgical short- and long-term complications, postoperative satisfaction level and quality of life in women who have undergone reconstructive breast surgery after mastectomy. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialised Register on 20 July 2015, MEDLINE (1985 to 20 July 2015), EMBASE (1985 to 20 July 2015) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 8, 2015). We also searched the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 16 July 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared different types of breast implants for reconstructive surgery. We considered the following types of intervention: implant envelope surfaces - texturised versus smooth; implant filler material - silicone versus saline, PVP-Hydrogel versus saline; implant shape - anatomical versus round; implant volume - variable versus fixed; brands - different implant manufacturing companies and implant generation (fifth versus previous generations). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed methodological quality and extracted data. We used standard Cochrane methodological procedures. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. MAIN RESULTS: Five RCTs with 202 participants met the inclusion criteria. The women participants were typically in their 50s, and the majority of them (about 82%) received reconstructive surgery following breast cancer, while the others had reconstructive surgery after prophylactic mastectomy. The studies were heterogenous in terms of implant comparisons, which prevented us from pooling the data.The studies were judged as being at an unclear risk of bias for most risk of bias items owing to poor quality of reporting in the trial publications. Three of the five RCTs were judged to be at high risk of attrition bias, and one at high risk of detection bias.Textured silicone versus smooth silicone implants: textured implants were associated with worse outcomes when compared to smooth implants (capsular contracture: risk ratio (RR) 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence; reintervention: RR 0.82, 95% CI 0.14 to 4.71; 1 study, 20 participants; very low quality evidence). No results in this comparison were statistically significant.Silicone versus saline implants: saline-filled implants performed better than silicone-filled implants for some outcomes; specifically, they produced less severe capsular contracture (RR 3.25, 95% CI 1.24 to 8.51; 1 study, 60 participants; very low quality evidence) and increased patient satisfaction (RR 0.60, 95% CI 0.41 to 0.88; 1 study, 58 participants; very low quality evidence). However reintervention was significantly more frequent in the saline-filled implant group than in the silicone-filled group (OR 0.08, 95% CI 0.01 to 0.43; 1 study, 60 participants; very low quality evidence).Poly(N-vinyl-2-pyrrolidone) hydrogel-filled (PVP-hydrogel) versus saline-filled implants: PVP-hydrogel-filled implants were associated with worse outcomes when compared to saline-filled implants (capsular contracture: RR 3.50, 95% CI 0.83 to 14.83; 1 study, 40 participants; very low quality evidence; short-term complications: RR 2.10, 95% CI 0.21 to 21.39; 1 study, 41 participants; very low quality evidence).Anatomical versus round implants: anatomical implants were associated with worse outcomes than round implants (capsular contracture: RR 2.00, 95% CI 0.20 to 20.15; 1 study, 36 participants; very low quality evidence; short-term complications: RR 2.00, 95% CI 0.42 to 9.58; 1 study, 36 participants; very low quality evidence; reintervention: RR 1.50, 95% CI 0.51 to 4.43; 1 study, 36 participants; very low quality evidence). No results in this comparison were statistically significant.Variable-volume versus fixed-volume implants: data about one-stage reconstruction using variable-volume implants were compared with data about fixed-volume implants positioned during the second surgical procedure of two-stage reconstructions. Fixed-volume implant reconstructions were possibly associated with a greater number of women reporting that their reconstruction corresponded with expected results (RR 0.25, 95% CI 0.10 to 0.62; 1 study, 40 participants; very low quality evidence) and fewer reinterventions (RR 7.00, 95% CI 1.82 to 26.89; 1 study, 40 participants; very low quality evidence) when compared to variable-volume implants. A higher patient satisfaction level (rated from 1 to 6, with 1 being very bad and 6 being very good) was found with the fixed-volume implants for overall aesthetic result (mean difference (MD) -1.10, 95% CI -1.59 to -0.61; 1 study, 40 participants; very low quality evidence).There were no studies that examined the effects of recent (fifth) generation silicone implants versus previous generations or different implant manufacturing companies. AUTHORS' CONCLUSIONS: Despite the central role of breast reconstruction in women with breast cancer, the best implants to use in reconstructive surgery have been studied rarely in the context of RCTs. Furthermore the quality of these studies and the overall evidence they provide is largely unsatisfactory. Some of our results can be interpreted as early evidence of potentially large differences between different surgical approaches, which should be confirmed in new high-quality RCTs that include a larger number of women. These days - even after a few million women have had breasts reconstructed - surgeons cannot inform women about the risks and complications of different implant-based breast reconstructive options on the basis of results derived from RCTs.

A rare case of true carcinosarcoma of the breast.

BACKGROUND: True carcinosarcoma of the breast is an extremely rare condition, accounting for 0.08-0.2% of all breast malignancies. The correct definition of this tumor requires both a carcinomatous component and a malignant non-epithelial component of mesenchymal origin, without evidence of a transition zone between the two elements. CASE PRESENTATION: We present a case of a 49-year-old woman presenting with a 4cm mass at the level of her left breast upper-outer quadrant with a histologic diagnosis of true carcinosarcoma of the breast. DISCUSSION: The most appropriate therapeutic regimens for breast carcinosarcoma are still unclear because of the rarity of this condition, but Breast Conserving Treatment (BCT) followed by adjuvant chemotherapy seems to provide a prognosis equalling that of usual Invasive Ductal Carcinoma of the breast.

Primary angiosarcoma of the breast.

Primary angiosarcoma (AS) of the breast is a rare neoplasia that is not related to radiation exposure. It represents less than 0.05% of all malignant breast tumors. This lesion is characterized by aggressive patterns and poor prognosis and by the absence of typical features at radiologic examination. Currently there are not evidence-based guidelines regarding surgical and adjuvant treatment for this tumor even though wide surgical resection followed by chemo- radiotherapy appears to improve both disease free survival and overall survival. The aim of this study was to analyze the available series of AS patients suggesting the most reliable treatment options for this rare neoplasia.