Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Un campus en mouvement : Les pratiques de mobilité des étudiant-e-s et du personnel de l'Université de Lausanne

Les universités génèrent d’importants flux de mobilité et la gestion des transports constitue un défi majeur pour leur fonctionnement. Cette recherche aborde cette problématique dans le cas de l’Université de Lausanne. Dans un premier temps, l’étude porte sur l’évolution du campus et de son accessibilité. Elle montre comment ce site suburbain a été relié au reste de l’agglomération et aborde les mesures prises pour réguler la mobilité. Deuxièmement, elle s’intéresse à la demande, soit aux choix modaux des 18’000 personnes qui travaillent et étudient à l’Université de Lausanne. Des enquêtes réalisées chaque année depuis 2005 permettent de mesurer les pratiques de mobilité et les différences au sein de la communauté universitaire. En conclusion sont esquissées les tendances qui influenceront à terme les flux de mobilité à destination du campus

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

Introduction: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. Results: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). Discussion: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

Introduction: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. Methods: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. Results: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). Discussion: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients� values. Despite areas of controversy, about one-third (36) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs. © 2021 The Author

Screening and diagnostic breast MRI: how do they impact surgical treatment? Insights from the MIPA study

Objectives: To report mastectomy and reoperation rates in women who had breast MRI for screening (S-MRI subgroup) or diagnostic (D-MRI subgroup) purposes, using multivariable analysis for investigating the role of MRI referral/nonreferral and other covariates in driving surgical outcomes. Methods: The MIPA observational study enrolled women aged 18–80 years with newly diagnosed breast cancer destined to have surgery as the primary treatment, in 27 centres worldwide. Mastectomy and reoperation rates were compared using non-parametric tests and multivariable analysis. Results: A total of 5828 patients entered analysis, 2763 (47.4%) did not undergo MRI (noMRI subgroup) and 3065 underwent MRI (52.6%); of the latter, 2441/3065 (79.7%) underwent MRI with preoperative intent (P-MRI subgroup), 510/3065 (16.6%) D-MRI, and 114/3065 S-MRI (3.7%). The reoperation rate was 10.5% for S-MRI, 8.2% for D-MRI, and 8.5% for P-MRI, while it was 11.7% for noMRI (p ≤ 0.023 for comparisons with D-MRI and P-MRI). The overall mastectomy rate (first-line mastectomy plus conversions from conserving surgery to mastectomy) was 39.5% for S-MRI, 36.2% for P-MRI, 24.1% for D-MRI, and 18.0% for noMRI. At multivariable analysis, using noMRI as reference, the odds ratios for overall mastectomy were 2.4 (p < 0.001) for S-MRI, 1.0 (p = 0.957) for D-MRI, and 1.9 (p < 0.001) for P-MRI. Conclusions: Patients from the D-MRI subgroup had the lowest overall mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). This analysis offers an insight into how the initial indication for MRI affects the subsequent surgical treatment of breast cancer. Key Points: • Of 3065 breast MRI examinations, 79.7% were performed with preoperative intent (P-MRI), 16.6% were diagnostic (D-MRI), and 3.7% were screening (S-MRI) examinations. • The D-MRI subgroup had the lowest mastectomy rate (24.1%) among MRI subgroups and the lowest reoperation rate (8.2%) together with P-MRI (8.5%). • The S-MRI subgroup had the highest mastectomy rate (39.5%) which aligns with higher-than-average risk in this subgroup, with a reoperation rate (10.5%) not significantly different to that of all other subgroups

Residual capacity of a reinforced concrete grillage deck exposed to corrosion

Grillage decks made of reinforced concrete (RC) with more than 40–60 years of service life may exhibit localised areas of severe damage or even entire elements exceeding the serviceability limits. In these cases, it is essential to quickly and efficiently assess the structure’s safety margins, and, in the worst cases, to also verify whether the damaged deck’s residual bearing capacity is sufficient for it to be used as a platform for the repair works. This article proposes an assessment based on a non-linear RC finite element specialised in dealing with systems working in bending and torsion. The damage, measured at a particular time after construction, is modelled by a reduction of the reinforcement section, supposed to be induced by chlorides diffusion and investigated through a Cellular Automata algorithm. Such an approach is applied in studying a bridge deck, having an edge beam damaged by leakage of salted water from the road platform. The results give a thorough description of the structural behaviour and the deformed shapes help in understanding the redistribution process of the internal forces. These results may provide a reliable reference to plan proper maintenance actions as well as to establish a hierarchy of repairing and strengthening interventions

Nonlinear Analysis of a R.C. grillage deck exposed to corrosion

In this paper, an approach consisting in the analysis of the diffusion of the deterioration processes induced by aggressive agents, followed by the analysis of the damaged structure is presented. The damage process, induced by chloride diffusion, is modelled through a Cellular Automata algorithm. The structural analysis is based on R.C. spatial beam element, dealing with both mechanical and geometrical nonlinearities. The proposed method is applied to studying the structural response, both at the serviceability and ultimate limit states, of a damaged, 50-years-old R.C. grillage deck exhibiting a severe corrosion state. The analyses show how damage effects at a given time reduce the overall bearing capacity of the deck and how the internal forces redistribute from damaged to undamaged structural parts. Such a methodology may be useful both in designing new bridges, in estimating their performance over time under given environmental and service condition, and for existing bridges, in assessing their residual bearing capacity in the damaged state after a certain period from constructio

Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer

Non-palpable breast cancers are often in situ or smaller and have less nodal and distant metastases than palpable lesions. They represent a heterogeneous group of tumours, which may have different prognostic behaviour. We analysed a retrospective series of 982 non-palpable breast cancers assessed histologically at the National Cancer Institute of Milan from 1985 to 1995, following pre-operative mammography-guided localization. The association between mammographic data (parenchymal pattern and findings), patient age and tumour histology was investigated by review of clinical records and statistical modelling. We also investigated the association between the presence or absence of microcalcification as a mammographic finding and pathological tumour characteristics (tumour size, axillary nodes status and grading) or receptor status for oestrogen (ER) and progesterone (PgR). In situ disease or invasive tumour with an intraductal component, whether extensive or not, were commoner in young women and mammography more frequently showed a dense parenchymal pattern and microcalcifications in these cases. In older women (55 years or more), a fatty breast pattern, nodular opacities with or without microcalcifications, and invasive tumours of the ductal, lobular, mixed or other types were closely related. When the relationships between mammographic findings, pathological tumour characteristics and receptor status were investigated for invasive cancers, there was an association between the presence of microcalcifications and less favourable tumour characteristics

Impact of contra-lateral breast reshaping on mammographic surveillance in women undergoing breast reconstruction following mastectomy for breast cancer

Background: The ultimate goal of breast reconstruction is to achieve symmetry with the contra-lateral breast. Contra-lateral procedures with wide parenchymal rearrangements are suspected to impair mammographic surveillance. This study aims to evaluate the impact on mammographic detection of mastopexies and breast reductions for contralateral adjustment in breast reconstruction. Patients and methods: We retrospectively evaluated 105 women affected by uni-lateral breast cancer who underwent mastectomy and immediate two-stage reconstruction between 2002 and 2007.We considered three groups according to the contra-lateral reshaping technique: mastopexy or breast reduction with inferior dermoglandular flap (group 1); mastopexy or breast reduction without inferior dermoglandular flap (group 2); no contra-lateral reshaping (group 3).We assessed qualitative mammographic variations and breast density in the three groups. Results: Statistically significant differences have been found when comparing reshaped groups with non reshaped groups regarding parenchymal distortions, skin thickening and stromal edema, but these differences did not affect cancer surveillance.The surveillance mammography diagnostic accuracy in contra-lateral cancer detection was not significantly different between the three groups (p = 0.56), such as the need for MRI for equivocal findings at mammographic contra-lateral breast (p = 0.77) and the need for core-biopsies to confirm mammographic suspect of contra-lateral breast cancer (p = 0.90). Conclusions: This study confirms previous reports regarding the safety of mastopexies and breast reductions when performed in the setting of contra-lateral breast reshaping after breast reconstruction. Mammographic accuracy, sensitivity and specificity are not affected by the glandular re-arrangement.These results provide a further validation of the safety of current reconstructive paradigms