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The world of metal–organic frameworks (MOFs) has become a hot topic in recent years due to the extreme variety and tunability of their structures. There is evidence of MOFs that exhibit intrinsic luminescence properties that arise directly from their organic components or from the interaction between them and metallic counterparts. A new perspective is to exploit the porous nature of MOFs by encapsulating luminescent guests, such as organic dyes, in order to explore possible changes in the luminescence activity of the combined systems. This work is focused on the optical study of zirconium-based MOF-808 and its interaction with encapsulated rhodamine B molecules. Using a plethora of different techniques, we were able to unravel its photocycle. MOF-808 displays intrinsic luminescence activity that derives from an energy transfer process from the linker to the metal sites occurring in 300 ps. The emission is a singlet–singlet transition in aqueous solution, and it is a triplet transition in powdered form. After exploring the bare MOF, we combined it with rhodamine B molecules, following an easy post-synthetic process. Rhodamine B molecules were found to be encapsulated in MOF pores and interact with the MOF's matrix through nanosecond energy transfer. We created a totally new dual-emitting system and suggested a way, based on the time-resolved studies, to clearly unravel the photocycle of MOFs from the very first photoexcitation. [ABSTRACT FROM AUTHOR]

Breast cancer is a growing global public health concern. Thanks to the recent treatments progress, the survival rate of BC patients has significantly improved (88% of 5-year survival rate) and the number of cancer survivors has also increased. Notwithstanding these brilliant results, many BC patients have long-term side effects as pain, oedema, limited mobility, cancer related fatigue, etc. as a consequence of surgical, radiotherapy and medical treatments. For example, posture appears to be frequently altered after mastectomy, due to the impairment of the mobility of the arm caused by surgical scars. All these aspects negatively affect the health-related Quality of Life (QoL) of BC patients. Recent several randomized clinical trials have shown benefits of regular and appropriate physical activity (PA) during and after BC treatment, particularly in terms of benefits for health, reducing fatigue, improving strength levels, QoL and physical function. In this context, two types of sports have demonstrated their affinity and efficacy as treatment support during and after treatments for BC patients: fencing and rowing. Here we report considerations shared with two sport champions: the fencing Olympic gold medal Daniele Garozzo and the rowing World Champion Giovanni Ficarra, with the aim to find the adapted PA for BC patients. [ABSTRACT FROM AUTHOR]

Sports nutrition is a topic that is often misinterpreted and sometimes abused. The often-used "shot-gun" method to meeting caloric needs by simply increasing caloric intake disregarding nutrient source is scientifically contrary to the need for a more careful study of the nutritional requirements of rowers. Rowing by itself is a very demanding sport as typical training sessions use exercise intensities that range from very low submaximal work to short term supramaximal efforts. The intake in calories should take into account also the type of race that the athlete will afford. In the case of the rower Giovanni Ficarra who won, in 16 months, three world competitions in the three different rowing disciplines, his dietary needs and training schedule significantly changed according to the type of competition, to be prepared for the extreme load of physical effort required to get the podium in such different conditions. This article in intended to provide recommendation for both coaches and athletes that are approaching rowing in its whole meaning and disciplines as Giovanni Ficarra did., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessandra Bitto reports article publishing charges was provided by SunNutraPharma srl. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Chronic post-surgical pain is a condition persisting for not less than 3 months after surgical intervention. It is evaluated that 25-60% of women who underwent breast cancer excision suffer from post-mastectomy pain syndrome, and anxiety, depression, sleep disturbance, and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. The aim of this study was to estimate the influence of physical activity on the intensity of pain, depression, and anxiety in women who underwent mastectomy for breast cancer removal., Methods: A prospective observational unicentric cohort study was performed. Patients were females who underwent unilateral or bilateral mastectomy. The Numerical Rating Scale (NRS) was used to measure pain intensity, Beck's Depression Inventory (BDI) for depression, and Generalized Anxiety Disorders-7 (GAD-7) for anxiety evaluation. Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH), and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All evaluations were assessed 3 and 6 months after the surgery., Results: Adequate physical activity reduced the intensity of pain, depression, and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequately active women showed a reduction in biomarkers of inflammation, cortisol, ACTH, and an increase of BDNF., Conclusions: Our results suggest that physical activity can improve the quality of life, reduce the intensity of pain and inflammatory markers, and be useful in the reduction of associated anxiety and depression.

Introduction: Serial follow-up with pulmonary function testing (PFT) and chest computed tomography (CT) after severe COVID-19 are recommended. As a result, many longitudinal studies have been published on COVID-19 of different grade of severity up to 1-year follow-up. Therefore, we aimed at a long-term observational study throughout 2 years after severe COVID-19., Methods: Severe COVID-19 patients were consecutively recruited after hospital discharge between March and June 2020 and prospectively followed up for 24 months, with mMRC dyspnea scale and PFT at 6, 12, and 24 months. Chest CT was performed when clinically indicated., Results: One hundred one patients enrolled completed the observational study. At 24 months, those with reduced total lung capacity (TLC) were 16%, associated with fibrotic ground glass opacity (GGO) and mMRC score >1, respectively, in 75% and 69% of them. At 24 months, those with a reduced diffusing capacity of the lung for CO were 41%, associated with fibrotic GGO and mMRC score >1, respectively, in 53% and 22% of them., Conclusion: Two years after hospitalization for severe COVID-19, a non-negligible number of patients still suffer from "long COVID" due to respiratory damage., (© 2024 S. Karger AG, Basel.)

Purpose: There is a lack of data regarding the stress and motivation response in adolescent athletes during competitions. The athletic performance can be highly influenced by stress rather than appropriate training, at this age. The aim of this investigation is to evaluate the level of stress markers in adolescent rowers in different competition settings that might alter their stress status and performance., Methods: Adolescent rowing athletes (12-18 yrs) have been tested for determining saliva content of stress biomarkers, cortisol and testosterone, before and after competitions that have been performed indoor and outdoor. Specifically, samples have been taken in the morning, before and after the race in 2 different settings: 1) an indoor rowing competition with an ergometer, 2) an outdoor rowing competition on boats., Results: A reduction in cortisol levels has been observed in athletes right before the outdoor race, while testosterone levels increased at the same time point before either the ergometer or boat competition and kept rising at the end of the race. Significant differences have been found comparing the testosterone/cortisol ratio between indoor and outdoor data, being higher in the indoor race at all considered time-point. Furthermore, the linear regression demonstrated that the increased ratio correlated with a better podium position in the indoor race., Conclusion: Despite the age differences among athletes might have an influence on their hormone levels, these data suggest that rowing athletes subjected to different kind of competitions show a different stress and motivation response profile that might influence their performance., Competing Interests: No competing interest is declared by any of the authors. Alessandra Bitto is co-founder of the Academic Spin-off of the University of Messina., (© 2023 The Authors.)

Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease.

Several authors reported an increased risk of cancer in SSc patients, including breast cancer (BC). Nevertheless, the mechanisms underlying this association have not yet been clarified. SSc and BC share several molecular pathways, which seem to play a common etiopathogenetic role. The previously published Sclero-Breast study demonstrated the development of BC with a good prognosis among these patients, which could be explained by an autoimmune background as a possible mechanism for limiting tumor extension. Here, we report the results of an IHC analysis of molecular pathways known to be common drivers for both diseases, with the aim to better define the mechanisms underlying a good prognosis of BC in patients affected by SSc. The analysis demonstrated higher TILs rates in all BC subgroups, with a high rate of PD-L1 expression especially in TNBC and HER2-positive BC, suggesting a less aggressive behavior in these patients compared to the general population. These results support a possible de-escalation strategy of cancer therapies in these fragile patients. These data could represent a starting point for future prospective studies based on the clinical application of these biomarkers with a larger sample size to promote a personalized and targeted oncological treatment for this specific subset of patients.

Introduction: Triple-negative breast cancer (TNBC) patients who do not obtain pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Risk factors for relapse in this subset of patients are poorly characterized. This study aimed to identify the predictive factors for relapse in TNBC patients without pCR after NACT., Methods: Women with TNBC treated with NACT from January 2008 to May 2020 at the Modena Cancer Center were included in the analysis. In patients without pCR, univariate and multivariable Cox analyses were used to determine factors predictive of relapse., Results: We identified 142 patients with a median follow-up of 55 months. After NACT, 62 patients obtained pCR (43.9%). Young age at diagnosis (<50 years) and high Ki-67 (20%) were signi!cantly associated with pCR. Lack of pCR after NACT resulted in worse 5-year event-free survival (EFS) and overall survival (OS). Factors independently predicting EFS in patients without pCR were the presence of multifocal disease [hazard ratio (HR), 3.77; 95% CI, 1.45-9.61; p=0.005] and residual cancer burden (RCB) III (HR, 3.04; 95% CI, 1.09-9.9; p=0.04). Neither germline BRCA status nor HER2-low expression were associated with relapse., Discussion: These data can be used to stratify patients and potentially guide treatment decision-making, identifying appropriate candidates for treatment intensi!cation especially in neo-/adjuvant setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer EP declared a past co-editorship with one of the authors AT to the handling Editor., (Copyright © 2022 Toss, Venturelli, Civallero, Piombino, Domati, Ficarra, Combi, Cabitza, Caggia, Barbieri, Barbolini, Moscetti, Omarini, Piacentini, Tazzioli, Dominici and Cortesi.)

Dietary supplements are used to implement and balance common dietary habits. The general belief is that natural substances reduce the risk of chronic diseases and amplify sports performance with no harmful side effects. Since sports science students will become professionals of sport activities and may also have a role in suggesting the use of dietary supplements to athletes, the aim of this study was to evaluate if physical activity influences the use of drugs and dietary supplements. A modified version of the International Physical Activity Questionnaire-Short Form (IPAQSF) was administered to perform these evaluations. A total of 1452 students from the University of Messina, Italy, enrolled in sports science courses completed the survey; of these, 1075 (704 male and 371 female students) were physically active in moderate- or high-intensity training. Of those physically active students, 709 (440 male and 269 female) were competitive athletes, identified on the basis of their answer to a specific question also indicating the type of sport they practice. The results suggest that 5.6% of all respondents were regular consumers of pharmaceutical products, compared to just 1.0% of the cohort of competing athletes. In contrast, the consumption of natural supplements was similar (14% vs. 15%) between groups. The most frequently used supplements were vitamins, including vitamin C, vitamin B complex, and multivitamin complex, followed by minerals and amino acids or protein complex. The probability of using dietary supplements was mostly related to the male gender (OR 1.64; 95% CI: 1.17-2.30), having a job (OR 1.45; 95% CI: 1.07-1.96), and, most of all, performing physical activity (OR 3.53; 95% CI: 2.18-5.71). The only factor related to a higher use of drugs was female gender (OR 2.40; 95% CI: 1.52-3.79), and the most used class was antihistaminic, followed by FANS. These results suggest that among the specific population of sports science students, those performing physical activity are less prone to using pharmaceutical products and have healthier habits.

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.

Introduction: Almost 50% to 70% of patients who undergo axillary lymph node dissection (ALND) because of a single metastatic sentinel lymph node (SLN) have no further metastatic nodes at the axillary histology. On these grounds, the one-step nucleic acid amplification (OSNA) nomogram was designed and validated. As a mathematical model, calculated through tumor size (expressed in millimeters) and CK19 mRNA copy number, it is thought to predict nonsentinel lymph node (NSLN) status. The aim of the study is to verify the diagnostic accuracy of the OSNA nomogram in a group of patients with macrometastatic SLN, with a retrospective analysis., Methods: The OSNA nomogram was retrospectively applied to a group of 66 patients with macrometastatic SLN who underwent ALND. The result of the final histology of the axillary cavity was compared to the nomogram prediction. We calculated the prevalence of NSLN metastasis in patients who underwent ALND, sensitivity and specificity, negative and positive predictive value of the nomogram., Results: In patients with macrometastasis in SLN, the prevalence of patients with metastatic NSLN was 45%. The sensitivity of the nomogram was excellent (90%). The specificity was low (36%). Positive predictive value amounted to 54%, while negative predictive value was good (81%)., Conclusions: These results suggest that the OSNA nomogram is a valid instrument that can help choose the best surgical strategy for the treatment of axillary cavity. The mathematical model is useful to avoid surgery in a selected group of patients because it accurately predicts NSLN status., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Little is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2- breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2- early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones.

Radiomics is defined as the use of automated or semi-automated post-processing and analysis of multiple features derived from imaging exams. Extracted features might generate models able to predict the molecular profile of solid tumors. The aim of this study was to develop a predictive algorithm to define the mutational status of EGFR in treatment-naïve patients with advanced non-small cell lung cancer (NSCLC). CT scans from 109 treatment-naïve patients with NSCLC (21 EGFR -mutant and 88 EGFR -wild type) underwent radiomics analysis to develop a machine learning model able to recognize EGFR -mutant from EGFR -WT patients via CT scans. A "test-retest" approach was used to identify stable radiomics features. The accuracy of the model was tested on an external validation set from another institution and on a dataset from the Cancer Imaging Archive (TCIA). The machine learning model that considered both radiomic and clinical features (gender and smoking status) reached a diagnostic accuracy of 88.1% in our dataset with an AUC at the ROC curve of 0.85, whereas the accuracy values in the datasets from TCIA and the external institution were 76.6% and 83.3%, respectively. Furthermore, 17 distinct radiomics features detected at baseline CT scan were associated with subsequent development of T790M during treatment with an EGFR inhibitor. In conclusion, our machine learning model was able to identify EGFR -mutant patients in multiple validation sets with globally good accuracy, especially after data optimization. More comprehensive training sets might result in further improvement of radiomics-based algorithms. SIGNIFICANCE: These findings demonstrate that data normalization and "test-retest" methods might improve the performance of machine learning models on radiomics images and increase their reliability when used on external validation datasets., (©2020 American Association for Cancer Research.)

Vascular inflammation is responsible for many cardiovascular diseases and endothelial dysfunction is often the first trigger. Many factors can contribute to altering vascular homeostasis and despite that some risk factors cannot be changed, some lifestyle changes might dramatically improve vascular function. In this regard, physical activity has been identified as one of the most important interventions that can positively affect endothelial dysfunction. In recent years, the discovery of irisin, a novel myokine with pleiotropic effects, has caught the attention of many researchers. This review summarizes the most relevant intervention trials, evaluating irisin modifications in subjects with or without cardiovascular risk factors assigned to physical activity programs, to improve cardiovascular risk markers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Surrogate molecular classification identifies different subtypes of invasive breast carcinoma on the basis of their immunohistochemical markers. The purpose of the study is to verify whether the immunohistochemical markers and surrogate molecular subtypes can be correctly assessed on the core needle biopsy (CNB) when compared with the corresponding surgical excision (SE), with or without neoadjuvant treatment (NAT). Cases with invasive carcinomas identified on both CNB and SE were retrospectively selected. With immunohistochemistry for estrogen receptors (ER), progesterone receptors (PgR), Ki67, human epidermal growth factor receptor 2 (Her2), and molecular analysis for Her2, surrogate molecular classification was determined in 4 and 5 groups, according to the 2013 St Gallen consensus. A total of 1067 cases was considered and complete data for surrogate molecular classification were available for 988 cases (655 without NAT, 333 with NAT). Without NAT, concordance was strong for ER and Her2, moderate for PgR, and weak for Ki67; concordance for surrogate molecular classification was moderate. After NAT, lower concordance rates were recorded, with significant reduction of PgR (P<0.001) and Ki67 (P<0.001). Without NAT, the surrogate molecular subtypes of breast carcinoma can be reliably assessed on CNB; Ki67 and/or PgR may be repeated on SE when values are close to cutoffs to avoid tumor subtype misclassification. After NAT, it seems advisable to repeat at least Ki67 and PgR.

The standard of care for breast cancer has gradually evolved from empirical treatments based on clinical-pathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. Consequently, an increasing number of molecularly targeted drugs have been developed. These drugs target specific alterations, called driver mutations, which confer a survival advantage to cancer cells. To date, the main challenge remains the identification of predictive biomarkers for the selection of the optimal treatment. On this basis, we evaluated a panel of 25 genes involved in the mechanisms of targeted treatment resistance, in 16 primary breast cancers and their matched recurrences, developed during treatment. Overall, we found a detection rate of mutations higher than that described in the literature. In particular, the most frequently mutated genes were ERBB2 and those involved in the PI3K/AKT/mTOR and the MAPK signaling pathways. The study revealed substantial discordances between primary tumors and metastases, stressing the need for analysis of metastatic tissues at recurrence. We observed that 85.7% of patients with an early-stage or locally advanced primary tumor showed at least one mutation in the primary tumor. This finding could explain the subsequent relapse and might therefore justify more targeted adjuvant treatments. Finally, the mutations detected in 50% of relapsed tissues could have guided subsequent treatment choices in a different way. This study demonstrates that mutation events may be present at diagnosis or arise during cancer treatment. As a result, profiling primary and metastatic tumor tissues may be a major step in defining optimal treatments., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Background: Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available., Methods: Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry., Results: TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant)., Conclusions: Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.

Breast cancer (BC) is a heterogeneous disease, including different subtypes having diverse incidence, drug-sensitivity and survival rates. In particular, claudin-low and basal-like BC have mesenchymal features with a dismal prognosis. Disialoganglioside GD2 is a typical neuroectodermal antigen expressed in a variety of cancers. Despite its potential relevance in cancer diagnostics and therapeutics, the presence and role of GD2 require further investigation, especially in BC. Therefore, we evaluated GD2 expression in a cohort of BC patients and its correlation with clinical-pathological features.Sixty-three patients with BC who underwent surgery without prior chemo- and/or radiotherapy between 2001 and 2014 were considered. Cancer specimens were analyzed by immunohistochemistry and GD2-staining was expressed according to the percentage of positive cells and by a semi-quantitative scoring system.Patient characteristics were heterogeneous by age at diagnosis, histotype, grading, tumor size, Ki-67 and receptor-status. GD2 staining revealed positive cancer cells in 59% of patients. Among them, 26 cases (41%) were labeled with score 1+ and 11 (18%) with score 2+. Notably, the majority of metaplastic carcinoma specimens stained positive for GD2. The univariate regression logistic analysis revealed a significant association of GD2 with triple-receptor negative phenotype and older age (> 78) at diagnosis.We demonstrate for the first time that GD2 is highly prevalent in a cohort of BC patients clustering on very aggressive BC subtypes, such as triple-negative and metaplastic variants.

Background: The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate compared with chemotherapy plus either trastuzumab or lapatinib. A biomarker program was prospectively planned to identify potential predictors of sensitivity to different treatments and to evaluate treatment effect on tumor biomarkers., Materials and Methods: Overall, 121 breast cancer patients positive for human epidermal growth factor 2 (HER2) were randomly assigned to neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib. Pre- and post-treatment samples were centrally evaluated for HER2, p95-HER2, phosphorylated AKT (pAKT), phosphatase and tensin homolog, Ki67, apoptosis, and PIK3CA mutations. Fresh-frozen tissue samples were collected for genomic analyses., Results: A mutation in PIK3CA exon 20 or 9 was documented in 20% of cases. Overall, the pCR rates were similar in PIK3CA wild-type and PIK3CA-mutated patients (33.3% vs. 22.7%; p = .323). For patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild-type tumors (48.4% vs. 12.5%; p = .06). Ki67, pAKT, and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. The integrated analysis of gene expression and copy number data demonstrated that a 50-gene signature specifically predicted the lapatinib-induced pCR., Conclusion: PIK3CA mutations seem to identify patients who are less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of phosphoinositide 3-kinase pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib., Implications for Practice: HER2 is currently the only validated marker to select breast cancer patients for anti-HER2 treatment; however, it is becoming evident that HER2-positive breast cancer is a heterogeneous disease. In addition, more and more new anti-HER2 treatments are becoming available. There is a need to identify markers of sensitivity to different treatments to move in the direction of treatment personalization. This study identified PIK3CA mutations as a potential predictive marker of resistance to dual anti-HER2 treatment that should be further studied in breast cancer., (©AlphaMed Press.)

Aims and Background: The aim of this retrospective multicenter study was to evaluate the impact of progesterone receptor (PgR) loss on locoregional recurrence in patients with estrogen receptor (ER)-positive primary breast cancer and ER-positive locoregional recurrence., Patients and Methods: Eight Italian oncology centers collected data from consecutive patients with ER-positive breast cancer and a subsequent ER-positive locoregional recurrence., Results: Data were available for 265 patients diagnosed with breast cancer between 1990 and 2009. Median metastasis-free survival was 111 months in patients with PgR-positive primary tumors and locoregional recurrence (PgRpos), 38 months in patients with PgR-negative primary tumors and locoregional recurrence (PgRneg), and 63 months in patients with PgR-positive primary tumors and PgR-negative locoregional recurrence (PgRloss). In multivariate analysis, PgR status was independently associated with metastasis-free survival, with a hazard ratio of 2.84 (95% CI 1.34-6.00) for PgRneg compared with PgRpos, and 2.93 (95% CI: 1.51-5.70) for PgRloss compared with PgRpos., Conclusions: PgR absence was found to be a negative prognostic factor in breast cancer patients with ER-positive locoregional recurrence. Thus, PgR status could be a biological marker in ER-positive recurrent breast cancer.