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COVID‐19 vaccine hesitancy poses serious challenges in achieving adequate vaccine coverage in the general population. While most studies on vaccine hesitance determinants during the COVID‐19 pandemic were quantitative, qualitative research on the reasons for vaccine resistance is still lacking. To fill this gap, this study aims to qualitatively investigate cognitive and emotional factors associated with COVID‐19 vaccine hesitancy. This qualitative pilot study was conducted between October and November 2021 in Italy. A total of 40 COVID‐19 vaccine‐hesitant (“hesitant not vaccinated” or “hesitant but vaccinated”) individuals completed anonymous questionnaires with open‐ended questions. Data were analysed using the Interpretive Description approach. The central theme that emerged about vaccine hesitancy was the lack of control. This construct included four different sub‐categories: distrust of the government, infodemic, influence of family, and general anti‐vaccine opinions. The results also showed that the most important emotional and cognitive factors associated with hesitancy were anger related to a perceived sense of oppression; emotional avoidance to minimize risk; anxiety related to potential vaccine side effects. Identifying and understanding factors influencing COVID‐19 vaccination hesitancy is crucial to improving communication strategies that will ultimately result in increased confidence and vaccine acceptance.

Purpose. Return to work (RTW) after breast cancer (BC) may easily impact on women recovery and quality of life. Literature on RTW hightlighed several factors associated to RTW after BC, and there is still some concern for exploring the main sociodemographic, clinical, psychological and work-related predictors of RTW after BC treatments especially when considering the first 6 months. The present study aims to explore which baseline factors are associated with RTW at 6-month after BC surgery. Methods. A 6-month follow-up study was performed among patients recruited from a Hospital in Northern Italy after their cancer-related surgery. Partecipants filled in a battery of questionnaires at baseline and at 6-month follow-up. Measurements were on job stress, work engagement, quality of life, anxiety, depression and resilience. Moreover, sociodemographic, clinical and work-related data were collected. Univariate and multivariate analyses were performed. Results. We recruited a sample of 149 patients, whose 73.9% returned to work after surgery. The women who returned to work were more likely to be not in a relationship, nor to have children. Also, they were not treated by chemiotherapy, and had higher scores in expectations of job changes after illness, RTW expectations, perception of physical quality of life and psychological resilience. In the multivariate model, chemiotherapy and women’s RTW expectations resulted as significant predictors of RTW at 6-month after BC surgery. Conclusion Most patients returned to work within first 6 months from breast surgery. Return to work was influenced by chemiotherapy and RTW expectations at baseline. A carefully individual screening of risk factors at baseline can prevent from occupational disability and long sickness absence.

Despite the improvement in the early diagnosis and the use of modern therapies, breast cancer is the second cause of death, after lung cancer, in women around the world, and this is mainly due to metastasis development distant organs. PI3K/Akt pathway is deregulated in almost 50% of breast carcinomas, and is associated to therapy resistance. Currently, there are increasing clinical trials that combine endocrine treatments with PI3K/Akt inhibitors to delay tumor resistance and to avoid tumor progression. However, these inhibitors do not distinguish between the isoform specific function of Akt1, Akt2 and Akt3. Several evidences in different models of cancer show that Akt1 and Akt2 are expressed in different stages of cancer progression, with Akt1 involved in tumor proliferation during the first steps of the carcinogenic process, and Akt2 involved in the invasive phenotype. The aim of this work was to study Akt1 and Akt2 isoforms, focusing on their particular role in cell migration and invasion in human breast tumor samples and in two human breast cancer cell lines. Tissue microarray analysis in a small cohort of human advanced breast cancer samples showed a positive association between invasive grade, Akt2 expression and E-cadherin loss. Interestingly, E-cadherin presents a heterogeneous staining in each sample, being weaker in the more invasive areas and stronger in the non-invasive areas. To understand the specific role of each isoform of Akt on tumor phenotype, T47D and IBH-6 human breast cancer cell lines were stably transfected to specifically inhibit Akt1 (shAkt1) or Akt2 (shAkt2) and the resulting phenotype in cell culture and in xenografts were analyzed. We found that Akt1 silencing inhibited cell growth through S6 and cyclin-D1 regulation, but induced cell migration and invasion in IBH-6 2D and 3D cell cultures. Contrarily, Akt2 silencing had no effect on cell proliferation but significantly inhibited cell adhesion and invasion. These phenotypes were accompanied by an opposite regulation of β1-Integrin, FAK, MMP9, F-actin and vimentin expression. Simultaneous silencing of Akt1 and Akt2 isoforms showed that Akt1 has an anti-migratory effect per se and not by upregulating Akt2 levels. Interestingly, in IBH-6 and T47D xenograft studies we observed that shAkt1 cells grew significantly more slowly than control tumors, but displayed a ducto-lobulillar invasive phenotype, similar to the phenotype gained with Akt2 overactivation by myristoylated Akt2. Contrarily, shAkt2 tumors showed no differences in growth rate, with no infiltrating morphology when compared to control tumors. Immunohistochemical analysis showed low E-cadherin and high vimentin expression in invasive T47D shAkt1 tumors, and the opposite pattern in T47D shAkt2 tumors. We are currently assessing Akt1 status, vimentin, β1-integrin, FAK and MMP9 levels in human samples to relate them with in vitro and xenografts results. Altogether, these results indicate that Akt2 overexpression as well as Akt1 inhibition play important roles in the acquisition of an invasive and aggressive phenotype. The status of each isoform-driven pathway is relevant in the design of targeted therapies that could be more effective and selective in each tumor stage. Citation Format: Cecilia Perrone, Marina Riggio, Maria May, Maria Laura Polo, Jimena Rodriguez, Diego Lucas Kaen, Claudia Lanari, Virginia Novaro. Akt2 gain or Akt1 loss drives invasion and aggressiveness in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A70.