PRIN 2022 Scorrimento - Prot. 2022HS7NLA

Breast cancer (BC) is a leading cause of death among women with cancer. Although only 5-10% of BC bears harmful mutations in the DNA damage repair genes BReast CAncer (BRCA) 1 and 2; women with BRCA1/2 mutations have higher risk of developing BC and 40-65% of them will encounter the disease by the age of 70. Due to having a high tumor mutational burden, BRCA1/2 tumors are considered good candidates for immune-based treatment. However, how BRCA1/2 mutations modulate the tumor- microenvironment and impact on anti-tumor immunity is still debated. Along with genetic alterations, psychological dispositions and personal characteristics - e.g. cognitive flexibility, self-efficacy, resilience and coping strategies - have emerged as critical players in favoring cancer development by altering homeostatic neuro-endocrine-immune (NEI) functions. Recent studies showed that having BRCA 1/2 is associated with higher endocrine dysfunction, anxiety, depression, distress. Furthermore, gut bacteria contribute in shaping systemic immune responses and are engaged in a mutual modulation of the neuro-endocrine axes. Thus, different psychologic assets may impact on the anti-tumor immune response in BC patients and, in turn, influence their clinical outcome. In this perspective, there is a need to gain a deep understanding about the relationship between cognitive mechanisms, phenotypes and immune microenvironments to find new effective immune therapeutic strategies against these tumors. The present project aims to explore the predictive role of psychological variables on cancer progression and immune functions in BRCA1/2 high-risk BC population.

Consistently, the main aim of the ImmuneMind project is to develop a predictive model of the impact of psychological, social and clinical variables on T cell functionality and microbiota in BRCA1/2 mutation carriers. The ImmuneMind project will gather data on 180 high-risk breast cancer patients from 3 clinical centers in partnership with the University Units participating in this project. Psychological, social, clinical, and biological variables will be collected at the beginning of oncological therapies (T0), and after 3 (T1), 6 (T2), 9 (T3) and 12 months (T4) from T0. Results from this project will shed light on the multi-facet mechanisms that affect the somatic environment, profiling quantitatively the influence of psychological variables and personal characteristics on the function of the immune system and on gut microbiota. Results will help reconcile previous observations while providing evidence of the potential benefits of psychological interventions on ameliorating clinical outcome in BRCA1/2 high-risk BC patients.

Working group:

• Daniela Pia Rosaria Chieffo - Responsabile scientifico UCSC

Partners:

• Università degli Studi di Milano
• Libera Università "Vita Salute S. Raffaele" Milano