Assessing mental health, cognitive function and quality of life of breast cancer patients: exploring associations with gut microbiota in an observational and preliminary study

Catarina Calafate^1*Diogo Alpuim Costa^1,2,3,4*Teresa Campos¹Pedro Ribeiro⁵Filipa Martinho⁴Cristina Freitas²Carolina Botelho De Sousa⁴Ida Negreiros⁴Ana Canastra⁶Paula Borralho^4,6,7Ana Guia Pereira⁵Cristina Marçal⁵Rita Ribeiro⁵José Germano Sousa⁵Catarina Dinis⁸Renata Chaleira⁹Rita Calha¹⁰Júlio César Rocha^11,12Conceição Calhau^11,12,13,14André Moreira-Rosário^11,12,14Ana Faria^11,12,14

• ¹NOVA University of Lisbon, Lisbon, Portugal
• ²Haematology and Oncology Department, CUF Oncologia, Lisbon, Portugal
• ³Medical Oncology Department, Hospital de Cascais, Cascais, Portugal
• ⁴Breast Unit, CUF Oncologia, Lisbon, Portugal
• ⁵Centro de Medicina Laboratorial Germano de Sousa, Lisbon, Portugal
• ⁶Anatomic Pathology Department, CUF Oncologia, Lisbon, Portugal
• ⁷Faculty of Medicine, University of Lisbon, Lisbon, Portugal
• ⁸Psychology Department, CUF Cascais Hospital, Cascais, Portugal
• ⁹Psychology Department, CUF Descobertas Hospital, Lisbon, Portugal
• ¹⁰Nutrition Department, CUF Cascais Hospital, Cascais, Portugal
• ¹¹NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa (UNL), Lisbon, Portugal
• ¹²CINTESIS@RISE, NOVA Medical School (NMS), Faculdade de Ciências Médicas (FCM), Universidade NOVA de Lisboa (UNL), Lisbon, Portugal
• ¹³Unidade Universitária Lifestyle Medicina José de Mello Saúde by NOVA Medical School, Lisbon, Portugal
• ¹⁴CHRC - Comprehensive Health Research Centre, NOVA Medical School, Faculdade de Ciências Médicas, Lisbon, Portugal

Introduction: Breast cancer patients face several physical and psychological problems, such as anxiety, depression, and cognitive dysfunction. The disease and treatments can also impact the microbiota, which is associated with cognitive and psychological issues and, consequently, affected quality-of-life (QoL). This study aimed to correlate the initial gut microbiota of newly diagnosed HR+ (Hormone Receptor)/HER2- breast cancer patients with their mental health, cognitive function, and QoL at baseline and after 3 months of neoadjuvant chemotherapy. Materials and Methods: This is a prospective, longitudinal, observational, exploratory study. Newly diagnosed HR+/HER2- breast cancer patients undergoing neoadjuvant chemotherapy were recruited upon diagnosis. At baseline (before neoadjuvant chemotherapy), general and lifestyle information, adherence to the Mediterranean diet, biochemical analysis, gut microbiota profile, the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core-30 (EORTC QLQ-C30), the Montreal Cognitive Assessment (MoCA) and the Hospital Anxiety and Depression Scale (HADS), were collected. The EORTC QLQ-C30, MoCA, and HADS were repeated 3 months later. Results: From the 11 participants, most showed mild cognitive impairment at baseline, and there was no clear trend of improvement or deterioration at 3 months. Participants had borderline anxiety at baseline, which improved to a normal range, while depression remained stable. QoL declined for most women, with over 70% experiencing problems at 3 months. The association of these parameters with microbiota profile suggested that women with poorer cognitive function over time had lower Shannon index and microbial richness. Women with improved scores in the depression subscale of the HADS appear to have higher Shannon index and lower richness. Contrarily, Shannon index was lower and richness was higher for improved anxiety and global QoL scores. The results also suggest that changes in the abundance of various genera and phyla may be linked to the evolution of scores for the 3 questionnaires. Conclusion: Our study suggests a link between the microbiota profile at diagnosis and the psychological symptoms that develop at 3 months of breast cancer treatment. These findings shed light on potential strategies for positively modulating the microbiota to help enhance the body's resilience, particularly mental health, throughout the disease and treatments.