Prehabilitation based on resistance-exercise training in women with Breast Cancer undergoing neoadjuvant therapy: from molecular mechanism to clinical benefits

• Grant number: 22/09341-4
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2023
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Universidad de la Frontera
• Principal Investigator: Rui Curi
• Grantee: Rui Curi
• Principal researcher abroad: Gabriel Nasri Marzuca-Nassr
• Institution abroad: Universidad de La Frontera (UFRO), Chile
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated researchers: Alice Cristina Rodrigues ; Laureane Nunes Masi ; Renata Gorjao ; Sandro Massao Hirabara ; Tania Cristina Pithon Curi

Abstract

Breast cancer is the leading cause of cancer mortality among women worldwide and is the type of cancer with the highest incidence worldwide, a fact that also occurs in Latin American countries in economic transition such as Chile and Brazil. In relation to the therapeutic options, depending on the stage of the cancer, cell subtype and size of the tumor, the treatment of choice is decided. For this reason, women with more aggressive tumors (HER+2 and Triple negative) and larger tumors are candidates to be treated with neoadjuvant chemotherapy prior to breast surgery. Antineoplastic treatments produce side effects such as cancer-related fatigue, decreased functional capacity, and alterations in body composition, which translates mainly into skeletal muscle atrophy, a variable associated with higher mortality, cardiotoxicity, and lower quality of life in these patients, even before the surgery. For this reason, it is important to apply therapeutic strategies, from the initial stages (prior to breast surgery), that increase skeletal muscle mass during the course of the disease, such as prehabilitation through resistance-exercise training (RET). RET has shown favourable effects on prostate cancer, however, its molecular and clinical effects in women with breast cancer undergoing neoadjuvant therapy are unknown. Thus, the aim of this study is to determine the effects of prehabilitation based on resistance-exercise training versus usual care, before and after breast surgery, on skeletal muscle mass in women with breast cancer undergoing neoadjuvant chemotherapy. A single-blind, randomized controlled clinical trial will be developed. Sixty-eight women with breast cancer undergoing neoadjuvant therapy and with an indication for breast surgery will be divided into two groups: usual care (CONTROL n=34) versus Prehabilitation, (P-REHAB n=34). All participants will receive an education session 20 weeks before surgery + neoadjuvant chemotherapy for 16-20 weeks. Only participants in the P-REHAB group will undergo 16-20 weeks of full-body resistance exercise training (twice a week). At baseline, later prehabilitation and 4 weeks after surgery, the cross-sectional area of the quadriceps muscle and of the musculature at lumbar level 3 will be measured by means of CT-Scan. Also, fasting blood samples will be obtained to measure biochemical and molecular markers (e.g. miRNAs). Maximal strength will be determined by 1 repetition maximum (1RM) leg press, leg extension, lat pull down, chest press, horizontal row, and handgrip. In addition, physical functioning will be assessed with the short physical performance battery (SPPB), functional capacity with the 6-minute walk test, quality of life with the BR23 questionnaire, and cancer-related fatigue with the Brief Fatigue Inventory scale at the same time points. Finally, samples of tumor and muscle tissue will be obtained on the day of breast surgery. It is expected that prehabilitation based on resistance-exercise training to result in increased muscle mass in women with breast cancer undergoing neoadjuvant chemotherapy compared to participants receiving usual care. Also, it is expected that this intervention before surgery in women with breast cancer undergoing neoadjuvant therapy will generate better results in clinical parameters (serious adverse events, hospital readmission, infection, complications) and quality of life one month after discharge. hospital compared to usual care. These results will allow the creation of national and international strategies within Latin America to combat the adverse effects of cancer and its antineoplastic treatment, especially in women who undergo neoadjuvant chemotherapy. The foregoing will lead to an increase in muscle mass, functionality and quality of life in these patients, reducing dependency and health costs and improving their general well-being. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARZUCA-NASSR, GABRIEL NASRI; PENAILILLO, LUIS; VALLADARES-IDE, DENISSE; MARTINEZ-HUENCHULLAN, SERGIO; CURI, RUI; HIRABARA, SANDRO MASSAO; VITZEL, KAIO FERNANDO. Editorial: Spotlight on aging: physiology, prevention, and management of skeletal muscle atrophy. FRONTIERS IN PHYSIOLOGY, v. 14, p. 3-pg., 2023-12-05. (18/09868-7, 22/09341-4)

ARTIGAS-ARIAS, MACARENA; CURI, RUI; MARZUCA-NASSR, GABRIEL NASRI. Myogenic microRNAs as Therapeutic Targets for Skeletal Muscle Mass Wasting in Breast Cancer Models. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 25, n. 12, p. 16-pg., 2024-06-01. (18/09868-7, 22/09341-4)

ARTIGAS-ARIAS, MACARENA; ALEGRIA-MOLINA, ANDREA; VIDAL-SEGUEL, NICOLAS; MUNOZ-COFRE, RODRIGO; CARRANZA-LEIVA, JUAN; SEPULVEDA-LARA, ALEXIS; VITZEL, KAIO FERNANDO; HUARD, NOLBERTO; SAPUNAR, JORGE; SALAZAR, LUIS A.; et al. Skeletal muscle mass, strength, and physical performance gains are similar between healthy postmenopausal women and postmenopausal breast cancer survivors after 12 weeks of resistance exercise training. SUPPORTIVE CARE IN CANCER, v. 32, n. 12, p. 12-pg., 2024-12-01. (22/09341-4)