Background: In postmenopausal women, an alteration in body composition occurs as a consequence of the secretion of low levels of serum estrogens by the ovaries. Observing an increase in abdominal and mammary fat mass and a decrease in skeletal muscle mass, which is also accompanied by loss of muscle strength and physical function, which leads early to a sarcopenia.

On the other hand, the increase in estrogen production by adipose tissue has been associated with an increased risk of breast cancer during menopause because the mammary parenchyma is particularly sensitive to this type of estrogen. For this reason, Hormone Therapy (Aromatase Inhibitors and Tamoxifen) is prescribed in women with estrogen receptor-positive breast cancer. Antineoplastic treatments (Chemotherapy and Hormonal Therapy) have contributed to non-metastatic breast cancer currently presenting a high survival rate, not without adverse effects associated with the course of the disease, age and antineoplastic treatment, affecting various systems, but particularly skeletal muscle mass.

Therefore, resistance exercise training has been proposed as an effective intervention strategy to increase muscle mass and strength in different populations. However, the level of muscle response to this type of training in postmenopausal women survivors of breast cancer with and without hormone treatment (Aromatase Inhibitors and Tamoxifen) is unknown.

Hypothesis: The increase in skeletal muscle mass after 12 weeks of progressive resistance-type exercise training is less in postmenopausal breast cancer survivors compared to healthy women of the same age range.

Postmenopausal breast cancer survivors without hormonal therapy will have greater gains in skeletal muscle mass compared to breast cancer survivors with Hormone Therapy (Aromatase Inhibitors or Tamoxifen) of the same age range after 12 weeks of progressive resistance-type exercise training.

Goals: The primary aim of this study is to compare the effects of a 12-week progressive resistance-type exercise training on muscle mass (whole body muscle mass) in healthy postmenopausal women versus postmenopausal women survivors of breast cancer with and without Hormone Therapy (Aromatase Inhibitors and Tamoxifen).

Specific goals Determine whether resistance-type exercise training can increase muscle strength and quality of life in healthy postmenopausal women versus postmenopausal women survivors of breast cancer with and without Hormone Therapy (Aromatase Inhibitors and Tamoxifen).

Identify whether circulating biochemical markers are up- or down-regulated in in healthy postmenopausal women versus postmenopausal women survivors of breast cancer with and without Hormone Therapy (Aromatase Inhibitors and Tamoxifen) after resistance-type exercise training

Methodology:

Study design Twenty-six postmenopausal women between 45 to 59 years will be divided into two groups: participants without cancer (CLIMHEALTHY, n=13) and participants survivors of breast cancer without or with Hormone Therapy (CLIMCANCER, n=13). All volunteers will be subjected to 12 weeks of whole-body resistance-type exercise training (3x/wk). Before, and after 12 weeks of training, whole-body dual energy x-ray absorptiometry (DEXA) scan will be performed for measured skeletal muscle mass and fasting blood samples will be obtained. Maximal strength will be determined by 1-repetition maximum (1RM), physical functioning by the short physical performance battery (SPPB) and quality of life by QLQ-BR23 at the same time points.

Study parameters/endpoints:

The main study endpoint is the increase in the skeletal muscle mass of whole-body assessed vial dual energy x-ray absorptiometry (DEXA).

Secondary endpoints include: Maximal strength assessment (1RM); Hand grip strength; Short physical performance battery (SPPB); quality of life (QLQ-BR23), Inflammatory and molecular markers (blood samples analysis).

Other study parameters include: Age, body weight, body height, body mass index (BMI), lipid profile, glucose, and insulin.

Expected results:

The impact of resistance-type exercise training to increase muscle mass in postmenopausal women survivors of breast cancer with or without hormonal therapy remains unclear. With the proposed project, the investigators expect that resistance-type exercise training will increase skeletal muscle mass, although the impact will be relatively lower in the participants survivors of breast cancer when compared with a group of healthy postmenopausal woman. The potential findings will define the efficacy of resistance-type exercise training to increase muscle mass in individuals with postmenopausal woman survivors of breast cancer. Better maintenance, or even an increase in muscle mass and strength increases independence, prolonging good health, recovery from disease and illness, and ultimately decreases burden on healthcare systems. These results will allow the creation of local, regional, national and international strategies to combat the adverse effects of breast cancer and its antineoplastic treatment, especially in postmenopausal women.

Inclusion Criteria:

• Healthy postmenopausal women and postmenopausal women survivors of breast cancer with and without Hormonal Therapy (Aromatase Inhibitors and Tamoxifen) between 45 to 59 years.
• Women survivors of breast cancer with active Hormone Therapy in the last 12 months.
• Women breast cancer survivors with luminal molecular profile and positive estrogen receptors.
• Body mass index 18.5 < BMI < 30 kg/m2.
• Volunteers without cognitive impairment (abbreviated Minimental >13 points).

Exclusion Criteria:

• Active antineoplastic treatment in the last 12 months.
• >200 mL of volume difference between upper limbs and/or stage IV breast cancer.
• Performing regular resistance training (2 or more times per week, carrying out progressive training) in the previous 6 months.
• Cardiovascular diseases that are contradictory for physical activity (not included controlled Hypertension).
• All co-morbidities interacting with mobility and muscle metabolism of the body and that do not allow to (safely) perform the resistance-type exercise training (e.g. debilitating arthritis, spasticity/rigidity, all neurological disorders and paralysis).