Preventing Breast Cancer Therapy-related Cardiovascular Toxicity With a Daily-adapted Program With Mhealth Support

More and more women are experiencing breast cancer at younger ages, yet survival rates have become very promising. However, years after cancer treatment, related sequelae (physical, psychological, or emotional) may emerge, responsible for post-disease fatalities in many women. The occurrence of these sequelae largely depends on treatment-induced toxicity and individual health status, which is related to lifestyle habits. Among these sequelae, cancer-related cardiovascular toxicity (CTR-CVT) is noteworthy, with an incidence close to 40% in breast cancer, closely linked to treatments such as chemotherapy (especially anthracyclines), targeted therapy (trastuzumab), and radiotherapy (left side or mediastinum), causing DNA and mitochondrial damage. Traditionally defined as a reduction in left ventricular ejection fraction (LVEF) ≥50% in its mildest form, and a decrease in global longitudinal strain (GLS) of >15% from baseline and/or an increase in cardiac markers (cardiac troponin I or T cTnI/cTnT >99th percentile, brain natriuretic peptide BNP ≥35 pg/mL, or NT-proBNP ≥125 pg/mL) to severe (requiring inotropic support, mechanical circulatory support, or consideration for transplantation), adding the need for monitoring through various tests, not just LVEF, as it would be too late to detect it. The risk detection of TCVRC is based on medical treatments, which sometimes are insufficient since many patients theoretically considered low-risk develop TCVRC. This has led to the need to study and include other patient-related factors at the time of diagnosis, such as previous presence of cardiovascular diseases, age, lifestyle habits, and comorbidities, to be considered for overall cardiovascular and oncological prognosis and individualized surveillance of TCVRC, along with additional factors that add to the complexity of risk assessment such as cancer type, duration, and doses of oncological treatment. However, the scientific evidence supporting the inclusion of some of these parameters is of questionable quality (level C) and, moreover, they are not usually included in routine assessments, making them less applicable.

To improve the situation and achieve proper prevention of TCVRC, it is necessary to identify parameters with good sensitivity for early detection that can preferably be performed routinely by different healthcare professionals involved in the continuum of care, as well as related risk factors. With this information, the implementation of interventions that could limit treatment interruptions and improve survival after breast cancer would be facilitated. In this context, the European Society of Cardiology Guidelines highlight, in addition to the improvement of detection tools, the inclusion of new parameters, the creation of large data registries, the use of artificial intelligence, or the determination of new risk stratification algorithms, among others.

There is a lack of access to structured physical exercise programs for cancer patients, even though adaptation of exercise to their health status is crucial, as excessive doses could be harmful. Ondulatory exercise prescription may be more suitable for cancer patients, as it allows better adaptation to their health status. So far, one of the systems to achieve this has been prescription based on heart rate variability (HRV) previously used in the sports world and in some cardiovascular pathologies but promising and little studied in the cancer world. However, given the complexity of this disease, its treatments, and the impact it has on different spheres of these patients' health, the inclusion of additional markers is suggested to further optimize personalized exercise programs based on individual needs. With the support of current technologies, monitoring and control of physiological parameters are facilitated, potentially reducing the costs of in-person supervision by healthcare professionals but also the potential health risks in these patients when engaging in physical exercise.

Regarding these interventions, both physical activity and exercise have been recognized as potent multi-effect non-pharmacological therapies in the treatment of TCVRC, although to achieve optimal physiological adaptations and individualization, physical exercise programs must be correctly prescribed. In recent years, interest has shifted towards supervised high-intensity interval exercise, which has been shown to be safe, well-tolerated, effective for TCVRC treatment, and cost-effective. However, most physical exercise programs implemented are general programs with linear prescriptions and questionable adherence. To address adherence issues, physical exercise programs have been combined with behavioral change programs, showing promising short-term results but with loss in the medium/long term. In this regard, the use of technology and patient monitoring, which provide continuous feedback and have proven to be an effective and useful tool for establishing a healthy lifestyle, could offer a solution for both patients and professionals in improving adherence.

ATOPE-PRO aims to integrate into the usual care continuum of women with breast cancer a personalized and individualized mhealth model (ATOPE+ 2.0) for TCVRC prevention, which will allow us to advance towards precision clinical care, to complete its implementation and transfer of results, resulting in an improvement in quality of life, recurrence, and death, meeting the standards requested, through refining and automating the process, ensuring adherence, and offering safe and effective doses of physical exercise.