A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling

Abstract

Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.

The role of NLRP3 inflammasome in aging and age-related diseases

“…In the context of inflammation, the normal inflammatory processes become dysregulated during cellular aging, resulting in cellular damage and the prolonged release of pro-inflammatory factors. The accumulation of damaged cells within the tissue can precipitate cancerous transformations within the tissue landscape [ 59 ].…”

Myths and Methodologies: Standardisation in human physiology research—should we control the controllables?

“…However, not all studies differentiate between participants who have—or have not had—a medical condition in the past, so‐long as the condition resolved within an arbitrary period (e.g., 10 years). However, past treatment of conditions, especially cancer, leaves a lasting fingerprint on physiology (Arana Echarri et al., 2023), and differences between individuals can even be detected whether they have previously encountered mild asymptomatic infections or not (e.g., Cytomegalovirus ; Turner et al., 2010). While inclusion and exclusion of stable traits is beyond the scope of this paper, some medical conditions require participants to take pharmacological agents (i.e., medications) that may introduce bias, and therefore some degree of standardisation should be considered.…”

Immune cell status, cardiorespiratory fitness and body composition among breast cancer survivors and healthy women: a cross sectional study

“…In doing so, cells with specific functions can be quantified, providing a more detailed understanding and nuanced interpretation of the direction of changes to cell counts. However, a contributing explanation for different results between studies is that age and lifestyle factors–which are known to affect the numbers and characteristics of leukocyte sub-types in blood–are often not considered ( Arana Echarri et al, 2021 ). These factors include age, regular exercise, cardiorespiratory fitness, and body composition.…”

“…In summary, immune cell profiles in blood can influence clinical outcomes and can change with cancer treatment. If these profiles are assessed to stratify patients and inform treatment decisions or post-treatment care, age, lifestyle and other participant characteristics such as cardiorespiratory fitness and body composition should also be considered due to the impact that these factors can have on immune cells in blood ( Arana Echarri et al, 2021 ). Thus, the aim of this study was to examine whether there are differences in blood immune cell profiles between healthy women and breast cancer survivors, and whether immune cell profiles were influenced by age, cytomegalovirus infection, cardiorespiratory fitness and body composition.…”