Integrating Biological Advances Into the Clinical Management of Breast Cancer Related Lymphedema

Abstract

Breast cancer-related lymphedema (BCRL) occurs in a significant number of breast cancer survivors as a consequence of the axillary lymphatics' impairment after therapy (mainly axillary surgery and irradiation). Despite the recent achievements in the clinical management of these patients, BCRL is often diagnosed at its occurrence. In most cases, it remains a progressive and irreversible condition, with dramatic consequences in terms of quality of life and on sanitary costs. There are still no validated pre-surgical strategies to identify individuals that harbor an increased risk of BCRL. However, clinical, therapeutic, and tumor-specific traits are recurrent in these patients. Over the past few years, many studies have unraveled the complexity of the molecular and transcriptional events leading to the lymphatic system ontogenesis. Additionally, molecular insights are coming from the study of the germline alterations involved at variable levels in BCRL models. Regrettably, there is a substantial lack of predictive biomarkers for BCRL, given that our knowledge of its molecular milieu remains extremely puzzled. The purposes of this review were (i) to outline the biology underpinning the ontogenesis of the lymphatic system; (ii) to assess the current state of knowledge of the molecular alterations that can be involved in BCRL pathogenesis and progression; (iii) to discuss the present and shortterm future perspectives in biomarker-based patients' risk stratification; and (iv) to provide practical information that can be employed to improve the quality of life of these patients.

The impact of high-intensity interval training exercise on breast cancer survivors: a pilot study to explore fitness, cardiac regulation and biomarkers of the stress systems

“…Protection from pathogens may be compromised in cancer patients for whom radiation, chemotherapy, surgery or effects induced by the cancer itself lead to immunosuppression [ 24 – 28 ]. Immunity, specifically cell-mediated immunity, is critical for defence against some types of tumours and has been shown to be decreased in metastatic breast cancer patients, related to a dysfunctional HPA axis (our central stress response system) [ 23 ].…”

Longitudinal Assessment of Physical Activity, Fitness, Body Composition, Immunological Biomarkers, and Psychological Parameters During the First Year After Diagnosis in Women With Non-Metastatic Breast Cancer: The BEGYN Study Protocol

“…Multiple studies in cancer patients have demonstrated that physical activity and exercise correlate with an improved outcome regarding the course of the underlying disease and with a better tolerance to the antineoplastic treatments ( 13 ). For example, exercise had positive effects on the fatigue syndrome and quality of life in cancer ( 12 , 14 ), the course of lymphedema ( 13 , 15 ) and osteoporosis in breast cancer ( 16 ) and prostate cancer ( 17 ). Moreover, physical activity influences various functions of the immune system, such as the proportions of circulating leukocyte subsets and the expression of cytokines ( 4 , 18 – 21 ).…”

Effects of Intermittent Pneumatic Compression on Lower Limb Lymphedema in Patients with Type 2 Diabetes Mellitus: A Pilot Randomized Controlled Trial

“…This chronic condition most commonly occurs in the lower extremities (legs and feet) [ 14 ]. The precise arm volume measurement allows the early detection of the interstitial accumulation of liquid and could reduce the incidence of irreversible stages [ 15 ]. Several methods were proposed in the literature to evaluate and monitor the upper and lower limbs lymphedema.…”

“…Moreover, the 3DLS detects extremely small variations of volume including the presence and reduction of gibbousness and swelling (e.g., a consequence of bandages, press therapy, manual lymph drainage) [ 25 ]. The lymphoscintigraphy provides an objective measurement and adequately characterizes the severity of lymphedema [ 15 ]. In fact, this imaging technique allows the regional lymph nodes visualization and deep lymphatic nodes localization; nevertheless, this approach is difficult to be applied in the common clinical practice [ 15 ].…”

“…The lymphoscintigraphy provides an objective measurement and adequately characterizes the severity of lymphedema [ 15 ]. In fact, this imaging technique allows the regional lymph nodes visualization and deep lymphatic nodes localization; nevertheless, this approach is difficult to be applied in the common clinical practice [ 15 ]. The indocyanine green (ICG) lymphangiography is a newly developed diagnostic approach that consents to delineating the lymphatics vessels, without any radioactive exposure [ 26 ].…”