Abstract
Excess adipose tissue is a hallmark of an overweight and/or obese state as well as a primary risk factor for breast cancer development and progression. In an overweight/obese state adipose tissue becomes dysfunctional due to rapid hypertrophy, hyperplasia, and immune cell infiltration which is associated with sustained low-grade inflammation originating from dysfunctional adipokine synthesis. Evidence also supports the role of excess adipose tissue (overweight/obesity) as a casual factor for the development of chemotherapeutic drug resistance. Obesity-mediated effects/modifications may contribute to chemotherapeutic drug resistance by altering drug pharmacokinetics, inducing chronic inflammation, as well as altering tumor-associated adipocyte adipokine secretion. Adipocytes in the breast tumor microenvironment enhance breast tumor cell survival and decrease the efficacy of chemotherapeutic agents, resulting in chemotherapeutic resistance. A well-know chemotherapeutic agent, doxorubicin, has shown to negatively impact adipose tissue homeostasis, affecting adipose tissue/adipocyte functionality and storage. Here, it is implied that doxorubicin disrupts adipose tissue homeostasis affecting the functionality of adipose tissue/adipocytes. Although evidence on the effects of doxorubicin on adipose tissue/adipocytes under obesogenic conditions are lacking, this narrative review explores the potential role of obesity in breast cancer progression and treatment resistance with inflammation as an underlying mechanism.
Highlights
Breast cancer continues to be a major health risk for women globally [1, 2]
This results in dysfunctional synthesis of several adipokines in coordination with immune cell infiltration leading to a state of sustained low-grade inflammation, which activates downstream signaling pathways favoring cancer cell survival and contributing to cancer progression and metastasis [10,11,12]
We proposed that using doxorubicin treatment on dysfunctional adipose tissue and/or adipocytes, may exacerbate the negative effects of obesity per se, and further dysregulate adipokine secretion
Summary
Breast cancer continues to be a major health risk for women globally [1, 2]. Lifestyle-related risk factors including overweight and obesity (adiposity) have reached epidemic proportions [3, 4], and are considered major risk factors for breast cancer development and progression [5].Adipose tissue plays an important physiological role as a metabolically active storage compartment and endocrine organ due to its diverse ability to secrete various adipokines [6]. We proposed that using doxorubicin treatment on dysfunctional adipose tissue and/or adipocytes, may exacerbate the negative effects of obesity per se, and further dysregulate adipokine secretion.
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