Breast cancer and social environment: getting by with a little help from our friends

Abstract

Social environment is a well-recognized determinant in health and wellbeing. Among breast cancer patients, inadequate social support is associated with a substantial increase in cancer-related mortality. A common explanation is that socially isolated individuals fare worse due to reduced instrumental support (i.e., assistance meeting the demands of treatment). However, the ability to replicate the detrimental effects of social isolation on mammary tumor growth in rodents strongly suggests an alternative explanation; i.e., socially isolated individuals have a physiological milieu that promotes tumor growth. This review summarizes the clinical and basic science literature supporting social influences on breast cancer, and provides a conceptual physiological framework for these effects. We propose that social environment contributes to the vast individual differences in prognosis among breast cancer survivors because social environment is capable of altering basic physiological processes, which in turn can modulate tumor growth. Appreciation of the role of social environment in breast cancer progression could promote the identification of patients at increased risk for poor outcomes. In addition, characterization of the underlying physiological mechanisms could lead to targeted disruption of detrimental pathways that promote tumor progression in socially isolated individuals, or exploitation of protective pathways activated through social engagement as novel therapeutic complements to contemporary treatments.

Keywords: Breast cancer; Catecholamines; Glucocorticoids; Oxytocin; Social isolation.

Fig. 1

Social isolation is a risk factor for mortality on par with obesity and smoking among patients with breast cancer (BC). A plot of all-cause and BC-specific mortality from three representative studies among patients with BC who are socially isolated (relative to socially integrated), obese at time of diagnosis (relative to normal weight), or heavy smokers (relative to never having smoked). Circles indicate the hazard ratios (HR) and horizontal lines indicate the 95 % confidence interval provided in the representative cited paper [74, 75]

Fig. 2

Proposed mechanisms through which social isolation influences breast cancer outcomes in women. Socially isolated individuals tend to exhibit increased activation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). Among patients with breast cancer (BC), increased cortisol is associated with reduced natural killer cell (NKC) count and cytotoxicity, and increased risk of early mortality. There is also the supposition that increased concentrations of endogenous catecholamines (adrenaline and noradrenaline) promote tumor development, metastasis, and tumor progression because the use of β_1/β₂ receptor antagonists for other health conditions is associated with less aggressive tumors and reduced early mortality among patients with BC

Fig. 3

Social environment alters an animal’s hormonal milieu in a way that could either promote or suppress tumor development. Socially isolated rodents are prone to increased hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) activity, characterized by increased endogenous concentrations of corticosterone, adrenaline, and noradrenaline. These hormones have been shown in vivo and in vitro to promote tumor growth through a variety of well-described tumor-associated pathways. In contrast, central nervous system (CNS) oxytocin is relatively low among socially isolated animals. Among socially integrated animals there is increased release of CNS oxytocin, which in turn restrains both the HPA axis and ANS. In addition, oxytocin may indirectly influence tumor development via its modulation of macrophages