Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone ( ) or visceral sites ( ). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone ( ). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups ( ). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%; ). Triple-negative tumors that metastasized to visceral sites were larger ( ). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors. 1. Introduction Despite the progress that has been made in the diagnosis and treatment of early stage breast cancer, a substantial proportion of patients still go on to develop incurable distant metastatic disease. The lack of estrogen receptor (ER) and progesterone receptor (PR) expression in breast cancer is associated with an increased likelihood of visceral metastases and a particularly poor prognosis [1–4]. So-called triple-negative breast cancers lack both ER and PR and also human epidermal growth factor 2 receptor (HER2) expression. This phenotype is particularly common in younger women [5–7] and is likely to be accompanied by distant, hematogenous metastases that usually occur in the first five years after the initial diagnosis and are associated with relatively short relapse-free and overall survival times [6, 8, 9]. Both steroid hormone receptor-negative breast cancers [10–12] and triple-negative tumors [5, 12, 13] are more common in women with a socioeconomically deprived background. Bone is the most commonly observed site for distant metastases and is the location of 30–40% of first tumor recurrence [14, 15]. Women with their first recurrence occurring in the skeleton have a better prognosis than those with visceral metastases to the liver, lung, or
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