Obesity increases the risk of developing breast cancer and worsens the prognosis for women who are diagnosed. During the initial stages of disease progression, breast cancer cells invade out of the mammary gland and through the surrounding adipose tissue. Notably, obesity remodels adipose tissue but how these changes impact the pathogenesis of breast cancer remains unclear. Adipocytes, which constitute the functional cells of adipose tissue, expand through a combination of hyperplasia (increase in number) and hypertrophy (increase in size) in obese individuals. How these distinct modes of expansion influence the behavior of invasive breast cancer cells has been limited by insufficient strategies to manipulate and maintain adipocytes after isolation. Here, we apply bioengineering principles to develop improved methods to culture and characterize primary adipocytes for mechanistic studies. Using these approaches, we find that larger, hypertrophic adipocytes are distinct from smaller adipocytes isolated from the same donor. In particular, hypertrophic adipocytes are enriched for transcriptional programs related to adipose tissue dysfunction and exhibit altered cell structure and mechanics. Moreover, in co-culture studies, hypertrophic adipocytes transfer greater quantities of neutral lipid to breast cancer cells by releasing intact triglycerides packaged into extracellular vesicles. This intercellular communication ultimately increases breast cancer cell migration and proliferation in a manner dependent on lipid metabolism. Moving forward, additional studies will confirm the relevance of our findings to other obesity-associated cancers and identify adipocyte-related biomarkers or therapeutic targets to improve clinical outcomes for these patients.