Dense fibrosis of the breast as assessed by mammography may be associated with early disease diagnosis. Radiation-induced fibrosis occurs in a large fraction of patients following breast conserving therapy and may be modified by genetic susceptibility. TGFBR1*6A is a high frequency, low penetrance TGFBR1 hypomorphic variant, which is associated with breast cancer risk. Here we show an association of TGFBR1*6A with breast cancer tissue fibrosis in mice and in patients with HER2-positive breast cancer.