She battled the disease for two years, but chose to keep her illness private.
Kelly leaves behind her famous actor husband John and their daughter Ella, 20, and nine-year-old son Benjamin. Their eldest son, 16-year-old Jett, died in 2009.
A family representative released a statement to People, saying: "On the morning of July 12, 2020, Kelly Preston, adored wife and mother, passed away following a two-year battle with breast cancer.
"Choosing to keep her fight private, she had been undergoing medical treatment for some time, supported by her closest family and friends.
"She was a bright, beautiful and loving soul who cared deeply about others and who brought life to everything she touched.