- Breast cancer (BC) is currently one of the most common cancers in women worldwide with a rising tendency. Epigenetics, generally inherited variations in gene expression that occur independently of changes in DNA sequence, and their disruption could be one of the main causes of BC due to inflammatory processes often associated with different lifestyle habits. In particular, hormone therapies are often indicated for hormone-positive BC, which accounts for more than 50–80% of all BC subtypes. Although the cure rate in the early stage is more than 70%, serious negative side effects such as secondary osteoporosis (OP) due to induced estrogen deficiency and chemotherapy are increasingly reported. Approaches to the management of secondary OP in BC patients comprise adjunctive therapy with bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDs), and cortisone, which partially reduce bone resorption and musculoskeletal pain but which are not capable of stimulating the necessaryBreast cancer (BC) is currently one of the most common cancers in women worldwide with a rising tendency. Epigenetics, generally inherited variations in gene expression that occur independently of changes in DNA sequence, and their disruption could be one of the main causes of BC due to inflammatory processes often associated with different lifestyle habits. In particular, hormone therapies are often indicated for hormone-positive BC, which accounts for more than 50–80% of all BC subtypes. Although the cure rate in the early stage is more than 70%, serious negative side effects such as secondary osteoporosis (OP) due to induced estrogen deficiency and chemotherapy are increasingly reported. Approaches to the management of secondary OP in BC patients comprise adjunctive therapy with bisphosphonates, non-steroidal anti-inflammatory drugs (NSAIDs), and cortisone, which partially reduce bone resorption and musculoskeletal pain but which are not capable of stimulating the necessary intrinsic bone regeneration. Therefore, there is a great therapeutic need for novel multitarget treatment strategies for BC which hold back the risk of secondary OP. In this review, resveratrol, a multitargeting polyphenol that has been discussed as a phytoestrogen with anti-inflammatory and anti-tumor effects at the epigenetic level, is presented as a potential adjunct to both support BC therapy and prevent osteoporotic risks by positively promoting intrinsic regeneration. In this context, resveratrol is also known for its unique role as an epigenetic modifier in the regulation of essential signaling processes—both due to its catabolic effect on BC and its anabolic effect on bone tissue.…