Rethinking contralateral breast cancer: latest insights on risk, prevention, and outcomes

Contralateral breast cancer is a second primary breast cancer in the opposite breast of a unilateral breast cancer survivor. While its incidence has declined in recent decades due to advancements in systemic therapies, including endocrine therapy and targeted agents, its occurrence remains associated with a significant increase in breast cancer-specific mortality. Valuable efforts have been recently made to introduce risk stratification models and identify key underlying factors, suggesting factors such as young age at primary breast cancer diagnosis, hormone receptor-negative status, BRCA mutations, and lack of specific prior treatments, as the potential risk factors of developing contralateral breast cancer. However, predictive models require further refinement for effective clinical application. Moreover, surveillance strategies should be personalized for each patient based on their individual risk profiles, with emerging modalities such as magnetic resonance imaging (MRI), tomosynthesis and contrast-enhanced mammography, and liquid biopsy offering potential improvements in early detection, while systemic therapies, particularly adjuvant endocrine agents, targeted treatments, and immune checkpoint inhibitors, might be helpful in optimizing preventive strategies—the extent of which is still being investigated through studies. This paper aims to review the latest insights on contralateral breast cancer risk assessment, prevention, and surveillance, opening a discussion on current landscape and challenges.