| Summary: | The uptake of contralateral prophylactic mastectomy is rising with increasing trends that are possibly highest in the USA. Whilst its role is generally accepted in carriers of recognized high-risk predisposition genes such as <i>BRCA1</i> and <i>BRCA2</i> when the affected individual is premenopausal, controversy surrounds the benefit in less understood risk-profile clinical scenarios. This comprehensive review explores the current evidence underpinning the role of contralateral prophylactic mastectomy and its impact on contralateral breast cancer risk and survival in three distinct at-risk groups affected by unilateral breast cancer: known genetic carriers, those with strong familial risk but no demonstrable genetic mutation and women who are of young age at presentation. The review supports the role of contralateral prophylactic mastectomy in “high risk” groups where the evidence suggests a reduction in contralateral breast cancer risk. However, this benefit is less evident in women who are just young at presentation or those who have strong family history but no demonstrable genetic mutation. A multidisciplinary and personalized approach to support individuals in a shared-decision making process is recommended.
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