Risk of second primary cancer in young breast cancer survivors: an important yet overlooked issue

Currently, female breast cancer (BC) represents the highest incidence of cancer globally. This trend has raised significant attention regarding breast cancer young women (BCYW). With advancements in treatment technology, BCYW survivors are living longer; however, the risk of developing or succumbing to a second primary cancer (SPC) has greatly increased. In addition, several factors, including age, menstrual cycle, hormonal changes, obesity, pregnancy, and breastfeeding, interact to influence the development of SPC in BCYW and make its treatment more difficult. This study investigates the relationship between BCYW and SPC, focusing on morbidity trends, pathological genomics, recurrence rates, survival times, treatment modalities, and physiological fertility. Most BCYW involve BRCA pathogenic variants or fall under triple-negative and human epidermal growth factor receptor 2-overexpressing subtypes, increasing the risk of SPC. While there are regional variations in survival time following the diagnosis of an SPC, the long-term survival outcomes remain unfavorable. In addition, the choice of treatment for BCYW survivors has a prolonged cumulative toxic effect. The combination of endocrine therapy and chemotherapy is effective in treating BC, but it simultaneously increases the risk of developing an SPC, specifically endometrial cancer. Furthermore, radiotherapy is associated with a heightened risk of contralateral BC and lung cancer. We aim to address existing gaps in the literature and to enhance awareness of the risks associated with SPC in BCYW, thereby offering valuable insights for clinical diagnosis and treatment.