Second malignancies after breast cancer: The impact of adjuvant therapy

Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stimulating factors and estrogen receptor modulators. Furthermore, analytical investigations have demonstrated that BC patients may be at an increased risk of leukemia following chemotherapy. In addition, correlations between an increased dose of hormonal therapy and solid tumor risk have been identified. Considering the ongoing alterations in the treatment of BC, with respect to lowering the daily as well as the cumulative dose of chemo-therapeutic agents, it is anticipated that leukemias will have a considerably lower impact on BC survivors in the future. However, diligent follow-up is required to accurately evaluate the long-term risks associated with chemotherapy.