Department of Radiation Sciences, Radiobiology, University of the Witwatersrand, Johannesburg, South Africa.
Department of Surgery, Donald Gordon Medical Centre, Johannesburg, South Africa.
Int J Radiat Biol. 2019 Nov;95(11):1507-1516. doi: 10.1080/09553002.2019.1649502. Epub 2019 Aug 12.
Based on clinical and molecular data, breast cancer is a heterogeneous disease. Breast cancers that have no expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are defined as triple negative breast cancers (TNBCs); luminal cancers have different expressions of ER, PR and/or HER2. TNBCs are frequently linked with advanced disease, poor prognosis and occurrence in young African women, and about 15% of the cases are associated with germline mutations. Since radiotherapy is utilized as a principle treatment in the management of TNBC, we aimed to investigate the chromosomal instability and radiosensitivity of lymphocytes in TNBC patients compared to luminal breast cancer patients and healthy controls using the micronucleus (MN) assay. The effect of mutations in breast cancer susceptibility genes on chromosomal radiosensitivity was also evaluated. Chromosomal radiosensitivity was evaluated in the G0 (83 patients and 90 controls) and S/G2 (34 patients and 17 controls) phase of the cell cycle by exposing blood samples from all patients and controls to 2 and 4 Gy ionizing radiation (IR). In the G0 MN assay, the combined cohort of all breast cancer, TNBC and luminal patients' exhibit significantly elevated spontaneous MN values compared to controls indicating chromosomal instability. Chromosomal radiosensitivity is also significantly elevated in the combined cohort of all breast cancer patients compared to controls. The TNBC patients, however, do not exhibit enhanced chromosomal radiosensitivity. Similarly, in the S/G2 phase, 76% of TNBC patients do not show enhanced chromosomal radiosensitivity compared to the controls. In both the G0 and S/G2 phase, luminal breast cancer patients demonstrate a shift toward chromosomal radiosensitivity compared to TNBC patients and controls. The observations of the MN assay suggest increased chromosomal instability and chromosomal radiosensitivity in South African breast cancer patients. However, in TNBC patients, the irradiated MN values are not elevated. Our results suggest that the healthy lymphocytes in TNBC patients could handle higher doses of IR.
基于临床和分子数据，乳腺癌是一种异质性疾病。不表达雌激素受体 (ER)、孕激素受体 (PR) 和人表皮生长因子受体 2 (HER2) 的乳腺癌被定义为三阴性乳腺癌 (TNBC)；腔隙性癌症具有不同的 ER、PR 和/或 HER2 表达。TNBC 常与晚期疾病、预后不良和年轻非洲女性发病有关，约 15%的病例与种系突变有关。由于放疗是 TNBC 治疗管理中的主要治疗方法，我们旨在使用微核 (MN) 测定法研究与腔隙性乳腺癌患者和健康对照相比，TNBC 患者的淋巴细胞染色体不稳定性和放射敏感性。还评估了乳腺癌易感性基因突变对染色体放射敏感性的影响。通过将所有患者和对照的血液样本暴露于 2 和 4 Gy 电离辐射 (IR)，在细胞周期的 G0（83 名患者和 90 名对照）和 S/G2（34 名患者和 17 名对照）期评估染色体放射敏感性。在 G0-MN 测定中，与对照组相比，所有乳腺癌、TNBC 和腔隙性患者的组合队列显示自发 MN 值显着升高，表明染色体不稳定性。与对照组相比，所有乳腺癌患者的组合队列中的染色体放射敏感性也显着升高。然而，TNBC 患者并未表现出增强的染色体放射敏感性。同样，在 S/G2 期，与对照组相比，76%的 TNBC 患者没有表现出增强的染色体放射敏感性。在 G0 和 S/G2 期，腔隙性乳腺癌患者的染色体放射敏感性较 TNBC 患者和对照组向染色体放射敏感性转变。MN 测定的观察结果表明南非乳腺癌患者的染色体不稳定性和染色体放射敏感性增加。然而，在 TNBC 患者中，受照射的 MN 值没有升高。我们的结果表明，TNBC 患者的健康淋巴细胞可以处理更高剂量的 IR。
