Department of Radiation Oncology, Institut Gustave Roussy, Villejuif, France.
Radiat Oncol. 2010 Nov 8;5:104. doi: 10.1186/1748-717X-5-104.
There are no specific recommendations for the management of breast cancer patients with germ-line p53 mutations, an exceptional genetic condition, particularly regarding postoperative radiotherapy. Preclinical data suggested that p53 mutations conferred enhanced radiosensitivity in vitro and in vivo and the few clinical observations showed that Li-Fraumeni families were at a higher risk of secondary radio-induced malignancies.
We reviewed a cohort of patients with germ-line p53 mutations who had been treated for breast cancer as the first tumor event. We assessed their outcome and the incidence of secondary radio-induced malignancies.
Among 47 documented Li-Fraumeni families treated from 1997 to 2007 at the Institut Gustave Roussy, 8 patients had been diagnosed with breast cancer as the first tumor event. Three patients had undergone conservative breast surgery followed by postoperative radiotherapy and five patients had undergone a mastectomy (3 with postoperative radiotherapy). Thus, 6/8 patients had received postoperative radiotherapy. Median follow-up was 6 years. Median age at the diagnosis of the primary breast cancer was 30 years. The histological characteristics were as follows: intraductal carcinoma in situ (n = 3), invasive ductal carcinoma (n = 4) and a phyllodes tumor (n = 1). Among the 6 patients who had received adjuvant radiotherapy, the following events had occurred: 3 ipsilateral breast recurrences, 3 contralateral breast cancers, 2 radio-induced cancers, and 3 new primaries (1 of which was an in-field thyroid cancer with atypical histology). In contrast, only one event had occurred (a contralateral breast cancer) among patients who had not received radiation therapy.
These observations could argue in favor of bilateral mastectomy and the avoidance of radiotherapy.
存在胚系 p53 突变的乳腺癌患者（一种特殊的遗传情况）的管理尚无具体建议，特别是关于术后放疗。临床前数据表明，p53 突变赋予了体外和体内的放射敏感性，而少数临床观察表明，Li-Fraumeni 家族发生二次放射性诱导恶性肿瘤的风险更高。
我们回顾了一组因乳腺癌作为首发肿瘤事件而接受治疗的胚系 p53 突变患者。我们评估了他们的结局和二次放射性诱导恶性肿瘤的发生率。
在 1997 年至 2007 年期间在 Gustave Roussy 研究所接受治疗的 47 个记录在案的 Li-Fraumeni 家族中，有 8 名患者被诊断为乳腺癌作为首发肿瘤事件。3 名患者接受了保乳手术，随后接受了术后放疗，5 名患者接受了乳房切除术（3 名患者接受了术后放疗）。因此，8 名患者中有 6 名接受了术后放疗。中位随访时间为 6 年。原发性乳腺癌的中位年龄为 30 岁。组织学特征如下：导管内原位癌（n=3）、浸润性导管癌（n=4）和叶状肿瘤（n=1）。在接受辅助放疗的 6 名患者中，发生了以下事件：3 例同侧乳房复发、3 例对侧乳腺癌、2 例放射性癌症和 3 例新原发肿瘤（其中 1 例为典型组织学的放射性场内甲状腺癌）。相比之下，未接受放疗的患者仅发生了 1 次事件（对侧乳腺癌）。
这些观察结果可能支持双侧乳房切除术和避免放疗。
