Hancock S L, Tucker M A, Hoppe R T
Department of Radiation Oncology, Stanford University School of Medicine, Calif.
J Natl Cancer Inst. 1993 Jan 6;85(1):25-31. doi: 10.1093/jnci/85.1.25.
Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings.
This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment.
To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race.
Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0).
Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy.
The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.
多数针对霍奇金淋巴瘤幸存者的研究表明，其后续患乳腺癌的风险较低，尽管在其他情况下，已证实比用于治疗霍奇金淋巴瘤的剂量低得多的辐射剂量也可诱发乳腺癌。
本研究根据治疗时的年龄和治疗类型，对霍奇金淋巴瘤治疗后患乳腺癌的风险进行量化。
为评估放疗导致乳腺癌的风险，我们回顾了1961年至1990年间接受霍奇金淋巴瘤治疗的885名女性的记录（平均随访10年）。通过与按年龄和种族匹配的一般女性人群的预期发病率进行比较，计算乳腺癌发病率和死亡率的风险。
25例患者发生浸润性乳腺癌，相对风险（RR）为4.1（95%置信区间[CI]=2.5 - 5.7）。另有1例患者发生多灶性原位癌。放疗时的年龄对风险有强烈影响：15岁之前接受治疗的女性RR为136（95%CI = 34 - 371）。RR随放疗时年龄的增加而下降（趋势P <.0001），但对于放疗时年龄小于30岁的受试者，风险升高仍具有统计学意义（15 - 24岁者，RR = 19[95%CI = 10.3 - 32]；24 - 29岁者，RR = 7[95%CI = 3.2 - 14.4]）。30岁以上女性的风险未升高（RR = 0.7；95%CI = 0.2 - 1.8）。乳腺癌风险随治疗后的时间显著增加（趋势P <.0001）。随访15年以下时RR为2.0（95%CI = 1.0 - 3.5），随访15年及以上时RR为13.6（95%CI = 7.9 - 18.2）。放疗联合氮芥、长春新碱、丙卡巴肼和泼尼松化疗会增加前15年的风险。大多数乳腺癌（26例中的22例）发生在放射野内或边缘，为浸润性导管癌。分期分布和结局表明，发病率增加并非完全归因于严密筛查。乳腺癌死亡的RR为5.1（95%CI = 2.2 - 10.0）。
30岁之前接受放疗治疗霍奇金淋巴瘤的女性患乳腺癌的风险显著增加，且在治疗15年多后风险急剧上升。
30岁以下接受治疗性放疗的女性患乳腺癌的高RR值引发了关于霍奇金淋巴瘤、乳腺癌和其他癌症患者最佳治疗策略的重要问题。
