Travis Lois B, Hill Deirdre A, Dores Graça M, Gospodarowicz Mary, van Leeuwen Flora E, Holowaty Eric, Glimelius Bengt, Andersson Michael, Wiklund Tom, Lynch Charles F, Van't Veer Mars B, Glimelius Ingrid, Storm Hans, Pukkala Eero, Stovall Marilyn, Curtis Rochelle, Boice John D, Gilbert Ethel
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Md 20892 , USA.
JAMA. 2003 Jul 23;290(4):465-75. doi: 10.1001/jama.290.4.465.
Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.
To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.
DESIGN, SETTING, AND SUBJECTS: Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.
Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.
Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P =.03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P =.003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.
Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
第二原发性癌症是霍奇金淋巴瘤（HD）长期存活者的主要死因，年轻女性接受治疗后患乳腺癌的风险格外高。迄今为止，尚未有关于大样本系列中乳房接受的放疗剂量与化疗之间的定量关联报道，也未提及卵巢暴露对后续风险的影响。
量化放疗和化疗用于治疗年轻HD女性患者后乳腺癌的长期风险。
设计、地点和研究对象：在1965年1月1日至1994年12月31日期间确诊为HD且年龄在30岁及以下的3817名女性1年存活者队列中，以及6个基于人群的癌症登记处内进行乳腺癌病例对照匹配研究。该研究于1996年3月1日至1998年9月30日开展。
与乳腺癌或卵巢部位接受的辐射剂量以及烷化剂累积剂量相关的乳腺癌相对风险（RR）。
105例HD患者发生乳腺癌，与266例未患乳腺癌的HD患者匹配。与接受较低剂量且未使用烷化剂的患者相比，乳房接受4 Gy或更高剂量的辐射与风险增加3.2倍（95%置信区间[CI]，1.4 - 8.2）相关。剂量超过40 Gy时，风险增至8倍（95% CI，2.6 - 26.4）（趋势P<.001）。辐射风险在暴露时的年龄或生殖史方面无明显差异。放疗后25年或更长时间风险持续增加（RR，2.3；95% CI，0.5 - 16.5；趋势与剂量相关，P =.03）。单独使用烷化剂治疗导致乳腺癌风险降低（RR，0.6；95% CI，0.2 - 2.0），烷化剂与放疗联合使用使风险增加1.4倍（95% CI，0.6 - 3.5）。乳腺癌风险随烷化剂疗程数增加而降低（趋势P =.003）。与接受较低剂量的女性相比，卵巢接受5 Gy或更高剂量的女性风险也较低（RR，0.4；95% CI，0.1 - 1.1）。
激素刺激似乎对辐射诱导的乳腺癌发展很重要，这由烷化剂或辐射导致的卵巢损伤相关风险降低所证明。然而，高辐射相关风险在最高剂量或最长随访时并未降低，这表明需要进行终身监测以及开展患者和公众意识项目。
