Lo Shelly S, Vogel Victor G
Section of Hematology/Oncology, Department of Medicine, Magee/University of Pittsburgh Cancer Institute Breast Program, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Best Pract Res Clin Endocrinol Metab. 2004 Mar;18(1):97-111. doi: 10.1016/s1521-690x(03)00043-5.
Breast cancer remains the most common malignancy in women worldwide. Oestrogen levels appear to be associated with an increased risk for the development of breast cancer. The Early Breast Cancer Trialists' Cooperative Group reported in a 1998 meta-analysis of 37000 breast cancer patients in 55 randomized adjuvant trials that tamoxifen, a selective oestrogen receptor modulator, reduced the incidence of contralateral breast cancers by 47% at 5 years. Tamoxifen has been shown in numerous prevention studies to decrease the incidence of breast cancer in high-risk women. Overall, the tamoxifen prevention trials showed a 38% reduction in the incidence of breast cancer (95% CI 28-46; P<0.0001). In the largest risk-reduction trial, the Breast Cancer Prevention Trial conducted by the National Surgical Adjuvant Breast and Bowel Project, tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<0.00001), and non-invasive breast cancer by 50% (P<0.002). The occurrence of oestrogen receptor-(OR)-positive tumours decreased by 69%. Tamoxifen reduces the risk of developing oestrogen receptor-positive tumours, but OR-negative tumours are not affected. Rare but life-threatening side-effects of tamoxifen include endometrial carcinoma, thromboembolic events and cerebrovascular events. Less serious side-effects include cataracts, vasomotor instability, nausea and vaginal discharge. Raloxifene, a second-generation selective oestrogen receptor modulator, is approved for treatment of osteoporosis in post-menopausal women in the USA but it is not currently approved for breast cancer prevention outside of a clinical trial. Prevention studies involving raloxifene and aromatase inhibitors are currently being conducted.
乳腺癌仍是全球女性中最常见的恶性肿瘤。雌激素水平似乎与乳腺癌发生风险增加有关。早期乳腺癌临床试验协作组在1998年对55项随机辅助试验中的37000例乳腺癌患者进行的荟萃分析中报告，选择性雌激素受体调节剂他莫昔芬在5年时使对侧乳腺癌的发生率降低了47%。在众多预防研究中已表明，他莫昔芬可降低高危女性患乳腺癌的发生率。总体而言，他莫昔芬预防试验显示乳腺癌发生率降低了38%（95%置信区间28 - 46；P<0.0001）。在最大规模的降低风险试验中，即由国家外科辅助乳腺和肠道项目开展的乳腺癌预防试验，他莫昔芬使浸润性乳腺癌风险降低了49%（双侧P<0.00001），非浸润性乳腺癌风险降低了50%（P<0.002）。雌激素受体（ER）阳性肿瘤的发生率降低了69%。他莫昔芬可降低发生雌激素受体阳性肿瘤的风险，但对ER阴性肿瘤无影响。他莫昔芬罕见但危及生命的副作用包括子宫内膜癌、血栓栓塞事件和脑血管事件。不太严重的副作用包括白内障、血管舒缩不稳定、恶心和阴道分泌物。雷洛昔芬是第二代选择性雌激素受体调节剂，在美国被批准用于治疗绝经后女性的骨质疏松症，但目前在临床试验之外未被批准用于预防乳腺癌。目前正在开展涉及雷洛昔芬和芳香化酶抑制剂预防研究。
