Mokbel Kefah
Brunel Institute of Cancer Genetics, and The Princess Grace Hospitals, London, UK.
Int J Fertil Womens Med. 2003 Nov-Dec;48(6):274-7.
The incidence of newly diagnosed breast cancer cases world-wide is expected to double by 2020. Risk-reducing strategies for breast cancer include lifestyle modifications, chemoprevention and surgery (bilateral mastectomy and/or oophorectomy). Lifestyle modifications include avoidance of postmenopausal obesity and hormone replacement therapy (HRT), regular physical activity, and restriction of alcohol and animal fat intake. Tamoxifen is a selective estrogen receptor modulator (SERM) shown in randomized controlled trials to reduce the incidence of estrogen receptor (ER)-positive breast cancer in high-risk healthy women. However, its routine use cannot be recommended for breast cancer prevention in healthy women due to its significant adverse effects, specifically in terms of endometrial carcinoma and thromboembolism. On the other hand, tamoxifen may be used for chemoprevention in women at high risk of developing ER-positive breast cancer and at low risk of developing complications. Raloxifene, another SERM, also appears to be effective in reducing breast cancer risk, and lacks the unwanted stimulatory effect on the uterus. Other promising chemopreventive agents currently under investigation include cyclo-oxygenase 2 (COX-2) inhibitors, fenretinide, aromatase inhibitors, and goserelin. Prophylactic mastectomy can reduce breast cancer risk by 90% in high-risk women. Bilateral oophorectomy has the potential of reducing the risk of both breast and gynecologic cancer in women carrying BRCA-1 or BRCA-2 mutations. Further research is required to identify novel strategies to prevent ER-negative breast cancer, minimize the adverse effects of tamoxifen and other SERMs, and evaluate the role of mammary ductal lavage and ductoscopy in guiding risk-reducing strategies.
预计到2020年，全球新诊断出的乳腺癌病例发病率将翻倍。乳腺癌的风险降低策略包括生活方式改变、化学预防和手术（双侧乳房切除术和/或卵巢切除术）。生活方式改变包括避免绝经后肥胖和激素替代疗法（HRT）、定期进行体育锻炼，以及限制酒精和动物脂肪的摄入。他莫昔芬是一种选择性雌激素受体调节剂（SERM），在随机对照试验中显示可降低高危健康女性中雌激素受体（ER）阳性乳腺癌的发病率。然而，由于其显著的不良反应，特别是在子宫内膜癌和血栓栓塞方面，不建议在健康女性中常规使用他莫昔芬进行乳腺癌预防。另一方面，他莫昔芬可用于发生ER阳性乳腺癌风险高且发生并发症风险低的女性的化学预防。另一种SERM雷洛昔芬似乎也能有效降低乳腺癌风险，并且对子宫没有不良刺激作用。目前正在研究的其他有前景的化学预防药物包括环氧化酶-2（COX-2）抑制剂、芬维A胺、芳香化酶抑制剂和戈舍瑞林。预防性乳房切除术可使高危女性的乳腺癌风险降低90%。双侧卵巢切除术有可能降低携带BRCA-1或BRCA-2突变女性患乳腺癌和妇科癌症的风险。需要进一步研究以确定预防ER阴性乳腺癌的新策略，将他莫昔芬和其他SERM的不良反应降至最低，并评估乳腺导管灌洗和导管镜检查在指导风险降低策略中的作用。
