Eeles R A, Powles T J
Institute of Cancer Research, The Royal Marsden National Health Service (NHS) Trust, Sutton, Surrey, United Kingdom.
J Clin Oncol. 2000 Nov 1;18(21 Suppl):93S-9S.
BRCA1 and BRCA2 breast cancer predisposition gene mutation carriers are at markedly increased risk of breast and other cancers. The consideration of chemopreventative options will depend on the cancer site and age-specific penetrance curve. Most chemoprevention studies to date have investigated the role of endocrine intervention in women at increased risk of breast cancer, and study results are conflicting. At the present time, there is uncertainty regarding whether endocrine intervention, particularly with tamoxifen, is as effective in BRCA1 and BRCA2 mutation carriers as in other women who are at increased risk of breast cancer because of hormonal factors or genes with moderately conferred cancer risks. Furthermore, if chemoprevention were needed for at least 10 years to produce an effect, new chemoprevention agents will need to be developed for women in their 30s, as the breast cancer risk curves are steepest between 40 and 50 years of age. Consideration is now being given to types of chemoprevention in this younger age group. There is also an increased risk of other cancers (in particular ovarian cancer and, in men, prostate cancer), and considerations regarding chemoprevention will have to encompass cancer at these sites.
携带乳腺癌易感基因BRCA1和BRCA2的突变者患乳腺癌及其他癌症的风险显著增加。对化学预防方案的考量将取决于癌症发生部位以及特定年龄的发病风险曲线。迄今为止,大多数化学预防研究都调查了内分泌干预在乳腺癌高危女性中的作用,研究结果相互矛盾。目前,对于内分泌干预,尤其是他莫昔芬,在BRCA1和BRCA2突变携带者中是否与因激素因素或具有中度癌症风险的基因而患乳腺癌风险增加的其他女性中一样有效尚不确定。此外,如果化学预防至少需要10年才能产生效果,那么就需要为30多岁的女性开发新的化学预防药物,因为乳腺癌风险曲线在40至50岁之间最为陡峭。目前正在考虑针对这个较年轻年龄组的化学预防类型。患其他癌症(特别是卵巢癌,男性则为前列腺癌)的风险也会增加,化学预防的考量将不得不包括这些部位的癌症。