Sella Tal, Ruddy Kathryn J, Carey Lisa A, Partridge Ann H
Dana-Farber Cancer Institute, Boston, MA.
Harvard Medical School, Boston, MA.
JCO Oncol Pract. 2022 Mar;18(3):211-216. doi: 10.1200/OP.21.00482. Epub 2021 Oct 12.
Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor-positive, human epidermal growth factor receptor 2-negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.
近期流行病学数据显示，在许多高收入国家，绝经前女性乳腺癌发病率呈上升趋势。在绝经前女性中，40岁以下被诊断出患乳腺癌的患者长期预后较差，尤其是在激素受体阳性、人表皮生长因子受体2阴性疾病的情况下。除了疾病表现更晚期和/或疾病生物学特性更不利外，辅助内分泌治疗（ET）欠佳已成为这种年龄相关差异的一个重要驱动因素。从历史上看，年轻女性一直被排除在芳香化酶抑制剂（AI）治疗之外，化疗导致闭经的发生率较低，且对ET的依从性也较低。最近，几项研究表明，在诊断后的前5年进行卵巢功能抑制（OFS）治疗与乳腺癌复发率和死亡率的改善相关，将OFS与AI联合使用可带来额外益处。随着绝经前女性ET的前5年治疗模式发生转变，在诊断后5 - 10年进行的延长ET也变得更为普遍。然而，关于绝经前女性延长ET的唯一研究是在最初5年使用他莫昔芬后再额外使用5年他莫昔芬，而关于在第二个5年使用AI的研究仅限于绝经后女性。在此，我们回顾了在为绝经前女性提供延长ET（包括继续使用OFS）咨询时需要考虑的潜在益处和风险的现有数据。鉴于目前的知识体系，我们提供了一个实用的框架来支持决策，并指出有必要对这一问题进行更多研究。
