Background: Endocrine therapy initiation after ductal carcinoma in situ (DCIS) is highly variable and largely unexplained. National guidelines recommend considering tamoxifen for women with estrogen receptor-positive (ER+) DCIS or who undergo excision alone. We evaluated endocrine therapy use after DCIS over a 15-year period in an integrated health care setting to identify factors related to initiation.
Methods: Female Group Health Cooperative enrollees ages 18-89 years with a DCIS diagnosis during 1996-2011 were eligible for inclusion. Endocrine therapy was identified through pharmacy records. Tumor and treatment information were from tumor registry reports; demographics and other risk factors were from questionnaires and electronic medical records. Relative risks (RRs) and 95% confidence intervals (CIs) for endocrine therapy initiation were calculated using multivariable generalized linear models.
Results: We identified 727 women with a DCIS diagnosis, including 163 (22%) who initiated endocrine therapy (149 tamoxifen, 14 aromatase inhibitor). Younger women were more likely to initiate endocrine therapy (RR 1.69; 95% CI 1.16-2.46 for ages 45-54 vs. 65-74 years). Compared with breast-conserving surgery (BCS) with radiation, women who had BCS alone (RR 0.46; 95% CI 0.25-0.84) or mastectomy (RR 0.54; 95% CI 0.39-0.75) were less likely to use endocrine therapy. ER testing increased from 4% of DCIS cases in 2001 to 71% in 2011; however, endocrine therapy initiation decreased from 58% of ER+ DCIS in 2001-2005 to 37% in 2009-2011.
Conclusion: Increasing ER testing since 2001 has not corresponded to parallel increases in endocrine therapy initiation. Age, surgery, and radiation were the primary factors associated with initiation.
Implications for practice: National guidelines recommend considering tamoxifen for women with ductal carcinoma in situ (DCIS) who are estrogen receptor-positive (ER+) or who undergo excision alone. In this study, the rapid increase in ER testing caused by tamoxifen's approval in 2000 did not lead to increases in endocrine therapy initiation, despite recognition of an increasing number of DCIS tumors as ER+ each year. Contrary to the suggested guidelines, women who had breast-conserving surgery without radiation were less likely to use tamoxifen than those who had radiation. Future Food and Drug Administration approval of new endocrine agents for DCIS (such as aromatase inhibitors) may provide an opportunity to reemphasize benefits by ER and surgery status.
摘要
背景. 乳腺导管原位癌 (DCIS) 诊断后内分泌治疗的起始治疗时机变异性很大, 且多数无法解释其原因。国家级指南建议对雌激素受体阳性 (ER+) DCIS 或仅接受切除术的女性患者考虑他莫昔芬治疗。本研究评价了一家综合性卫生健康组织 15 年来 DCIS 确诊后的内分泌治疗使用情况, 旨在鉴别该治疗起始的相关因素。
方法. 在 1996∼2011 年间, 女性健康协作组织的成员中 18∼89 岁且诊断为 DCIS 者符合入选标准。通过处方记录确定内分泌治疗。从肿瘤注册报告中获得肿瘤和治疗信息, 通过问卷和电子病历记录获得人口统计学和其他危险因素。使用多变量广义线性模型计算开始内分泌治疗的相对危险度 (RR) 和 95%可信区间 (CI)。
结果. 共确定 727 例确诊为 DCIS 的女性患者, 其中有 163 例 (22%) 开始内分泌治疗 (149 例接受他莫昔芬治疗, 14 例接受芳香化酶抑制剂治疗)。较年轻的女性开始内分泌治疗的可能性较高 (45∼54 岁vs. 65∼74 岁, RR 1.69; 95%CI 1.16∼2.46)。与保乳术 (BCS) 联合化疗相比, 单行BCS (RR 0.46; 95%CI 0.25∼0.84) 和乳房切除术 (RR 0.54; 95%CI 0.39∼0.75) 较少使用内分泌治疗。ER 检测在 DCIS 病例中的使用比例从 2001 年的 4% 增加到 2011 年的 71%。但 ER+ DCIS 患者接受内分泌治疗的比例从 2001∼2005 年间的 58%下降至 2009∼2011 年间的 37%。
总结. 2001 年以来 ER 检测的增加未导致内分泌治疗的平行增加。与开始内分泌治疗相关的主要因素包括年龄、术式和放疗。The Oncologist 2016;21:134–140
对临床实践的提示: 国家级指南建议雌激素受体阳性 (ER+) 或接受切除术的乳腺导管内原位癌 (DCIS) 患者考虑接受他莫昔芬治疗。本研究中, 由于 2000 年他莫昔芬获批引起的 ER 检测的快速发展虽然使得 ER+ DCIS 的确诊逐年递增, 但并未导致内分泌治疗的增加。与指南建议相反, 单行保乳术不联合放疗的患者接受他莫昔芬治疗的可能性低于接受放疗者。将来食品和药物监督管理局批准用于 DCIS 的内分泌治疗新药 (诸如芳香化酶抑制剂) 可能有望根据不同 ER 和手术状态为患者重新带来获益。
Keywords: Aromatase inhibitor; Breast cancer; Ductal carcinoma in situ; Endocrine therapy; Tamoxifen.
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