Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
Oncologist. 2019 Jul;24(7):e467-e474. doi: 10.1634/theoncologist.2018-0010. Epub 2019 Jan 3.
The aim was to study the impact of comorbidities and age on breast cancer mortality, taking into account competing causes of death.
SUBJECTS, MATERIALS, AND METHODS: Cohort analysis of Dutch and Belgian patients with postmenopausal, early hormone receptor-positive breast cancer included in the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial between 2001 and 2006. This is a randomized controlled trial of patients who had completed local treatment with curative intent and were randomized to receive exemestane for 5 years, or sequential treatment of tamoxifen followed by exemestane for a duration of 5 years. Patients were categorized by number of comorbidities (no comorbidities, 1-2 comorbidities, and >2 comorbidities) and age (<70 years and ≥70 years). Main outcome was breast cancer mortality considering other-cause mortality as competing event; cumulative incidences were calculated using the Cumulative Incidence Competing Risk Methods, and the Fine and Gray model was used to calculate the effect of age and comorbidities for the cause-specific incidences of breast cancer death, taking into account the effect of competing causes of death.
Overall, 3,159 patients were included, of which 2,203 (69.7%) were aged <70 years and 956 (30.3%) were aged ≥70 years at diagnosis. Cumulative incidence of breast cancer mortality was higher among patients ≥70 without comorbidities (22.2%, 95% CI, 17.5-26.9) compared with patients <70 without comorbidities (15.6%, 95% CI, 13.6-17.7, reference group), multivariable subdistribution hazard ratio (sHR) 1.49 (95% CI, 1.12-1.97, = .005) after a median follow-up of 10 years. Use of chemotherapy was lower in older patients (1%, irrespective of the number of comorbidities) compared with younger patients (50%, 44%, and 38% for patients with no, 1-2, or >2 comorbidities, < .001).
Older patients without comorbidities have a higher risk of dying due to breast cancer than younger counterparts, even when taking into account higher competing mortality, while use of chemotherapy in this group was low. These findings underline the need to take into account comorbidities, age, and competing mortality in the prognosis of breast cancer for accurate decision making.
Older patients without comorbidity are at increased risk of dying from breast cancer, despite a higher other-cause mortality. This study shows that including age and comorbidity for the assessment of breast cancer mortality and other-cause mortality is indispensable for treatment decision making in older patients. Future prognostic tools for breast cancer prognosis should incorporate these items as well as risk of toxicity of adjuvant chemotherapy to adequately predict outcomes to optimize personalized treatment for older patients with early breast cancer.
本研究旨在探讨合并症和年龄对乳腺癌死亡率的影响,同时考虑到其他死因的竞争。
对象、材料和方法:该队列分析纳入了 2001 年至 2006 年间参加 Tamoxifen 和 Exemestane 辅助多国(TEAM)试验的绝经后、早期激素受体阳性乳腺癌的荷兰和比利时患者。这是一项针对已完成局部治愈性治疗且随机接受依西美坦治疗 5 年或他莫昔芬序贯依西美坦治疗 5 年的患者的随机对照试验。患者按合并症数量(无合并症、1-2 种合并症和>2 种合并症)和年龄(<70 岁和≥70 岁)进行分类。主要结局是考虑其他死因作为竞争事件的乳腺癌死亡率;使用累积发生率竞争风险方法计算累积发生率,并使用 Fine 和 Gray 模型计算年龄和合并症对乳腺癌死亡的特定原因发生率的影响,同时考虑其他死因的影响。
共有 3159 例患者纳入研究,其中 2203 例(69.7%)年龄<70 岁,956 例(30.3%)年龄≥70 岁。与年龄<70 岁且无合并症的患者(15.6%,95%CI,13.6-17.7,参考组)相比,无合并症的≥70 岁患者(22.2%,95%CI,17.5-26.9)的乳腺癌死亡率累积发生率更高,多变量亚分布危险比(sHR)为 1.49(95%CI,1.12-1.97,P=0.005),中位随访 10 年后。与年轻患者相比,老年患者(无论合并症数量如何,均为 1%)接受化疗的比例较低(<0.001)。
无合并症的老年患者死于乳腺癌的风险高于年轻患者,即使考虑到更高的竞争死亡率,但在该组中使用化疗的比例较低。这些发现强调了在为乳腺癌的预后做出准确决策时,需要考虑合并症、年龄和竞争死亡率。
无合并症的老年患者死于乳腺癌的风险增加,尽管其他原因的死亡率较高。本研究表明,对于乳腺癌死亡率和其他原因死亡率的评估,纳入年龄和合并症是不可或缺的,这对于老年患者的治疗决策至关重要。未来的乳腺癌预后预测工具也应纳入这些项目以及辅助化疗毒性的风险,以充分预测结果,从而优化对早期乳腺癌老年患者的个体化治疗。