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. 2019 Mar;22(1):96-108.
doi: 10.4048/jbc.2019.22.e13.

Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death

Jianfei Fu  1 , Chenhan Zhong  2   3 , Lunpo Wu  4   5 , Dan Li  2   3 , Tiantian Xu  6 , Ting Jiang  7 , Jiao Yang  8 , Jinlin Du  9
Affiliations

Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death

Jianfei Fu et al. J Breast Cancer. 2019 Mar.

Abstract

Purpose: Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups.

Methods: Surveillance, Epidemiology, and End Results databases were utilized to identify 181,108 breast cancer patients with > 5 years survival. The cumulative incidence of LP-BCSD and LP-non-BCSD was calculated using the Gray method. The subdistribution hazard ratio (SHR) of variables was estimated via the Fine and Gray proportional hazard regression model. Subgroup analyses for LP-BCSD and LP-non-BCSD were performed according to the HR status.

Results: The risk of LP-BCSD was exceeded by that of LP-non-BCSD at > 5 years since the diagnosis, particularly in old women. The competing risk regression model indicated that hormone receptor-positive (HR+) was an independent factor for more LP-BCSD (hazard ratio, 1.54; 95% confidence interval, 1.44-1.54; p < 0.001). However, stratified analysis indicated that HR+ was only associated with more LP-BCSD in the young women subgroup. Although HR+ was associated with more LP-non-BCSD, the predictive value of HR+ for LP-non-BCSD was eliminated after adjusting for age.

Conclusions: HR+ was related to LP-BCSD in the premenopausal population. LP-BCSD should be an optimal endpoint in future trials designed to evaluate the role of extended adjuvant endocrine therapy.

Keywords: Breast neoplasms; Drug therapy; Estrogen receptors; Prognosis.

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Conflict of interest statement

Conflict of Interest: The authors declare that they have no competing interests. The study was partially supported by the Medical Science & Technology Plan Project of Zhejiang Province (grant numbers: 2013KYA212). Moreover, the work was sponsored by the Zheng Shu Medical Elite Scholarship Fund.

Figures

Figure 1
Figure 1. Cumulative incidence of LP-BCSD and LP-non-BCSD for HR+ and HR− breast cancer. HR+ breast cancer had more LP-BCSD in the whole cohort compared to HR− breast cancer (SHR, 1.18; 95% CI, 1.13–1.24; p < 0.001). Moreover, HR+ was associated with more LP-non-BCSD (SHR, 1.41; 95% CI, 1.35–1.47; p < 0.001). The risk of LP-BCSD was exceeded by that of LP-non-BCSD in the HR+ and HR− subgroups. The curves were plotted using the Gray method.
LP-BCSD = later period breast cancer-specific death; LP-non-BCSD = later period non-breast cancer-specific death; HR = hormone receptor; SHR = subdistribution hazard ratio; CI = confidence index.
Figure 2
Figure 2. Forest plot of the subgroup analysis for LP-BCSD and LP-non-BCSD according to HR status. (A) The forest plot of subgroup (HR+ vs. HR−) analysis for LP-BCSD. In the low-stage subgroups (including T1, N0 and stage I), patients with HR+ tumors had less LP-BCSD. (B) The forest plot of subgroup (HR+ vs. HR−) analysis for LP-non-BCSD; there was no difference in all 4 age subgroups.
LP-BCSD = later period breast cancer-specific death; LP-non-BCSD = later period non-breast cancer-specific death; HR = hormone receptor; IDC = infiltrating duct carcinoma; ILC = infiltrating lobular carcinoma; SHR = subdistribution hazard ratio; CI = confidence index.
Figure 3
Figure 3. Impact of HR status on LP-BCSD and LP-non-BCSD by subgroup analysis according to age subgroups. (A) In the 20–40 year-old subgroup, patients with HR+ breast cancer had more LP-BCSD than patients with HR− breast cancer (SHR, 2.30; 95% CI, 2.02–2.62; p < 0.001). Moreover, the risk of LP-BCSD was higher than LP-non-BCSD in both the HR+ and HR− subgroups. (B) In the 40–60 year-old subgroup, patients with HR+ breast cancer had more LP-BCSD than patients with HR− breast cancer (SHR, 1.18; 95% CI, 1.11–1.26; p < 0.001). Moreover, the risk of LP-BCSD was higher than LP-non-BCSD in both the HR+ and HR− subgroups. (C) In the 60–70 year-old subgroup, the risk of LP-BCSD in HR+ breast cancer was similar to that of HR− breast cancer (SHR, 0.98; 95% CI, 0.88–1.09; p = 0.644). Moreover, the risk of LP-BCSD was exceeded by that of LP-non-BCSD in both the HR+ and HR− subgroups. (D) In the 70–80 year-old subgroup, the risk of LP-BCSD in the HR+ subgroup has a decreasing trend compared to that of the HR− subgroup, without a statistically significant difference (SHR, 0.93; 95% CI, 0.81–1.05; p = 0.241). The risk of LP-BCSD had been exceeded by LP-non-BCSD in both the HR+ and HR− subgroups at the beginning of follow up.
LP-BCSD = later period breast cancer-specific death; LP-non-BCSD = later period non-breast cancer-specific death; HR = hormone receptor; SHR = subdistribution hazard ratio; CI = confidence index.
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