Patients characteristics
A total of 1094 women with early-stage breast cancer were included in the analysis. The median age at diagnosis was 68 years (range 65-94 years) for the whole patients. The demographic and tumor characteristics of patients are summarized in Table 1. The majority of patients had lower education level (55.9%) and normal BMI (40.2%). Overall, invasive ductal carcinoma was the most common histological type (78.9%). And most of tumors were diagnosed at stage II (46.7%), with positive HR status (69.2%) and negative HER2 status (70.9%).
All patients were categorized into two subgroups based on their age at diagnosis: the control group (65-74 years old) versus the elderly group (≥ 75 years old). The total number of control group patients was 930 (85.0%), and that of elderly group was 164 (15.0%). The elderly group patients were more likely to be underweight when compared with the control group (P < 0.001). No significant differences were found between two age groups in terms of the education level, tumor histological type, clinical stage, T stage, N stage, HR status, HER2 status, molecular subtype, Ki-67 level and tumor grade.
Follow-up and survival outcomes
The median follow-up time for this cohort was 59 months. Death events differed between the two groups, 102 (11.0%) cases died in the control group, and 41 (25.0%) cases died in the elderly group during the follow-up period (P < 0.001). However, recurrence and metastasis rate was not different between the two groups (9.1% vs 10.4%, P=0.619).
In this cohort, the 5-year and 10-year survival rates of all patients were 89.0% and 77.5%. Table 2 shows the results of univariate and multivariate analysis of overall survival in all patients. In the univariate analysis, patients who aged over 75 years, had underweight, diagnosed at stage III, negative for HR status, with high Ki-67 level or with poorly differentiated tumor grade showed trends toward worse survival (all P < 0.05). Whereas, in the multivariate analysis, only age older than 75 years (HR = 1.935, 95% CI 1.109-3.376, P = 0.020), underweight (HR = 3.262, 95% CI 1.526-6.974, P = 0.002), stage III (HR = 6.215, 95% CI 2.713–14.235, P < 0.001) and high Ki-67 level (HR = 1.900, 95% CI 1.065–3.388, P = 0.030) were independently associated with poor survival.
Treatmentpatterns
Surgery
The majority of patients (1043/1094, 95.3%) in this cohort underwent surgery (Table 3). Surgery rates were high for both groups (95.1% vs. 97.0%, respectively, P = 0.288). Of those who underwent surgery, 963 patients (92.3%) received modified radical mastectomy, while 54 patients (5.2%) received radical mastectomy, very few patients (n = 26, 2.5%) were treated with breast conserving surgery or palliative surgery.
In the survival analysis, patients who underwent surgery had longer survival than those who did not (5-year survival rate: 90.0% vs. 60.0%, P < 0.001, Fig 1A). And there was no significant difference in OS between patients who received modified radical mastectomy and those did radical mastectomy when clinical stage was considered (data not shown). In subgroup analyses, the effect of surgery on survival in older breast cancer patients was consistently favorable across all subgroups (all HR < 1.0, Fig 2A). After adjusting for age and clinical stage, surgery was an independent prognostic factor associated with a significant reduction in mortality (HR 0.476, 95% CI 0.250-0.904, P = 0.023, Table 4).
Adjuvant and neoadjuvant chemotherapy
We analyzed the efficacy of adjuvant chemotherapy in older patients who had undergone surgery. Among them, most patients (68.7%) received adjuvant chemotherapy, but elderly group patients were less likely to receive it when compared with those in the control group (35.8% vs 74.7%, P < 0.001, Table 3). With regard to the type of chemotherapy, most patients were treated with anthracyclines and/or taxanes, especially for the control group. In Kaplan-Meier analysis, adjuvant chemotherapy seemed to have no effect on OS (Fig 1B). However, multivariate analysis demonstrated that adjuvant systemic chemotherapy was associated with a lower risk of death (HR 0.521, 95% CI 0.284-0.955, P = 0.035, Table 4). In the subgroup analysis, adjuvant chemotherapy offered significant survival benefit for patients with grade III disease (HR 0.487, 95% CI 0.269-0.881, P = 0.015, Fig 2B).
According to current guideline for neoadjuvant chemotherapy in breast cancer, we only assessed the effect of neoadjuvant chemotherapy on older patients staged at II or III (n = 734). Among these patients, only 90 (12.3%) cases received neoadjuvant chemotherapy, including 83 (13.2%) cases in the control group and 7 (6.7%) in the elderly group. Neoadjuvant chemotherapy was not associated with survival in multivariate analysis (HR 1.430, 95% CI 0.791-2.587, P = 0.237, Table 4).
Radiotherapy
Among the patients who underwent mastectomy, we evaluated the role of adjuvant radiotherapy in older patients with positive-lymph node diseases (n =453). Of these, only 134 (29.6%) patients received postmastectomy radiotherapy, and the control group was more likely to receive adjuvant radiotherapy compared with the elderly group (31.8% vs. 14.0% respectively, P = 0.006, Table 3). In the survival analysis, radiotherapy did not confer a benefit in OS or LRFS on these patients (Fig 1C). Moreover, receipt of radiotherapy had no impact on OS and LRFS in all subgroups (Fig 2C). After adjusting for the potential confounding factors, however, adjuvant radiotherapy following mastectomy showed a significant effect on LRFS, but not OS. (LRFS: HR 0.247, 95% CI 0.072-0.839, P = 0.025; OS: HR 0.733, 95% CI 0.415-1.295, P = 0.285, Table 4).
Endocrine therapy
We examined the effect of adjuvant endocrine therapy on survival in older patients with HR-positive breast cancer. Elderly group patients were as likely to be treated with endocrine therapy as those in control group, and the proportion of receiving endocrine therapy were high for both groups (81.7% vs 81.8% respectively, P = 0.978, Table 3). Notably, endocrine therapy conferred a significant survival benefit on HR+ patients (Fig 1D). However, in subgroup analysis, endocrine therapy could only provide a significant survival benefit for the control group, but not for the elderly group (Fig 2D). After adjusting for other tumor characteristics, adjuvant endocrine therapy was indeed an effective treatment option in HR-positive older breast cancer patients (HR 0.440, 95% CI 0.261-0.741, P = 0.002, Table 4).
Stratified analyses were conducted to determine which group of patients would benefit from additional chemotherapy based on endocrine therapy. Among HR-positive patients who received endocrine therapy, patients diagnosed at grade III were more likely to benefit from additional chemotherapy (HR 0.305, 95% CI 0.107-0.871, P = 0.019, Fig 2E).
Targeted therapy
We analyzed the efficacy of trastuzumab therapy in HER2-positive breast cancer patients (n=143), approximately one-third of patients received trastuzumab treatment. And no difference was observed in the proportion of patients receiving trastuzumab between two groups (Table 3). In the survival analysis, there was no significant difference in survival between patients treated with trastuzumab and those who did not (Fig 1E). In multivariate analysis, however, receipt of trastuzumab was associated with a lower risk of mortality for HER2-positive patients after adjustment for multiple confounders (HR 0.168, 95% CI 0.029-0.958, P = 0.045, Table 4).