Optimal treatment of breast cancer in women older than 75 years: a Korea Breast Cancer Registry analysis

The KBCR database was previously described in detail [13]. Briefly, the KBCR database is a Web-based, prospectively maintained nationwide database managed by the Korean Breast Cancer Society (KBCS). One hundred and two institutions have voluntarily participated in this registry since 1997. Before inserting personal information, along with various datasets, written informed consent is mandatory from the patient. From the initial conception of the KBCR database, principal investigators from every institution have agreed on the principles and processes of utilizing this database for research purposes. Essential registry items include patient age, sex, surgical method used, and breast cancer stage according to the seventh edition of the American Joint Committee on Cancer classification [14], biological status (hormone receptor [HR] and human epidermal growth factor receptor 2 [HER2]) and adjuvant treatment (endocrine treatment, radiation therapy and chemotherapy). The Korean Central Cancer Registry provides only mortality data, and the KBCR does not include information on tumor recurrence. According to the guidelines of utilizing the KBCR database, this study was approved by the Institutional Review Board (IRB) of Uijeongbu St. Mary’s Hospital, Catholic University of Korea (UC18RCSE0045). The KBCS approved our research objective and request for data in March 2018.

From the KBCS registry, we assessed female patients with invasive breast cancer who underwent curative surgery between January 2005 and December 2010. To achieve a more accurate analysis, we excluded patients treated with neoadjuvant therapy and patients for whom essential registry data (gender, age, and cancer stage) were not available. Patients with distant metastasis (stage IV) and advanced stage (stage IIIc) at the time of diagnosis were excluded because these stages have the worst prognosis compared to other prognoses and serve as confounding factors for survival analysis. See Fig. 1 for a detailed list of excluded cases.

Data on the remaining 53,582 patients were included in the final analysis. All patients were categorized into one of two subgroups based on their age: elderly patients (≥ 75 years old) versus control patients (< 75 years old).

The means and standard deviations of physiological and demographic characteristics were calculated. A t test was used to compare the means when there were 2 categories. Proportions were compared using two-way tables and Chi-square tests. Survival curves were estimated using the Kaplan–Meier method, and log-rank tests were performed for comparison of survival curves. The primary end point was the comparison of overall survival between the administration and omission of adjuvant treatment modalities, including endocrine treatment, radiation therapy, and chemotherapy, in elderly patients. Overall survival (OS) was defined as the time from initial diagnosis of primary breast cancer to death from any cause. Multivariate analyses were conducted using a Cox proportional hazard regression model to study the effects of each therapeutic modality (endocrine treatment, radiation therapy and chemotherapy) on OS. Parameters included in the multivariate analysis model were as follows: breast surgery type, breast cancer stage, endocrine treatment, radiation therapy, and chemotherapy. All tests were two-sided, and a p value < 0.05 was considered to be statistically significant. All statistical analyses were performed using IBM SPSS software version 22.0 for Windows (IBM Corp., Armonk, USA).

According to the eligibility criteria, we identified 53,582 patients who underwent curative surgery between January 2005 and December 2010 from the KBCS registry. The total number of elderly patients was 901 (1.7%), and the number of control patients was 52,681 (98.3%). Clinical and pathological characteristics are listed in Table 1.

The median age of patients in the elderly group was 77 years (range 75–94 years) and that of the control group was 48 years (range 20–74 years). Compared with the control group, the elderly group was more likely to undergo mastectomy (p < 0.001) and was less likely to undergo axillary surgery (p = 0.005). Elderly patients were found to have larger tumor sizes (2.280 ± 1.74 cm vs. 2.017 ± 3.35 cm, p = 0.024) and higher pathological stages (p < 0.001) than the control group. HR and HER-2 status were different between the elderly and control groups, with the elderly group having a higher rate of the HR(+)/HER2(−) subtype (p < 0.001).

The median follow-up for survival analysis was 69 months (range 5–134 months) in the elderly group and 77 months (range 5–119 months) in the control group. Three hundred and seventeen (35.2%) cases experienced death in the elderly group, and 4934 (9.4%) cases experienced death in the control group, during the study period. The cause of death in the elderly group is listed in Table 2. Despite the 157 cases of missing data for cause of death, the most prevalent cause of death in elderly patients was breast cancer (98 cases, 61.3% of all deaths), and the second most prevalent cause of death was other malignant disease (23 cases, 14.4% of all deaths).

The life expectancy in elderly patients was analyzed and is shown in Table 3. Age ranges were subdivided into three categories (75–78, 79–83, and ≥ 84 years) according to patient distribution (60.7%, 29.6%, 9.7% each). Mean life expectancy of the entire elderly group was 121.51 months, which is approximately 10 years.

To examine the therapeutic efficacy of adjuvant endocrine treatment in HR-positive patients, we extracted data for adjuvant endocrine treatment in HR-positive patients. From the registry, 471 patients in the elderly group and 28,511 patients in the control group were HR-positive breast cancer patients (Table 1). Among these patients, adjuvant endocrine treatment was administered to 342 (72.6%) patients in the elderly group and 26,292 (92.2%) patients in the control group. When compared with the control group, HR-positive elderly patients were less likely to undergo adjuvant endocrine treatment (72.6% vs 92.2%, p < 0.001).

Notably, in the survival analysis (Fig. 2a, b), adjuvant endocrine treatment conveys statistically significant overall survival gains in both groups (elderly group: p = 0.023; control group: p < 0.001). Furthermore, adjuvant endocrine treatment was an effective treatment option in elderly HR-positive breast cancer patients based on the multivariate analysis (adjusted OR 0.417; 95% CI 0.240–0.726; p = 0.002) (Table 4).

We analyzed the therapeutic efficacy of adjuvant radiation therapy in patients who underwent breast-conserving surgery for initial treatment in each group. In the elderly group, 300 patients underwent breast-conserving surgery (Table 1). Among these patients, 159 (53.1%) patients received adjuvant radiation therapy, and 141 (46.9%) patients did not. In the control group, 29,304 patients underwent breast-conserving surgery. Among these patients, 27,194 (92.8%) received adjuvant radiation therapy, and 2110 (7.2%) did not. Elderly patients were less likely to undergo adjuvant radiation therapy after breast-conserving surgery compared with the control group (53.1% vs 92.8%, p < 0.001).

In the survival analysis, radiation therapy had a statistically significant overall survival benefit in the control group (p < 0.001) (Fig. 2c). However, adjuvant radiation therapy after breast-conserving surgery was not significant for overall survival benefit in elderly patients (p = 0.123) (Fig. 2d). Furthermore, in multivariate analysis, adjuvant radiation therapy did not show statistically significant effects on prognosis (adjusted OR 0.467; 95% CI 0.209–1.040; p = 0.062), even in early-stage breast cancer (Stage I–II; OR 0.594, p = 0.258) (Table 4).

We analyzed the therapeutic efficacy of adjuvant systemic chemotherapy in patients with stage II and III disease in each group. Stage II and III breast cancer were identified in 520 patients from the elderly group and in 24,966 patients from the control group (Table 1). Among these patients, adjuvant systemic chemotherapy was administered to 129 (24.9%) patients in the elderly group and 14,655 (58.7%) patients in the control group. Elderly patients with stage II and III breast cancer were less likely to undergo adjuvant systemic chemotherapy compared with those in the control group (p < 0.001). This result was also consistent when classified by breast cancer stage (from IIA to IIIB) (Table 5).

In the survival analysis, adjuvant systemic chemotherapy had a statistically significant overall survival benefit in the control group (p < 0.001) (Fig. 2e) but not in the elderly patients (p = 0.349) (Fig. 2f). Although the use of this treatment slightly improved overall survival in the elderly group with stage IIIA disease, the influence on survival of adjuvant systemic chemotherapy in the elderly group was not significant compared with results from the control group (Table 5). However, in the multivariate analysis, after adjusting for multiple confounders (breast surgery type, breast cancer stage, endocrine treatment, and radiation therapy), adjuvant systemic chemotherapy was an effective treatment modality that extended overall survival for elderly patients with stage II and III breast cancer (adjusted OR 0.657; 95% CI 0.462–0.934; p = 0.019).