Patient Characteristics
Among the 1474 patients analyzed, the median age was 51 years (range, 23-86 years). 1418 patients (96.2%) were diagnosed with invasive ductal carcinoma. The median invasive tumor size was 2.3cm (range, 0.1-5cm). The primary tumor staging was T1 in 45.3% of patients (n = 668), and T2 in 54.7% of patients (n = 806). The median number of ALNs examined was 17 (range, 10-39); the percentage of patients having 1, 2, and 3 positive lymph nodes was 52.2% (n = 770), 28.9% (n = 426), and 18.9% (n = 278), respectively. On IHC staining, HR was positive in 79.5% of patients (n = 1172). HER2 was positive in 20.5% of patients (n = 302).
Adjuvant chemotherapy was administered in 93.1% of patients (n = 1373). The most common regimen was the combination of anthracycline and taxane (935; 68.1%), followed by anthracycline-based or taxane-based regimens. About 97.8% of patients completed 4-8 cycles of adjuvant chemotherapy before radiotherapy (RT). Adjuvant endocrine therapy was administered in 95.1% (n=1115) of HR-positive patients, and anti-HER2 therapy was in 47.0% (n=142) of HER2-positive patients.
PMRT was applied in 45.0% of patients (n=663). Of them, 592 patients received irradiation to both CW and regional lymph nodes, 1 patient received irradiation to CW only, and the rest received irradiation as well, while irradiated sites were not well described in the medical record.
Table 1 compared patients’ clinical and treatment characteristics between PMRT and non-PMRT subgroups. Patients associated with high risk factors were more likely to be directed to PMRT, including young age, high histological grade, LVI+, larger tumor, advanced lymph nodes, and HER2-positive subtype.
Recurrence and Survival Outcomes
With the median follow-up duration of 93 months (range, 5-168 months), a total of 78 patients (5.3%) developed LRR. Overall, the most common recurrence site was regional nodes alone (55.1%), followed by CW alone (32.1%). Of regional recurrences, the most common site was SCV/ICV, followed by IMN. Table 2 compared the anatomical distribution of LRR between PMRT and non-PMRT subgroups, but the chi-square test did not show a statistically significant difference (𝜒2 = 2.54, p = 0.281). For the entire cohort, the 7.7-year cumulative LRC was 94.9%. PMRT significantly improved 7.7-year LRC from 93.4% to 96.6% (p = 0.005) (Fig. 1a).
By the date of the last follow-up, 220 (14.9%) patients experienced any recurrence. Among these, 209 patients had DM, including 67 patients with concomitant LRR; and 11 patients had isolated LRR. Table 3 compared the recurrence patterns between PMRT and non-PMRT subgroups, and the difference was statistically significant (𝜒2 = 7.652, p = 0.022). For the entire cohort, the actuarial 7.7-year DFS was 85.4%. No statistically significant difference was observed between the non-PMRT and PMRT subgroups for the 7.7-year DFS interval (84.2% vs. 86.7%, p = 0.335) (Fig. 1b).
Prognostic Risk Factors
The correlation of LRC and DFS with various prognostic factors is shown in Table 4. In univariate analysis, multiple factors including age, histological grade, number of positive ALNs, and PMRT were significantly associated with LRC. With the exception of PMRT, these factors along with tumor size were also significantly associated with DFS. Triple-negative breast cancer was associated with worse LRC and DFS in comparison with other molecular subtypes, however, the difference was not statistically significant. Additionally, subgroup analysis showed that the application of anti-HER2 therapy could improve both LRC (p = 0.024) and DFS (p < 0.001) in HER2-positive patients, and the use of endocrine therapy could improve DFS (p = 0.015) in HR-positive population.
Advanced multivariate analysis confirmed that clinical-pathological factors including younger age of ≤ 40 years (adjusted hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.17–3.50; p = 0.012), tumor size of 3-5cm (HR, 1.73; 95% CI, 1.01–2.97; p = 0.045), histological grade 3 (HR, 1.97; 95% CI, 1.24–3.12; p = 0.004), 2-3 positive ALNs (HR, 2.46; 95% CI, 1.51–3.99; p < 0.001), and no PMRT delivery (HR, 3.36; 95% CI, 2.11–6.14; p < 0.001) were significantly associated with a poorer LRC. Besides the newly identified factor of PMRT (HR, 1.63; 95% CI, 1.22–2.18; p = 0.001), younger age of ≤ 40 years, tumor size of 3-5cm, histological grade 3, and 2-3 positive ALNs remained independent predictors of a shorter DFS interval (Table 5).
Outcomes of Risk Groups
In total, 1398 patients were stratified into three groups by recurrence risk, including 377 patients (27.0%) in low-risk group (no risk factor), 572 patients (40.9%) in intermediate-risk group (1 risk factor), and 449 patients (32.1%) in high-risk group (2-4 risk factors).
Figure 2 presents the Kaplan-Meier analyses of LRR and DFS stratified by recurrence risk. The 7.7-year LRC for patients in low-, intermediate-, and high-risk group was 97.7% / 98.9% (P = 0.233), 95.3% / 98.0% (P = 0.092), and 80.3% / 94.8% (P < 0.001) in the non-PMRT and PMRT subgroups, respectively. Meanwhile, PMRT was significantly associated with a longer DFS time in high-risk patients, with 7.7-year DFS of 66.6% in non-PMRT subgroup and 80.5% in PMRT subgroup (P = 0.002). However, no benefit from PMRT was observed in low-risk (P = 0.309) and intermediate-risk (P = 0.388) patients.