Patient Characteristics
Table 1 presents the main demographic and clinicopathologic characteristics of patients based on the year of diagnosis. The final analysis involved 370,729 hormone receptor-positive BC patients, of whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990–1994, 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively. Among the included patients, a total of 308,672 (83.3%) were diagnosed with ER-positive/PR-positive, 54,709 (14.8%) were ER-positive/PR-negative, and 7348 (1.9%) were ER-negative/PR-positive tumors. Patients between 60 and 69 years of age (25.2%) were most frequent, followed closely by those 50–59 years of age (22.5%), and patients < 30 years of age were least common (0.4%). The racial distribution showed that 306,153 women (82.6%) were white, 24,092 women (6.5%) were black, 39,217 women (10.6%) were classified as another race (American Indian/Alaska native or Asian/Pacific Islander), and the race of 1267 women (0.3%) was not reported by SEER.
The frequency of hormone receptor-positive BC increased significantly in black patients over the interval study (1990–1994, 4.4%; 1995–1999, 4.8%; 2000–2004, 5.3%; 2005–2009, 6.5%; 2010–2014, 7.6%; and 2015–2019, 8.2%; P for trend <0.0001), whereas the frequency of hormone receptor-positive BC decreased in white patients (1990–1994, 88.6%; 1995–1999, 87.0%; 2000–2004, 85.2%; 2005–2009, 82.8%; 2010–2014, 80.1%; and 2015–2019, 77.8%; P for trend <0.0001). The proportion of patients with ER-positive/PR-positive BC increased stepwise from 78.2% during the 1990-1994 time period to 85.3% during the 2015–2019 time period (7.1% increase). In contrast, the ER-positive/PR-negative and ER-negative/PR-positive disease rates steadily decreased from 16.8% to 13.7% (3.1% decrease) and 5.0% to 2.0% (3.0% decrease), respectively. The frequency of low grade (I and II) hormone receptor-positive BC increased from 43.9% to 71.7%, while the frequency of high grade (III and IV) decreased from 27.0% to 17.9% between 1990 and 2019. The prevalence of early stage (Tis and I) hormone receptor-positive BC increased 19.5%, stage II–III decreased 12.6%, and stage IV remained low (2.8%–4.2%) in the 6 diagnostic groups. The deaths attributed to BC among women diagnosed with hormone receptor-positive BC decreased from 26.3% in 1990–1994 to 3.3% in 2015–2019.
Incidence Rates for Hormone Receptor-Positive BC
Age-adjusted IRs of hormone receptor-positive BC increased from 70 per 100,000 women-years in 1990 to 113 per 100,000 women-years in 2019, with an AAPC of 1.59% (95% CI, 1.18–1.99; Figure 2). The AAPCs were 1.95% (95% CI, 1.56–2.35), 0.62% (95% CI, 0.38–0.85), and 4.83% (95% CI, −7.24 to −2.36; P < 0.001) for ER-positive/PR-positive, ER-positive/PR-negative, and ER-negative/PR-positive BC, respectively (Figure 2).
There was an age heterogeneity in the incidence of hormone receptor-positive BC. The highest IR (362.5 per 100,000 women-years) occurred among all hormone receptor-positive women 75–79 years of age. ER-positive/PR-positive women, 70–74 years of age, had the highest IR (300.5 per 100,000 women-years), ER-positive/PR-negative women, 75–79 years of age, had the highest IR (58.3 per 100,000 women-year), and ER-negative/PR-positive women, 65–69 years of age, had the highest IR (4.7 per 100,000 women-year; Supplementary Figure 1). Nearly all age groups had an increase in trends (0.5%–4.0%) from 1990–2019, and a statistically significantly difference except women > 85 years of age (Supplementary Table 1) for the AAPC in each age group.
Survival Analysis
The cut-off for follow-up was 31 December 2019. The median follow-up among all patients was 108 months (range, 1–359 months). The mean OS and BCSS was 208.9 (95% CI, 208.4–209.5 months) and 294.8 months (95% CI, 294.3–295.4 months) for hormone receptor-positive BC, respectively. A total of 128,714 patients (34.7%) died from all causes and 49,018 patients (13.2%) died from BC. We used the Kaplan-Meier algorithm to estimate the 5-year survival rates (OS and BCSS) for hormone receptor-positive BC patients. A LOWESS curve was used to fit the individual survival estimates reflecting the variation trends (Figure 3). The 5-year OS rate increased from 78.5% (95% CI, 77.5%–79.4%) among patients diagnosed in 1990 to 86.1% (95% CI, 85.6%–86.7%) among patients diagnosed in 2014, and the 5-year BCSS rate increased from 87.7% (95% CI, 86.8%–88.5%) in 1990 to 92.7% (95% CI, 92.3%–93.1%) in 2014 (P < 0.0001 for both OS and BCSS). Similar trends were observed for the 2-year OS and BCSS in hormone receptor-positive patients, with the 2-year OS rate increasing from 92.7% (1990–1994) to 95.1% (2015–2019) and the 2-year BCSS rate increasing from 95.9% (1990–1994) to 97.2% (2015–2019; Supplementary Figure 2). The survival curves for OS and BCSS stratified by diagnostic group, as well pairwise comparisons among each of two diagnostic groups and along with log-rank P-value are provided in Figure 4. Patients diagnosed during 2015–2019 had the best OS and BCSS, followed by 2010–2014, 2005–2009, 2000–2004, 1995–1999, and 1990–1994 (P < 0.0001; Figure 4A and B). The 5-year OS and BCSS rates were highest for hormone receptor-positive BC patients diagnosed in 2010–2014 (85.5% and 92.4%), followed closely by 2005–2009 (85.2% and 92.3%), 2000–2004 (84.6% and 92.3%), 1995–1999 (82.3% and 91.0%), and 1990–1994 (79.3% and 88.5%). Similarly, there was a significantly increased trend for 2- and 5-year relative survival (OS and BCSS) for ER-positive/PR-positive BC and ER-positive/PR-negative BC (Supplementary Figures 3–6). However, although the relative survival rate among ER-negative/PR-positive BC differed statistically significantly over the study period, no apparent trend was observed.
Subgroup analyses were performed based on age at diagnosis, race, stage, radiation, and chemotherapy (Supplementary Figures 7–11). In patients first diagnosed with hormone receptor-positive BC < 60 years of age, those who were diagnosed between 1990 and 1994 had the significantly worst OS and BCSS, followed by 1995–1999, 2000–2004, and 2005–2009. There was no significant difference in OS and BCSS between 2005–2009, 2010–2014, and 2015–2019 (Supplementary Figure 7A-D and Supplementary Tables 2–3). For patients > 60 years of age, the OS increased significantly between 1990 and 2019; however, no significant difference in BCSS was detected in pairwise comparisons of the two diagnostic groups in 2005–2009 versus 2000–2004, and 2010–2014 versus 2000–2004 (Supplementary Figure 7E-F and Supplementary Tables 2–3). Among white patients with stage 0–II tumors, the OS did not differ statistically significantly between 2005–2009 and 2010–2014, and the BCSS did not differ statistically significantly between 2000–2004, 2005–2009, 2010–2014, and 2015–2019 (Supplementary Figure 8-9 and Supplementary Tables 2–3). Among patients who received radiation therapy, both OS and BCSS improved significantly over the entire study period, except for the pairwise comparisons between 2005–2009 and 2010–2014 (Supplementary Figure 10 and Supplementary Tables 2–3). Among hormone receptor-positive BC patients between 2000 and 2019 who underwent chemotherapy, no statistically significant differences for pairwise comparison of 2010-2014 vs. 2000-2004, 2015–2019 vs. 2000-2004, 2010-2014 vs. 2005-2009, and 2015-2019 vs. 2010-2014 were observed (Supplementary Figure 11 and Supplementary Tables 2-3).
Based on multivariate Cox proportional hazards regression analysis, the risk of all-cause mortality decreased 5% (HR, 0.95; 95% CI, 0.94–0.97), 6% (HR, 0.94; 95% CI, 0.92–0.96), 10% (HR, 0.90; 95% CI, 0.88–0.92), 15% (HR, 0.85; 95% CI, 0.83–0.87), and 22% (HR, 0.78; 95% CI, 0.76–0.81) for patients diagnosed with hormone receptor-positive BC during 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively, when compared to patients diagnosed during 1990–1994 (P < 0.0001). The risk of BC-specific mortality decreased 9% (HR, 0.91; 95% CI, 0.88–0.93), 16% (HR, 0.84; 95% CI, 0.81–0.86), 21% (HR, 0.79; 95% CI, 0.76–0.81), 25% (HR, 0.75; 95% CI, 0.73–0.78), and 27% (HR, 0.73; 95% CI, 0.70–0.76) for patients diagnosed with hormone receptor-positive BC during 1995–1999, 2000–2004, 2005–2009, 2010–2014, and 2015–2019, respectively, compared to patients diagnosed during 1990–1994 (P < 0.0001). By setting the year of diagnosis as a continuous variable, the risk of all-cause and BC-specific mortality decreased 0.8% (HR, 0.992; 95% CI, 0.991–0.993; P < 0.0001) and 1.3% (HR, 0.987; 95% CI, 0.985–0.988; P < 0.0001) each year since 1990, respectively (Table 2).