The present study showed that most breast cancer patients receive BCT, followed by MAS and MAS + RT. Patients who received BCT were more likely to be of white race and have a smaller tumor size, lower tumor grade, fewer positive lymph nodes, and larger number of ER- and PR-positive tumors than patients in other groups. Compared with the MAS and MAS + RT groups, the BCT group had a lower short-term recurrence risk but a higher long-term recurrence risk, especially at the 10 and 15-year follow-ups. Age ≥ 90 years, black race, tumor grade II, and PR-negative tumors were independent predictors for long-term recurrence.
We confirmed that the BCT group has a higher long-term recurrence risk than the MAS and MAS + RT groups; this result sheds some light on what has been a long-disputed issue in the literature. A large observational study in Germany between 1998 and 2014 reported that BCT allows better local control (HR: 1.52; 95% CI: 1.09–2.11) than MAS [14]. In addition, the BCT cohort had a lower 10-year cumulative incidence of lymph node recurrence (2.0% vs. 5.8%, p < 0.001), lower 10-year distant-metastasis-free survival (85.5% vs. 89.4%, p = 0.013), and better 10-year overall survival (85.3% vs. 79.3%, p < 0.001) than the MAS cohort [14]. A retrospective study in China between 1999 and 2014 reported that BCT has locoregional recurrence-free survival rates similar to that of MAS but better distant metastasis-free survival and overall survival rates [15]. A prospective Swedish multicenter cohort study carried out between 2000 and 2004 reported that local recurrence rates do not differ between BCT and MAS in patients with clinically node-negative breast cancer [16]. A randomized study with a 20-year follow-up in Italy in 2002 reported that the cumulative incidence of local recurrence in women with early breast cancer receiving BCT is 8.8%, which is higher than that in women receiving MAS (2.3%) [17]. However, the above studies included patients of all ages, and the characteristics of the populations studied may differ from those of patients aged ≥ 50 years, as in the present study. In addition, because these previous studies included all types of breast cancer, their results may be different when compared with a study specific to IDC, such as the present work. Therefore, further studies specific to middle-aged and old women and early-stage IDC are needed to confirm our findings.
Risk of recurrence has a great influence on patients with breast cancer because this risk causes patients to live with a constant fear of death [18]. The reasons behind local recurrence remain largely unknown [18], but the possible mechanisms include the existence of cancer stem cells and transformation of cancer cells into a relatively aggressive phenotype [18]. Cancer stem cells and transformed cancer cells are highly metastatic and resistant to conventional therapies [18]. A high percentage of aggressive cells is a feature of recurrent breast cancers [18]. Many clinical predictors for recurrence, including ER-negative, PR-negative, human epidermal growth factor receptor 2 (HER-2)-positive, triple-negative breast cancers, age, race, menopausal status, smoking, mammographic features, tumor morphology, tumor size, tumor stage, lymph node metastases, and gene expression profiling, have been proposed [18, 19].
Age ≥ 90 years, which has not been fully studied in the literature, was identified to be an independent predictor for long-term recurrence in the present study. A large population-based study in the Netherlands in 2020 reported that patients aged 75–79 years were at higher risk of distant recurrence than patients aged 70–74 years (subdistribution HR: 1.25; 95% CI: 1.11–1.41); however, age ≥ 80 years did not show this higher risk [20]. The authors attributed their findings to several reasons: (1) patients in the aged 75–79 years were undertreated, (2) the risk of death without recurrence increases with age, and (3) patients with a high competing mortality risk were overtreated [20]. Another population-based study in Germany in 2019 revealed that patients aged < 70 years have higher 5- and 10-year locoregional recurrence and distant metastasis rates than those aged ≥ 70 years (17% vs. 13%) [21]. More evidence is needed to clarify this finding. Black race was a risk factor for cancer recurrence in the present study, consistent with findings in previous studies [19]. Racial disparities may be due to socioeconomic factors and a more aggressive tumor biology among African–Americans [19]. Tumor grade was also associated with poor outcomes [19]. The present study revealed that tumor grade II is associated with long-term recurrence. While patients with tumor grades III and IV were at higher risk for long-term recurrence than those with tumor grade I, the difference between grades was not significant. PR-negative is a predictor for recurrence, and the results between the present and previous studies are consistent [19]. In general, breast cancers that are single hormone receptor-positive appear to have a poorer prognosis than those that are both ER- and PR-positive [19]. The present study also revealed a higher long-term recurrence risk in patients with ER-negative breast cancer than in those with ER-positive breast cancer; however, the difference was not significant (HR: 1.13; 95% CI: 0.97–1.33).
The major strengths of the present study include its nationwide population-based design, large sample size, and clear delineation of the knowledge gap in research on the recurrence rate of early-stage IDC in women aged ≥ 50 years. The limitations are as follows. First, the data were obtained from various institutions and may have bias in terms of treatment and quality. Second, because the present study conducts a secondary analysis of data, the results can only suggest associations between variables rather than causal relationships. Third, some variables, including genetic data, lymphovascular invasion, size of metastatic lymph nodes, resection margins, adjuvant therapies (e.g., chemotherapy and endocrine therapy), and HER2, were not considered in the present study because data on these variables were made available only after 2010. Fourth, because the data used for our analyses are from the United States, their generalization to other countries requires further validation.