Biology-driven lead-time considerations for endocrine therapy de-escalation in elderly patients with favorable breast cancer.

e12726 Background: Small breast cancers are generally assumed to have a favorable prognosis because of their limited size. However, whether small tumor size itself confers a good prognosis or merely reflects indolent tumor biology remains unclear. This distinction is particularly relevant when considering treatment de-escalation in elderly patients with hormone receptor–positive breast cancer. Methods: We retrospectively analyzed 1,058 patients with surgically treated invasive breast cancer (cohort 1), including 944 patients with HER2-negative disease (cohort 2), treated between 2007 and 2020. Tumors were classified into favorable, intermediate, and unfavorable prognostic groups based on estrogen receptor (ER), progesterone receptor (PR), and nuclear grade (NG). Tumor size distribution, age distribution, and breast cancer–specific survival (BCSS) were evaluated across groups. The impact of adjuvant endocrine therapy was explored in the favorable subgroup. Results: Biologically favorable tumors were disproportionately represented among small tumors, whereas unfavorable tumors were more prevalent among larger tumors. Favorable tumors demonstrated excellent long-term BCSS regardless of tumor size, and patients with larger favorable tumors had better outcomes than those with smaller unfavorable tumors. The distribution of favorable tumor biology was similar across age groups, suggesting that biological indolence is not age-dependent. In the favorable subgroup, no significant difference in BCSS was observed between patients who did and did not receive adjuvant endocrine therapy, although this analysis was limited by its retrospective and non-randomized nature. Conclusions: Our findings suggest that small tumor size is more likely a consequence of favorable tumor biology than an independent determinant of prognosis. When tumor biology is considered alongside patient age and life expectancy, selected elderly patients with favorable, hormone receptor–positive breast cancer may derive limited absolute benefit from adjuvant endocrine therapy. These results support a biology- and time-informed framework for individualized treatment decision-making and warrant prospective evaluation of endocrine therapy de-escalation strategies.