Clinicopathological characteristics and potential impact of previous treatment history in metachronous contralateral breast cancer: Insights from a real‑world retrospective study

Metachronous contralateral breast cancer (mCBC) accounts for 40‑50% of new secondary cancers in breast cancer survivors. With improved breast cancer treatment outcomes, the number of long‑term survivors is increasing. To better understand the clinical features of mCBC in real‑world practice, patients who developed mCBC, defined as contralateral second primary breast cancer diagnosed ≥12 months after the first primary breast cancer (FBC), were retrospectively analyzed. Two types of comparisons were conducted: i) A within‑patient comparison between FBC and mCBC (n=115) to evaluate paired differences in tumor characteristics; and ii) a between‑patient comparison of the mCBC cohort with a unilateral breast cancer (UBC; n=1,877) cohort of patients who remained recurrence‑free for ≥5‑10 years to assess differences in baseline clinical features and indicators related to hereditary cancer risk, thereby identifying features unique to mCBC. The median age at diagnosis was 48 years for FBC in patients who subsequently developed mCBC and 55 years for UBC, with a significant difference (P<0.001). The median time interval from FBC to mCBC onset was 9 (1‑44) years. The stage at diagnosis was significantly earlier in mCBC than in FBC (P<0.001). Among patients with mCBC, prior chemotherapy (CTx) for FBC was associated with lower odds of the luminal subtype relative to the triple‑negative subtype compared with no prior CTx, although this association was not statistically significant (P=0.086). The proportion of patients with a first‑degree family history was significantly higher in patients with mCBC than in patients with UBC (P=0.025). No significant association was observed between family history and the timing of mCBC onset. Further adequately powered studies are warranted to clarify whether prior CTx influences the molecular subtype of mCBC (P=0.602). The present results highlighted the importance of family history assessment and the need for lifelong surveillance in breast cancer survivors.