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Background: Metachronous contralateral breast cancers with discordant histology are uncommon and may reflect both intrapatient tumor heterogeneity and hereditary susceptibility. Case presentation: A 59-year-old postmenopausal Iranian woman with hypertension and a sister with breast cancer presented in December 2024 with a right-breast mass. Breast-conserving surgery with axillary dissection showed a 2.2 cm, grade II invasive ductal carcinoma (IDC), estrogen receptor and progesterone receptor (ER/PR) 100%, human epidermal growth factor receptor (HER2)-positive, Ki-67 approximately 5%, pT2N0Mx. After systemic anti-HER2 therapy and radiotherapy, a new left-breast mass appeared in October 2025, exactly 10 months after the first presentation. Modified radical mastectomy demonstrated a 2.8 cm, grade III signet-ring-cell invasive lobular carcinoma (ILC), ER 90%, PR-negative, HER2-negative, Ki-67 20–25%, with E-cadherin loss, pT2N0Mx. Dual-probe in situ hybridization showed no HER2 amplification, establishing HER2-negative status for the second tumor. Conclusion: The rapid IDC-to-ILC sequence illustrates that a contralateral lesion requires independent pathological characterization. Discordant histology does not exclude a shared hereditary driver; genetic assessment and individualized bilateral surveillance are warranted.
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Negahdari et al. (2026) studied this question.
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