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Purpose <p>Hormone receptor (HR) status may be unstable during breast cancer (BC) progression, and changes occur in approximately 20–30% of BC patients at the time of recurrence. The biologic tumor switch from HR+ to HR− status is associated with worse clinical outcomes and warrants alternative management. We aimed to characterize clinical and pathologic features of a subset of ER+/HER2− breast cancer patients who converted to triple negative phenotype upon recurrence, and investigate the molecular alterations associated with HR loss during BC progression.</p> Methods <p>We retrospectively identified 112 patients who had primary ER+/HER2− breast cancer and developed local or distant recurrence through our institutional database. Patients were divided into two cohorts based on receptor profile of recurrent tumor: discordant TNBC (<i>n</i> = 20) and concordant ER+/HER2− tumors. The following variables were collected: tumor histology, grade, pT, pN, ER, PR, HER2 expression in primary and recurrent tumors, molecular profiling, and adjuvant treatment history.</p> Results <p>The average time for HR+ tumors to recur as TNBC was 148&#xa0;months. The two cohorts showed similar clinicopathologic characteristics, including patient’s age at diagnosis, tumor type, grade, stage, ER expression, and treatment history before tumor recurrence. <i>PTEN</i> inactivating mutations were more frequently identified in the discordant TNBC (6/20, 30%) compared to the concordant ER+/HER2− tumors (6/92, 5.5%) (<i>p</i> = 0.007).</p> Conclusion <p>Increased signaling via the <i>PI3K/AKT/PTEN</i> pathway may be a mechanism for the transition to hormone independence in recurrent diseases.</p>

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PTEN inactivating mutations are associated with hormone receptor loss during breast cancer recurrence

  • 期刊论文

  • 发表日期：

    2025年3月10日

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  • Haiying Zhan,
  • Vijay Mariadas Antony,
  • Haiming Tang,
  • Janie Theriot,
  • Yuanxin Liang,
  • Pei Hui,
  • Uma Krishnamurti,
  • Michael P. DiGiovanna

摘要

Purpose

Hormone receptor (HR) status may be unstable during breast cancer (BC) progression, and changes occur in approximately 20–30% of BC patients at the time of recurrence. The biologic tumor switch from HR+ to HR− status is associated with worse clinical outcomes and warrants alternative management. We aimed to characterize clinical and pathologic features of a subset of ER+/HER2− breast cancer patients who converted to triple negative phenotype upon recurrence, and investigate the molecular alterations associated with HR loss during BC progression.

Methods

We retrospectively identified 112 patients who had primary ER+/HER2− breast cancer and developed local or distant recurrence through our institutional database. Patients were divided into two cohorts based on receptor profile of recurrent tumor: discordant TNBC (n = 20) and concordant ER+/HER2− tumors. The following variables were collected: tumor histology, grade, pT, pN, ER, PR, HER2 expression in primary and recurrent tumors, molecular profiling, and adjuvant treatment history.

Results

The average time for HR+ tumors to recur as TNBC was 148 months. The two cohorts showed similar clinicopathologic characteristics, including patient’s age at diagnosis, tumor type, grade, stage, ER expression, and treatment history before tumor recurrence. PTEN inactivating mutations were more frequently identified in the discordant TNBC (6/20, 30%) compared to the concordant ER+/HER2− tumors (6/92, 5.5%) (p = 0.007).

Conclusion

Increased signaling via the PI3K/AKT/PTEN pathway may be a mechanism for the transition to hormone independence in recurrent diseases.