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Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer
Yoo-Na Kim1, Yun Soo Chung1, Eunhyang Park2
1Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Korea.
Abstract:
Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location. Among 200 patients, 28% and 6% exhibited expression scores of 2+ and 3+, respectively. HER2 3+ scores were observed in 23%, 11%, 9%, and 5% of mucinous, endometrioid, clear cell, and high-grade serous tumors, respectively, and were exclusively identified in BRCA-wildtype, mismatch repair-proficient, or PD-L1-low-expressing tumors. The TP53 mutation rate was low, whereas ARID1A, KRAS, and PIK3CA mutations were relatively more prevalent with HER2 scores of 2+ or 3+ than with 0 or 1+. Four of the five tumors with an HER2 3+ score exhibited ERBB2 amplification. Among 19 patients who underwent multiple time-lagged biopsies, 11 showed increased HER2 expression in subsequent biopsies. Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.
Insights
HER2 expression is present in ovarian cancer (OC), with dynamic changes observed over time. HER2-targeting drugs may benefit BRCA-wildtype OC patients, especially in later treatment lines.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Human epidermal growth factor receptor-2 (HER2) targeting is expanding beyond breast cancer.
- HER2 expression data in ovarian cancer (OC) remains limited.
- Understanding HER2 status is crucial for novel therapeutic strategies in OC.
Purpose of the Study:
- To investigate the prevalence and dynamic changes of HER2 expression in ovarian cancer.
- To correlate HER2 status with clinicopathological and genomic features.
- To evaluate the potential of HER2-targeted therapies in OC.
Main Methods:
- Retrospective review of 200 ovarian cancer patients undergoing HER2 testing.
- Analysis of immunohistochemistry (IHC) for HER2 expression.
- Evaluation of histology, BRCA status, and genomic mutations (TP53, ARID1A, KRAS, PIK3CA).
- Assessment of dynamic HER2 changes in 19 patients with serial biopsies.
Main Results:
- 28% and 6% of OC cases showed HER2 expression scores of 2+ and 3+, respectively.
- HER2 3+ was most frequent in mucinous (23%) and endometrioid (11%) subtypes.
- HER2 overexpression was associated with BRCA-wildtype, MMR-proficient, and PD-L1-low profiles.
- ARID1A, KRAS, and PIK3CA mutations were more common with higher HER2 scores.
- 11 out of 19 patients demonstrated increased HER2 expression in serial biopsies.
Conclusions:
- HER2-overexpressing OC exhibits distinct histological and genomic profiles.
- HER2 expression can dynamically change in ovarian cancer.
- HER2-targeted agents represent a potential therapeutic avenue for BRCA-wildtype OC patients, particularly in later treatment stages.
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