PD 15 - GYN 2 - Poster Discussion
1126 - HER2/neu Overexpression and Recurrence Risk in Early Stage Uterine Serous Carcinoma
Wednesday, October 24
11:00 AM - 11:06 AM
Location: Room 217 A/B
HER2/neu Overexpression and Recurrence Risk in Early Stage Uterine Serous Carcinoma
A. Blakaj1, V. Jairam2, N. Buza3, P. Schwartz4, A. Santin4, and S. Damast1; 1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 2Yale School of Medicine, New Haven, CT, 3Department of Pathology, Yale School of Medicine, New Haven, CT, 4Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT
Purpose/Objective(s): A randomized phase II trial has recently demonstrated that anti-HER2 therapy in combination with cytotoxic chemotherapy improves outcomes for HER2 positive advanced FIGO stage III-IV or recurrent uterine serous carcinoma (USC). Whether such treatment is beneficial for early FIGO stage I-II USC is unknown. We examined whether HER2 overexpression was associated with an increased recurrence risk in a large cohort of early stage USC patients treated with multi-modality therapy (without anti-HER2 therapy) at a single institution.
Materials/Methods: The cohort consisted of 117 patients with FIGO stage I-II USC treated between 2000-2015 in a consistent manner with carboplatin and paclitaxel chemotherapy and high-dose-rate intravaginal brachytherapy following surgical staging. HER2 status was available in patients treated after 2009. HER2 positivity was defined as overexpression of HER2 at a level of 3+ by immunohistochemistry (IHC) and/ or HER2 gene amplification with a HER2/CEP17 ratio of >2.1 by fluorescence in situ hybridization (FISH). For the total cohort, we analyzed clinical, pathologic, and treatment-related factors influencing recurrence-free survival (RFS). In the cohort of patients with known HER2 status, we examined the impact of HER2 positivity on RFS. Kaplan-Meier statistics were performed, and the log-rank test was used for univariable statistical comparisons. Multivariate analyses were not performed due to few events. This retrospective study was granted approval by the institutional human investigations committee.
Results: Stage IA, IB and II comprised 75%, 17%, and 8% of patients, respectively. Histology was pure serous in 68% and mixed serous in 32%. Treatment included pelvic and para-aortic dissections in 96%, brachytherapy in 100%, and full chemotherapy (6 cycles) in 91%. For the total cohort, the median follow-up time was 4.85 years (range: 0.26 – 16.68), the 5-year RFS was 86.3%, and the median time to recurrence was 32.8 months. Factors associated with worse RFS were higher stage (p=0.025) and lymphovascular invasion (LVI) (p=0.0092). Stage IB versus IA was associated with higher recurrence (HR 4.4; 95% CI 1.3-14.4; p=0.015). Among the 52 patients with known HER2 status, IHC levels were 0 (21%), 1+ (40%), 2+ (21%), and 3+ (17%). In combination with FISH results, a total of 13 patients (25%) were HER2 positive. HER2 overexpression was associated with worse RFS (p=0.005). The estimated 5-year RFS was 94.6% and 41.1% in the HER2 negative and Her2 positive populations, respectively.
Conclusion: Our results indicate that HER2 overexpression is associated with increased risk of recurrence. These data, in combination with other published trials, may support the use of anti-HER2 therapy in early stage disease, especially when other poor prognostic features (+LVI, deep myometrial invasion) are present.
Author Disclosure: A. Blakaj: None. N. Buza: None. P. Schwartz: None.