Abstract P2-10-08: Assessment of risk factors for HER2+ breast cancer recurrence: A literature review
Authors: O'Shaughnessy Joyce , Gradishar William , O’Regan Ruth , Gadi Vijayakrishna 
Published: March 2022

Abstract
Introduction: Overexpression of HER2 occurs in 15%-20% of early breast cancers (EBC) and is considered more aggressive than other types of breast cancer. Though HER2-targeted therapies have improved patient outcomes, up to 25% of patients will suffer relapse within 10 years, from which the majority of patients will die from incurable metastatic disease. Previous review articles have identified prognostic factors for recurrence for EBC, such as pathological complete response (pCR), hormone receptor (HR) status, and residual cancer burden (RCB). However, most of these were not specific for HER2+ EBC. The goal of this literature analysis was to confirm and identify patient and disease factors that correlate with recurrence in patients with HER2+ EBC. Methods: Primary research articles (inclusive of randomized controlled trials, retrospective cohort analyses, and database analyses) were identified using NCBI PubMed via the search criteria “HER2+ breast cancer,” followed by “early-stage” or “adjuvant” therapy, followed by “relapse” or “recurrence.” Search results were restricted to publications from 2019-2021 that were written in English to account for modern treatment options, including trastuzumab + pertuzumab, ado-trastuzumab emtansine, and neratinib. These same terms were applied to oncology abstracts presented at ASCO 2019-2021; ESMO 2019-2020; ESMO Breast 2019 and 2021; SABCS 2019 and 2020; and St Gallen 2019 and 2021. All results were analyzed for risk factors for recurrence associated with HER2+ EBC. Results: Using the search criteria, we identified 351 research articles, and listed conferences were searched for relevant abstracts. Of these, 53 journal articles and 57 abstracts that assessed risk factor terms, including “age at diagnosis,” “BMI,” “tumor size at diagnosis,” “lymph node status,” “hormone receptor status,” “pCR status,” “smoking history,” and/or “biomarkers,” were analyzed. These were evaluated individually, where possible. Various prognostic scoring methods were also evaluated for their ability to assess the risk factors of recurrence for HER2+ EBC. The RCB prognostic scoring system correlated most strongly to identifying EBC at risk of recurrence amongst all factors evaluated. We also confirmed the results of prior reviews listing non-pCR and fewer tumor-infiltrating lymphocytes (TILs) as risk factors for HER2+ EBC recurrence. HR status remained an important risk factor for recurrence, with HER2+/HR+ disease more likely to occur. In addition, patients with a lower BMI were more likely to have HR- EBC, but no conclusive relationship to risk of recurrence could be determined for BMI. Clinical factors including tumor size, involvement of ≥2 lymph nodes, and a younger age at diagnosis (≤50 years) were also risk factors for recurrence. Of the biomarkers identified, Ki67 represented the strongest association with recurrence. Further analyses of the risk factors identified by the literature review will be presented at the meeting. Conclusion: In this literature analysis, non-pCR, fewer TILs, HR status, younger age at diagnosis, and low Ki67 were identified as potential risk factors for HER2+ recurrence. Finally, RCB correlated strongly with a risk of progression in patients with HER2+ EBC. Patients who have these risk factors could potentially benefit from additional treatments for their early-stage disease in an effort to reduce their risk of recurrence.
Citation Format: Joyce O'Shaughnessy, William Gradishar, Ruth O’Regan, Vijayakrishna Gadi. Assessment of risk factors for HER2+ breast cancer recurrence: A literature review [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-08.