The difference of clinical and molecular characteristics between HR-positive/HER2-positive and HR-negative/HER2-positive early breast cancer: A secondary analysis of 11 clinical trials.

Abstract

533 Background: HER2+ early breast cancer (EBC) are treated as an identical cluster of patients in clinical practice. However, the various status of hormone receptor (HR) leads to different outcomes. We aimed to clarify the difference of clinical and molecular characteristics between HR+/HER2+ and HR-/HER2+ EBC. Methods: This secondary analysis assessed pathologically complete response (PCR) and disease free survial (DFS) among HR+/HER2+ and HR-/HER2+ EBC patients enrolled in the 11 clinical trials. These studies included 16866 HER2+ EBC patients, with available immunohistochemistry and/or in situ hybridization results. There are five neoadjuvant trials (TRYPHAENA, Kristine, Neosphere, BERENICE and Peony) and six adjuvant trials (HERA, HannaH, Aphinity, Katherine, PrefHer and SafeHer). The primary endpoints of the trials were PCR, DFS, overall preference proportions and adverse event rates. Kaplan–Meier approach and Cox proportional hazards model were applied to estimate the association of treatment strategies with PCR and DFS among HR+ and HR- populations. The 11 trials were all registered with ClinicalTrials.gov, number NCT00976989, NCT02131064, NCT00545688, NCT02132949, NCT02586025, NCT00045032, NCT00950300, NCT01358877, NCT01772472, NCT01401166 and NCT01566721. Results: In the16866 HER2+ EBC patients, except for PrefHer and SafeHer trials, which has no information about HR status, there are 13801 patients with HR details, of which, HR+ 8004 (58.0%) and HR- 5713 (41.4%). In HER2+ EBC, the various status of HR leads to different outcomes. Our study revealed an interesting phenomenon that compared to HR-/HER2+ EBC, HR+/HER2+ EBC has a lower pCR rate. However, trials from adjuvant therapy studies suggested HR+/HER2+ EBC has a longer DFS, which is not consistent with other subtype patterns. The pCR rate is a near-term indicator that visualizes the response rate to a particular treatment, and the DFS is a distant indicator that reflects the overall biological behavior of the individual. The HR+/HER2+ EBC, despite its low pCR rate, potentially improves its long-term DFS due to the addition of adjuvant endocrine therapy postoperatively. Conclusions: Compared to HR-/HER2+ EBC, HR+/HER2+ patients has a lower pCR rate, but has a longer DFS, which deserve further exploration. The stratification of the HER2+ early breast cancer patients according to HR status in the 11 clinical trials. Trial Total, n HR+, n(%) HR-, n(%) Unknown, n TRYPHAENA 225 114(50.6) 111(49.4) 0 Kristine 444 276(62.2) 168(37.8) 0 Neosphere 417 197(47.2) 219(52.5) 1 BERENICE 401 252(62.8) 140(34.9) 9 Peony 329 173(52.6) 156(47.4) 0 HERA 5099 2571(50.4) 2528(49.6) 0 HannaH 596 265(44.5) 257(43.1) 74 Aphinity 4804 3082(64.2) 1722(35.8) 0 Katherine 1486 1074(72.3) 412(27.7) 0 PrefHer 488 NA NA NA SafeHer 2577 NA NA NA HR, hormone receptor.