Abstract
Abstract
Background: Breast cancer is the commonest cancer in Saudi Arabia and worldwide. Nineteen percent of breast cancers are HER2-positive. Both trastuzumab and pertuzumab inhibit cancer cell proliferation by blocking HER2 activation and HER2-mediated downstream signals. They also induce extracellular antibody-dependent cell-mediated cytotoxicity (ADCC), exerted by immune cells expressing surface CD16 Fcγ receptors (FcγRs), such as NK cells subset of human blood monocytes. Inside tissue, monocytes differentiate to macrophages and potentiate anti-cancer innate immunity. Increased macrophages' infiltration in the tumor tissue was associated with enhanced efficacy of trastuzumab antitumor efficacy in mouse xenograft tumor models. In Metastatic HER2-positive breast cancer, increased M1 polarized macrophages improved survival and were independent prognostic predictors. Herceptin significantly increased peripheral blood monocyte (PBMC) cytotoxicity against HER-2 positive cancer cells. This study aims to determine the impact of peripheral blood monocyte (PBMC) count on response rate (RR) and progression-free survival (PFS) in metastatic HER2-positive breast cancer patients treated with trastuzumab and pertuzumab.
Method: A retrospective chart review at Princess Norah Oncology Center (PNOC) that included histopathology-proven metastatic HER2-positive breast cancer patients receiving first-line anti-HER2 systemic therapy from January 2008 to May 2018. Younger patients (< 18 years old) and those with cranial and immeasurable metastases were excluded. Before each chemotherapy cycle, peripheral blood monocyte counts (PBMC) were checked, and values were classified as high, low, or normal according to hospital lab reference ranges. Chi-square and Kaplan-Meier curves were applied to estimate response rate (RR) and progression-free survival (PFS).
Results: Of 307 identified cases, 81 were analyzed. The median age was 62 years, 73% were postmenopausal, and 70% had grade 3 tumors. All had visceral metastases, treated with chemotherapy, along with an anti-HER2 agent. We found improved RR with high PBMC before the second cycle (P = 0.025) and increased PFS for high PBMC before the third cycle (P = 0.048).
Conclusion(s): Peripheral blood monocyte count before cycle 2 and 3 might predict a favorable outcome of chemotherapy anti-HER2 combination in metastatic HER2-positive breast cancer.
Citation Format: Amer Naeem Radwi, Reyadh Khalid Albeladi, Shahrazad Abdulsalam Alzahrani, Raghad Abdulrahman Alahmadi, Haneen Abdulrahman Aljohani, Dalia Ismaiel Ahmed. Peripheral blood monocyte count prediction for anti-HER2 combination therapy: Outcomes in HER2-positive metastatic breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 338.