Abstract P3-06-34: Platelet predominant breast cancer is a new predictor for pathological complete response to neoadjuvant chemotherapy
Authors: Ishikawa Satoko , Inokuchi Masafumi , Hayashi Hironori , Oyama Katsunobu , Nakagawara Hisatoshi , Miyashita Tomoharu , Tajima Hidehiro , Takamura Hiroyuki , Ninomiya Itasu , Kitagawa Hirohisa , Fushida Sachio , Fujimura Takashi , Ohta Tetsuo 
Published: May 2015

Background and Objective: Platelets, the smallest anucleate hematopoietic cells, are increasingly recognized as the key regulator of tumor progression and metastasis in breast cancer. They contribute significantly to hematogenous metastasis, which increases tumor invasiveness, by protecting tumor cells from shear stress or immune surveillance and facilitating their extravasation to distant sites. Additionally, recent studies have demonstrated direct signaling between platelets and tumor cells during epithelial–mesenchymal transition (EMT) in the blood stream. However, the existence of platelets in primary breast cancer and its relationship with clinicopathological factors and pathological response to chemotherapy remain poorly understood. This study aimed to investigate (1) the presence of platelet infiltration in tumor tissue, (2) relationships between platelets and clinicopathological features, and (3) the association of platelets with pathological complete response (pCR) to neoadjuvant chemotherapy and EMT markers in primary breast cancer.

Methods: We retrospectively analyzed the pre-chemotherapeutic biopsy specimens from 100 breast cancer patients who underwent surgical resection after anthracycline/taxane-based neoadjuvant chemotherapy at Kanazawa University Hospital. Platelet subsets (glycoprotein Ib [CD42b]) and the expression of EMT markers (E-cadherin, vimentin, and β-catenin) were evaluated by immunohistochemistry and correlated with pCR after neoadjuvant chemotherapy. Platelet-predominant breast cancer (PPBC) was defined as the presence of ≥10% of anucleate cells positively stained for CD42b in direct contact with tumor cells. pCR was defined as the absence of residual invasive tumor cells in breast and lymph nodes (ypT0/is, ypN0).

Results: PPBC was observed in 48 patients (48%). The prevalence of PPBC was significantly higher in human epidermal growth factor receptor 2 (HER2)-negative patients (HER2 [+] vs. HER2 [-]; 65% vs. 90%, p = 0.008). There was no significant association between CD42b expression and stage, nuclear grade, histology, and estrogen receptor status. PPBC patients had a significantly decreased pCR rate (6/48, 12.5%) compared to non-PPBC patients (33/51, 64.7%; p &lt; 0.001). Tumor cells surrounded by platelets exhibited EMT-like morphological changes, EMT marker expression, nuclear-staining of β-catenin, loss of E-cadherin expression, and expression of vimentin.

Conclusions: Our results suggested the presence of tumor-associated platelets in breast cancer as a new predictor of response to neoadjuvant chemotherapy. Platelets might facilitate EMT at the primary site by potentiating tumor cell adhesion. Platelet-tumor interaction might be a new therapeutic strategy for breast cancer. If our finding is validated in further investigations, it might serve as the basis for novel therapeutic approaches of combining conventional chemotherapy with antiplatelet therapy. Our data also identified new predictive parameters to stratify patients with an increased chance of response to anthracycline/taxane-based neoadjuvant chemotherapy.

Citation Format: Satoko Ishikawa, Masafumi Inokuchi, Hironori Hayashi, Katsunobu Oyama, Hisatoshi Nakagawara, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Hirohisa Kitagawa, Sachio Fushida, Takashi Fujimura, Tetsuo Ohta. Platelet predominant breast cancer is a new predictor for pathological complete response to neoadjuvant chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-34.