Down-regulation of heat-shock protein 70 (HSP-70) correlated with responsiveness to neoadjuvant aromatase inhibitor therapy in breast cancer patients

Abstract

Background: Aromatase inhibitor (AI) has been established as an effective endocrine therapy in estrogen receptor (ER)-positive postmenopausal breast cancer patients. Our recent proteomic analysis demonstrated that ten proteins were significantly altered in their expression levels before and after the therapy in the patients receiving neoadjuvant AI. Among these newly identified proteins, heat-shock protein 70 (HSP-70) was the most significantly correlated with both clinical and pathological responses. Therefore, in this study, we further evaluated the significance of this HSP-70 alteration using immunohistochemistry. Materials and Methods: A total of 32 patients treated with neoadjuvant exemestane or letrozole in whom pre- and post-treatment tumor tissues were available were included. Immunohistochemical evaluation of ER, progesterone receptor (PgR), Her-2, Ki-67 and HSP-70 was performed. Results obtained were compared to both clinical and biological responses of the patients. Results: The majority of the patients responded to treatment (16 patients with partial response, 14 with stable disease and 2 with progressive disease). The means of ER, Ki-67 and HSP-70 were significantly different between treatment responders and non-responders. Decrement of HSP-70 and Ki-67 after AI treatment and pretreatment Ki-67 labeling index of >10% tumor cells were significantly associated with clinical responsiveness to AI treatment (p<0.0001). There was a significant positive correlation between changes of HSP-70 and Ki-67 before and after the therapy. Conclusion: Decrement of HSP-70 in breast carcinoma cells plays important roles in therapeutic mechanisms of AIs through suppressing tumor cell proliferation in breast cancer patients.