Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status

Jihye Choi; Chan Sub Park; Min-Ki Seong; Hyesil Seol; Jae-Sung Kim; In-Chul Park; Woo Chul Noh; Hyun-Ah Kim

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저자정보: Jihye Choi (Department of Surgery Korea Cancer Center Hospital Korea Institute of Radiological and Medical Scie) Chan Sub Park (Department of Surgery Korea Cancer Center Hospital Korea Institute of Radiological and Medical Scie) Min-Ki Seong (Department of Surgery Korea Cancer Center Hospital Korea Institute of Radiological and Medical Scie) Hyesil Seol (Departments of Pathology Korea Cancer Center Hospital Korea Institute of Radiological & Medical) Jae-Sung Kim (Division of Basic Radiation Bioscience Korea Institute of Radiological and Medical Sciences Seoul) In-Chul Park (Division of Basic Radiation Bioscience Korea Institute of Radiological and Medical Sciences Seoul) Woo Chul Noh (Departments of Surgery Korea Cancer Center Hospital Korea Institute of Radiological & Medical S) Hyun-Ah Kim (Departments of Surgery Korea Cancer Center Hospital Korea Institute of Radiological & Medical S)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.23 No.1

발행연도: 2020.1

수록면: 10 - 19 (10page)

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Purpose: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer. Methods: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis. Results: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1–90). In patients with positive pS6K1 expression, AIs significantly improved diseasefree survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16–0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188). Conclusion: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian functionsuppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

#Aromatase inhibitors #Biomarkers #tumor #Breast neoplasms #Ribosomal protein S6kinase #70kD #polypeptide 1 #Tamoxifen

참고문헌 (30)

참고문헌 신청

Early Breast Cancer Trialists' Collaborative Group / 1998 / Tamoxifen for early breast cancer : an overview of the randomised trials / Lancet 351:1451~1467

Brodie AM / 1998 / Aromatase inhibitors in advanced breast cancer : mechanism of action and clinical implications / J Steroid Biochem Mol Biol 66:1~10

Howell A / 2005 / Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer / Lancet 365:60~62

Gradishar WJ / 2018 / Breast cancer, version 4.2017, NCCN clinical practice guidelines in oncology / J Natl Compr Canc Netw 16:310~320

Garreau JR / 2006 / Side effects of aromatase inhibitors versus tamoxifen : the patients' perspective / Am J Surg 192:496~498

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Jihye Choi

소속기관 Department of Surgery Korea Cancer Center Hospital Korea Institute of Radiological and Medical Scie