Differences in clinical importance of Bcl-2 in breast cancer according to hormone receptors status or adjuvant endocrine therapy

BMC Cancer

Research Article

Yoshinori Ito¹  Takuji Iwase²  Shigehira Saji³  Mamoun Younes⁴  Rie Horii⁵  Futoshi Akiyama⁵  Naoko Honma⁶ 

[1] Breast Medical Oncology, Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, 135-8550, Koto-ku, Tokyo, Japan;Breast Oncology Center, Cancer Institute Hospital, 3-8-31 Ariake, 135-8550, Koto-ku, Tokyo, Japan;Department of Medical Oncology, Fukushima Medical University, School of Medicine, 1 Hikarigaoka, 960-1295, Fukushima City, Fukushima, Japan;Department of Pathology and Laboratory Medicine, University of Texas Medical School, 6431 Fannin, MSB 2.270, 77030, Houston, TX, USA;Department of Pathology, Cancer Institute, 3-8-31 Ariake, 135-8550, Koto-ku, Tokyo, Japan;Department of Pathology, School of Medicine, Toho University, 5-21-16 Omori-Nishi, 143-8540, Ota-ku, Tokyo, Japan;Department of Pathology, Cancer Institute, 3-8-31 Ariake, 135-8550, Koto-ku, Tokyo, Japan;

关键词: Breast cancer;    Bcl-2;    Triple-negative;    Prognosis;    Tamoxifen;    Estrogen receptor;    Progesterone receptor;   

DOI  :  10.1186/s12885-015-1686-y

 received in 2014-12-05, accepted in 2015-10-06,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundBcl-2 plays an anti-apoptotic role, resulting in poor clinical outcome or resistance to therapy in most tumor types expressing Bcl-2. In breast cancer, however, Bcl-2 expression has been reported to be a favorable prognostic factor. The positive correlation of Bcl-2 with estrogen receptor (ER)/progesterone receptor (PR) status, and endocrine therapy frequently given for hormone receptor-positive tumors, may obscure the independent pathobiological role of Bcl-2. We constructed a large systematic study to determine whether Bcl-2 has an independent role in breast cancer.MethodsBcl-2 expression was immunohistochemically evaluated and compared with other clinicopathological factors, including clinical outcome, in 1081 breast cancer cases with long follow-up, separately analyzing 634 cases without any adjuvant therapy and 447 cases with tamoxifen monotherapy. The χ2-test for independence using a contingency table, the Kaplan-Meier method with the log-rank test, and a Cox proportional hazards model were used for the comparison of clinicopathological factors, assessment of clinical outcome, and multivariate analyses, respectively.ResultsIn both patient groups, Bcl-2 expression strongly correlated with positive ER/PR status, low grade, negative human epidermal growth factor receptor 2 (HER2) status, and small tumor size, as previously reported. Bcl-2 expression did not independently predict clinical outcome in patients with ER-positive and/or PR-positive tumors or in those who received tamoxifen treatment; however, it was an independent unfavorable prognostic factor in patients with ER-negative/PR-negative or triple-negative (ER-negative/PR-negative/HER2-negative) tumors who received no adjuvant therapy. The latter was even more evident in postmenopausal women: those with hormone receptor-negative or triple-negative tumors lacking Bcl-2 expression showed a favorable outcome.ConclusionBcl-2 expression is an independent poor prognostic factor in patients with hormone receptor-negative or triple-negative breast cancers, especially in the absence of adjuvant therapy, suggesting that the anti-apoptotic effect of Bcl-2 is clearly exhibited under such conditions. The prognostic value of Bcl-2 was more evident in postmenopausal women. The present findings also highlight Bcl-2 as a potential therapeutic target in breast cancers lacking conventional therapeutic targets such as triple-negative tumors. The favorable prognosis previously associated with Bcl-2-positive breast cancer probably reflects the indirect effect of frequently coexpressed hormone receptors and adjuvant endocrine therapy.

【 授权许可】

CC BY   
© Honma et al. 2015