New insights on PI3K/AKT pathway alterations and clinical outcomes in breast cancer

被引:191
作者
Yang, Sherry X. [1 ]
Polley, Eric [2 ,4 ]
Lipkowitz, Stanley [3 ]
机构
[1] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA
[2] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA
[3] NCI, Womens Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[4] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
基金
美国国家卫生研究院;
关键词
Breast cancer; Chemotherapy; HER2; Paclitaxel; pAKT; PIK3CA mutations; FACTOR RECEPTOR 2; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; PATHOLOGICAL COMPLETE RESPONSE; PIK3CA MUTATIONS; ESTROGEN-RECEPTOR; ADJUVANT CHEMOTHERAPY; PTEN LOSS; PHOSPHORYLATED AKT; PHASE-III; TRASTUZUMAB RESISTANCE;
D O I
10.1016/j.ctrv.2016.03.004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PI3K/AKT signaling pathway plays an important role in tumorigenesis and regulates critical cellular functions including survival, proliferation and metabolism. PIK3CA mutations and AKT activation by phosphorylation (pAKT) are often detected in many cancers and especially at high frequencies in breast cancer. Mounting data suggest that PIK3CA mutations or pAKT are mostly associated with better or insignificant outcomes in estrogen receptor-positive (ER+) early stage breast cancer and tend to be with worse prognosis in ER disease. pAKT expression has been identified to predict paclitaxel chemotherapy benefit in node-positive breast cancer. Preclinical and neoadjuvant trial data suggest that PIK3CA alterations confer resistance to HER2-targeted therapy and are associated with lower pathological complete response (pCR) rate in HER2-positive breast cancer. However, recent results from randomized clinical trials of adjuvant and metastatic settings show that patients with mutant and wildtype PIK3CA tumors derived similar benefit from anti-HER2 therapy. This article, with our new insights, aims to decipher the mixed data and discusses the influence of the potential confounding factors in the assessments. We also share our views for validation of PI3K/AKT alterations in relation to clinical outcome in the context of specific breast cancer subtypes and treatment modalities towards further advance of the precision medicine for breast cancer treatment. Published by Elsevier Ltd.
引用
收藏
页码:87 / 96
页数:10
相关论文
共 104 条
[1]   Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials [J].
Albain, K. ;
Anderson, S. ;
Arriagada, R. ;
Barlow, W. ;
Bergh, J. ;
Bliss, J. ;
Buyse, M. ;
Cameron, D. ;
Carrasco, E. ;
Clarke, M. ;
Correa, C. ;
Coates, A. ;
Collins, R. ;
Costantino, J. ;
Cutter, D. ;
Cuzick, J. ;
Darby, S. ;
Davidson, N. ;
Davies, C. ;
Davies, K. ;
Delmestri, A. ;
Di Leo, A. ;
Dowsett, M. ;
Elphinstone, P. ;
Evans, V. ;
Ewertz, M. ;
Gelber, R. ;
Gettins, L. ;
Geyer, C. ;
Goldhirsch, A. ;
Godwin, J. ;
Gray, R. ;
Gregory, C. ;
Hayes, D. ;
Hill, C. ;
Ingle, J. ;
Jakesz, R. ;
James, S. ;
Kaufmann, M. ;
Kerr, A. ;
MacKinnon, E. ;
McGale, P. ;
McHugh, T. ;
Norton, L. ;
Ohashi, Y. ;
Paik, S. ;
Pan, H. C. ;
Perez, E. ;
Peto, R. ;
Piccart, M. .
LANCET, 2012, 379 (9814) :432-444
[2]   Clinicopathologic and molecular significance of phospho-Akt expression in early invasive breast cancer [J].
Aleskandarany, Mohammed A. ;
Rakha, Emad A. ;
Ahmed, Mohamed A. ;
Powe, Desmond G. ;
Ellis, Ian O. ;
Green, Andrew R. .
BREAST CANCER RESEARCH AND TREATMENT, 2011, 127 (02) :407-416
[3]   Human epidermal growth factor receptor-2 and estrogen receptor expression, a demonstration project using the residual tissue respository of the Surveillance, Epidemiology, and End Results (SEER) program [J].
Anderson, W. F. ;
Luo, S. ;
Chatterjee, N. ;
Rosenberg, P. S. ;
Matsuno, R. K. ;
Goodman, M. T. ;
Hernandez, B. Y. ;
Reichman, M. ;
Dolled-Filhart, M. P. ;
O'Regan, R. M. ;
Garcia-Closas, M. ;
Perou, C. M. ;
Jatoi, I. ;
Cartun, R. W. ;
Sherman, M. E. .
BREAST CANCER RESEARCH AND TREATMENT, 2009, 113 (01) :189-196
[4]   Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer [J].
Andre, F. ;
Nahta, R. ;
Conforti, R. ;
Boulet, T. ;
Aziz, M. ;
Yuan, L. X. H. ;
Meslin, F. ;
Spielmann, M. ;
Tomasic, G. ;
Pusztai, L. ;
Hortobagyi, G. N. ;
Michiels, S. ;
Delaloge, S. ;
Esteva, F. J. .
ANNALS OF ONCOLOGY, 2008, 19 (02) :315-320
[5]   Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial [J].
Andre, Fabrice ;
O'Regan, Ruth ;
Ozguroglu, Mustafa ;
Toi, Masakazu ;
Xu, Binghe ;
Jerusalem, Guy ;
Masuda, Norikazu ;
Wilks, Sharon ;
Arena, Francis ;
Isaacs, Claudine ;
Yap, Yoon-Sim ;
Papai, Zsuzsanna ;
Lang, Istvan ;
Armstrong, Anne ;
Lerzo, Guillermo ;
White, Michelle ;
Shen, Kunwei ;
Litton, Jennifer ;
Chen, David ;
Zhang, Yufen ;
Ali, Shyanne ;
Taran, Tetiana ;
Gianni, Luca .
LANCET ONCOLOGY, 2014, 15 (06) :580-591
[6]   Chemotherapy in patients with anthracycline and taxane-pretreated metastatic breast cancer: An overview [J].
Andreopoulou E. ;
Sparano J.A. .
Current Breast Cancer Reports, 2013, 5 (1) :42-50
[7]  
[Anonymous], CLIN CANC RES S
[8]  
Asakuma J, 2003, CANCER RES, V63, P1365
[9]   Role of AKT isotypes in breast cancer [J].
Badve, Sunil ;
Nakshatri, Harikrishna .
JOURNAL OF PATHOLOGY, 2013, 229 (03) :e1-e1
[10]   Subcellular Localization of Activated AKT in Estrogen Receptor- and Progesterone Receptor-Expressing Breast Cancers Potential Clinical Implications [J].
Badve, Sunil ;
Collins, Nikail R. ;
Bhat-Nakshatri, Poornima ;
Turbin, Dmitry ;
Leung, Samuel ;
Thorat, Mangesh ;
Dunn, Sandra E. ;
Geistlinger, Tim R. ;
Carroll, Jason S. ;
Brown, Myles ;
Bose, Shikha ;
Teitell, Michael A. ;
Nakshatri, Harikrishna .
AMERICAN JOURNAL OF PATHOLOGY, 2010, 176 (05) :2139-2149