Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen.
Tamoxifen treatment substantially improves the 10-year survival of women with estrogen-receptor (ER)-alpha-positive tumors. However, approximately one-third of all breast cancer patients with ER-alpha-positive tumors progress on antiestrogen therapy. The molecular mechanism(s) involved in antiestrogen-resistant phenotype of breast carcinoma is not completely understood. The PTEN (phosphatase and tensin homolog deleted on chromosome Ten) gene is a novel candidate tumor suppressor that plays an important role in cell cycle regulation and apoptosis by regulating Protein kinase-B/Akt activity. Previous studies have shown that PTEN downregulation in breast cancer is associated with high-grade tumor, distant metastases and poorer disease-free survival. Decreased PTEN and/or increased protein kinase B/Akt activity in breast cancer cells has recently been associated with resistance to tamoxifen-induced apoptosis. In this study, we have evaluated PTEN expression by immunohistochemistry in 100 tamoxifen-treated ER-alpha-positive breast cancer patients. Reduced PTEN protein expression was associated with shorter relapse-free survival. When stage I patients were analyzed separately, reduced PTEN expression was a strong predictor of both, shorter relapse-free survival and shorter disease-specific survival. An association of reduced PTEN expression with shorter relapse-free survival and disease-specific survival in stage I patients was still observed after stratification by stage, axillary lymph node status, tumor size, grade, and expression of ER-alpha, progesterone receptor, and Her-2/neu. In summary, our results showed a strong association between downregulation of PTEN expression in ER-alpha-positive tumors and failure to tamoxifen treatment.
Department of Pathology, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.
Nael
N
Shoman
Shannon
S
Klassen
Andrew
A
McFadden
Miķelis G
MG
Bickis
Emina
E
Torlakovic
Rajni
R
Chibbar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human