title: Prognostic value of PIK3CA mutation status, PTEN and androgen receptor expression for metastasis-free survival in HER2-positive breast cancer patients treated with trastuzumab in adjuvant setting.
abstract: Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN). HER2-overexpressing breast cancer patients (n=75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry. In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p=0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p=0.042, p=0.016, p=0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2+3) stage (p=0.040) and with tumors characterized by low Ki-67LI (≤50% vs. >50%) (p=0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p=0.007). The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.
authors.affiliation: Agnieszka Adamczyk, Department of Applied Radiobiology, Maria Sklodowska-Curie Memorial, Cancer Centre and Institute of Oncology, Cracow Branch, ul. Garncarska 11, 31-115 Krakow, Poland, tel. +48 12 634 83 71, fax +48 12 423 10 76, e-mail: aa.adamczyk@yahoo.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Adamczyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Niemiec
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Harazin-Lechowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Ambicka
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Grela-Wojewoda
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Domagała-Haduch
authors.forename: Ida
authors.initials: I
authors.lastname: Cedrych
authors.forename: Kaja
authors.initials: K
authors.lastname: Majchrzyk
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczak
authors.forename: Janusz
authors.initials: J
authors.lastname: Ryś
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jakubowicz
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D058534:Class I Phosphatidylinositol 3-Kinases; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D057285:Precision Medicine; D011237:Predictive Value of Tests; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D011944:Receptors, Androgen / Q000032:analysis*; D012189:Retrospective Studies; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D000068878:Trastuzumab; C410798:AR protein, human; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human