Comparing the prognostic value of PTEN and Akt expression with the Mitotic Activity Index in adjuvant chemotherapy-treated node-negative breast cancer patients aged <55 years
Affiliations: Department of Pathology, Stavanger University Hospital, Stavanger, Norway | Department of Surgery, Stavanger University Hospital, Stavanger, Norway | Institute of Surgical Sciences, University of Bergen, Norway | Department of Pathology, the Gade Institute, University of Bergen, Norway | Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
Note: [] Address for correspondence: Prof. dr. J.P.A. Baak, Department of Pathology, Stavanger University Hospital, Box 8100, 4068 Stavanger, Norway. Tel.: +47 51 519534; Fax +47 51 519920; E-mail: [email protected].
Abstract: Background: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in invasive breast cancer (IBC) is controversial. Cell proliferation, especially the Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative (LNneg) invasive breast cancer. However, its prognostic value has not been compared with the value of Akt and PTEN expression. Material and methods: Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy. Results: Twenty-one (17%) patients developed distant metastases=DMs (median follow-up: 134 months). p110alpha correlated (p=0.01) with pAkt but only in PTEN-negatives; pAkt correlated (p=0.02) with mTOR. PTEN-negativity correlated with high MAI, high grade and ER-negativity (p=0.009). The MAI was the strongest prognosticator (Hazard Ratio=HR=2.9, p=0.01). Her2Neu/p110α/Akt/mTOR features have no additional prognostic value to the MAI. PTEN had additional value but only in MAI<3 (39/125=31%; 8% DMs). 19/39=49% of the MAI<3 patients have combined MAI<3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI<3 / PTEN− (p=0.03). Conclusions: In T1−3N0M0 adjuvant CMF-treated breast cancer patients aged <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway and cell-cycle regulator characteristics had no additional prognostic value, but PTEN has. Patients with combined MAI<3 & PTEN-positivity had 100% survival. The small subgroup of MAI<3 patients that died were PTEN-negative.
