scholarly journals LOH at 1p31 (ARHI) and Proliferation in Lymph Node-Negative Breast Cancer

2009 ◽  
Vol 31 (5) ◽  
pp. 335-343
Author(s):  
Emiel A. M. Janssen ◽  
Irene T. Øvestad ◽  
Ivar Skaland ◽  
Håvard Søiland ◽  
Einar Gudlaugsson ◽  
...  

Background: The mitotic activity index (MAI) is a strong prognosticator in node-negative invasive breast cancer patients. Recently, a correlation between the MAI and specific chromosomal aberrations at chromosome 1p was described.Methods: Analysis of MAI, immunohistochemical staining patterns for proliferation-associated phosphohistone H3 (PPH3), phosphorylated ERK1/2, p21, cyclin E, Ki67 and cyclin D1 proteins; and prognosis in 158 adjuvant chemotherapy-treated T1-2N0M0 invasive breast cancer patients, analysis of LOH at 1p31 (including ARHI) using the dinucleotide repeats D1S207, D1S430 and D1S464 in 76 patients. Single and multivariate survival analysis was used to evaluate the importance of the various markers tested.Results: LOH at 1p31 did not correlate with MAI nor provide prognostic information. Phosphohistone H3 was the best prognosticator for patients in all age groups with 20 year distant metastasis free survival of distant metastases 93% vs. 72% respectively (p = 0.004, HR = 4.5). In multivariate analysis, phosphohistone H3 < 13 vs. ≥13 exceeded the prognostic value of the mitotic activity index.Conclusions: LOH at 1p31 is common in breast cancer, and correlates with loss of proliferation-associated proteins, but not with MAI, PPH3 or prognosis. PPH3 is the best prognosticator in this study group of adjuvant chemotherapy-treated lymph node-negative breast cancer patients.

2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  

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.


2000 ◽  
Vol 15 (1) ◽  
pp. 73-78 ◽  
Author(s):  
A. Prechtl ◽  
N. Harbeck ◽  
C. Thomssen ◽  
C. Meisner ◽  
M. Braun ◽  
...  

In axillary node-negative primary breast cancer, 70% of the patients will be cured by locoregional treatment alone. Therefore, adjuvant systemic therapy is only needed for those 30% of node-negative patients who will relapse after primary therapy and eventually die of metastases. Traditional histomorphological and clinical factors do not provide sufficient information to allow accurate risk group assessment in order to identify node-negative patients who might benefit from adjuvant systemic therapy. In the last decade various groups have reported a strong and statistically independent prognostic impact of the serine protease uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 (plasminogen activator inhibitor type 1) in node-negative breast cancer patients. Based on these data, a prospective multicenter therapy trial in node-negative breast cancer patients was started in Germany in June 1993, supported by the German Research Association (DFG). Axillary node-negative breast cancer patients with high levels of either or both proteolytic factors in the tumor tissue were randomized to adjuvant CMF chemotherapy versus observation only. Recruitment was continued until the end of 1998, by which time 684 patients had been enrolled. Since then, patients have been followed up in order to assess the value of uPA and PAI-1 determination as an adequate selection criterion for adjuvant chemotherapy in node-negative breast cancer patients. This paper reports on the rationale and design of this prospective multicenter clinical trial, which may have an impact on future policies in prognosis-oriented treatment strategies.


Cancer ◽  
2010 ◽  
Vol 116 (8) ◽  
pp. 1987-1991 ◽  
Author(s):  
Elisa Rush Port ◽  
Sujata Patil ◽  
Michelle Stempel ◽  
Monica Morrow ◽  
Hiram S. Cody

2006 ◽  
Vol 12 (11) ◽  
pp. 3319-3328 ◽  
Author(s):  
Anieta M. Sieuwerts ◽  
Maxime P. Look ◽  
Marion E. Meijer-van Gelder ◽  
Mieke Timmermans ◽  
Anita M.A.C. Trapman ◽  
...  

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