Prospective Multicenter Validation of the Independent Prognostic Value of the Mitotic Activity Index in Lymph Node–Negative Breast Cancer Patients Younger Than 55 Years

2005 ◽  
Vol 23 (25) ◽  
pp. 5993-6001 ◽  
Author(s):  
Jan P.A. Baak ◽  
Paul J. van Diest ◽  
Feja J. Voorhorst ◽  
Elsken van der Wall ◽  
Louk V.A.M. Beex ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Mitotic Activity ◽  
Prognostic Value ◽  
Activity Index ◽  
Tumor Diameter ◽  
Breast Cancer Patients ◽  
Mitotic Activity Index ◽  
Er Status

Purpose To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN) –negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (< 10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P < .0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAI as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.

scholarly journals 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

2007 ◽  
Vol 29 (1) ◽  
pp. 25-35
Author(s):  
Emiel A. M. Janssen ◽  
Håvard Søiland ◽  
Ivar Skaland ◽  
Einar Gudlaugson ◽  
Kjell H. Kjellevold ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Mitotic Activity ◽  
Invasive Breast Cancer ◽  
Prognostic Value ◽  
Activity Index ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Mitotic Activity Index

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.

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 ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Activity Index ◽  
Breast Cancer Patients ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Phosphohistone H3 ◽  
Mitotic Activity Index

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.

scholarly journals In Patients Younger Than Age 55 Years With Lymph Node–Negative Breast Cancer, Proliferation by Mitotic Activity Index Is Prognostically Superior to Adjuvant!

2011 ◽  
Vol 29 (7) ◽  
pp. 852-858 ◽  
Author(s):  
Tone Hoel Lende ◽  
Emiel A.M. Janssen ◽  
Einar Gudlaugsson ◽  
Feja Voorhorst ◽  
Rune Smaaland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Mitotic Activity ◽  
Systemic Therapy ◽  
Activity Index ◽  
Multivariable Analysis ◽  
Adjuvant Systemic Therapy ◽  
Cancer Proliferation ◽  
Cancer Specific Survival ◽  
Mitotic Activity Index

PurposeIn breast cancer, different tools are used for prognostication and adjuvant systemic therapy selection. We compared the accuracy of the online program Adjuvant!, the Norwegian Breast Cancer Group (NBCG) guidelines, and the proliferation factor mitotic activity index (MAI) in patients with lymph node (LN) –negative disease (pN0).Patients and MethodsAdjuvant! and MAI thresholds were set to 90% to 95% breast cancer–specific survival (BCSS) rates. These thresholds were 95% for Adjuvant!, 3 for MAI, and as follows for NBCG: pT1 grade 1 + pT1a-b grade 2 to 3; all pN0M0 and estrogen receptor/progesterone receptor positive versus all others. In 516 patients younger than age 55 years (T1-3N0M0) without adjuvant systemic therapy, univariable and multivariable 10-year BCSS rates were estimated.ResultsMedian follow-up time was 118 months. The concordance between MAI and Adjuvant! or NBCG was fair (κ = 0.35 and κ = 0.29, respectively). Adjuvant!, NBCG, and MAI were all prognostically significant (P ≤ .001). In the univariable analysis, the 10-year BCSS of MAI less than 3 versus ≥ 3 was 95% v 71%, respectively, with a hazard ratio of 7.0. In multivariable analysis, MAI was superior to Adjuvant! and NBCG. The 10-year survival of Adjuvant! ≥ 95% versus less than 95% was 91% v 74%, respectively, but stratification by MAI identified subgroups with different prognosis. Similar results occurred for NBCG and MAI. Adjuvant! and NBCG were not prognostic to each other.ConclusionMAI is superior to Adjuvant! and NBCG in prognostication of patients with LN-negative breast cancer younger than age 55 years.

Risk of internal mammary lymph node metastases and its prognostic value in breast cancer patients

1993 ◽  
Vol 52 (1) ◽  
pp. 26-30 ◽  
Author(s):  
Masakuni Noguchi ◽  
Nagayoshi Ohta ◽  
Michael Thomas ◽  
Hirohisa Kitagawa ◽  
Itsuo Miyazaki
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Cancer Patients ◽  
Lymph Node Metastases ◽  
Prognostic Value ◽  
Breast Cancer Patients ◽  
Internal Mammary Lymph Node ◽  
Internal Mammary ◽  
Node Metastases
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