Retrospective Analysis of Topoisomerase IIa Amplifications and Deletions As Predictive Markers in Primary Breast Cancer Patients Randomly Assigned to Cyclophosphamide, Methotrexate, and Fluorouracil or Cyclophosphamide, Epirubicin, and Fluorouracil: Danish Breast Cancer Cooperative Group

2005 ◽  
Vol 23 (30) ◽  
pp. 7483-7490 ◽  
Author(s):  
Ann S. Knoop ◽  
Helle Knudsen ◽  
Eva Balslev ◽  
Birgitte B. Rasmussen ◽  
Jens Overgaard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Hazard Ratio ◽  
Predictive Markers ◽  
Final Conclusion ◽  
Cooperative Group ◽  
Breast Cancer Patients ◽  
Top2a Amplification ◽  
Her2 Positivity

Purpose The aim of the study was to evaluate the predictive value of HER2 and topoisomerase IIα gene (TOP2A) for the efficacy of epirubicin in the adjuvant setting of breast cancer patients. Patients and Methods In the Danish Breast Cancer Cooperative Group trial 89D, 980 pre- and postmenopausal primary patients were randomly allocated to either CMF (cyclophosphamide, methotrexate, and fluorouracil; n = 500) or CEF (cyclophosphamide, epirubicin, and fluorouracil; n = 480) times 9, between January 1990 and November 1999. Tumor tissue was retrospectively identified from 805 patients and was analyzed for HER2-positivity and for TOP2A-amplifications and deletions. Results HER2-positivity was found in 33% of the 805 investigated tumors and was not a predictive marker for epirubicin sensitivity. TOP2A changes were identified in 23% of the 773 investigated tumors: 12% had TOP2A amplifications and 11% had TOP2A deletions. We found that patients with TOP2A amplification had an increased recurrence-free (RFS; hazard ratio [HR], 0.43; 95% CI, 0.24 to 0.78) and overall survival (OS; HR, 0.57; 95% CI, 0.29 to 1.13), respectively if treated with CEF compared with CMF, and that patients with TOP2A deletions had an almost identical hazard ratio (RFS: HR, 0.63; 95% CI, 0.36 to 1.11; OS: HR, 0.56; 95% CI, 0.30 to 1.04). This is in contrast to patients with a normal TOP2A genotype for whom similar outcome was observed in both treatment arms (RFS: HR, 0.90; 95% CI, 0.70 to 1.17; OS: HR, 0.88; 95% CI, 0.66 to 1.17). Conclusion TOP2A amplification—and possibly deletion—seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.

Biological analysis of HER2 equivocal (2+) cases in primary breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12555-e12555
Author(s):  
Reiki Nishimura ◽  
Tomofumi Osako ◽  
Yasuhiro Okumura ◽  
Masahiro Nakano ◽  
Mamiko Fujisue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Invasive Carcinoma ◽  
Nuclear Grade ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
P53 Overexpression ◽  
Biological Variables ◽  
Her2 Positivity

e12555 Background: Overexpression and/or amplification of HER2 is observed in 15–20% of all invasive breast cancer cases. Breast cancer patients with HER2 overexpression can benefit from anti-HER2 therapy. HER2 IHC results are generally divided into four values (range, 0 to 3+). The cases with a HER2 (2+) value should be assessed using FISH. The aim of this retrospective study was to evaluate the biological variables and prognosis of HER2 (2+) cases according to the FISH status. Methods: Primary breast cancer patients (n = 5419) were enrolled in this study from January 2002 to September 2019. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression, and the Ki-67 index values. Positive for HER2 is categorized as having a HER2 value of 3 + or FISH amplified in equivocal cases. Results: The HER2 3+ rate in non-invasive carcinoma was higher than the rate in the invasive carcinoma cases (16.4% vs 12.9%; p < 0.0001). The distribution of HER2 IHC status in invasive carcinoma cases was 3+ (12.9%), 2+ (5.8%) and negative (84.3%). The FISH positive rate of the HER2 2+ cases was 57.0 % (158 cases). HER2 positivity significantly correlated with ER/PgR negative, p53 overexpression, higher Ki-67 value and nuclear grade. The FISH positivity of the HER2 2+ cases significantly correlated with PgR negative, p53 overexpression and higher grade. There were significant differences in biological variables between IHC 3+ and 2+/FISH positive, and between IHC 2+/FISH negative and IHC negative. Patients with HER2 3+ had significantly worse disease-free survival (DFS) rates than the cases before the approval of trastuzumab in Japan. However, there was no difference after trastuzumab was approved. Moreover, there was no difference in DFS according to the FISH status in HER2 2+ cases. Conclusions: HER2 positivity indicated a higher degree of malignancy. HER2 2+ had different independent biological characteristics from HER2 negative (0 & 1+) or positive (3+) cases. Therefore, the difference in biology of HER2 2+ cases may influence the prognosis and should be reconsidered in breast cancer cases.

Clinical relevance of H-RAS, K-RAS and N-RAS in a large cohort of primary breast cancer patients

2018 ◽  
Author(s):  
M Banys-Paluchowski ◽  
K Milde-Langosch ◽  
T Fehm ◽  
I Witzel ◽  
L Oliveira-Ferrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Relevance ◽  
Primary Breast Cancer ◽  
Large Cohort ◽  
Breast Cancer Patients

scholarly journals Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients

2021 ◽  
Author(s):  
Nils Martin Bruckmann ◽  
Julian Kirchner ◽  
Lale Umutlu ◽  
Wolfgang Peter Fendler ◽  
Robert Seifert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Bone Scintigraphy ◽  
Fdg Pet ◽  
Primary Breast Cancer ◽  
Whole Body ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Initial Staging

Abstract Objectives To compare the diagnostic performance of [18F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. Material and methods A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [18F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ2 test was performed to compare sensitivity and specificity between the modalities. Results Forty-one bone metastases were present in 7/154 patients (4.5%). Both [18F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%). Conclusion [18F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases. Key Points • [18F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.

scholarly journals Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

2017 ◽  
Vol 57 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Signe Korsgaard Skriver ◽  
Anne-Vibeke Laenkholm ◽  
Birgitte Bruun Rasmussen ◽  
Jürgen Handler ◽  
Bo Grundtmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Cooperative Group ◽  
Breast Cancer Patients ◽  
Estrogen Receptor Positive ◽  
Postmenopausal Estrogen

scholarly journals Influence of Covariates on Involved Lymph Nodes in Primary Breast Cancer Patients: Mixture Distribution Zero-Inflated Modeling Methodological Framework

2020 ◽  
Author(s):  
Madiha Liaqat ◽  
Shahid Kamal ◽  
Florian Fischer ◽  
Nadeem Zia
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Negative Binomial ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Node Involvement ◽  
Study Population

Abstract Background: Involvement of lymph nodes has been an integral part of breast cancer prognosis and survival. This study aimed to explore factors influencing on the number of auxiliary lymph nodes in women diagnosed with primary breast cancer by choosing an efficient model to assess excess of zeros and over-dispersion presented in the study population. Methods: The study is based on a retrospective analysis of hospital records among 5,196 female breast cancer patients in Pakistan. Zero-inflated Poisson and zero-inflated negative binomial modeling techniques are used to assess the association between under-study factors and the number of involved lymph nodes in breast cancer patients. Results: The most common breast cancer was invasive ductal carcinoma (54.5%). Patients median age was 48 years, from which women aged 46 years and above are the majority of the study population (64.8%). Examination of tumors revealed that over 2,662 (51.2%) women were ER-positive, 2,652 (51.0%) PR-positive, and 2,754 (53.0%) were Her2.neu-positive. The mean tumor size was 3.06 cm and histological grade 1 (n=2021, 38.9%) was most common in this sample. The model performance was best in the zero-inflated negative binomial model. Findings indicate that most factors related to breast cancer have a significant impact on the number of involved lymph nodes. Age is not contributed to lymph node status. Women having a larger tumor size suffered from greater number of involved lymph nodes. Tumor grades 11 and 111 contributed to higher numbers of positive lymph node.Conclusions: Zero-inflated models have successfully demonstrated the advantage of fitting count nodal data when both “at-harm” (lymph node involvement) and “not-at-harm” (no lymph node involvement) groups are important in predicting disease on set and disease progression. Our analysis showed that ZINB is the best model for predicting and describing the number of involved nodes in primary breast cancer, when overdispersion arises due to a large number of patients with no lymph node involvement. This is important for accurate prediction both for therapy and prognosis of breast cancer patients.

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