scholarly journals P178 Prospective comparison of uPA/PAI-1, Ki-67 based molecular classification, Recurrence Score and clinical–pathological characteristics in hormone-receptor (HR) positive primary breast cancer: Pilot phase of the randomized WSG PlanB trial

The Breast ◽  
2011 ◽  
Vol 20 ◽  
pp. S38
Author(s):  
C. Liedtke ◽  
O. Gluz ◽  
H. Kreipe ◽  
T. Degenhardt ◽  
R. Kates ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 552-552 ◽  
Author(s):  
Oleg Gluz ◽  
Hans Heinrich Kreipe ◽  
Matthias Christgen ◽  
Tom Degenhardt ◽  
Ronald E. Kates ◽  
...  

552 Background: Use of multi-gene real-time PCR (RT-PCR) based assays e.g. Recurrence Score (RS) and single markers (grade, uPA/PAI-1, ER/PR, HER2, KI-67) is currently controversially discussed in early BC. Here, we present the final WSG-planB trial correlation analysis of risk assessment tools and first prospective comparison of independent central pathology IHC/FISH assessment and RT-PCR for single markers. Methods: Plan B trial (n=2,448 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2- BC). RS has been used as selection criterion for cht omission in HR+ BC (if RS<11 in pN0 or pN1). uPA/PAI-1 was optionally obtained. Grade, ER/PR, HER2 (IHC/FISH), Ki-67 were evaluated by the independent trial pathologist in all tumors. Results: From 04/09 to 11/11, 3196 patients have been recruited and 2448 randomized. RS distribution in 2551 HR+ tumors: 0-11 (18%), 12-25 (60%), >25 (22%). In 354 pN0-1 patients, cht was omitted based on low risk RS (88% compliance). Central grade for n=3038 and IHC/FISH results are currently available in n=1476. Moderately significant correlations were only found between RS and both central grade (rs=0.313; p<0.001) as well as Ki-67 (rs=0.374; p<0.001) and a weak one for uPA/PAI-1, particularly due to poor correlations within the RS group <26. In 1476 locally HER2- cases, n=9 were found as 3+ and/or FISH+ by central analysis. In 6 HR+/HER2+ cases, RS revealed 2 positive, 2 equivocal and 2 negative results. In 7 cases positive for HER2 by RT-PCR central pathology revealed 4 negative results. 24 locally HR+ cases are assessed as HR- in central pathology (2%). Among these, 6 were ER positive by RT-PCR. Final correlation analyses will be presented at the meeting. Conclusions: These first prospective data demonstrate that high-risk status according to RS is predictive of high risk by other factors, but the converse is not true. Regarding controversial HER2 and HR status by RT-PCR and IHC/FISH, we found few cases with false-negative or positive RT-PCR results in HER2- BC by local pathology. However, these discrepancies could potentially have a substantial impact on clinical patient management.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12023-e12023
Author(s):  
Junqing Chen ◽  
Xiaojia Wang ◽  
Zhanhong Chen

e12023 Background: The 21-gene recurrence score assay is a validated genomic predictor of cancer recurrence and the benefits of adjuvant chemotherapy in hormone receptor-positive, HER2-negative early breast cancer patients. However, the assay is rather expensive and complex, and many patients in our country can not afford it. We performed a retrospective study to evaluate the association between traditional clinicopathological features and 21-gene recurrence score in patients with node-negative, hormone receptor-positive, HER2-negative breast cancer. Methods: A total of 76 consecutive patients with node-negative, hormone receptor-positive, HER2-negative breast cancer who underwent 21-gene recurrence score testing in our hospital from 2015 to 2016 were enrolled. Data including age, tumor size, histological type, tumor grade were collected. Estrogen receptor (ER) expression, progesterone receptor (PR) expression, Ki-67 index, p53 and androgen receptor (AR) expression were detected by immunohistochemical assay. 21-gene recurrence score assay was performed by RT-PCR. The correlation between clinicopathological characteristics and 21-gene recurrence score assay was analyzed by using nonparametric tests. Results: Among the 76 patients, 43 (56.6%) had a low recurrence score of < 18, 13 (17.1%) had an intermediate recurrence score of 18-31, and 20 (26.3%) had a high recurrence score of ≥31. There was a significant difference in recurrence score in patients divided by PR expression ( P=0.027). Patients with low PR expression (<20%) had a higher recurrence score as compared to those with high PR expression. Tumor grade was observed to be significantly correlated with recurrence score ( P=0.004). No significant associations were found between recurrence score and age, tumor size, histological type, ER expression, Ki-67 index, p53 or AR expression in this study. Conclusions: Our study shows that low PR expression is associated with higher 21-gene recurrence score, and PR expression may be a promising predictor of 21-gene recurrence score assay in node-negative, hormone receptor-positive, HER2-negative breast cancer patients.


Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 416
Author(s):  
Woo Young Sun ◽  
Jina Lee ◽  
Bong Kyun Kim ◽  
Jong Ok Kim ◽  
Joonhong Park

This study aimed to clarify the genetic difference between Korean triple-negative breast cancer (TNBC) and other breast cancer (BC) subtypes. TNBC was defined as the absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2) amplification. DNA panel of the Ion Torrent Oncomine Comprehensive Assay (OCA) v3 was performed to identify somatic alteration in 48 specimens. In a total of 102 alterations (37 nonsense, 35 missense, 8 frameshift and 22 amplifications), 30 nucleotide alterations (24 nonsense, 1 missense, and 5 frameshift) were newly identified. The eight most commonly altered genes were PIK3CA, TP53, ERBB2, BRCA2, FANCD2, AKT1, BRCA1, and FANCA. TNBC had significantly lower mutation frequency in PIK3CA (TNBC vs. hormone receptor-positive and HER2-negative BC [HRPBC], p = 0.009), but higher mutation frequency in TP53 (TNBC vs. HRPBC, p = 0.036; TNBC vs. hormone receptor-positive and HER2- positive BC [HHPBC], p = 0.004). TNBC showed frequently higher Ki-67 expression than any positive BC (p = 0.004) due to HRPBC (p < 0.001). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 appears at a younger age (52.2 ± 7.6 years), compared to other subtypes (63.7 ± 11.0 years). TNBC with high Ki-67/unmutated PIK3CA/mutated TP53 may be related to relatively early onset BCThese findings demonstrate the genomic heterogeneity between TNBC and other BC subtypes and could present a new approach for molecular targeted therapy in TNBC patients.


2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.


2002 ◽  
Vol 38 (9) ◽  
pp. 1201-1203 ◽  
Author(s):  
G.C Wishart ◽  
M Gaston ◽  
A.A Poultsidis ◽  
A.D Purushotham

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