Does progesterone receptor loss identifies two distinct Luminal A breast cancer subgroups in male

2017 ◽  
Author(s):  
Ilhem Bettaieb
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Luminal A

scholarly journals Progesterone Receptor B signaling Reduces Breast Cancer Cell Aggressiveness: Role of Cyclin-D1/Cdk4 Mediating Paxillin Phosphorylation

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1201 ◽  
Author(s):  
Francesca Ida Montalto ◽  
Francesca Giordano ◽  
Chiara Chiodo ◽  
Stefania Marsico ◽  
Loredana Mauro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Epithelial Cell ◽  
Luminal A ◽  
Progesterone Receptor B

Progesterone-Receptor (PR) positivity is related with an enhanced response to breast cancer therapy, conversely cyclin D1 (CD1) is a retained marker of poor outcome. Herein, we demonstrate that hydroxyprogesterone (OHPg) through progesterone receptor B (PR-B) reduces breast cancer cell aggressiveness, by targeting the cytoplasmic CD1. Specifically, OHPg diminishes CD1 expression by a transcriptional regulation due to the recruitment of PR-B at a canonical half-PRE site of the CD1 promoter, together with HDAC1, determining a chromatin conformation less prone for gene transcription. CD1, together with its kinase partner Cdk4, regulates cell migration and metastasis, through the association with key components of focal adhesion, such as Paxillin (Pxn). Kaplan-Meier analysis shows that low Pxn expression was associated with increased distant metastasis-free survival in luminal A PR+ breast carcinomas. Interestingly, OHPg treatment reduced Pxn content in T47-D and MCF-7 cells; besides, the interaction between endogenous cytoplasmic CD1/Cdk4 with Pxn was reduced. This was consistent with the reduction of p-Ser83Pxn levels, crucially causing the delay in cell migration and a concomitant inhibition of Rac1 activity and p-PAK. Collectively, these findings support the role of PR-B in breast epithelial cell integrity and reinforce the importance in targeting PR-B as a potential strategy to restrict breast tumor cell invasion and metastasis.

scholarly journals Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

2017 ◽  
Vol 3 (4) ◽  
pp. 314-322 ◽  
Author(s):  
Ettienne J. Myburgh ◽  
Lizanne Langenhoven ◽  
Kathleen A. Grant ◽  
Lize van der Merwe ◽  
Maritha J. Kotze
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Molecular Subtype ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Luminal A ◽  
Her2 Positive ◽  
Molecular Subtyping ◽  
Predictive Values ◽  
Her2 Positivity

Purpose Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping. Methods Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor–positive and/or progesterone receptor–positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study. Results The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal ( P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors ( P = .0002; 95% CI, 0.40 to 1.06). Conclusion Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value.

Breast cancer: First results of an institutional cancer registry 2007-2011 in Colombia.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12571-e12571 ◽  
Author(s):  
Andres Yepes ◽  
Luis Gonzalez ◽  
Isabel Cristina Durango ◽  
Beatriz Pineda ◽  
Juan D. Figueroa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Invasive Ductal Carcinoma ◽  
Cancer Registry ◽  
Hormone Receptor ◽  
Ductal Carcinoma ◽  
Stage I ◽  
Adjuvant Radiation ◽  
Luminal A ◽  
Patient Profile

e12571 Background: The aim of this retrospective study was to describe the clinical characteristics of patients with breast cancer (BC) treated at the Oncology Unit of the Hospital Pablo Tobon Uribe in Medellin, Colombia, an institution's 10-year experience. Methods: All cases were Identified from our institution's cancer registry from 2007-2011. Results: During the study period 1224 BC were cases identified. Men: 12 (1%). Median age at diagnosis was 56 years (range 23-88). Stage at diagnosis was stage 0 (6.1%), stage I (30%), stage IIA (24.5%), stage IIB (10.8%), stage IIIA (6.8%), stage IIIB ( 6.1%), stage IIIC (9.5%), stage IV (3.4%) and unknown (2.8%). Primary right breast (50.2%). Most common histology was invasive ductal carcinoma (71%) and histologic grade 2 (34.6%). Estrogen and progesterone receptor status assessed at diagnosis was positive in 74,7% and 69% of cases tested respectively. HER2/neu status was positive in 14.2% (with hormone receptor positive 8,1% and hormone receptor negative 6.1%). Triple-negative BC 12.2%. Median tumor size was 2.3 cm (range 0.4-14.0 cm). Procedure performed was mastectomy in 59% and lumpectomy in 35%. Nodal staging was performed by axillary dissection (AD) (81%) and sentinel node biopsy (SN) alone (19%). Neoadjuvant chemotherapy was given to 39%, adjuvant chemotherapy to 69%, adjuvant hormonal therapy to 62% and adjuvant radiation therapy was used in 40,6%. The preferred adjuvant regimens was AC (doxorubicin / cyclophosphamide) followed by weekly paclitaxel in 51%. The average time from diagnosis to entry into consultation with specialist breast surgery 12 days. Time from diagnosis and staging complete and the beginning of the treatment: 16 days. Conclusions: The patient profile inquiry to our hospital with breast cancer is a woman of 56 years, with commitment right breast, invasive ductal carcinoma, grade 2, luminal A (estrogen receptor positive and / or progesterone receptor positive, HER2 negative), stage I and most commonly treated with mastectomy and chemotherapy with AC and paclitaxel.

scholarly journals 10O_PR Prognostic Significance of Progesterone Receptor-Positive Tumor Cells Within Immunohistochemically-Defined Luminal A Breast Cancer

2012 ◽  
Vol 23 ◽  
pp. ii17-ii18 ◽  
Author(s):  
A. Prat ◽  
M.C. Cheang ◽  
M. Martín ◽  
E. Carrasco ◽  
R. Caballero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Tumor Cells ◽  
Prognostic Significance ◽  
Luminal A

scholarly journals Reclassification of early stage breast cancer into treatment groups by combining the use of immunohistochemistry and microarray analysis

2019 ◽  
Vol 115 (3/4) ◽  
Author(s):  
Kathleen A. Grant ◽  
Ettienne J. Myburgh ◽  
Elizabeth Murray ◽  
Fredrieka M. Pienaar ◽  
Martin Kidd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Early Stage ◽  
Single Gene ◽  
Gene Profiling ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Treatment Groups ◽  
Combined Use ◽  
Microarray Gene

Immunohistochemistry (IHC) is routinely used to approximate breast cancer intrinsic subtypes, which were initially discovered by microarray analysis. However, IHC assessment of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) status, is a poor surrogate of molecular subtype. Therefore, MammaPrint/BluePrint (MP/BP) microarray gene expression profiling is increasingly used to stratify breast cancer patients into different treatment groups. In this study, ER/PR status, as reported by standard IHC and single-gene mRNA analysis using TargetPrint, was compared with molecular subtyping to evaluate the combined use of MP/BP in South African breast cancer patients. Pathological information of 74 ER/PR positive, HER2 negative tumours from 73 patients who underwent microarray testing, were extracted from a central breast cancer genomics database. The IHC level was standardised by multiplying the intensity score (0–3) by the reported proportion of positively stained nuclei, giving a score of 0–300. Comparison between mRNA levels and IHC determination of ER/PR status demonstrated a significant correlation (pless than 0.001) for both receptors (ER: 0.34 and PR: 0.54). Concordance was shown in 61 (82%) cases and discordance in 13 (18%) of the 74 tumours tested. Further stratification by MP/BP identified 49 (66.2%) Luminal A, 21 (28.4%) Luminal B and 4 (5.4%) Basal-like tumours. Neither IHC nor TargetPrint could substitute BP subtyping, which measures the functional integrity of ER and can identify patients with false-positive tumours who are resistant to hormone therapy. These findings support the implementation of a pathology-supported genetic testing approach combining IHC and microarray gene profiling for definitive prognostic and predictive treatment decision-making in patients with early stage breast cancer. Significance: Single-gene genomic oestrogen and progesterone receptor reporting adds limited additional information to the molecular stratification of breast cancer tumours and does not supersede the immunohistochemistry results. Neither single-gene genomic mRNA nor immunohistochemistry reporting of oestrogen and progesterone receptor status can replace the combined use of MammaPrint/BluePrint genomic molecular subtyping. Reliable distinction between Luminal A and B type tumours is not possible using immunohistochemistry or single-gene genomic mRNA assessment of oestrogen/progesterone and HER2 receptor status. Combining immunohistochemistry and microarray gene profiling enables the identification of endocrine treatment resistant hormone-positive tumours lacking ERα function (Basal-like), despite positive expression at the protein and single-gene RNA level.

scholarly journals Quantitative Multiparametric MRI as an Imaging Biomarker for the Prediction of Breast Cancer Receptor Status and Molecular Subtypes

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhiqi Yang ◽  
Xiaofeng Chen ◽  
Tianhui Zhang ◽  
Fengyan Cheng ◽  
Yuting Liao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Molecular Subtypes ◽  
Proliferation Index ◽  
Imaging Biomarkers ◽  
Luminal A ◽  
Receptor Status ◽  
Estrogen Receptor Positivity ◽  
Adc Values

ObjectivesTo assess breast cancer receptor status and molecular subtypes by using the CAIPIRINHA-Dixon-TWIST-VIBE and readout-segmented echo-planar diffusion weighted imaging techniques.MethodsA total of 165 breast cancer patients were retrospectively recruited. Patient age, estrogen receptor, progesterone receptor, human epidermal growth factorreceptor-2 (HER-2) status, and the Ki-67 proliferation index were collected for analysis. Quantitative parameters (Ktrans, Ve, Kep), semiquantitative parameters (W-in, W-out, TTP), and apparent diffusion coefficient (ADC) values were compared in relation to breast cancer receptor status and molecular subtypes. Statistical analysis were performed to compare the parameters in the receptor status and molecular subtype groups.Multivariate analysis was performed to explore confounder-adjusted associations, and receiver operating characteristic curve analysis was used to assess the classification performance and calculate thresholds.ResultsYounger age (<49.5 years, odds ratio (OR) =0.95, P=0.004), lower Kep (<0.704,OR=0.14, P=0.044),and higher TTP (>0.629 min, OR=24.65, P=0.011) were independently associated with progesterone receptor positivity. A higher TTP (>0.585 min, OR=28.19, P=0.01) was independently associated with estrogen receptor positivity. Higher Kep (>0.892, OR=11.6, P=0.047), lower TTP (<0.582 min, OR<0.001, P=0.004), and lower ADC (<0.719 ×10-3 mm2/s, OR<0.001, P=0.048) had stronger independent associations with triple-negative breast cancer (TNBC) compared to luminal A, and those parameters could differentiate TNBC from luminal A with the highest AUC of 0.811.ConclusionsKep and TTP were independently associated with hormone receptor status. In addition, the Kep, TTP, and ADC values had stronger independent associations with TNBC than with luminal A and could be used as imaging biomarkers for differentiate TNBC from Luminal A.

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