Molecular analysis in breast cancer subtypes and correlation with pathologic complete response (pCR) to neoadjuvant chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22119-e22119
Author(s):  
Maria Gonzalez Cao ◽  
Carlota Costa ◽  
Miguel Angel Molina-Vila ◽  
Maria Teresa Cusido ◽  
Santiago Viteri Ramirez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Neoadjuvant Chemotherapy ◽  
Breast Cancer Subtype ◽  
Pathologic Complete Response ◽  
Luminal A ◽  
Luminal B ◽  
Mutational Status ◽  
Cancer Subtype ◽  
Low Levels

e22119 Background: Although it is know that pCR following neoadjuvant chemotherapy is more frequent in some subtypes of breast cancer such as Triple Negative (TN) or erb2 tumors, the predictive role of gene expression and mutation status is not well defined in this setting. Methods: We analyzed samples from 41 patients (p) prospectively treated with neoadjuvant chemotherapy (sequential AC followed by weekly TXL, or inverse sequence, plus trastuzumab for erb2 positive p). Pathologic response (PR) was classified according to Miller-Payne and RCB criteria. Radiologic evaluation was performed by ultrasonography, dynamic MR and PET-TAC after each chemotherapy sequence. We performed expression analysis of AXL, BRCA1, RAP80, BIM, EZH2, ROR1, FGFR1, PTPN12, YAP, GAS6, beta-TRCP, HIF1 alpha and ZNF217 by RT-PCR, and mutational status of p53 and PI3K genes in pretreatment biopsies. Statistical analysis was performed using Mann-Whitney U and Pearson’s chi-squared tests. Results: pCR was detected in 5 p (3TN, 2 erb2) of 25 p (9 luminal A, 5 luminal B, 6 erb2 and 5 TN) evaluated for PR at time of submitting this abstract. TN tumors had lower levels of RAP80 (p=.0013), PTPN12 (p=.003), beta TRCP (p=.001), ZNF217 (p=.014) and YAP (p=.097). Luminal B tumors had low levels of YAP and the highest levels of FGFR1 (p=.09) and ZNF217 (p=.014). Luminal A tumors had high levels of beta-TRCP (p=.003). We found no differences in BRCA1, AXL, BIM, EZH2, ROR1, GAS6 and HIF1 levels by breast cancer subtype. P with low levels of FGFR1 (p=.087), HIF1alpha (p=.07) or EZH2 (p=.005) had higher probability of pCR. No pCR was observed in p with higher levels of AXL, EZH2, RAP80, GAS6, beta TRCP, HIF alpha. Four p had p53 mutations (1 luminal B, 1 erb2 and 2 TN) and 4 p had PI3K mutations (2 luminal A, 1 erb2, 1 luminal B). There was no correlation between p53 status and PR. P with PI3K mutations did not achieve pCR vs 46% of p with wild type PI3K (p=.23). Conclusions: Gene expression profile varies by breast cancer subtype. Chemosensitivity could be higher in tumors with lower levels of FGFR1, HIF1alpha or EZH2. Further results will be presented.

Epigenetic aspects of triple-negative in patients with breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1041-1041
Author(s):  
Joaquina Martínez-Galan ◽  
Sandra Rios ◽  
Juan Ramon Delgado ◽  
Blanca Torres-Torres ◽  
Jesus Lopez-Peñalver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Regulation Of Gene Expression ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p>0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

Towards cancer mega-cohorts: A novel homogenization algorithm applied to diverse breast cancer RNA-Seq datasets.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13507-e13507
Author(s):  
Talal Ahmed ◽  
Mark Carty ◽  
Stephane Wenric ◽  
Raphael Pelossof
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Breast Cancer Subtype ◽  
Model Performance ◽  
Test Results ◽  
Rna Seq ◽  
Luminal A ◽  
Test Set ◽  
Luminal B ◽  
Cancer Subtype

e13507 Background: Recent advances in transcriptomics have resulted in the emergence of several publicly available breast cancer RNA-Seq datasets, such as TCGA, SCAN-B, and METABRIC. However, molecular predictors cannot be applied across datasets without the correction of batch differences. In this study, we demonstrate a homogenization algorithm that allows the transfer of molecular subtype predictors from one RNA-Seq cohort to another. The algorithm only uses cohort-level RNA-Seq summary statistics, and therefore, does not require joint normalization of both datasets nor the transfer of patient information. Using this approach, we transferred a breast cancer subtype (Luminal A, Luminal B, HER2+, Basal) predictor trained on SCAN-B data to accurately predict subtypes from TCGA. Methods: First, we randomly split the TCGA cohort (n = 481 Luminal A, n = 189 Luminal B, n = 73 Her2+, n = 168 Basal) into two sets: TCGA-train and held-out TCGA-test (n = 455 and n = 456, respectively). Second, the SCAN-B cohort (n = 837) was homogenized with the TCGA-train set. Third, a molecular subtype predictor, based on a logistic regression model, was trained on homogenized SCAN-B RNA-Seq samples and used to predict the subtypes of TCGA-test RNA-Seq samples. For baseline comparison, a similar predictor trained on the non-homogenized SCAN-B cohort was tested on the TCGA-test set. The experimental framework was iterated 250 times. Reported P-values reflect a paired one-sided t-test. Results: To quantify model performance, we measured the average F1 score for each tumor subtype prediction from the held-out TCGA test set with and without cohort homogenization. The average F1 scores with vs. without homogenization were: Luminal A, 0.88 vs. 0.85 ( P< 1e-69); Luminal B, 0.74 vs. 0.51 ( P< 1e-183); Her2+, 0.73 vs. 0.53 ( P< 1e-99); Basal, 0.98 vs. 0.97 ( P< 1e-53). Overall, homogenization significantly outperformed no homogenization. Conclusions: We developed a novel homogenization algorithm that accurately transfers subtype predictors across diverse, independent breast cancer cohorts.

scholarly journals Identification of Breast Cancer Subtype-Specific Biomarkers by Integrating Copy Number Alterations and Gene Expression Profiles

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 261
Author(s):  
Claudia Cava ◽  
Mirko Pisati ◽  
Marco Frasca ◽  
Isabella Castiglioni
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Copy Number ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Breast Cancer Subtype ◽  
Gene Expression Profiles ◽  
Copy Number Alterations ◽  
Luminal A ◽  
Luminal B

Background and Objectives: Breast cancer is a heterogeneous disease categorized into four subtypes. Previous studies have shown that copy number alterations of several genes are implicated with the development and progression of many cancers. This study evaluates the effects of DNA copy number alterations on gene expression levels in different breast cancer subtypes. Materials and Methods: We performed a computational analysis integrating copy number alterations and gene expression profiles in 1024 breast cancer samples grouped into four molecular subtypes: luminal A, luminal B, HER2, and basal. Results: Our analyses identified several genes correlated in all subtypes such as KIAA1967 and MCPH1. In addition, several subtype-specific genes that showed a significant correlation between copy number and gene expression profiles were detected: SMARCB1, AZIN1, MTDH in luminal A, PPP2R5E, APEX1, GCN5 in luminal B, TNFAIP1, PCYT2, DIABLO in HER2, and FAM175B, SENP5, SCAF1 in basal subtype. Conclusions: This study showed that computational analyses integrating copy number and gene expression can contribute to unveil the molecular mechanisms of cancer and identify new subtype-specific biomarkers.

scholarly journals Influence of breast cancer subtype on pathological complete response

Mastology ◽  
2020 ◽  
Vol 30 ◽  
Author(s):  
Bruno de Carvalho Mancinelli ◽  
Marcelo Antonini ◽  
Flávia Vasconcelos da Silva ◽  
Odair Ferraro ◽  
Reginaldo Guedes Coelho Lopes
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptors ◽  
Pathological Complete Response ◽  
Breast Cancer Subtype ◽  
Clinical Stage ◽  
Complete Response ◽  
Luminal B ◽  
Cancer Subtype ◽  
Her 2

Objective: To compare the rates of pathological complete response (pCR) after treatment with neoadjuvant chemotherapy, in the different subtypes of breast cancer in patients followed at the Mastology Service of Hospital do Servidor Público Estadual. Methods: Descriptive and retrospective study, in which medical records of 213 patients diagnosed with breast cancer and submitted to neoadjuvant chemotherapy were reviewed, from February 2011 through January 2018. Histological data collected were: hormone receptors, hyperexpression of HER-2, grade, histological type and clinical data: age of the patient at diagnosis, tumor size and clinical stage at diagnosis and after chemotherapy, and rate of pCR. Results: The mean age of patients at diagnosis was 53.97 years. Forty-six patients (21,6%) had pCR, 77 (36.1%) were grade 2 and 136 (63.9%) were grade 3. Regarding cancer subtype, 29 patients (13.6%) were reported to have pure HER2 subtype, 48 patients (22.5%) corresponded to Luminal A subtype, 51 (23.9%) to Luminal B, and 66 patients (31.0%) were characterized as Triple Negative, while only 17 patients (7.9%) had Luminal B HER. Conclusion: The subtypes Pure HER 2 and Luminal B had the highest pCR rates.

scholarly journals Role of Tumor Subtypes in Response to Neoadjuvant Chemotherapy in Non-metastatic Breast Cancer

2021 ◽  
Vol 24 (12) ◽  
pp. 881-886
Author(s):  
Negar Mashoori ◽  
Ramesh Omranipour ◽  
Abdolali Assarian
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Metastatic Breast ◽  
Tumor Grade ◽  
Her2 Status ◽  
Luminal A ◽  
Luminal B ◽  
Female Patients

Background: Neoadjuvant chemotherapy (NAC) is an integral part of breast cancer treatment. Determination of the factors that can distinguish patients who will have best response to NAC is invaluable. In this study, we aimed to elucidate the factors influencing patient response to NAC. Methods: We retrospectively collected data of female patients with non-metastatic breast cancer that had received NAC followed by surgery, admitted to Imam Khomeini hospital between 2015–2019. We investigated the association between various tumor and patients’ characteristics with pathologic complete response (PCR). Results: Overall data of 205 female patients were collected. PCR was observed in 27.6% of cases. PCR rate in luminal A, luminal B, HER2 enriched, and TNB tumors was reported in 11.1%, 30.2%, 35.7%, and 36.4% of patients respectively (P=0.27). In patients with luminal B tumors, PCR was more prevalent in patients with positive HER2 only (P=0.006). In our study factors which was significantly associated with PCR were: tumor grade, progesterone receptor (PR) status, and HER2 status. In the multiple regression model, positive PR in the tumor lowered the odds of pathologic response 3.6 times (P=0.004). Conclusion: In our study, tumor grade, PR status, and HER2 status was associated with response to NAC. PCR was more prevalent in non-luminal tumors; however, PCR rate in luminal B patients-especially those with HER2 positive status- was slightly less than non-luminals.

Breast Cancer Subtype Approximated by Estrogen Receptor, Progesterone Receptor, and HER-2 Is Associated With Local and Distant Recurrence After Breast-Conserving Therapy

2008 ◽  
Vol 26 (14) ◽  
pp. 2373-2378 ◽  
Author(s):  
Paul L. Nguyen ◽  
Alphonse G. Taghian ◽  
Matthew S. Katz ◽  
Andrzej Niemierko ◽  
Rita F. Abi Raad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Breast Cancer Subtype ◽  
Distant Metastases ◽  
Breast Conserving Therapy ◽  
Luminal A ◽  
Luminal B ◽  
Cancer Subtype ◽  
Her 2

Purpose To determine whether breast cancer subtype is associated with outcome after breast-conserving therapy (BCT) consisting of lumpectomy and radiation therapy. Patients and Methods We studied 793 consecutive patients with invasive breast cancer who received BCT from July 1998 to December 2001. Among them, 97% had pathologically negative margins of resection, and 90% received adjuvant systemic therapy. No patient received adjuvant trastuzumab. Receptor status was used to approximate subtype: estrogen receptor (ER) or progesterone receptor (PR) positive and human epidermal growth factor receptor 2 negative = luminal A; ER+ or PR+ and HER-2+ = luminal B; ER–and PR –and HER-2+ = HER-2; and ER–and PR –and HER-2–= basal. Competing risks methodology was used to analyze time to local recurrence and distant metastases. Results Median follow-up was 70 months. The overall 5-year cumulative incidence of local recurrence was 1.8% (95% CI, 1.0 to 3.1); 0.8% (0.3, 2.2) for luminal A, 1.5% (0.2, 10) for luminal B, 8.4% (2.2, 30) for HER-2, and 7.1% (3.0, 16) for basal. On multivariable analysis (MVA) with luminal A as baseline, HER-2 (adjusted hazard ratio [AHR] = 9.2; 95% CI, 1.6 to 51; P = .012) and basal (AHR = 7.1; 95% CI, 1.6 to 31; P = .009) subtypes were associated with increased local recurrence. On MVA, luminal B (AHR = 2.9; 95% CI, 1.3 to 6.5; P = .007) and basal (AHR = 2.3; 95% CI, 1.1 to 5.2; P = .035) were associated with increased distant metastases. Conclusion Overall, the 5-year local recurrence rate after BCT was low, but varied by subtype as approximated using ER, PR, and HER-2 status. Local recurrence was particularly low for the luminal A subtype, but was less than 10% at 5 years for all subtypes. Although further follow-up is needed, these results may be useful in counseling patients about their anticipated outcome after BCT.

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy

2012 ◽  
Vol 48 (18) ◽  
pp. 3342-3354 ◽  
Author(s):  
Nehmat Houssami ◽  
Petra Macaskill ◽  
Gunter von Minckwitz ◽  
Michael L. Marinovich ◽  
Eleftherios Mamounas
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Meta Analysis ◽  
Breast Cancer Subtype ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Cancer Subtype ◽  
Response To Neoadjuvant Chemotherapy

scholarly journals The Survival of Locally Advanced Breast Cancer Patients with Luminal Subtype after Modified Radical Mastectomy

2021 ◽  
Vol 8 (11) ◽  
pp. 191-197
Author(s):  
Jefri Adi Kam Sitepu ◽  
Marjono Dwi Wibowo ◽  
Iskandar Ali
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Breast Cancer Subtype ◽  
Locally Advanced ◽  
Radical Mastectomy ◽  
Modified Radical Mastectomy ◽  
Luminal A ◽  
Luminal Subtype ◽  
Luminal B ◽  
Cancer Subtype

Background: Breast cancer is the leading cause of cancer death in women worldwide. Breast cancer has been classified into several molecular subgroups with different prognostic consequences based on immunohistochemistry and molecular pathology. The prognosis that commonly used is 5-years survival. In this study we aimed to examine the relationship between luminal subtype and 5-year survival rate in patients with early post-mastectomy breast cancer. Methods: We recruited early breast cancer patient who underwent modified radical mastectomy (MRM) in Dr. Soetomo General Hospital (Surabaya, Indonesia) between 2010 – 2014. Breast cancer tissues were collected during surgery for immunohistochemistry. The patients’ 5-years survival data was obtained from medical records and by phone call to the patients or to the close relatives of the patients. Breast cancer subtype was determined based on the result of immunohistochemistry Results: A total of 84 patients was included in this study. The majority of patients were aged >40 years (72/84; 85.7%). There were 39 patients (39/84; 46.4%) with luminal A subtype and 45 patients (45/84; 53.6%) with luminal B subtype. Seventy-four patients were diagnosed as invasive ductal carcinoma histologically. Almost all of the patients were able to survive within 5 years (81/84; 96.4%). We found that luminal B had a 1.071 times higher risk of dying within 5 years after therapy than luminal type A, although the analysis did not show significant results (P = 0.101). Conclusion: Luminal B was the most prevalent breast cancer subtype in Surabaya, Indonesia. The prevalence of breast cancer was higher in patients aged >40 years. There was no significant difference between the 5-years survival of luminal A and luminal B subtypes. Keywords: survival, locally advanced breast cancer, luminal subtype, mastectomy.

Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Yan Shou Zhang ◽  
Chao Yang ◽  
Lei Han ◽  
Lei Liu ◽  
Yun Jiang Liu
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Molecular Subtypes ◽  
Therapy Response ◽  
Luminal A ◽  
Luminal B ◽  
Response To Neoadjuvant Chemotherapy

Background: Breast cancer resistance protein (BCRP), or ABCG2 (ATP-binding cassette sub-family G member 2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma. Objectives: The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy. Methods: In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated. Results: The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (Luminal B, 80%; Luminal A, 78%), compared with other molecular subtypes (Triple-negative, 63%; HER-2+, 58%. P=0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (&#119875;=0.001) and tumor size (&#119875;=0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (P=0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (P=0.003, P=0.013. respectively). Conclusions: BCRP/ABCG2 is highly expressed in hormone receptor-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.

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