Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11516-e11516
Author(s):  
A. Guerrero-Zotano ◽  
J. Gavila ◽  
M. A. Climent ◽  
M. J. Juan ◽  
V. Guillem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Breast Cancer Subtypes ◽  
Nuclear Staining ◽  
Luminal A ◽  
Long Term Outcome ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

e11516 Background: Gene expression profiling identifies several breast cancer subtypes with different chemosensitivity and outcome. We used immunohistochemistry surrogate markers to classify tumors according to known breast cancer subtypes and examined the relationship between neoadjuvant chemotherapy (NAC) response and long-term end points, including distant disease-free survival (DDFS) and overall survival (OS). Methods: Review of clinical and pathological data from 271 breast cancer patients treated in our institution with NAC between 1991–2008. Breast cancer subtypes were defined as follows: Luminal A: Estrogen receptor positive (ER+) and/or progesterone peceptor positive (PR+), human epidermal growth factor receptor 2-positive (Her-2+); Luminal B: ER+ and/or PR+,Her-2+; Basal: ER-,PR-,Her-2-;HER2: ER-,PR-,Her-2 +. ER and PR positive scored as positive if tumor cell nuclear staining was at least 2+. Her-2 scored as positive if test DAKO scored 3+ or FISH ratio Her-2/CEP-17>2.2. Results: 121 (45.8%) patients were classifed as Luminal A; 22 (8.1%) as Luminal B; 75 (27.7%) as Basal, and 50 (18.5%) as HER2. Most patients (63%) received NAC based on anthracyclines and taxanes. 36% Her-2+ patients were treated with NAC based on trastuzumab, and 43% received trastuzumab as adjuvant treatment. Response and outcome results are shown below (Table). Independently from subtype, only four patients out of 58 with pCR relapsed. Among patients who didn´t achieved pathologic complete response (pCR), basal and HER2 subtypes have the worst outcome (4 years SG 80% and 72% respectevely) compared with Luminal A (4 years SG: 94.7%), (log-rank p=0.009). Conclusions: Basal and HER2 tumor despite high chemosensitivity have worst long term outcome, particularly if pCR is not achieved after NAC. [Table: see text] No significant financial relationships to disclose.

Can Oncotype DX recurrence score (RS) be used in luminal A and luminal B breast cancer patients (pts) to predict the likely benefit of chemotherapy? A retrospective study in the Spanish population.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11006-e11006 ◽  
Author(s):  
Laura García-Estevez ◽  
Ana C Contreras ◽  
Isabel Calvo ◽  
Maria Fernandez Abad ◽  
Juan J de la Cruz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Oncotype Dx ◽  
Breast Cancer Subtypes ◽  
Treatment Recommendation ◽  
Nuclear Staining ◽  
Luminal A ◽  
Ki 67 ◽  
Cancer Subtypes ◽  
Luminal B

e11006 Background: The 2011 St Gallen guidelines recommend the use of Ki67 as a surrogate marker for luminal A and Luminal B breast cancer subtypes. Pts with luminal B subtypes should be considered for adjuvant chemotherapy. The guidelines also recognize the Oncotype DX RS as a predictor of chemotherapy benefit. The aim of this study is to assess the distribution of the RS in luminal A and luminal B breast cancer subtypes as defined by Ki67. Methods: Data from 91 pts with invasive breast cancer for which Oncotype DX results and pathology data were available. Pathological assessment was evaluated by the same pathologist. Estrogen (ER) and progesterone (PR) receptor was assessed by immunostaining (cut-off 10% nuclear staining). Ki67 was assessed by IHC [high (≥14%) and low (< 14%)]. Grading was performed by using Nottingham grading system. Results: Median age: 50 years (range: 35-78); premenopausal status: 49 pts (53.8%). Median tumor size: 1.5 cm (0, 3-6); Median of Ki 67 index: 15. 5 (range: 3-63); Median ER: 93 (35-100) and PR: 85(0-100). Sixty nine pts (75.8%) had negative-lymph nodes. RS was low in 56 (61. 5%) cases, intermediate in 24 (26. 4%), and high in 11 (12. 1%). The median RS was 16 (range 3-55). Forty six (51%) tumors were classified as luminal B (according to high Ki 67) and 38 (41.7%) as Luminal A. In the Luminal B group RS was low in 28 (61%) pts, intermediate in 10 (22%) and high in 8 (17%) while in the Luminal A group 23 (61%) had low RS; 13 (34%) intermediate and 2 (5%) high RS. RS changed the first treatment recommendation in 23 (50%) cases of Luminal B subtype vs. 10 (26%) cases in Luminal A subtype (p=0.013). Conclusions: Although based in a small case series, the results show that a substantial number (61%) pts with Luminal B breast cancer subtype had a low RS, therefore preserving them from adjuvant chemotherapy treatment. In addition, 5% of patients with Luminal A breast cancer had a high RS and thereby likely to benefit from chemotherapy. The wide range of RS in both Luminal B and Luminal A breast cancer subtypes confirm the important role of Oncotype DX in treatment decision- making.

scholarly journals Breast Cancer Subtypes among Iraqi Patients: Identified By Their ER, PR and HER2 Status

2018 ◽  
Vol 59 (4) ◽  
pp. 303-307
Author(s):  
Nada A.S. Alwan ◽  
Furat N. Tawfeeq ◽  
Faisal H. Muallah
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Progesterone Receptors ◽  
Breast Cancer Subtypes ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

Background: Breast cancer ranks the first among the Iraqi population since three decades and is currently forming a major public health problem being the second cause of death women. Novel management of breast cancer depends upon precise evaluation of their molecular subtypes; identified by Hormone (Estrogen and Progesterone) receptors and HER2 contents of the primary tumor.Objective: To assess the rates of the different molecular breast cancer subtypes in the examined tissue specimens belonging to females diagnosed with breast cancer in Iraq; correlating the findings with those reported in the literature at the regional and global levels.Patients and Methods: This retrospective study documented the findings of tissue biopsy examination belonging to 686 female patients diagnosed with breast cancer. Formalin fixed paraffin-embedded blocks were utilized to assess the availability of Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions through semi quantitative immuno-histochemical staining technique. Breast carcinomas were classified into four main molecular subtypes: Luminal A: ER/PR(+) / HER2(-), Luminal B/Triple Positive: ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative: ER/PR(-) and HER2(-). Other phenotypes included: ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-) / HER2 (-) and ER (-)/PR (+) / HER2 (-).Results: Out of the exanimated cases of breast carcinomas, the registered rates of positive ER, PR and HER2 tumor contents in this study were 67.8%, 65.3% and 29.4% respectively. The main identified phenotype was the Luminal A in 309 cases (45%). That was followed by the Triple Negative in 107 cases (15.6%) and Triple Positive/Luminal B (96 cases, 14%), while 71 cases (10.3%) were HER2 enriched. The corresponding rates of the (E+/P-/H+), (E-/P+/H+), (E+/P-/H-) and (E-/P+/H-) subtypes were 3.1%, 2.0%., 5.7% and 4.2% respectively. Differences in in the expressions of these IHC molecular markers are illustrated among different countries.Conclusions: Due to the displayed variations in the socio-demographic characteristics and biological risk factors among patients in different populations, it is mandatory to identify the molecular marker subtypes of breast cancer expressions in order to assess the impact of management and response to therapy. The routine documentation of their patterns in the cancer registry reports and published research ensures the validity and reliability of the presented clinical data. الخلفية: سرطان الثدي يحتل المرتبة الأولى بين السكان العراقيين منذ ثلاثة عقود، ويشكل حاليا مشكلة صحية رئيسية حيث يعتبر السبب الثاني للوفاة عند النساء. تعتمد أسس العلاج الجديدة لسرطان الثدي على التقييم الدقيق لأنواعها الفرعية الجزيئية و التي تحددها مستويات مستقبلات هرمون (الاستروجين والبروجسترون) ومحتويات  HER2 في الورم الرئيسي. الهدف من الدراسة: تقييم معدلات مختلف الأنواع الفرعية لسرطان الثدي الجزيئي في عينات الأنسجة التي تم فحصها والتي تخص الإناث المصابات بسرطان الثدي في العراق؛ وربط النتائج مع تلك المسجلة على الصعيدين الإقليمي والعالمي المرضى والطرق: وثقت هذه الدراسة بأثر رجعي نتائج فحص خزعة الأنسجة التي تنتمي إلى 686 مريضة مشخصة بسرطان الثدي. واستخدمت لتقييم توافر مستقبلات الاستروجين (ER)، مستقبلات البروجسترون (PR) والتعبيرات HER2 من خلال تقنية الطيخ المناعي شبه الكمي. تم تصنيف سرطان الثدي إلى أربعة أنواع فرعية جزيئية رئيسية: Luminal A:  ER/PR(+) / HER2(-), Luminal B/Triple Positive:    ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative:   ER/PR(-) and HER2(-). و انواع اخرى ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-)  / HER2 (-) and ER (-)/PR (+) / HER2 (-). النتائج: من بين حالات سرطان الثدي المهددة، كانت المعدلات المسجلة لمحتوى الأورام الموجبة ER, PR و   HER2 في هذه الدراسة 67.8٪ و 65.3٪ و 29.4٪ على التوالي. وكان النمط الظاهري المحدد الرئيسي اللمعية A في 309 حالات (45٪). وأعقب ذلك السلبي الثلاثي في 107 حالات (15.6٪) وثلاثية إيجابية / لومينال B (96 حالة، 14٪)، في حين أن 71 حالة (10.3٪) كانت HER2 المخصب. وكانت المعدلات المقابلة من (E + / P- / H +)، (E / P + / H +)، (E + / P- / H-) و (E / P + / H-) فرعية 3.1٪، 2.0٪. ،   و 5.7٪ و 4.2٪ على التوالي. وتظهر الاختلافات في التعبير عن هذه العلامات الجزيئية بين مختلف البلدان. الاستنتاجات والتوصيات: نظرا للاختلافات المعروضة في الخصائص الاجتماعية الديموغرافية وعوامل الخطر البيولوجية بين المرضى في مختلف السكان، فمن الضروري تحديد الأنواع الفرعية الجزيئية من تعبيرات سرطان الثدي من أجل تقييم تأثير الاستجابة للعلاج . ان التوثيق الروتيني لأنماط سرطان الثدي في تقارير سجل السرطان والبحوث المنشورة يضمن صحة ودقة البيانات السريرية ذات العلاقة.

Expression of vascular endothelial growth factor (VEGF), p53 in Molecular breast cancer subtypes of pre-menopausal African-American women

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21084-21084
Author(s):  
C. U. Ihemelandu ◽  
L. D. Leffall ◽  
T. J. Naab ◽  
W. A. Frederick
Keyword(s):  
Breast Cancer ◽  
African American Women ◽  
Molecular Subtypes ◽  
P53 Protein ◽  
Survival Outcome ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

21084 Background: Tumor growth and metastasis have been shown to be dependent on angiogenesis. With the current classification of breast tumors into molecular subtypes with distinct prognosis and response to treatment, we sort to analyze the expression of the angiogenesis markers in molecular subtypes and determine their association with clinicopathologic variables of prognostic significance. Methods: A retrospective analysis of women diagnosed with breast cancer from 1998–2005, who had assessable data for ER, PR, and Her-2/neu status. The molecular subtypes were defined as: luminal A, luminal B, basal-like , and Her-2/neu. Results: All molecular breast cancer subtypes overexpressed VEGF, with no statistically significant difference noted between the subtypes: - luminal A (69.8%) basal-like (71.1%), luminal B (70.0%), Her-2/neu (71.0%) (p=.99). Subtypes differed significantly in expression of p53 (p<.000), with the basal-like and Her-2/neu subtypes more likely to be associated with p53 mutations (51.7%) and (54.1%) respectively. No statistically significant association between p53 protein and increased VEGF expression was noted (p=.176) Statistically significant associations between p53 protein and prognostic factors ER (p<.000), PR (p>.000), histologic grade (p<.000), S-phase fraction (p<.001) were noted. A significant inverse correlation was noted between p53 expression and thrombospodin for the age-group <35 years (rho -.810; p=.003). VEGF showed no significant association with the prognostic factors ER, PR, histologic grade and S-phase fraction. A tendency not reaching statistical significance was found between VEGF and angiogenesis (p=.09). A direct correlation between VEGF and thrombospodin was noted in the age- group < 35 years (rho .800; p=.01). Expression of VEGF and thrombospodin did not correlate with survival outcome; however angiogenesis seemed to correlate with survival outcome. Survival outcome was influenced by molecular subtypes with the basal-like and Her-2/neu subtypes having a poorer outcome (p=.01). Conclusions: VEGF expression is not related to p53 status or survival outcome in molecular breast cancer subtypes of pre-menopausal African-American women. No significant financial relationships to disclose.

scholarly journals Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes

2019 ◽  
Vol 178 (2) ◽  
pp. 451-458 ◽  
Author(s):  
Giuseppe Viale ◽  
Amy E. Hanlon Newell ◽  
Espen Walker ◽  
Greg Harlow ◽  
Isaac Bai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Ki 67 ◽  
Cancer Subtypes ◽  
Luminal B

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.

scholarly journals Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Nicole J. Chew ◽  
Terry C. C. Lim Kam Sian ◽  
Elizabeth V. Nguyen ◽  
Sung-Young Shin ◽  
Jessica Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Therapeutic Target ◽  
Breast Cancer Subtype ◽  
Breast Cancer Subtypes ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Luminal A ◽  
Tissue Samples ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor–stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. Methods MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue samples and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. Results Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated ‘omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 amplification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and amplification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. Conclusions This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.

scholarly journals Proposed new clinicopathological surrogate definitions of luminal A and luminal B (HER2-negative) intrinsic breast cancer subtypes

2014 ◽  
Vol 16 (3) ◽  
Author(s):  
Patrick Maisonneuve ◽  
Davide Disalvatore ◽  
Nicole Rotmensz ◽  
Giuseppe Curigliano ◽  
Marco Colleoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B
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