Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes

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.

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A2A Receptors Are Highly Expressed in Young Patients with Luminal B and Triple Negative Breast Cancer Subtypes and Are Associated with a Higher Proliferate Index

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.lb587 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Maha Guimei ◽

Mohamed Ahmed Eladl ◽

Dalia Ra'a Ahmed Tawfik ◽

Fuad Wardan Habbal ◽

Abdelkader Harrous ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Young Patients ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Luminal B ◽

A2a Receptors

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Identification of new therapeutic leads for triple negative breast cancer subtypes

Planta Medica ◽

10.1055/s-0035-1556254 ◽

2015 ◽

Vol 81 (11) ◽

Author(s):

AJ Robles ◽

L Du ◽

S Cai ◽

RH Cichewicz ◽

SL Mooberry

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Therapeutic Leads

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Faculty Opinions recommendation of Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13405017.14775138 ◽

2011 ◽

Author(s):

Thomas Egelhoff

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Targeted Therapies ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Preclinical Models ◽

Cancer Subtypes ◽

Selection Of

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Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies

Journal of Clinical Investigation ◽

10.1172/jci45014 ◽

2011 ◽

Vol 121 (7) ◽

pp. 2750-2767 ◽

Cited By ~ 2406

Author(s):

Brian D. Lehmann ◽

Joshua A. Bauer ◽

Xi Chen ◽

Melinda E. Sanders ◽

A. Bapsi Chakravarthy ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Targeted Therapies ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Preclinical Models ◽

Cancer Subtypes ◽

Selection Of

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An allomaltol derivative triggers distinct death pathways in luminal a and triple-negative breast cancer subtypes

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104403 ◽

2020 ◽

Vol 105 ◽

pp. 104403

Author(s):

A. Ercan ◽

S. Oncul ◽

G. Karakaya ◽

M. Aytemir

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Subtypes ◽

Luminal A ◽

Cancer Subtypes

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Response to neoadjuvant chemotherapy and outcome based on breast cancer subtype

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e11516 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1041 ◽

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.

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