Frequent Molecular Subtype Switching and Gene Expression Alterations in Lung and Pleural Metastasis From Luminal A–Type Breast Cancer

PURPOSE Conversion of tumor subtype frequently occurs in the course of metastatic breast cancer but is a poorly understood phenomenon. This study aims to compare molecular subtypes with subsequent lung or pleural metastasis. PATIENTS AND METHODS In a cohort of 57 patients with breast cancer and lung or pleural metastasis (BCLPM), we investigated paired primary and metastatic tissues for differential gene expression of 269 breast cancer genes. The PAM50 classifier was applied to identify intrinsic subtypes, and differential gene expression and cluster analysis were used to further characterize subtypes and tumors with subtype conversion. RESULTS In primary breast cancer, the most frequent molecular subtype was luminal A (lumA; 49.1%); it was luminal B (lumB) in BCLPM (38.6%). Subtype conversion occurred predominantly in lumA breast cancers compared with other molecular subtypes (57.1% v 27.6%). In lumA cancers, 62 genes were identified with differential expression in metastatic versus primary disease, compared with only 10 differentially expressed genes in lumB, human epidermal growth factor receptor 2 (HER2)–enriched, and basal subtypes combined. Gene expression changes in lumA cancers affected not only the repression of the estrogen receptor pathway and cell cycle–related genes but also the WNT pathway, proteinases ( MME, MMP11), and motility-associated cytoskeletal proteins (CK5, CK14, CK17). Subtype-switched lumA cancers were further characterized by cell proliferation and cell cycle checkpoint gene upregulation and dysregulation of the p53 pathway. This involved 83 notable gene expression changes. CONCLUSION Our results indicate that gene expression changes and subsequent subtype conversion occur on a large scale in metastatic luminal A–type breast cancer compared with other molecular subtypes. This underlines the significance of molecular changes in metastatic disease, especially in tumors of initially low aggressive potential.

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Differential Gene Expression Analysis of Breast Cancer by Combining Sequence-Tagged Reverse-Transcription PCR with Pyrosequencing

Springer Protocols Handbooks - Advances and Clinical Practice in Pyrosequencing ◽

10.1007/978-1-4939-3308-2_31 ◽

2016 ◽

pp. 361-369

Author(s):

Xiaodan Zhang ◽

Haiping Wu ◽

Zhiyao Chen ◽

Bingjie Zou ◽

Qinxin Song ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differential Gene Expression ◽

Expression Analysis ◽

Reverse Transcription ◽

Gene Expression Analysis ◽

Differential Gene Expression Analysis ◽

Reverse Transcription Pcr ◽

Differential Gene

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Comparative expressed sequence hybridisation revealed distinct chromosomal regions of differential gene expression in breast cancer subtypes

Breast Cancer Research ◽

10.1186/bcr1162 ◽

2005 ◽

Vol 7 (S2) ◽

Author(s):

I Vanden Bempt ◽

V Vanhentenrijk ◽

M Drijkoningen ◽

C De Wolf-Peeters

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differential Gene Expression ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Differential Gene ◽

Expressed Sequence

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Abstract P3-01-04: Differential Gene Expression Analysis among Post-Menopausal Caucasian Invasive Breast Cancer, Benign and Normal Subjects

10.1158/0008-5472.sabcs10-p3-01-04 ◽

2010 ◽

Author(s):

J Saini ◽

X Li ◽

L Kvecher ◽

C Larson ◽

D Croft ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differential Gene Expression ◽

Expression Analysis ◽

Invasive Breast Cancer ◽

Gene Expression Analysis ◽

Normal Subjects ◽

Differential Gene Expression Analysis ◽

Differential Gene ◽

Post Menopausal

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A resampling-based meta-analysis for detection of differential gene expression in breast cancer

BMC Cancer ◽

10.1186/1471-2407-8-396 ◽

2008 ◽

Vol 8 (1) ◽

Cited By ~ 12

Author(s):

Bala Gur-Dedeoglu ◽

Ozlen Konu ◽

Serkan Kir ◽

Ahmet Rasit Ozturk ◽

Betul Bozkurt ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Differential Gene Expression ◽

Meta Analysis ◽

Differential Gene

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Breast cancer molecular subtypes association with clinical outcomes and race.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12575 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12575-e12575 ◽

Cited By ~ 2

Author(s):

Ramses F. Sadek ◽

Li fang Zhang ◽

Houssein Talal Abdul Sater

Keyword(s):

Breast Cancer ◽

Black Women ◽

Clinical Outcomes ◽

Cox Regression ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Cancer Stage ◽

Luminal A ◽

Luminal B ◽

Race Disparity

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.

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Breast cancer in Angola, molecular subtypes: The first preliminary study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13075 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13075-e13075

Author(s):

Lúcio Lara Santos ◽

Fernando Miguel ◽

Lygia Vieira Lopes ◽

Julio Oliveira ◽

Eduardo Ferreira ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Locally Advanced ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Therapeutic Decisions ◽

Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

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