DTX3 copy number increase in breast cancer: a study of associations to molecular subtype, proliferation and prognosis

Abstract Purpose The degree of cell proliferation is important for subclassification of breast cancers into prognostic and therapeutic groups. DTX3 has been identified as a driver of proliferation in luminal breast cancer. In this study, we describe DTX3 copy number in breast cancer primary tumours and corresponding axillary lymph node metastases, and studied associations with molecular subtype, proliferation and prognosis. Methods Using fluorescence in situ hybridization, we assessed DTX3 and chromosome 12 centromere (CEP12) copy number in 542 primary breast cancers and 117 lymph node metastases, from a well-described cohort of Norwegian breast cancer patients. Proliferation was expressed as mitotic counts and Ki67 score. Associations between DTX3 copy number and molecular subtype and proliferation were assessed using Pearson’s χ2 test. We studied the effect of copy number increase on prognosis estimating cumulative incidence of breast cancer death and hazard ratios. Results Mean DTX3 copy number ≥ 4 was found in 23 tumours (4%), and mean ≥ 5 in 9 tumours (1.7%). Copy number increase was found within all molecular subtypes except the 5 negative phenotype and the Luminal B (HER2 +) subtype. DTX3 copy number increase was not accompanied by an increase in CEP12. Point estimates showed that there were associations between DTX3 copy number increase and high proliferation and poor prognosis; however, precision depended on copy number cut-off. Conclusions DTX3 copy number increase was present in a small proportion of breast cancer cases. There was an association between copy number increase and high tumour cell proliferation and poor prognosis.

Download Full-text

The use of one-step nucleic acid amplification (OSNA) and tumor-related factors in the axillary management of breast cancer: A predictive model.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.61 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 61-61

Author(s):

Shramana Mitul Banerjee ◽

Norman R. Williams ◽

Timothy Ian Davidson ◽

Soha El-Sheikh ◽

My-annh Tran-Dang ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Nucleic Acid ◽

Sentinel Lymph Node ◽

Copy Number ◽

Nucleic Acid Amplification ◽

Nodal Involvement ◽

Related Factors ◽

One Step ◽

Node Metastases

61 Background: Recent trends in surgical practice advocate selective use of axillary nodal clearance (ANC) following sentinel lymph node biopsy (SNB) in the treatment of breast cancer. We aimed to determine the effectiveness of one-step nucleic acid amplification (OSNA) using CK19 mRNA copy number and tumor-related factors in predicting non-sentinel axillary nodal involvement, in order to formulate local guidelines for ANC. Methods: Patients due to have SNB at our institution for invasive breast cancer as well as selected patients with high grade ductal carcinoma in situ with negative assessment of the axilla on pre-operative imaging were included. Alternate slices of each node were sent for assessment by either OSNA or Histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA copy number, the total tumor load (summation of m RNA copy number of positive nodes,TTL), the total nodal status at ANC and tumor characteristics including grade, tumor size and lymphovascular invasion (LVI) for each patient were determined. A model of risk probability was constructed using TTL and tumor related factors. Results: 664 nodes were examined from 425 patients who had SNB performed between 2011 and 2014. After excluding 8 patients who did not meet the study criteria, 648 nodes from 417 patients were included for analysis. The concordance between OSNA and histology was 91.4%; positive predictive value (PPV) and negative predictive value (NPV) was 77% and 97% respectively. Patients with TTL less than 1400 did not have additional non sentinel lymph node involvement. TTL (p<0.01), and presence of LVI (p<0.05) were predictive for additional nodal involvement. The risk model identified all patients with more than 2 positive nodes as requiring ANC. All patients with non-sentinel node metastases at ANC were selected. Conclusions: OSNA is a sensitive and reliable intraoperative method for the detection of sentinel node metastases. Our study has shown it can also be used to predict the presence of non-sentinel metastases. Patients deemed high risk may be offered immediate ANC while axillary surgery in other groups may be omitted or be decision-based on risk stratification.

Download Full-text

Basal Breast Cancer Molecular Subtype Predicts for Lower Incidence of Axillary Lymph Node Metastases in Primary Breast Cancer

Clinical Breast Cancer ◽

10.3816/cbc.2008.n.028 ◽

2008 ◽

Vol 8 (3) ◽

pp. 249-256 ◽

Cited By ~ 95

Author(s):

Simon J. Crabb ◽

Maggie C.U. Cheang ◽

Samuel Leung ◽

Taina Immonen ◽

Torsten O. Nielsen ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Node Metastases ◽

Lower Incidence ◽

Axillary Lymph Node ◽

Molecular Subtype ◽

Axillary Lymph ◽

Axillary Lymph Node Metastases ◽

Basal Breast Cancer ◽

Node Metastases

Download Full-text

Chromosomal Genotype in Breast Cancer Progression: Comparison of Primary and Secondary Manifestations

Analytical Cellular Pathology ◽

10.1155/2008/209142 ◽

2008 ◽

Vol 30 (1) ◽

pp. 39-50

Author(s):

Katrin Friedrich ◽

Theresa Weber ◽

Jens Scheithauer ◽

Wolfdietrich Meyer ◽

Gunter Haroske ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Cancer Progression ◽

Lymph Node Metastases ◽

Distant Metastases ◽

Comparative Genomic ◽

Breast Cancers ◽

Primary Tumors ◽

Local Recurrences ◽

Node Metastases

The purpose of this study was to compare the chromosomal genotype between breast cancers with and without secondary manifestations and between primary tumors and their secondary manifestations. Eighty six breast cancers, twenty lymph node metastases, ten distant metastases and ten local recurrences were analyzed by comparative genomic hybridization. Tumors with local recurrences showed significant more frequent losses at 2q32 than the tumors without recurrences. Lymph node positive cases showed significant more frequent losses at 9p21 than node negative cases. Lymph node metastases exhibited significant more frequent losses at 7q11, 14q24.3–q31 and 17q22–q24 than their primary tumors. In cases with distant metastases, losses at 5q23 were more frequent than in those without, but not reaching the significance level. The distant metastases showed significant more frequent losses at 5p15, 12q24 and 17q22–q24 than the primary tumors. These results reveal strong evidence that the potential for progression is determined in the primary tumor and that different ways of the development of local recurrences, lymph node and distant metastases exist. After confirmation of the results by interphase FISH on tissue micro arrays, the detection of these specific chromosomal imbalances may contribute to a more individual prediction of prognosis in breast cancer.

Download Full-text

Breast cancer in Accra, Ghana

Journal of Medical and Biomedical Sciences ◽

10.4314/jmbs.v3i3.4 ◽

2015 ◽

Vol 3 (3) ◽

pp. 21-26

Author(s):

SE Quayson ◽

EK Wiredu ◽

DN Adjei ◽

JT Anim

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Age Groups ◽

Lymph Node Status ◽

Breast Cancers ◽

Younger Age ◽

Control And Prevention ◽

Cancer Types ◽

Node Metastases ◽

Microcomputer Software

The aim of this study was to look at the pattern of breast cancer over a period of five years and to compare the findings to similar studies done in the Department and elsewhere within the African sub-region. All breast cancers diagnosed in the Department of Pathology of the Korle Bu Teaching Hospital, Accra, over a 5-year period were compiled. The slides for the cases were retrieved and reviewed. Invasive ductal carcinomas were graded according to the Scarff-Bloom-Richardson’s grading system. The data were entered and analyzed using the EPI-Info microcomputer software (Version 3.5.1, 2008, Center for Disease Control and Prevention (CDC) Atlanta). Breast cancer in Accra is mostly of the ductal type or its variants affecting relatively younger age groups. The mean age of incidence of cancer in Ghana is 48 years, and about 67% have lymph node metastases (at least Stage II or N1) and 74% are of high grade at the time of diagnoses. The percentage of male breast cancers in Ghana is 2.9% (2.0 - 3.75% within the West African sub-region) and is higher than what is reported in Western literature. The results of this study show that there has been no im-provement in the stage at which patients present with breast cancer in the past 30 years.Keywords: Breast cancer, cancer types, cancer grade, lymph node status, Accra

Download Full-text

FGFR1 copy number in breast cancer: associations with proliferation, histopathological grade and molecular subtypes

Journal of Clinical Pathology ◽

10.1136/jclinpath-2021-207456 ◽

2021 ◽

pp. jclinpath-2021-207456

Author(s):

Anna M Bofin ◽

Borgny Ytterhus ◽

Elise Klæstad ◽

Marit Valla

Keyword(s):

Breast Cancer ◽

Copy Number ◽

Chromosome 8 ◽

Axillary Lymph ◽

Fluorescence In Situ Hybridisation ◽

Axillary Lymph Node Metastases ◽

Histopathological Grade ◽

Luminal B ◽

Number Increase ◽

Copy Number Increase

AimsFGFR1 is located on 8p11.23 and regulates cell proliferation and survival. Increased copy number of FGFR1 is found in several cancers including cancer of the breast. ZNF703 is located close to FGFR1 at 8p11-12 and is frequently expressed in the luminal B subtype of breast cancer. Using tissue samples from a well-described cohort of patients with breast cancer with long-term follow-up, we studied associations between FGFR1 copy number in primary breast cancer tumours and axillary lymph node metastases, and proliferation status, molecular subtype and prognosis. Furthermore, we studied associations between copy number increase of FGFR1 and copy number of ZNF703.MethodsWe used fluorescence in situ hybridisation for FGFR1 and the chromosome 8 centromere applied to tissue microarray sections from a series of 534 breast cancer cases.ResultsWe found increased copy number (≥4) of FGFR1 in 74 (13.9%) of tumours. Only 6 of the 74 cases with increased copy number were non-luminal. Increased FGFR1 copy number was significantly associated with high Ki-67 status, high mitotic count and high histopathological grade, but not with prognosis. Forty-two (7.9%) cases had mean copy number ≥6. Thirty of these showed ZNF708 copy number ≥6.ConclusionsOur results show that FGFR1 copy number increase is largely found among luminal subtypes of breast cancer, particularly luminal B (HER2−). It is frequently accompanied by increased copy number of ZNF703. FGFR1 copy number increase is associated with high histopathological grade and high proliferation. However, we did not discover an association with prognosis.

Download Full-text

Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years’ follow-up

Breast Cancer Research and Treatment ◽

10.1007/s10549-013-2617-8 ◽

2013 ◽

Vol 140 (1) ◽

pp. 93-104 ◽

Cited By ~ 30

Author(s):

Anna-Karin Falck ◽

Pär-Ola Bendahl ◽

Gunilla Chebil ◽

Hans Olsson ◽

Mårten Fernö ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Cancer Patients ◽

Lymph Node Metastases ◽

Primary Breast Cancer ◽

Molecular Subtype ◽

Breast Cancer Patients ◽

Subtype Classification ◽

Node Metastases

Download Full-text

Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

PLoS ONE ◽

10.1371/journal.pone.0150979 ◽

2016 ◽

Vol 11 (3) ◽

pp. e0150979 ◽

Cited By ~ 7

Author(s):

Sura Aziz ◽

Elisabeth Wik ◽

Gøril Knutsvik ◽

Tor Audun Klingen ◽

Ying Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Lymph Node ◽

Tumor Cell ◽

Lymph Node Metastases ◽

Mitotic Count ◽

Tumor Cell Proliferation ◽

Ki 67 ◽

Node Metastases

Download Full-text

Aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases is an independent prognostic factor in ALDH1-positive breast cancer

Journal of International Medical Research ◽

10.1177/03000605211047279 ◽

2021 ◽

Vol 49 (10) ◽

pp. 030006052110472

Author(s):

Xin Guan ◽

Yi Dong ◽

Zhimin Fan ◽

Yue Zhan ◽

Xinpeng Xie ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Aldehyde Dehydrogenase ◽

Lymph Node Metastases ◽

Axillary Lymph Node ◽

Poor Prognosis ◽

Axillary Lymph ◽

Axillary Lymph Node Metastases ◽

Node Metastases

Objective To determine whether aldehyde dehydrogenase 1 (ALDH1) immunostaining in axillary lymph node metastases in patients with breast cancer is associated with poor clinical prognosis. Methods This retrospective study reviewed data from the medical records of patients with immunohistochemistry-confirmed invasive ductal carcinoma (IDC) and 1–3 metastatic lymph nodes in the ipsilateral axilla between December 2012 and July 2015. The association between ALDH1 immunostaining in axillary lymph node metastases and clinical parameters and prognosis was analysed using χ2-test, Kaplan–Meier survival analysis, univariate and multivariate Cox regression analyses. Results A total of 229 patients with IDC were enrolled in the study. The median follow-up was 61 months (range, 20–89 months). Patients with ALDH1-positive axillary lymph node metastases had significantly shorter relapse-free survival and overall survival compared with those with ALDH1-negative axillary lymph node metastases. ALDH1 immunostaining in axillary lymph node metastases was a significant predictor of poor prognosis in univariate and multivariate analyses. Conclusion This large study with long-term follow-up suggests that ALDH1 immunostaining in axillary lymph node metastases is an independent predictor of poor prognosis in patients with breast cancer. The clinical relevance of this finding should be confirmed in further well-designed prospective studies.

Download Full-text