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

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.

Triple-negative breast cancer and likelihood of nodal metastates.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 50-50
Author(s):  
Alexandra Gangi ◽  
James Mirocha ◽  
Trista Leong ◽  
Armando E. Giuliano
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Triple Negative Breast Cancer ◽  
Tumor Size ◽  
Axillary Lymph Node ◽  
Triple Negative ◽  
Axillary Lymph ◽  
Luminal A ◽  
Axillary Lymph Node Metastases ◽  
Luminal B

50 Background: Axillary lymph node metastases are a prognostic indicator for breast cancer. Studies suggest that breast cancer subtypes are associated with the presence of lymph node (LN) metastases. The purpose of this study was to determine if patients with triple negative breast cancer (TNBC) have a higher risk of LN metastases than those with non-TNBC. Methods: Prospective database review identified 2,967 female patients with invasive breast cancer treated with mastectomy or breast conserving surgery (BCS) between January 2000 and May 2012. Only patients who underwent sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND) were included. Those receiving neoadjuvant therapy were excluded. Patient and tumor characteristics evaluated included age, race, tumor size, grade, stage, histologic subtype, presence of lymphovascular invasion (LVI), estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) status. Results: BCS was performed in 1,889 and mastectomy in 1,078 patients. Breakdown by subtype included 2,201 (74%) patients with Luminal A, 344 (12%) with Luminal B, 144 (5%) with HER2, and 278 (9%) with TNBC. SNB was performed in 1,094 (37%), ALND in 756 (25%), and 1,117 (38%) patients had both. LN metastases were detected in 1050 (35%) patients. The LN positivity rate varied across subtypes with 734/2,201 (33%) in Luminal A, 143/344 (42%) in Luminal B, 108/278 (39%) in TNBC, and 65/144 (45%) in HER-2 (p = 0.0007). However, on multivariable analysis, there was no difference in LN positivity among subtypes (p=0.24). Only age < 50 (HR 1.5, CI 1.3 to 1.8), grade 2 or 3 tumors (HR 1.8, CI 1.4 to 2.5), size greater than 2cm (HR 3.2, CI 2.7 to 3.9), and presence of LVI (HR 3.9, CI 2.4 to 6.3) were significant predictors of LN positivity. Four or more involved nodes were seen most commonly in the HER2 (28/144; 19%) and Luminal B (47/344; 14%) subtypes, but not TNBC (26/278; 9%) or Luminal A (199/2201; 9%) (p < 0.0001). Conclusions: Predictors of LN metastases include younger age, higher grade, larger tumor size, and presence of LVI. Patients with TNBC are not more likely to have involved nodes than those with non-TNBC.

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

2021 ◽  
Author(s):  
Marit Valla ◽  
Signe Opdahl ◽  
Borgny Ytterhus ◽  
Anna Mary Bofin
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Lymph Node ◽  
Copy Number ◽  
Poor Prognosis ◽  
Molecular Subtype ◽  
Breast Cancers ◽  
Number Increase ◽  
Node Metastases ◽  
Copy Number Increase

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.

Neoadjuvant Chemotherapy Induces the Appearance of New Copy Number Aberrations in Breast Tumor and is Associated with Metastasis

2020 ◽  
Vol 20 (9) ◽  
pp. 681-688
Author(s):  
Nikolai V. Litviakov ◽  
Marina K. Ibragimova ◽  
Matvey M. Tsyganov ◽  
Artem V. Doroshenko ◽  
Eugeniy Y. Garbukov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Copy Number ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Luminal B ◽  
Cell Clones ◽  
Genetic Landscape ◽  
Intelligent Approach

Background: In this study, we examined the CNA-genetic landscape (CNA – copy number aberration) of breast cancer prior to and following neoadjuvant chemotherapy (NAC) and correlated changes in the tumor landscape with chemotherapy efficiency as well as metastasis-free survival. Objective: Breast cancer patients (n = 30) with luminal B molecular subtypes were treated with anthracycline- based therapy. Methods: To study CNAs in breast tumors, microarray analysis was performed. Results: Three effects of NAC on tumor CNA landscape were identified: 1 – the number of CNA-bearing tumor clones decreased following NAC; 2 – there were no alterations in the number of CNA-containing clones after NAC; 3 – the treatment with NAC increased the number of CNA-bearing clones (new clones appeared). All NAC-treated patients who had new tumor clones with amplification (20%) had a 100% likelihood of metastasis formation. In these cases, NAC contributed to the emergence of potential metastatic clones. Our study identified the following loci – 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 18Chr and 19p – that were amplified during the treatment with NAC and may be the markers of potential metastatic clones. In other patients who showed total or partial elimination of CNA-bearing cell clones, no new amplification clones were observed after NAC, and no evidence of metastases was found with follow-up for 5 years (р = 0.00000). Conclusion: Our data suggest that the main therapeutic result from NAC is the elimination of potential metastatic clones present in the tumor before treatment. The results showed the necessity of an intelligent approach to NAC to avoid metastasis stimulation.

Evaluating One Day versus Two Days Preoperative Lymphoscintigraphy Protocols for Sentinel Lymph Node Biopsy in Breast Cancer

2015 ◽  
Vol 81 (5) ◽  
pp. 454-457 ◽  
Author(s):  
Michael G. Mount ◽  
Nicholas R. White ◽  
Christophe L. Nguyen ◽  
Richard K. Orr ◽  
Robert B. Hird
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Sentinel Lymph Node Biopsy ◽  
Axillary Lymph Node ◽  
Lymph Node Biopsy ◽  
Axillary Lymph ◽  
Axillary Lymph Node Metastases ◽  
Node Biopsy ◽  
Node Negative Breast Cancer

Sentinel lymph node biopsy (SLNB) is used to detect axillary lymph node metastases in breast cancer. Preoperative radiocolloid injection with lymphoscintigraphy (PL) is performed before SLNB. Few comparisons between 1- and 2-day PL protocols exist. Opponents of a 2-day protocol have expressed concerns of radiotracer washout to nonsentinel nodes. Proponents cite lack of scheduling conflicts between PL and surgery. A total of 387 consecutive patients with clinically node-negative breast cancer underwent SLNB with PL. Lymphoscintigraphy images were obtained within 30 minutes of radio-colloid injection. Axillary lymph node dissection was performed if the sentinel lymph node (SLN) could not be identified. Data were collected regarding PL technique and results. In all, 212 patients were included in the 2-day PL group and 175 patients in the 1-day PL group. Lymphoscintigraphy identified an axillary sentinel node in 143/212 (67.5%) of patients in the 2-day group and 127/175 (72.5%) in the 1-day group ( P = 0.28). SLN was identified at surgery in 209/212 (98.6%) patients in the 2-day group and 174/175 (99.4%) in the 1-day group ( P = 0.41). An average of 3 SLN was found at surgery in the 2-day group compared with 3.15 in the 1-day group ( P = 0.43). SLN was positive for metastatic disease in 54/212 (25.5%) patients in the 2-day group compared with 40/175 (22.9%) in the 1-day group ( P = 0.55). A 2-day lymphoscintigraphy protocol allows reliable detection of the SLN, of positive SLN and equivalent SLN harvest compared with a 1-day protocol. The timing of radiocolloid injection before SLNB can be left at the discretion of the surgeon.

Predictors of axillary lymph node metastases in patients with impalpable breast cancer

The Breast ◽  
1997 ◽  
Vol 6 (3) ◽  
pp. 143-145 ◽  
Author(s):  
C.I. Perre ◽  
V.C.M. Koot ◽  
E.P.A. van der Heijden ◽  
V. Vossen ◽  
J.R. de Jong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Axillary Lymph Node ◽  
Axillary Lymph ◽  
Axillary Lymph Node Metastases ◽  
Node Metastases

Are Breast Cancer Nomograms Still Valid to Predict the Need for Axillary Dissection?

Oncology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Vilma Madekivi ◽  
Antti Karlsson ◽  
Pia Boström ◽  
Eeva Salminen
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Axillary Dissection ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Axillary Lymph Node Metastases ◽  
Node Negative ◽  
Node Metastases ◽  
External Population

Background: Nomograms can help in estimating the nodal status among clinically node-negative patients. Yet their validity in external cohorts over time is unknown. If the nodal stage can be estimated preoperatively, the need for axillary dissection can be decided. Objectives: The aim of this study was to validate three existing nomograms predicting 4 or more axillary lymph node metastases. Method: The risk for ≥4 lymph node metastases was calculated for n = 529 eligible breast cancer patients using the nomograms of Chagpar et al. [Ann Surg Oncol. 2007;14:670–7], Katz et al. [J Clin Oncol. 2008;26(13):2093–8], and Meretoja et al. [Breast Cancer Res Treat. 2013;138(3):817–27]. Discrimination and calibration were calculated for each nomogram to determine their validity. Results: In this cohort, the AUC values for the Chagpar, Katz, and Meretoja models were 0.79 (95% CI 0.74–0.83), 0.87 (95% CI 0.83–0.91), and 0.82 (95% CI 0.76–0.86), respectively, showing good discrimination between patients with and without high nodal burdens. Conclusion: This study presents support for the use of older breast cancer nomograms and confirms their current validity in an external population.

The Importance of Extracapsular Extension of Axillary Lymph Node Metastases in Breast Cancer

2004 ◽  
Vol 90 (1) ◽  
pp. 107-111 ◽  
Author(s):  
Görken Bilkay İlknur ◽  
Alanyali Hilmi ◽  
Canda Tülay ◽  
Çetinayak Oguz ◽  
Sengiz Selma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Node Metastases ◽  
Axillary Lymph Node ◽  
Axillary Lymph ◽  
Extracapsular Extension ◽  
Axillary Lymph Node Metastases ◽  
Node Metastases

Prediction of prognosis in primary breast cancer by detection of a high molecular weight mucin-like antigen using monoclonal antibodies DF3, F36/22, and CU18: a Cancer and Leukemia Group B study.

1991 ◽  
Vol 9 (7) ◽  
pp. 1113-1123 ◽  
Author(s):  
D F Hayes ◽  
R Mesa-Tejada ◽  
L D Papsidero ◽  
G A Croghan ◽  
A H Korzun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Weight ◽  
Monoclonal Antibodies ◽  
High Molecular Weight ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Immunoperoxidase Staining ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Axillary Lymph Node Metastases

Three monoclonal antibodies (MAbs) (DF3, F36/22, CU18) were used to monitor expression of distinct epitopes present within a family of mucin-like, breast carcinoma-associated molecules. Primary tumor specimens from more than 190 stage II breast cancer patients were evaluated for expression of the high molecular weight antigens. With a median follow-up of 6 years, patients whose tumors exhibited high immunoperoxidase staining scores (greater than 50% positive cells) with MAb DF3 had a superior disease-free survival ([DFS] 56% +/- 6% v 37% +/- 5% at 6 years; P = .0088) and overall survival ([OS] 72% +/- 5% v 59% +/- 5% at 6 years; P = .025). Staining scores with the other two antibodies did not correlate with improved prognosis. For MAbs DF3 and CU18, patients whose tumors exhibited predominantly apical cellular reactivity patterns had improved DFS, although differences reached conventional levels of statistical significance only with MAb CU18. In multivariate analyses, the prognostic value of MAb DF3 staining was independent of other identified prognostic factors. Furthermore, the concordance between primary and axillary lymph node metastases staining with each MAb was 73%, 80%, and 85% for MAbs DF3, F36/22, and CU18, respectively. These results suggest that staining with MAb DF3 identifies a group of node-positive women with a relatively favorable prognosis. Expression of the DF3 mucin-like glycoprotein is related to better differentiation, and staining with MAb DF3 provides an accurate and objective estimate of clinical outcome independent of histopathologic evaluation.

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