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Synchronous Breast Cancer: Phenotypic Similarities on MRI.

ABSTRACT: BACKGROUND:Previous studies have shown discrepancies between index and synchronous breast cancer in histology and molecular phenotype. It is yet unknown whether this observation also applies to the MRI phenotype. PURPOSE:To investigate whether the appearance of breast cancer on MRI (i.e. phenotype) is different from that of additional breast cancer (i.e. synchronous cancer), and whether such a difference, if it exists, is associated with prognosis. STUDY TYPE:Retrospective. POPULATION:In all, 464 consecutive patients with early-stage ER+/HER2- breast cancer were included; 34/464 (7.3%) had 44 synchronous cancers in total (34 ipsilateral, 10 contralateral). SEQUENCE:1.5T, contrast-enhanced T1 -weighted. ASSESSMENT:We assessed imaging phenotype using 50 quantitative features from each cancer and applied principal component analysis (PCA) to identify independent properties. The degree of phenotype difference was assessed. An association between phenotype differences and prognosis in terms of the Nottingham Prognostic Index (NPI) and PREDICT score were analyzed. STATISTICAL TESTS:PCA; Wilcoxon rank sum test; Benjamini-Hochberg to control the false discovery rate. RESULTS:PCA identified eight components in patients with ipsilateral synchronous cancer. Six out of eight were significantly different between index and synchronous cancer. These components represented features describing texture (three components, P < 0.001, P < 0.001, P = 0.004), size (P < 0.001), smoothness (P < 0.001), and kinetics (P = 0.004). Phenotype differences in terms of the six components were split in tertiles. Larger phenotype differences in size, kinetics, and texture were associated with significantly worse prognosis in terms of NPI (P = 0.019, P = 0.045, P = 0.014), but not for the PREDICT score (P = 0.109, P = 0.479, P = 0.109). PCA identified six components in patients with contralateral synchronous cancer. None were significantly different from the index cancer (P = 0.178, P = 0.178, P = 0.178, P = 0.326, P = 0.739, P = 0.423). DATA CONCLUSION:The MRI phenotype of ER+/HER2- breast cancer was different from that of ipsilateral synchronous cancer and a large phenotype difference was associated with worse prognosis. No significant difference was found for synchronous contralateral cancer. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;51:1858-1867.

SUBMITTER: Wang H

PROVIDER: S-EPMC7318126 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Synchronous Breast Cancer: Phenotypic Similarities on MRI.

Wang Hui H van der Velden Bas H M BHM Chan Hui Shan M HSM Loo Claudette E CE Viergever Max A MA Gilhuijs Kenneth G A KGA

Journal of magnetic resonance imaging : JMRI 20191219 6

<h4>Background</h4>Previous studies have shown discrepancies between index and synchronous breast cancer in histology and molecular phenotype. It is yet unknown whether this observation also applies to the MRI phenotype.<h4>Purpose</h4>To investigate whether the appearance of breast cancer on MRI (i.e. phenotype) is different from that of additional breast cancer (i.e. synchronous cancer), and whether such a difference, if it exists, is associated with prognosis.<h4>Study type</h4>Retrospective. ...[more]

PMID: 31854487

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Project description:BACKGROUND:Today, no objective criteria exist to differentiate between individual primary tumors and intra- or intermammary dissemination respectively, in patients diagnosed with two or more synchronous breast cancers. To elucidate whether these tumors most likely arise through clonal expansion, or whether they represent individual primary tumors is of tumor biological interest and may have clinical implications. In this respect, high resolution genomic profiling may provide a more reliable approach than conventional histopathological and tumor biological factors. METHODS:32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters. RESULTS:Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 x 10-5) unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29) displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses. CONCLUSION:Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and underscores the importance of evaluating the clonality of multiple tumors for optimal patient management. In summary, our findings demonstrate the importance of evaluating the properties of both tumors in order to determine the most optimal patient management.

Project description:Whether the expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) receptor and Ki-67 show concordance between the primary tumors and the synchronous axillary lymph node (ALN) metastases has been discussed in numerous studies. However, to date, the results of these studies remain controversial. Therefore, the present study aimed to investigate whether the expression of ER, PR, HER-2 and Ki-67 was in concordance between the primary tumors and synchronous ALN metastases in patients with operable breast cancer (BC). A total of 60 tissue samples were collected from patients with primary operable BC diagnosed with primary tumors and synchronous ALN metastases. The expression levels of the four biomarkers, ER, PR, HER-2 and Ki-67, were assessed in primary lesions and synchronous ALN metastases samples using immunohistochemistry. The cut-off values were set to 10% for ER and PR, while the labeling index of Ki-67 was set to 14%. The immunostaining intensity of ER and PR was scored as negative (?), 1+, 2+ and 3+. The criteria for HER-2 testing in BC were implemented according to the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines. The concordance rates for ER, PR and HER-2 were 96.7 (58/60), 96.7 (58/60) and 90% (54/60), respectively. In addition, the kappa values of consistency in the primary lesions and the synchronous ALN metastases were 0.773 for ER, 0.654 for PR and 0.785 for HER-2. Furthermore, the P-values of ER, PR and Ki-67 numerical variables between the two groups were 0.393, 0.400 and 0.331, respectively, as demonstrated using a non-parametric Wilcoxon signed rank test. The findings of the present study demonstrated a high degree of concordance between the expression of ER, PR, HER-2 and Ki-67 in the primary tumors and that in the synchronous ALN metastases, suggesting that the BC primary tumor biomarkers may be used for the prognosis of synchronous ALN metastases in patients with operable BC.

Project description:Although intratumoral genomic heterogeneity can impede cancer research and treatment, less is known about the effects of phenotypic heterogeneities. To investigate the role of cell migration heterogeneities in metastasis, we phenotypically sorted metastatic breast cancer cells into two subpopulations based on migration ability. Although migration is typically considered to be associated with metastasis, when injected orthotopically in vivo, the weakly migratory subpopulation metastasized significantly more than the highly migratory subpopulation. To investigate the mechanism behind this observation, both subpopulations were assessed at each stage of the metastatic cascade, including dissemination from the primary tumor, survival in the circulation, extravasation, and colonization. Although both subpopulations performed each step successfully, weakly migratory cells presented as circulating tumor cell (CTC) clusters in the circulation, suggesting clustering as one potential mechanism behind the increased metastasis of weakly migratory cells. RNA sequencing revealed weakly migratory subpopulations to be more epithelial and highly migratory subpopulations to be more mesenchymal. Depletion of E-cadherin expression from weakly migratory cells abrogated metastasis. Conversely, induction of E-cadherin expression in highly migratory cells increased metastasis. Clinical patient data and blood samples showed that CTC clustering and E-cadherin expression are both associated with worsened patient outcome. This study demonstrates that deconvolving phenotypic heterogeneities can reveal fundamental insights into metastatic progression. More specifically, these results indicate that migratory ability does not necessarily correlate with metastatic potential and that E-cadherin promotes metastasis in phenotypically sorted breast cancer cell subpopulations by enabling CTC clustering. SIGNIFICANCE: This study employs phenotypic cell sorting for migration to reveal a weakly migratory, highly metastatic breast cancer cell subpopulation regulated by E-cadherin, highlighting the dichotomy between cancer cell migration and metastasis.

Dataset Information

Synchronous Breast Cancer: Phenotypic Similarities on MRI.

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Synchronous Breast Cancer: Phenotypic Similarities on MRI.

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