Patient-private disease evolution and heterogeneity in bilateral breast cancer

Fountzila, E.; Kotoula, Vassiliki; Zagouri, Flora; Giannoulatou, Eleni; Kouvatseas, George; Pentheroudakis, George; Κoletsa, Triantafyllia; Bobos, Mattheos; Papadopoulou, Kyriaki; Samantas, Epaminontas; Demiri, Efterpi; Miliaras, S.; Chrisafi, Sofia; Razis, E.; Fostira, Florentia; Pectasides, Dimitrios; Zografos, George; Fountzilas, George

doi:10.1093/annonc/mdw364.38

Cited by 5 publications

(8 citation statements)

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“…Tumor profile of SBBC included correlations with age and lobular histology . BBC demonstrated extensive inter‐tumoral and intra‐tumoral heterogeneity with pathogenic germline mutations including BRCA1 and TP53 and a distinct miRNA profile with higher level of miR‐21, miR‐10b, and miR‐31 . A small subset of contralateral BC was clonally related to metastatic dissemination from the index tumor regardless of whether the two tumors occurring as SBBC or MBBC .…”

Section: Discussionmentioning

confidence: 99%

The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta‐analysis of studies from recent decade (2008‐2018)

Pan

Zhou

et al. 2019

Cancer Medicine

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Background The incidence of bilateral breast cancer (BBC) is increasing nowadays comprising 2%‐11% of all breast cancer (BC). According to the interval time between the first and second cancer, BBC could be divided into synchronous (SBBC) and metachronous (MBBC). However, this interval time is quite different across studies. It remains controversial whether the survival of BBC, SBBC, and MBBC is similar or worse compared to that of unilateral breast cancer (UBC), and whether the survival of SBBC is similar or worse compared to MBBC. To better understand the survival of UBC, BBC, SBBC, and MBBC and how the interval time would influence the prognosis of SBBC and MBBC, we performed this meta‐analysis on studies from recent 10 years (2008‐2018). Methods Databases of PubMed, Embase, and Web of Science were searched for relevant studies within recent 10 years. Hazard ratio (HR) was adopted to evaluate the difference of overall survival (OS) of UBC, BBC, SBBC, and MBBC. HR of OS comparisons were performed between BBC vs UBC, SBBC vs UBC, MBBC vs UBC, and SBBC vs MBBC with 3, 6, 12 months as the interval time, respectively. Results There were 15 studies of 72 302 UBC and 2912 BBC included in the meta‐analysis. The summary HR of OS comparison between BBC vs UBC was 1.68 (95% CI: 1.28‐2.20), SBBC vs UBC was 2.01 (95% CI: 1.14‐3.55), MBBC vs UBC was 3.22 (95% CI: 0.75‐13.78). When 3, 6, 12 months were used as the interval time, the summary HR of the OS comparison between of SBBC vs MBBC were 0.64 (95% CI: 0.44‐0.94), 1.17 (95% CI: 0.84‐1.63) and 1.45 (95% CI: 1.10‐1.92), respectively. Conclusion BBC and SBBC showed worse prognosis in terms of OS compared to UBC while MBBC manifested similar or non‐superior survival as UBC. The OS comparison between SBBC and MBBC changed with different interval time used. The longer the interval time used, the worse the survival of SBBC. SBBC with interval of 3‐12 months between the two cancers had the worst prognosis. When 6 months was used to differentiate SBBC from MBBC, these two clinical entities showed similar OS.

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Section: Discussionmentioning

confidence: 99%

The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta‐analysis of studies from recent decade (2008‐2018)

Pan

Zhou

et al. 2019

Cancer Medicine

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“…Previous findings have shown that synchronous BBCs are often of the same histological type and show an association between hormone receptor status and tumor grade ( 1 , 4 ). Despite these similarities, synchronous BBCs are commonly considered as two separate primary tumors evolving in a similar microenvironment and with the same genetic background ( 13 , 14 , 36 , 37 ). Notably, there are a number of cases on record with histologically different synchronous bilateral breast tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies using genome-wide genomic profiling methods have facilitated the molecular characterization of synchronous and metachronous BBCs and have made it possible to rule out whether they are separate tumors or have a common origin. Thus far, available data indicate that the majority of BBC evolve independently and have distinct genotypes ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Genomic imbalances and MYB fusion in synchronous bilateral adenoid cystic carcinoma and invasive lobular carcinoma of the breast

Kovács

Persson

et al. 2017

Molecular and Clinical Oncology

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Abstract. The incidence of synchronous bilateral breast carcinomas (BBCs) has increased with a more frequent use of magnetic resonance imaging screening of the contralateral breast in women with newly diagnosed breast cancer. A total of 30% of all BBCs occur synchronously. In the present study, we describe a unique case of synchronous BBC in a 59-year-old previously healthy woman with no known family history of breast or ovarian cancer. At the time of diagnosis the patient had an invasive lobular carcinoma (ILC) in the right breast and an adenoid cystic carcinoma (ACC) in the left breast. To the best of our knowledge, this is the first published case of bilateral, simultaneously occurring ACC and ILC of the breast. Genome-wide genomic profiling of the tumors revealed that they had distinctly different genomic imbalances. The ACC had a 5.7 Mb interstitial 6q deletion with a breakpoint located in the 3'-part of MYB, resulting in loss of the last coding exon of MYB and its 3'-UTR. RT-PCR analysis confirmed that the tumor expressed an ACC-specific MYB-NFIB fusion transcript. In contrast, the ILC had no rearrangements of 6q or MYB-NFIB gene fusion but showed instead gain of 1q21.1-qter, loss of 16q11.2-qter, and 22q12.2-q12.3 as the sole genomic imbalances. Notably, concurrent gains of 1q and losses of 16q are characteristic features of ILC. Collectively, our findings indicate that the ACC and ILC had originated independently of each other and that the MYB-NFIB fusion is a specific biomarker for breast ACC.

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“…Genotyping data from 3,084 tumors were retrieved from 14 NGS datasets obtained from 2013 to 2017 in the context of HeCOG translational projects [7][8][9][10][11][12][13][14][15]. Eight tumor types were genotyped on the basis of tissue sample availability, research interests of the respective investigators, and funding opportunities: breast, colorectal, pancreatic, nasopharyngeal, glioma, gastric, biliary, and ovarian.…”

Section: Ngs Genotypingmentioning

confidence: 99%

“…HeCOG has previously investigated the genomic profiles of different tumor types using cancer-specific panels designed on the basis of available published data [7][8][9][10][11][12][13][14][15]. From 2013 to 2017, NGS was performed in the Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki, to assess clinically relevant molecular alterations in patients with cancer.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative

et al. 2020

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Copyright: Fountzilas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACTBackground: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group-affiliated Departments.Patients and methods: Patients referred from 12/1980 to 1/2017 had molecular testing (for research) of archival tumor tissue collected at the time of first diagnosis (non-metastatic, 81%; metastatic, 19%). Tumor-specific gene panels (16-101 genes) were used to identify pathogenic mutations in clinically relevant genes. NGS genotyping was performed at the Laboratory of Molecular Oncology, Aristotle University of Thessaloniki. Annotation of mutations was performed at MD Anderson Cancer Center.Results: We analyzed 3,084 patients (median age, 57 years; men, 22%) with sequencing data. Overall, 1,775 (58% of 3,084) patients had pathogenic mutations. The median follow-up was 7.52 years (95% CI, 7.39-7.61). In patients with nonmetastatic tumors, after stratification by tumor type, increasing age, higher grade, and histology other than adenocarcinoma were associated with shorter OS. OS was also shorter in patients with pathogenic TP53 (HR=1.36; p<0.001), MLL3 (HR=1.64; p=0.005), and BRCA1 (HR=1.46; p=0.047) mutations compared to wild-type genes. In multivariate analyses, independent prognostic factors predicting shorter OS were pathogenic mutations in TP53 (HR=1.37, p=0.002) and MLL3 (HR=1.50, p=0.027); increasing age (HR=1.02, p<0.001); and increasing grade (HR=1.46, p<0.001). In patients with metastatic cancer, older age and higher grade were associated with shorter OS and maintained their independent prognostic significance (increasing age, HR=1.03, p<0.001 and higher grade, HR=1.73, p<0.001).Conclusions: Analysis of molecular data reveals prognostic biomarkers, regardless of tissue or organ of origin to improve patient management.

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Patient-private disease evolution and heterogeneity in bilateral breast cancer

Cited by 5 publications

References 0 publications

The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta‐analysis of studies from recent decade (2008‐2018)

The prognostic comparison among unilateral, bilateral, synchronous bilateral, and metachronous bilateral breast cancer: A meta‐analysis of studies from recent decade (2008‐2018)

Genomic imbalances and MYB fusion in synchronous bilateral adenoid cystic carcinoma and invasive lobular carcinoma of the breast

Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative

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