Assessment of clonal relationships in ipsilateral and bilateral multiple breast carcinomas by comparative genomic hybridisation and hierarchical clustering analysis

Teixeira, Manuel R.; Ribeiro, Franclim R.; Torres, Lurdes; Pandis, Nikos; Andersen, Johan A.; Lothe, Ragnhild; Heim, S.

doi:10.1038/sj.bjc.6602021

Cited by 58 publications

(52 citation statements)

References 24 publications

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“…Imyanitov et al determined status for all but one of 28 investigated cases, using 14 fixed markers for each tumor [5], showing a higher similarity between synchronous CBC than metachronous CBC. Two studies have used CGH to investigate the relationship between the tumors, showing that investigation of genomic imbalances can be used to detect recurrent breast tumors in both the ipsilateral and contralateral settings [6,7]. In each study, a single patient was detected to have a metastasis instead of a second primary, out of 8 bilateral cases in the Brommesson et al study, and 9 bilateral cases in the Teixeira et al study.…”

Section: Discussionmentioning

confidence: 99%

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Exome sequencing of contralateral breast cancer identifies metastatic disease

Klevebring

Lindberg

Rockberg

et al. 2015

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

“…It is likely that for a subset of the patients, the second cancer is not a new primary tumor, but instead a metastasis of the first cancer, which could, in part, explain the poor prognosis of these patients. Several [6,7].…”

Section: Introductionmentioning

confidence: 99%

Exome sequencing of contralateral breast cancer identifies metastatic disease

Klevebring

Lindberg

Rockberg

et al. 2015

Breast Cancer Res Treat

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“…show some CBC to have features similar enough to BC1 that a metastatic spread is possible (11)(12)(13)(14)(15).…”

Section: Discussionmentioning

confidence: 99%

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Alkner¹,

Ehinger²,

Bendahl³

et al. 2015

European Journal of Cancer

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Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy.Alkner, Sara; Ehinger, Anna; Bendahl, Pär-Ola; Rydén, Lisa; Fernö, Mårten Link to publication Citation for published version (APA): Alkner, S., Ehinger, A., Bendahl, P-O., Rydén, L., & Fernö, M. (2015). Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy. European Journal of Cancer, 51(16), 2304 -2313 . DOI: 10.1016 /j.ejca.2015 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Role of the Funding Sources:None of the funding sources had any impact on study design; the collection, analysis and interpretation of data; the writing of the report; or in the decision to submit the article for publication.3 Abstract Aim: A contralateral breast cancer (CBC) is today treated as an independent primary tumor, although recent data suggest risk and prognosis of CBC to be influenced by characteristics of and treatment given for the first tumor (BC1). We hereby investigate phenotypical and prognostic features of the second tumor (BC2) in relation to prior endocrine treatment and radiotherapy.Methods: From a well-defined population-based cohort of CBC-patients, we have constructed a unique tissue-microarray including 600 pairs of primary tumors and CBCs.Breast cancer mortality was primary end-point for prognosis. Results: Both estrogen receptor (ER) status and stage was strongly correlated between BC1and BC2 within CBC-pairs. Although BC2 had the highest prognostic impact, BC1 continued to influence prognosis after diagnosis of CBC. Patients diagnosed with two high stage tumors within a short time-interval had a particularly bad prognosis. Prior endocrine therapy and radiotherapy both correlated to ER-negativity of BC2. An ER-negative BC2 was associated with an inferior prognosis compared to an ER-positive BC2 regardless of ER-status of BC1 or prior endocrine therapy. Conclusions:Our results suggest that both the residual prognostic impact of BC1, the possibility of contralateral metastasis, as well as prior treatment given, need to be considered when determining appropriate diagnostic work-up and treatment of CBC. In addition, radiation to the contralateral breast and risk of inducing CBC with an aggressive ER-negative phenotype should be considered when establishing new radiation treatm...

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“…15 Accumulating literature presents contradicting results. 11,[17][18][19][20][21][22][23][24][25] Some authors have demonstrated similarity in histologic subtype, 12,23 tumor grade, 17 and hormone receptor status 16,18 between the two tumors, suggesting a single-cell origin, whereas others had different results. 25 In addition, similar mammographic appearance may be seen in bilateral breast carcinomas with a mirror image location.…”

mentioning

confidence: 99%

“…Using molecular techniques, few studies showed the presence of similarities in bilateral breast cancer, indicating that these carcinomas may result from a metastatic event, 11,24 while other investigators present evidence for the independent pathogenesis in majority of these tumors. 16,[19][20][21][22]25 This controversy reflects the lack of a definitive methodology to distinguish de novo primary from metastatic tumor deposition. Comparative mutational profiling offers a novel and highly detailed means to understand the relationship between different tumors deposits suitable for clinical application in surgical pathology.…”

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confidence: 99%

Diagnostic and Prognostic Utility of Molecular Markers in Synchronous Bilateral Breast Carcinoma

et al. 2008

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Histologic criteria have a limited role in determining whether the synchronous bilateral breast carcinomas represent two primaries or a metastasis to the contralateral breast. We studied the molecular analysis of synchronous bilateral breast carcinoma and whether they are originating from a single or different clone. We examined 17 patients with breast carcinoma, including 12 patients with synchronous bilateral carcinomas and control group of 5 infiltrating ductal carcinomas with regional lymph node metastases. Mutations were quantitatively determined to detect loss of heterozygosity (LOH) and microsatellite size alterations for a broad panel of 15 markers, involving 10 chromosomes using polymerase chain reaction. The carcinomas were classified as de novo or metastasis based on three levels of concordance: (1) marker-affected tumors were considered concordant if 50% or more of the same markers were mutated, (2) same gene copy affected, and (3) temporal sequence of mutation acquisition. In synchronous bilateral breast carcinoma patients, molecular analysis showed discordant mutations in all cases, supporting the diagnosis of de novo bilateral primary breast carcinomas. In patients with lymph node metastases, the primary breast carcinoma and metastases shared the same mutations, revealing a metastatic lesion. In conclusion, the application of molecular technology may play an important role for the differential diagnosis of dual primary carcinomas vs a metastatic breast cancer to contralateral breast. In this study, synchronous bilateral breast cancers represent two independent primaries rather than metastatic events. Keywords: synchronous bilateral breast carcinoma; molecular pathology; LOH Contralateral breast carcinoma is the most common second malignancy for breast carcinoma patients, with an incidence as high as 12%.1-3 Bilateral breast carcinomas exist in two forms, synchronous, in which both tumors occur at the same time, or metachronous, in which the carcinomas occur at different times. Synchronous bilateral breast carcinoma is uncommon, reported to range from 0.3 to 8% in the literature. [4][5][6][7] This wide range of reported incidence rates for synchronous bilateral breast carcinoma is a result of different time cutoff. Although some authors require both breast carcinomas to be diagnosed simultaneously or within less than 1 month, 7-10 others used up to 12 months as a cutoff time to differentiate synchronous from metachronous bilateral breast carcinomas.11-13 Using criteria of less than 1 month, the incidence of synchronous bilateral breast is less than 2%. 7,14 When cancer is detected in the opposite breast, the question arises whether this tumor is a second cancer (polyclonal origin) or a metastatic spread from the first breast cancer (monoclonal origin). The answer to this question is critical as both tumor staging and management will be different depending upon the results.11 Currently, this distinction is attempted using histopathologic features. Different histologic types, a better histologic diff...

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Assessment of clonal relationships in ipsilateral and bilateral multiple breast carcinomas by comparative genomic hybridisation and hierarchical clustering analysis

Cited by 58 publications

References 24 publications

Exome sequencing of contralateral breast cancer identifies metastatic disease

Exome sequencing of contralateral breast cancer identifies metastatic disease

Prognosis, stage and oestrogen receptor status of contralateral breast cancer in relation to characteristics of the first tumour, prior endocrine treatment and radiotherapy

Diagnostic and Prognostic Utility of Molecular Markers in Synchronous Bilateral Breast Carcinoma

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