Contralateral breast cancers: Independent cancers or metastases? Journal Article


Authors: Begg, C. B.; Ostrovnaya, I.; Geyer, F. C.; Papanastasiou, A. D.; Ng, C. K. Y.; Sakr, R. A.; Bernstein, J. L.; Burke, K. A.; King, T. A.; Piscuoglio, S.; Mauguen, A.; Orlow, I.; Weigelt, B.; Seshan, V. E.; Morrow, M.; Reis-Filho, J. S.
Article Title: Contralateral breast cancers: Independent cancers or metastases?
Abstract: A cancer in the contralateral breast in a woman with a previous or synchronous breast cancer is typically considered to be an independent primary tumor. Emerging evidence suggests that in a small subset of these cases the second tumor represents a metastasis. We sought to investigate the issue using massively parallel sequencing targeting 254 genes recurrently mutated in breast cancer. We examined the tumor archives at Memorial Sloan Kettering Cancer Center for the period 1995–2006 to identify cases of contralateral breast cancer where surgery for both tumors was performed at the Center. We report results from 49 patients successfully analyzed by a targeted massively parallel sequencing assay. Somatic mutations and copy number alterations were defined by state-of-the-art algorithms. Clonal relatedness was evaluated by statistical tests specifically designed for this purpose. We found evidence that the tumors in contralateral breasts were clonally related in three cases (6%) on the basis of matching mutations at codons where somatic mutations are rare. Clinical data and the presence of similar patterns of gene copy number alterations were consistent with metastasis for all three cases. In three additional cases, there was a solitary matching mutation at a common PIK3CA locus. The results suggest that a subset of contralateral breast cancers represent metastases rather than independent primary tumors. Massively parallel sequencing analysis can provide important evidence to clarify the diagnosis. However, given the inter-tumor mutational heterogeneity in breast cancer, sufficiently large gene panels need to be employed to define clonality convincingly in all cases. © 2017 UICC
Keywords: clonality; next generation sequencing; bilateral breast cancer
Journal Title: International Journal of Cancer
Volume: 142
Issue: 2
ISSN: 0020-7136
Publisher: John Wiley & Sons  
Date Published: 2018-01-15
Start Page: 347
End Page: 356
Language: English
DOI: 10.1002/ijc.31051
PROVIDER: scopus
PUBMED: 28921573
PMCID: PMC5749409
DOI/URL:
Notes: Article -- Export Date: 4 December 2017 -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    282 Seshan
  2. Monica Morrow
    434 Morrow
  3. Colin B Begg
    230 Begg
  4. Irene Orlow
    190 Orlow
  5. Jonine L Bernstein
    100 Bernstein
  6. Rita Sakr
    58 Sakr
  7. Britta Weigelt
    258 Weigelt
  8. Jorge Sergio Reis
    283 Reis
  9. Kiu Yan Charlotte Ng
    152 Ng
  10. Kathleen   Burke
    55 Burke