Patterns of metastasis in women with metachronous contralateral breast cancer

King's College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, Research Oncology, 3rd Floor, Bermondsey Wing London, Guy's Hospital, London SE1 9RT, UK.
British Journal of Cancer (Impact Factor: 4.84). 06/2012; 107(2):221-3. DOI: 10.1038/bjc.2012.273
Source: PubMed


The understanding of metastatic patterns after metachronous contralateral breast cancer (CBC) may help determine the biological nature of CBC.
A cohort of 8478 women with breast cancer treated at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2006 were studied. Organ-specific 5-year cumulative incidence and incidence rate ratios were assessed for women diagnosed with unilateral breast cancer (UBC), CBC within 5 years and CBC more than 5 years of the initial diagnosis.
Women diagnosed with CBC within 5 years had a higher incidence of metastases in all organs compared with UBC. Women with a short interval time to CBC developed metastasis more rapidly and were more likely to develop visceral and distant cutaneous metastases compared with bone metastasis.
These findings explain poor prognosis of women with early occurring CBC and suggest that some of these CBCs are indicators of aggressive and/or systemic disease.

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Available from: Ian S Fentiman, Mar 19, 2014
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    ABSTRACT: To compare overall survival between women with unilateral breast cancer (UBC) and contralateral breast cancer (CBC). Women with UBC (N = 182,562; 95 %) and CBC (N = 8,912; 5 %) recorded in the Netherlands Cancer Registry between 1989 and 2008 were included and followed until 2010. We incorporated CBC as a time-dependent covariate to compute the overall mortality rate ratio between women with CBC and UBC. Prognostic factors for overall death were examined according to age at first breast cancer. Women with CBC exhibited a 30 % increase in overall mortality (Hazard Ratio (HR), 95 % Confidence Interval: 1.3, 1.3-1.4) compared with UBC, decreasing with rising age at diagnosis of first breast cancer (<50 years: 2.3, 2.2-2.5 vs. ≥70 years: 1.1, 1.0-1.1). Women older than 50 years at CBC diagnosis and diagnosed 2-5 years after their first breast cancer exhibited a 20 % higher death risk (1.2, 1.0-1.3) compared to those diagnosed within the first 2 years. In women younger than 50 years, the HR was significantly lower if the CBC was diagnosed >5 years after the first breast cancer (0.7, 0.5-0.9). The prognosis for women with CBC significantly improved over time (2004-2008: 0.6, 0.5-0.7 vs. 1989-1993). Women with CBC had a lower survival compared to women with UBC, especially those younger than 50 years at first breast cancer diagnosis. A tailored follow-up strategy beyond current recommendations is needed for these patients who, because of their age and absence of known familial risk, are currently not invited for population-based screening.
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    ABSTRACT: By convention, a contralateral breast cancer (CBC) is treated as a new primary tumor, independent of the first cancer (BC1). Although there have been indications that the second tumor (BC2) sometimes may represent a metastatic spread of BC1, this has never been conclusively shown. We sought to apply next-generation sequencing to determine a "genetic barcode" for each tumor and reveal the clonal relationship of CBCs. Ten CBC patients with detailed clinical information and available fresh frozen tumor tissue were studied. Using low-coverage whole genome DNA-sequencing data for each tumor, chromosomal rearrangements were enumerated and copy number profiles were generated. Comparisons between tumors provided an estimate of clonal relatedness for tumor pairs within individual patients. Between 15-256 rearrangements were detected in each tumor (median 87). For one patient, 76 % (68 out of 90) of the rearrangements were shared between BC1 and BC2, highly consistent with what has been seen for true primary-metastasis pairs (>50 %) and thus confirming a common clonal origin of the two tumors. For most of the remaining cases, BC1 and BC2 had similarly low overlap as unmatched randomized pairs of tumors from different individuals, suggesting the CBC to represent a new independent primary tumor. Using rearrangement fingerprinting, we show for the first time with certainty that a contralateral BC2 can represent a metastatic spread of BC1. Given the poor prognosis of a generalized disease compared to a new primary tumor, these women need to be identified at diagnosis of CBC for appropriate determination of treatment. Our approach generates a promising new method to assess clonal relationship between tumors. Additional studies are required to confirm the frequency of CBCs representing metastatic events.
    Breast Cancer Research 08/2015; 17(1). DOI:10.1186/s13058-015-0608-x · 5.49 Impact Factor