Clonal Analysis of Bilateral Mammary Carcinomas by Clinical Evaluation and Partial Allelotyping

Abstract

Bilateral breast carcinomas may represent contralateral metastases or new primary tumors. The presence of carcinoma in situ, a lower grade, or a different histotype in the second tumor is considered a clinical criterion for a second primary tumor. In this study, 26 bilateral breast carcinomas from 13 patients were analyzed based on clinical criteria, and the results were compared with those obtained by partial allelotyping using 47 markers at 7 chromosomal arms. Of the 8 synchronous tumors, 5 were concluded to be distinct primary tumors using clinical criteria; some were confirmed by partial allelotyping. In the remaining 3 cases, partial allelotyping showed distinct primary tumors. Five patients had metachronous carcinomas with 3 distinct primary tumors, 1 metastasis, and 1 that was uncertain by clinical criteria. Three cases were confirmed by partial allelotyping, and the uncertain case was shown to be distinct primary tumors. No discrepant results were noted. Stringent application of clinical criteria is accurate for differentiating second primary tumors from metastases.

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

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

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

“…28 Only a few reports have investigated the genetic findings in synchronous bilateral breast cancer. [19][20][21][22]25 Whether bilateral breast cancers have an independent origin or are the result of a breast-to-breast metastasis may be crucial since the therapeutic management of independent breast carcinoma is different from the treatment of metastatic disease. 12,16,19,29 Dissimilarity in histology between bilateral breast carcinoma in the same patient was often cited in support of the independent primaries theory.…”

“…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. 26,27 Neither clinical nor histopathologic features can definitively determine the relationship between multiple deposits of breast cancer at the individual patient level with certainty.…”

“…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.…”

The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

“…In general, these studies have shown that clonality is quite common for mucosal cancers of the head and neck (23) and bladder (24). However, for sites with paired organs, such as breast (25)(26)(27)(28) and lung (29)(30)(31), the vast majority of new contralateral primaries seem to be biologically independent. The issue does not seem to have been studied in melanoma, but the wide anatomic distribution of melanomas and the absence of a plausible mechanism for the seeding of clonal cells in distant parts of the skin argue against the frequent clonality of multiple primaries in this disease.…”