Pathological and molecular characteristics distinguishing contralateral metastatic from new primary breast cancer.

BACKGROUND Breast cancer patients have a cumulative lifetime risk of 2%-15% of developing a contralateral metastatic or ex novo primary cancer. From prognostic and therapeutic viewpoints, it is important to differentiate metastatic from second primary. To distinguish these entities, we investigated whether the pattern of X chromosome inactivation could determine whether the two tumors derived from different progenitor cells. MATERIALS AND METHODS The clonality of bilateral breast cancer was evaluated through the X-inactivation analysis using the human androgen receptor gene (HUMARA) polymorphism and the histopathologic and molecular results were compared. A different or an identical pattern of X inactivation was considered as indicator of a second primary cancer or not informative, respectively. We considered morphological indicators of a new primary cancer the absence of concordance in the histological type or a better histological differentiation. RESULTS Ten patients with bilateral breast cancer were evaluated. Morphological criteria indicated that eight were second primary, a conclusion confirmed by the X-inactivation analysis. Two cases classified as recurrence according to morphological criteria were classified as second tumor by molecular analysis. CONCLUSION Our results show that the HUMARA clonality assay can improve the histological parameters in differentiating metastatic cancer from second primary cancer.

[1]  M. Ringnér,et al.  Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs , 2008, BMC clinical pathology.

[2]  J. Squire,et al.  Genomic alterations in sporadic synchronous primary breast cancer using array and metaphase comparative genomic hybridization. , 2007, Neoplasia.

[3]  F. Vicini,et al.  The use of molecular assays to establish definitively the clonality of ipsilateral breast tumor recurrences and patterns of in‐breast failure in patients with early‐stage breast cancer treated with breast‐conserving therapy , 2007, Cancer.

[4]  F. Vicini,et al.  Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy: comparison with clinical and biologic factors. , 2005, American journal of clinical pathology.

[5]  I. Casciano,et al.  p16INK4a promoter methylation and protein expression in breast fibroadenoma and carcinoma , 2005, International journal of cancer.

[6]  B. Bonanni,et al.  Clinicopathologic characteristics of 143 patients with synchronous bilateral invasive breast carcinomas treated in a single institution , 2004, Cancer.

[7]  P. S. Larson,et al.  Quantitative DNA fingerprinting may distinguish new primary breast cancer from disease recurrence. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  E. Kliewer,et al.  Incidence of Second Primary Breast Cancer Among Women with a First Primary in Manitoba, Canada , 2001, Breast Cancer Research and Treatment.

[9]  J. Andersen,et al.  Contralateral prophylactic mastectomy improves the outcome of selected patients undergoing mastectomy for breast cancer. , 2000, American journal of surgery.

[10]  W. Thompson,et al.  Epidemiology of contralateral breast cancer. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[11]  D. Rimm,et al.  Polymerase chain reaction‐based detection of clonality as a non‐morphologic diagnostic tool for fine‐needle aspiration of the breast , 1998, Cancer.

[12]  A. Pinchera,et al.  Polyclonal origin of medullary carcinoma of the thyroid in multiple endocrine neoplasia type 2 , 1997, Human Genetics.

[13]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[14]  B. Henderson,et al.  Clonal analysis of bilateral breast cancer. , 1996, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  G. Mutter,et al.  X chromosome inactivation in the normal female genital tract: implications for identification of neoplasia. , 1995, Cancer research.

[16]  S. Hirohashi,et al.  Identification of multiple breast cancers of multicentric origin by histological observations and distribution of allele loss on chromosome 16q. , 1995, Cancer research.

[17]  F. Mitelman,et al.  Chromosome abnormalities in bilateral breast carcinomas. Cytogenetic evaluation of the clonal origin of multiple primary tumors , 1995, Cancer.

[18]  G. Mutter,et al.  PCR bias in amplification of androgen receptor alleles, a trinucleotide repeat marker used in clonality studies. , 1995, Nucleic acids research.

[19]  J. Fletcher,et al.  A polymerase chain reaction assay for non-random X chromosome inactivation identifies monoclonal endometrial cancers and precancers. , 1995, The American journal of pathology.

[20]  S. Noguchi,et al.  Discrimination between multicentric and multifocal carcinomas of the breast through clonal analysis , 1994, Cancer.

[21]  L. E. McDonald,et al.  A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  P. Gimotty,et al.  Bilateral breast cancer: one disease or two? , 1991, Breast Cancer Research and Treatment.

[23]  R. Willemze,et al.  Studies on clonality by PCR analysis of the PGK-1 gene. , 1991, Nucleic acids research.

[24]  S. Groshen,et al.  Contralateral breast carcinoma: an assessment of risk and prognosis in stage I (T1N0M0) and stage II (T1N1M0) patients with 20-year follow-up. , 1989, Surgery.

[25]  T. Murad,et al.  Bilateral breast cancer. , 1989, The American surgeon.

[26]  A. Feinberg,et al.  Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. , 1985, Science.

[27]  B. Hankey,et al.  A retrospective cohort analysis of second breast cancer risk for primary breast cancer patients with an assessment of the effect of radiation therapy. , 1983, Journal of the National Cancer Institute.

[28]  I. Seidman,et al.  Bilateral primary breast cancer. , 1976, JAMA.

[29]  G F ROBBINS,et al.  Bilateral primary breast cancers. A prospective clinicopathological study , 1964 .

[30]  Y. Fukushima,et al.  A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR , 1999, Human Genetics.

[31]  M. Reiss,et al.  Ipsilateral breast tumor recurrence as a predictor of distant disease: implications for systemic therapy at the time of local relapse. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  H. Zoghbi,et al.  Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. , 1992, American journal of human genetics.