Bilateral breast tumors, malignant phyllodes tumor and invasive lobular carcinoma in a 46, XX/46, XY mosaic female with family history of breast cancer*

Bllateral breast tumors, a malignant phyllodes tumor in the right breast and an Invasive Iobular carcinoma in the left breast, occurred In a 47-yearold woman with 46XX/46XY mosalc karyotype in her peripheral blood lymphocytes and intersex external genitalia. Postmortem examinatlon revealed bllateral ovotestls. Three of the patient's sisters also had breast cancer. In situ hybridization with a Y-specific probe revealed Yehromosome-speciflc signal in both tumors, suggesting that the clonal origin of tumors in this patient was Y-contalnlng cells. Androgen-receptor polymorphlsm also revealed a monoallelic X chromosome pattern in the recurrent phyllodes tumor tlssue taken at autopsy, in addltlon to loss of heterozygoslty demonstrated at locus TP53. The slippage of the CA repeats In the tumor was also shown at the locl of D5S82 and D11S527. The mechanistlc basis for the occurrence of bilateral malignant tumors of the breast, XX/MY mosalcism, and famllial clustering of breast cancer is still unknown. The present study, however, suggests that the sex chromosome abnormality may have modtfied the cancer phenotype in a manner simllar to breast cancer In Klinefel-ter's syndrome (though phenotypically male) and the Y chromosome may have promoted cell growth.