Relation of a Recurrent Intraductal Carcinoma (Ductal Carcinoma In Situ) to the Primary Tumor

Extract

Chromosomal instability has long been recognized as a feature of malignant neoplasms. In 1975 (1,2), we described quantitative differences in chromosomal aberrations in premalignant lesions and in methylcholanthrene-induced cancers in rats; in 1978 (3), we noted these differences between women with both premalignant lesions and breast cancer. The use of digital image analysis of the DNA content of intraductal carcinomas (ductal carcinoma in situ, or DCIS) and the invasive cancers associated with them subsequently (4) revealed a close concordance in DNA ploidy and S-phase content. Although it was tempting to consider our observations as evidence that DCIS was a precursor of the invasive component, we were uncertain whether similarity in itself was a reliable indicator of such a pathogenic pathway, since it was possible that an etiologic agent could have induced the same phenotype in both the large ducts and the ductolobular units of the breast. In about 10 000 cases of DCIS associated with overt invasive cancer, one of us (E. R. Fisher) has rarely observed unequivocal microscopic extension of neoplastic elements of DCIS through its ductal basement membrane into the surrounding stroma. Moreover, although gaps in the ultrastructural basement membrane may be identified, no tumor cell extension through them or through intact membranes has been observed with the use of electron microscopy (5). The phenomenon of microinvasion associated with DCIS lacks a clear definition, since it is more easily explained by what it isn't rather than by what it is (6). In that regard, ipsilateral breast tumor recurrences of invasive cancer following excision of DCIS are a conundrum, since we have observed that the survival of patients with DCIS is 98% through 8 years of follow-up, despite the finding that 40% of such recurrences were invasive and that about 50% of deaths occurred in the absence of an ipsilateral breast tumor recurrence (7-10).