Laszlo tabar
Falun Central Hospital, SwedenPresentation Title:
Why are we failing to cure so many cases of lobular breast cancer?
Abstract
Invasive lobular cancer of the breast (ILC) is responsible for more than its share of treatment failures. Long-term survival of women with classic ILC has not improved significantly over the past half century, despite major improvements in breast cancer therapy and diagnosis. Foote and Stewart considered lobular carcinoma in situ (LCIS) to be the precursor of ILC, and that the “the mass eruption of tumor cells” occurred through “some lytic action of the tumor cells, naturally not to be detected by anatomic study.” Ackerman and Del Regato accepted this proposed mechanism, concluding that ILC arises from the acinar epithelium of the breast lobule. Despite the absence of clear evidence, these speculations were accepted as established fact more than 70 years ago. An inconvenient observation, the lack of E-cadherin staining, was assumed to result from a “loss” of that protein during tumor development. Our research group, the Swedish Organized Service Screening Evaluation Group, has examined all histologically proven ILC cases from Dalana County Sweden diagnosed from 1996-2019 with follow-up to the end of 2021. Histopathologic study of large section (8x10 cm) pathology slides, imaging and molecular biomarkers of 329 consecutive diffuse form of ILC showed a macroscopic structure unlike breast cancers of epithelial origin, a 19-year survival (56 %), poorer than expected from the histochemical biomarkers, and a growth pattern closely resembling that of normal breast tissue, hindering mammographic detection. Our group considered that ILC may originate from mesenchymal hybrid cells through the process of mesenchymal-epithelial transition (MET). Our cell culture studies from typical ILC cases progressed through more than 10 cell cycles in one year’s time and produced cells with the properties of mesenchymal hybrid cells. Histopathology-breast imaging correlation indicated two ILC subgroups with separate sites of origin. The classic, diffuse type of ILC appears to evolve from the extralobular mesenchyme of the breast. A second subgroup appears to evolve from and generally remain within the intralobular mesenchyme of the breast, appearing as multiple small colonies, each surrounding the acini and terminal ducts of the lobule, which invariably have normal, nonmalignant epithelium. This intralobular subgroup has distinctly different imaging biomarkers, appearing as a distinct tumor mass easily detected at mammography. The 231 consecutive intralobular cases had 84% survival at 19-year follow-up. Differentiating the two is difficult based on the limited field of view offered by the conventional 1x3 inch glass slides. However, low-power histopathology of large sections correlates well with imaging findings and assists in differentiating these two subtypes. This translational research is consistent with new directions in precision medicine.
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