Lobular Carcinoma In Situ of the Breast.

Abstract

LCIS was first described in 1941 as a distinct pathologic entity by Foote and Stewart who called it a "rare form of mammary carcinoma." It is thought to represent a transitional intra-epithelial, or in situ, stage in the evolution of breast cancer from hyperplastic breast epithelium. With the wide application of mammography, its detection has increased in recent years, being found in approximately 1% of all breast biopsy specimens and 5% of all breast malignancies. Its true incidence is unknown, because the absence of any clinical or radiographic manifestations makes its detection completely arbitrary and random. LCIS has distinct pathologic features characterized by proliferation of bland, homogeneous malignant cells within the terminal duct-lobular apparatus. The lobular architecture and investing basement membrane remain intact with no evidence of invasion into the surrounding stoma. It is assumed to be widely disseminated throughout all breast tissue whenever it is found, having close to 100% incidence of multicentricity and bilaterality. The cells are typically of low histologic and nuclear grade, highly estrogen receptor positive, and have tumor marker characteristics of indolent growth and good prognosis. This is very different from its noninvasive ductal counterpart, DCIS, which is typified by more aggressive cytologic and biologic characteristics. Although LCIS imparts as much as a 12-fold increased risk of subsequent invasive breast carcinoma, its natural history suggests it is more of a marker of risk rather than a true premalignant lesion. Most subsequent malignancies occur more than 15 years after diagnosis, and are ductal rather than lobular. This risk is also equally applied to both breasts, regardless of which breast contains the diagnosed focus. Subsequent invasive breast cancers are typically early with very low mortality, most likely due to the strict mammographic surveillance provided to these women. Although originally treated by mastectomy, most now manage LCIS by careful non-operative observation, in the same way that other risk factors such as family history or atypical hyperplasia are managed. In fact, it has been questioned whether there should be any real distinction between lobular hyperplasia and LCIS. There is no role for excision of biopsy sites of LCIS to obtain clear margins, nor for cytotoxic chemotherapy. However, the NSABP P-1 Prevention Trial strongly suggests that subsequent risk can be significantly reduced by tamoxifen. The only rational surgical treatment, if ablation is judged necessary, would be bilateral mastectomy, which appears far too aggressive in view of its low overall risks. Further investigation should clarify the optimal management of LCIS.