What Is Atypical Lobular Hyperplasia and What Does It Mean for the Patient?
Authors: David L. Page, Jean F. Simpson
Journal: Journal of Clinical Oncology (2005)

One of the most remarkable things about invasive lobular carcinoma and its certain nonobligate precursors (atypical lobular hyperplasia[ALH] and lobular carcinomain-situ [LCIS]) is that, unless presenting in a higher cytologic and histologic grade, it has the clinical pattern of a slow-growing tumor, invariably expressing estrogen and progesterone receptors, with responsiveness to modulators of the estrogen receptor complex. Therefore, in the spectrum of precursor lesions of invasive breast cancer, where do lobular neoplasia (ALH/LCIS) and its variable presentations stand? Minimal examples (so-called minimal ALH) contain the characteristic cells without distention of the lobules; we reserve the diagnosis of LCIS for characteristic changes that grossly distort lobular units. In the formal cohort follow-up studies that have been performed on these lesions since 1980, the concept of ALH has been used by the two largest studies from Vanderbilt and Harvard. Neither of these groups diagnose LCIS often in their series of patients; when they do, a higher risk for more extensive lesions has been indicated. The study by Chuba et al in this issue presents balanced conclusions from a Surveillance, Epidemiology, and End Results (SEER) database in which the specific pathologic type of lobular neoplasia is not specified and undoubtedly includes a dominant number of patients with ALH. The overall 7.1% incidence of invasive breast cancer after a diagnosis of lobular neoplasia is lower than what others have reported, and this is probably a result of the inclusion of so-called minimal examples of ALH, which is a lesion that was not associated with increased risk of invasive breast cancer in early studies. The fact that the subsequent risk of invasive breast cancer in the SEER study is equal in the two breasts is remarkable because most of the formal studies that have looked at laterality have actually documented an incidence of invasive cancer in the contralateral breast that is less than one half of the incidence documented in the ipsilateral breast. The reasons for this discrepancy are not apparent. We know that there is a risk for the contralateral breast when lobular neoplasia is diagnosed, and it is possible that removal of larger amounts of breast tissue in women who had partial mastectomy in this SEER study led to equal risk of the opposite breast. The importance of unilateral risk is documented in the experience of Rosen et al presented in 1981. Women in that study who underwent single mastectomy experienced no deaths from cancer and had a risk in the contralateral breast that was not demonstrably greater than the general population. It is important to note that some women with demonstrated LCIS in the contralateral breast were offered bilateral mastectomy. Also, there is an important indication that there is a regional risk associated with ALH that should be studied carefully. Anecdotal experience indicates there are anatomic areas of the breast that are more likely to be involved than others. Indeed, occasionally, a patient has quite dense disease that presents in a single location similar to ductal carcinoma-in-situ that has lobular cytology. This is another special area that needs some formal attention. Both the Nashville series and the Nurses’ Health Study found that the incidence of invasive breast cancer after a diagnosis of lobular neoplasia decreased after menopause. However, the SEER data show an increasing incidence after menopause; more than half of the patients at risk were greater than 50 years old, and more than a quarter of the patients were diagnosed with LCIS after the age of 60 years. As Chuba et al point out, the time frame of the study included patients who were detected later through mammography, which also will introduce ambiguity in the results. One wonders how many of the LCIS lesions diagnosed in the SEER database were truly incidental (ie, unassociated with prebiopsy detection), as was the case in the early defining studies of lobular neoplasia. JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 24 AUGUST 2