Prognostic value of morphometry in patients with normal breast tissue or usual ductal hyperplasia of the breast

Women with usual ductal hyperplasia have a relative risk of 1.6-1.9 of subs equent breast cancer development. This slightly increased risk is generally not considered sufficiently high to justify (chemo)preventive therapy. It is therefore important to identify high-risk ductal hyperplastic lesions th at would benefit from such a treatment. Nuclear morphometric features have been shown in previous work to be useful for objectively describing morphol ogic features associated with high risk in (pre)invasive breast lesions. Th e aim of this study was to evaluate whether such morphometric features can also predict subsequent invasive cancer development in patients with the co mmon pattern of usual ductal hyperplasia or a normal breast biopsy. The pre sent case-control study included 423 women with normal breast biopsies (n = 89) or biopsies containing usual ductal hyperplasia (n = 334). Of these 42 3 women, 132 developed invasive breast cancer during follow-up (mean 16.7 /- 7.0 years). On the original hematoxylin and eosin-stained sections, nucl ear morphometry was performed with a digitizing video overlay system, and m itotic and apoptotic indices were assessed. Patients with mean nuclear feat ure values for area, perimeter, diameter or longest axis above the 75(th) p ercentile had 1.6-1.7 times the breast cancer risk of women with mean nucle ar feature values below this value. Pairwise combinations of these features yielded slightly higher cancer risks for the fourth quartile patients, wit h the highest risk (1.9) for patients with SID of nuclear area and perimete r values above the 75(th) percentile. The number of apoptotic or mitotic ce lls had no prognostic value for patients with apparently normal tissue or u sual ductal hyperplasia. Our results give a first indication that normal br east tissue or usual ductal hyperplasia harbor nuclear morphologic changes that, when assessed by morphometry, may be used to predict breast cancer de velopment. It is worthwhile studying this further in independent groups of patients with long-term follow-up. (C) 2001 Wiley-Liss, Inc.