Normal breast lobular architecture in breast biopsy samples from breast cancer cases and benign disease controls

Rodent studies suggest a relationship between lobular maturation and breast cancer risk. Human data are sparse, and were developed using whole mounts of mastectomy or mammoplasty samples, without consideration of menstrual phase in premenopausal women. We studied normal breast lobules in relation to cancer risk in 284 women, using surgical biopsy material (mean two sections and 43.2 lobular structures per subject): 167 were premenopausal; 89 with breast cancer (cases) and 78 undergoing benign breast biopsy (controls). Of 117 postmenopausal women, 67 were cases and 50 were controls. Normal lobular type was classified based on size, and was designated predominant if it constituted 60% or more of the total lobules classified. The control group showed 66% type I, 34% type II and 1% type III lobules while cases showed 69% type I, 31% type II and 7% type III structures. Predominant lobule type showed no association with cancer (p = 0.9). Postmenopausal women had a substantially higher proportion of type I lobules compared to premenopausal women, irrespective of the parity or cancer status (p < 0.001). Lobule type was not associated with menstrual phase classified by dates; however, when menstrual phase was classified using breast morphological characteristics, type I lobules were more abundant in follicular phase and type II in the luteal phase (p < 0.001). In conclusion, we did not observe a relationship between lobular architecture and breast cancer susceptibility when using smaller breast samples usually available in epidemiological studies, but these data highlight the need for menstrual phase stratification in future investigations.