Differences in Breast Cancer Risk Between Atypical Lobular Hyperplasia and Atypical Ductal Hyperplasia

Women with atypical hyperplasia of the breast have an approximately 3-fold to 5-fold increased risk for the development of breast carcinoma, when compared with women having nonproliferative breast lesions or those in the general population. Most studies examining the risk associated with atypical hyperplasia have grouped both atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) into a single category for the purposes of statistical analysis. Little information is available regarding what, if any, differences in breast cancer risk exist between ADH and ALH. In an update from the Nurses’ Health Study, Collins et al evaluated the breast cancer risk associated with these two types of atypical hyperplasia. The authors performed a nested case-control study among participants in the Nurses’ Health Study (begun in 1976) and Nurses’ Health Study II (begun in 1989). Women with nonproliferative disease constituted the reference group. The criteria of Page et al were used to categorize the atypical hyperplasias as either ADH or ALH. Consistent with prior observations by their group and others, the authors found that women with any form of atypical hyperplasia had an odds ratio (OR) of 4.04 for the development of invasive breast cancer and an OR of 4.11 for invasive or in situ breast cancer. When the two subtypes of atypical hyperplasia were analyzed independently, they found that ALH was associated with a greater risk for subsequent cancer than ADH (Table 1). Women with ALH had an OR of 5.46 for development of invasive cancer and an OR of 5.49 for any cancer (invasive or in situ). In contrast, women with ADH had an OR of 2.82 for invasive cancer and an OR of 3.09 for any cancer. The difference approached statistical significance (P=0.09 for any cancer). As the ORs were very similar when invasive cancer or any cancer was used as an end point, the authors used the development of either invasive or in situ breast cancer as the end point for the remaining analyses. The difference in risk between ALH and ADH was most striking among women who were premenopausal at the time of their initial diagnosis of atypical hyperplasia. Premenopausal women diagnosed with ALH had an OR for cancer of 7.30, compared with those having ADH who had an OR of 2.72. This difference was statistically significant (P=0.02). Among women who were postmenopausal at the time of the index biopsy, however, the breast cancer risk associated with ALH and ADH was similar (OR, 3.41 vs. 4.04, respectively). These data suggest that premenopausal women diagnosed with ALH represent a particularly high-risk group. The authors also evaluated the risk for breast cancer over time and found that for the general category of atypical hyperplasia, the risk of developing cancer Z10 years after index biopsy was slightly greater than the risk within the first 10 years (OR, 5.15 vs. 3.31, respectively). The risk associated with ALH seemed relatively constant over time, with an OR of 5.57 for breast cancer within 10 years and an OR of 5.80 for cancer Z10 years after index biopsy. The risk associated with ADH increased over time, with an OR of 2.40 for the first 10 years and an OR of 4.82 for Z10 years after index biopsy. These data highlight the long-term breast cancer risk associated with a diagnosis of atypical hyperplasia. They also suggest that women with ALH may be more likely to develop carcinoma with the first 10 years after diagnosis than women with ADH (P=0.06). Subsequent breast carcinomas in women with ALH and ADH showed similar rates of ipsilaterality, 61.3% and 55.9%, respectively. The rates of ipsilateral cancer for the atypical hyperplasias were similar to those seen in women with a history of non-proliferative lesions (51.7%) and proliferative lesions without atypia (50.3%). Although other studies have found a higher rate of ipsilateral cancer associated with ALH, the Nurses’ Health Study data lend support to the current clinical approach to atypical hyperplasias where they are managed as generalized risk factors. The update from Collins et al substantiates in a larger study population the group’s previously reported observations regarding atypical hyperplasia. Interestingly, the magnitude of breast cancer risk for ALH and ADH in the Nurses’ Health Study differs somewhat from that found in the Nashville cohort, in which there was a lower risk associated with ALH (relative risk, 3.1) and a greater risk associated with ADH (relative risk, 4.7). Variations in the characteristics of the study populations may be contributing to these different risk estimates, as may differences in the length of follow-up time. Although some of the confidence intervals were broad in the TABLE 1. Adjusted ORs for Development of Invasive or In Situ Breast Carcinoma