Estrogen Receptor Expression in Atypical Hyperplasia: Lack of Association with Breast Cancer

Abstract

Estrogen receptor (ER) is expressed in normal and malignant breast epithelium, and expression levels have been found to increase with age in normal breast epithelium but not in atypical hyperplasia (AH) and carcinoma in situ. Here we assess ER expression in AH and its association with later breast cancer. ER expression was assessed immunohistochemically in archival sections from 246 women with AH who had open benign breast biopsy from 1967 to 1991. The ACIS III (Dako) was utilized to calculate ER expression in all atypical foci. Using multivariate linear regression, we examined associations of ER expression with age at biopsy, indication for biopsy, type of atypia, number of atypical foci, involution status, and family history. Breast cancer risk across levels of ER expression was also assessed compared with the Iowa SEER control population. Among 246 women, 87 (35%) had atypical ductal hyperplasia (ADH), 141 (57%) had atypical lobular hyperplasia (ALH), and 18 (7%) had both. Forty-nine (20%) developed breast cancer (median follow-up of 14.4 years). Multivariate analysis indicated that type of atypia and age at diagnosis were significantly associated with ER percent staining and intensity (P < 0.05). ER expression was increased in women with ADH and/or those over age 55. ER expression did not significantly impact breast cancer risk in patients diagnosed with atypia. We found increasing ER expression in AH with increasing age. ER expression in AH does not further discriminate breast cancer risk in women with atypia.

Understanding the Premalignant Potential of Atypical Hyperplasia through Its Natural History: A Longitudinal Cohort Study

“…(30, 33–40) Second, molecular classification methods have provided evidence that ER-positive and ER-negative BC are fundamentally different diseases, with different etiologies, (reviewed in 41,42) where lower grade and better prognosis BCs are generally ER-positive (in the intrinsic classification system, these usually associate with the luminal category), and higher grade/poorer prognosis BCs are generally ER negative (associating with the HER2 and basal categories). That atypias are generally ER positive (43–44) provides further circumstantial evidence for a role of atypias as a precursor or risk factor for development of lower grade/better prognosis BC.…”

Atypical Hyperplasia of the Breast — Risk Assessment and Management Options

“…Of note, both the percentage of positive cells and the staining intensity were greater in ductal lesions than in lobular lesions (P<0.001). 25 …”

“…69,70 The high level of estrogen-receptor expression in atypical hyperplasia 25 and the estrogen-receptor positivity of the large majority of breast cancers that develop in women with atypical hyper-plasia provide additional rationale for the use of antiestrogen therapy for prevention.…”

ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias

“…The cohort and verification of atypical hyperplasia has been described previously. [32] Among 334 women in the cohort diagnosed with atypia between 1967 and 1991, adequate tissue for ERβ staining was available for the 171 women who form the basis of this study. Median follow-up of this atypia subcohort was 15 (range 1 to 36) years.…”

“…[34] Immunostaining and assessment for ERα and Ki-67 was performed as previously described. [32,35] For this analysis of ERβ expression the tissues studied included the epithelia of the atypical hyperplasia lesion(s), referred to as “the atypia”, and epithelia of histologically normal lobules from the same tissue section as the atypia, hereafter called normal or adjacent normal lobules.…”