Possible role of anastrozole-induced hormonal alterations in pathogenesis of mammary apocrine carcinoma and follicular lymphoma: a case report and review of the literature

Abstract

Background: In postmenopausal women, aromatase inhibitors decrease estrogen levels and increase local dihydrotestosterone concentrations. In this case report, we describe interesting associations between aromatase-inhibitor-induced hormonal changes and the development of apocrine mammary carcinoma and follicular lymphoma. Case presentation: Here we report an 83-year-old Caucasian female patient who initially presented with Paget's disease of the right nipple and associated small focus of invasive ductal carcinoma (ERα + PR + HER2-). The patient did not pursue surgical resection and was treated only with anastrozole, and 5 years later, she was diagnosed with a 1.1 cm ipsilateral periareolar apocrine mammary carcinoma (ERα-ERβ + PR - AR + HER2-) that was detected during surveillance mammography. In addition to this tumor, the subsequent mastectomy specimen revealed an adjacent residual focus of the original invasive ductal carcinoma (ERα + ERβ + PR + AR + HER2-) within the nipple and a focus of follicular lymphoma (ERα-ERβ + ARlow) in the retroareolar area. Sentinel lymph nodes and imaging studies were negative for malignancy. The patient was continued on observation. Anastrozole was stopped after 10 months, and 2 months later, during a routine screening, a 1.8 cm invasive apocrine carcinoma (ERα-ERβ + PR-AR + HER2-) was detected in the patient's contralateral breast and she underwent simple mastectomy with sentinel lymph node biopsy. The sentinel lymph node was negative. No chemotherapy or radiation therapy was recommended. All carcinomas exposed to anastrozole expressed androgen-responsive molecules (GCDFP-15, NKX3.1). Germline genetic testing for 19 genes associated with hereditary breast cancer syndromes was negative, and 3 years later, the patient is still alive with no recurrences. Conclusion: Our case suggests that unopposed local androgen exposure and loss of ERβ-mediated suppressive effect of estrogens may be involved in development of apocrine mammary tumors and lymphomas, respectively. However, further studies are necessary to clarify the roles of steroid hormones in pathogenesis of apocrine carcinoma and follicular lymphoma. This case also illustrates the importance of patient follow-up during and after aromatase inhibitor therapy. Appropriate surveillance for lymphoma may also be considered for those patients. Finally, when lymphoid aggregates are encountered in specimens from patients with breast cancer, a clinical history of hormonal therapy should alert the pathologist for a possibility of lymphoma.