Current perspectives on diagnosis and management of primary and secondary breast endometriosis and potential risk of breast cancer

Abstract

Breast endometriosis represents an exceptionally rare extragenital manifestation of ectopic endometrial tissue, with only a few histologically confirmed breast cases reported worldwide. There appears to be a potential relationship between endometriosis and an increased risk of developing breast cancer. The proposed mechanisms include chronic inflammation, oxidative stress, hormonal dysregulation, and genetic factors such as mutations in the GATA binding protein 2, phosphatase and tensin homolog, Kirsten rat sarcoma viral oncogene homolog, and AT-rich interactive domain-containing protein 1A genes, as well as alterations in circulating microRNAs, primarily miR-199a and the let-7 family of miRNAs. However, the molecular mechanisms underlying this association are not yet fully understood. A structured literature search revealed a small number of primary and secondary breast cases, all of which were confirmed by histopathology. Primary lesions occurred spontaneously, whereas secondary cases were associated with prior breast surgery, suggesting possible implantation of endometrial tissue during surgical manipulation. Morphologic diagnosis relies on identifying endometrial glands and stroma, supported by immunoreactivity for CD10 and paired box gene 8 and negativity for GATA binding protein 2. Clinically, lesions may present as palpable nodules or painful masses, often mimicking malignancy or fat necrosis, particularly in patients with a history of reconstructive or reduction surgery. Complete surgical excision was curative in all reported cases, with no recurrence or malignant transformation documented during follow-up. Although exceedingly rare, recognition of this entity is essential to avoid misdiagnosis and to enhance the understanding of the mechanisms underlying ectopic endometrial implantation in extrapelvic sites such as the breast.

Keywords: Endometriosis; Mammary endometriosis; Rare breast lesions; Genomic profile of endometriosis; Ectopic extrapelvic location; Palpable nodules; Painful masses; Malignant transformation risk

Core Tip: Breast endometriosis constitutes an exceedingly uncommon extragenital presentation of ectopic endometrial tissue, with only a limited number of histologically verified cases documented globally. Endometriosis is associated with increased risks of breast, endometrial, ovarian, and thyroid cancers; melanoma; and non-Hodgkin lymphoma. Given its potential for clinical and radiologic mimicry of malignancy and its implications for surgical management, breast endometriosis warrants awareness among pathologists and breast surgeons. Current genomic research has opened new horizons in both diagnosis and therapy. Surgical excision is the method of choice, offering a permanent cure and no recurrence.