Abstract
Extramammary Paget’s disease (EMPD) is a rare, slow-growing, cutaneous adenocarcinoma that usually originates in the anogenital area and axillae outside the mammary glands. EMPD mostly progresses slowly and is often diagnosed as carcinoma in situ; however, upon becoming invasive, it promptly and frequently metastasizes to regional lymph nodes, leading to subsequent distant metastasis. To date, several chemotherapy regimens have been used to treat metastatic EMPD; however, they present limited effect and patients with distant metastasis exhibit a poor prognosis. Recently, basic and translational investigative research has elucidated factors and molecular mechanisms underlying the promotion of metastasis, which can lead to targeted therapy-based emerging treatment strategies. Here, we aim to discuss current therapies and their limitations; advancements in illustrating mechanisms promoting invasion, migration, and proliferation of EMPD tumor cells; and future therapeutic approaches for metastatic EMPD that may enhance clinical outcomes.
Highlights
Type of responseYoshino et al [7] Mikoshiba et al [8] Kato et al [9] Matsushita et al [10] Ogata et al [11] Egashira et al [12] Hirai and Funakoshi [13] Karam et al [24] Wakabayashi et al [27] Barth et al [28] Takahagi et al [25] Hanawa et al [26] Ichiyama et al [29] Yoneyama et al [45]
Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology
It was reported that an anti PD-1 antibody induced robust antitumor immunity and attained durable disease control in heavily treated patients with colorectal cancer with MMR-deficient or microsatellite instability-high (MSI-H) status [62]. These results propose that the MMR status or MSI-H is a useful biomarker to predict the clinical benefit of anti-PD-1 antibody, serving as the basis for the Food and Drug Administration (FDA)’s approval of an anti-PD-1 antibody for unresectable or metastatic MMR-deficient or MSI-H cancers, irrespective of cancer’s original location
Summary
Yoshino et al [7] Mikoshiba et al [8] Kato et al [9] Matsushita et al [10] Ogata et al [11] Egashira et al [12] Hirai and Funakoshi [13] Karam et al [24] Wakabayashi et al [27] Barth et al [28] Takahagi et al [25] Hanawa et al [26] Ichiyama et al [29] Yoneyama et al [45]. Several EMPD studies have focused on investigating the HER2–PI3K/ERK signaling in EMPD because it is characterized by the presence of Paget cells, large round, vacuolated, pale-staining cells, as mammary Paget’s disease (MPD) and the clinical success in targeting aberrant receptor tyrosine kinase signaling pathways in breast cancer. Both immunohistochemistry and fluorescence in situ hybridization studies of primary and LN metastatic lesions have revealed the HER2 overexpression (HER2 score of 3+ or 2+) in 15–58% of patients with EMPD and that all cases with a HER2 score of 3+ had amplified ERBB2, the gene encoding HER2 [16, 22]. The expression of HER1, HER3, and HER4 has never been detected in EMPD as well as in MPD, and targeting the dimerization of HER2 is unlikely to prove clinical significance in HER2-positive metastatic EMPD [38, 39]
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