Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2-positive extramammary Paget's disease: A case report and review of the literature

Ichiyama, Takashi; Gomi, Daisuke; Fukushima, Toshirou; Kobayashi, Takashi; Sekiguchi, Nodoka; Sakamoto, Akiyuki; Sasaki, Shigeru; Mamiya, Keiko; Koizumi, Tomonobu; Hama, Yoshihisa

doi:10.3892/mco.2017.1422

Cited by 39 publications

(38 citation statements)

References 13 publications

(20 reference statements)

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“…Furthermore, about 90% of patients exhibited no difference in the HER2 protein overexpression and ERBB2 gene amplification between primary tumors and corresponded LN metastasis ( 23 ), suggesting that HER2’s contribution to the pathogenesis and progression in a subset of metastatic EMPD and implying the possibility that HER2 blockade disrupts the progression of both primary and metastatic lesions of this population. In corroboration with the hypothesis, six case reports determined that both primary and metastatic lesion of HER2-overexpressed EMPD responded well and attained partial or complete response for 6 months to 2 years by anti-HER2 antibody, trastuzumab alone, or trastuzumab with paclitaxel (Table 1 ) ( 24 – 29 ). A phase 2 study of trastuzumab with docetaxel for HER2-positive unresectable or metastatic EMPD (UMIN000021311) is ongoing based on these results.…”

Section: Her2–pi3k/erk Signaling In Empdmentioning

confidence: 64%

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Fukuda

Funakoshi

2018

Front. Oncol.

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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.

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Section: Her2–pi3k/erk Signaling In Empdmentioning

confidence: 64%

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Fukuda

Funakoshi

2018

Front. Oncol.

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“…Selected cases of EMPD (with amplified ERBB2/HER2 gene) have been successfully treated with trastuzumab alone or in combinations with chemotherapy. 4,[15][16][17][18][19][20][21] In contrast to MPD, we found overexpression and HER2 gene amplification in a minority of cases, and a co-amplification with TOPO2 in a single case of vulvar disease. Amplification of TOPO2 gene and expression of Topo2 protein in several cases of EMPD is a novel finding in our cohort.…”

Section: Discussionmentioning

confidence: 97%

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

et al. 2020

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Background Primary Extra‐mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. Methods Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy‐relevant protein biomarkers). Results Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD‐L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a “high” tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. Conclusions EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD‐L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.

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“…5 Except for traditional chemotherapy, previous studies have reported HER2-targeted monoclonal antibody (trastuzumab) could yield significant clinical benefit in lymph node-metastatic penoscrotal EMPD patients with HER2 amplification. 9 Pyrotinib is an oral irreversible tyrosine kinase inhibitor capable of inhibiting the HER1, HER2, and HER4. Until now, there has been no any report about the effectiveness of pyrotinib in those patients with HER2 gene alteration.…”

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confidence: 99%

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

Guo¹,

Jiao²,

Wu³

et al. 2020

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Background: Previous studies have suggested the efficacy of HER2 antibody (trastuzumab) in scrotal Paget's disease with HER2 amplification or overexpression. However, no report about the effectiveness of HER2 inhibitor (pyrotinib) in those patients has been provided until now. Case Presentation: We present a case of a Chinese patient with bone-metastatic scrotal Paget's disease harboring triple uncommon HER2 mutations (R678Q/S310Y/S310F). Due to poor conditions (severe anemia, thrombocytopenia, ECOG PS3), this patient could not tolerate traditional chemotherapy and radiotherapy. Then, the patient participated in a registered clinical trial (NCT03239015) about basket trial for intractable cancer. The patient received pyrotinib (400 mg po qd) and achieved a partial response for 4.0 months. Conclusion: This is the first report describing a patient with scrotal Paget's disease harboring triple uncommon HER2 mutation who responds well to pyrotinib. This case suggested that HER2 mutation is also a potential biomarker for treatment in extramammary Paget's disease and pyrotinib may be an ideal choice for these patients.

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Successful and long-term response to trastuzumab plus paclitaxel combination therapy in human epidermal growth factor receptor 2-positive extramammary Paget's disease: A case report and review of the literature

Cited by 39 publications

References 13 publications

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Metastatic Extramammary Paget’s Disease: Pathogenesis and Novel Therapeutic Approach

Comparison of the biomarkers for targeted therapies in primary extra‐mammary and mammary Paget's disease

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

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