Molecular subtyping of mammary‐like adenocarcinoma of the vulva shows molecular similarity to breast carcinomas

Tessier‐Cloutier, Basile; Asleh, Karama; Shah, Veena; McCluggage, W. Glenn; Tinker, Anna V.; Gilks, C. Blake

doi:10.1111/his.13239

Cited by 26 publications

(22 citation statements)

References 40 publications

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“…A recent IHC study showed that MLAV can be classified into four breast intrinsic subtypes, including a HER2 + /ER − group ( Tran et al 2015 ; Tessier-Cloutier et al 2017 ). Here we note that during the initial pathology workup for the vulvar biopsy for this cancer, the diagnosis of MLAV was not favored on the basis of ER, mammaglobin, and GCDFP-15 negativity.…”

Section: Discussionmentioning

confidence: 99%

“…Current understanding suggests they are modified vulvar eccrine glands that can give rise to a variety of tumors including vulvar adenocarcinomas ( van der Putte 1994 ). Treatment guidelines are traditionally the same across vulvar carcinomas, but new evidence suggests the transposition of some of the preexisting diagnostic and treatment approaches for breast carcinomas to mammary-like adenocarcinomas of the vulva ( McMaster et al 2013 ); these include sentinel node biopsy and molecular subtyping combined with adjuvant therapy ( Abbott and Ahmed 2006 ; Perrone et al 2009 ; Kazakov et al 2011 ; Butler et al 2014 ; Tessier-Cloutier et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Detection and genomic characterization of a mammary-like adenocarcinoma

Grewal

Eirew

Jones

et al. 2017

Cold Spring Harb Mol Case Stud

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Whole-genome and transcriptome sequencing were performed to identify potential therapeutic strategies in the absence of viable treatment options for a patient initially diagnosed with vulvar adenocarcinoma. Genomic events were prioritized by comparison against variant distributions in the TCGA pan-cancer data set and complemented with detailed transcriptome sequencing and copy-number analysis. These findings were considered against published scientific literature in order to evaluate the functional effects of potentially relevant genomic events. Analysis of the transcriptome against a background of 27 TCGA cancer types led to reclassification of the tumor as a primary HER2+ mammary-like adenocarcinoma of the vulva. This revised diagnosis was subsequently confirmed by follow-up immunohistochemistry for a mammary-like adenocarcinoma. The patient was treated with chemotherapy and targeted therapies for HER2+ breast cancer. The detailed pathology and genomic findings of this case are presented herein.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detection and genomic characterization of a mammary-like adenocarcinoma

Grewal

Eirew

Jones

et al. 2017

Cold Spring Harb Mol Case Stud

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“…Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that principally affects the genital and axillary regions. Although the pathogenesis remains to be clarified, it has been reported to resemble breast cancer (BC) in immunohistochemical and molecular profiles . As EMPD typically grows slowly and is diagnosed in situ, the prognosis after surgical resection is generally favorable.…”

Section: Introductionmentioning

confidence: 99%

Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease

et al. 2019

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Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma that clinicopathologically resembles breast cancer. The prognosis of metastatic EMPD is poor. Although several chemotherapies have been tried, the effects are temporary; better drugs and combinations are required. In the present study, we retrospectively analyze the efficacy and safety of combination of cisplatin, epirubicin, and paclitaxel in five metastatic EMPD cases. The efficacy was better than that for previously reported regimens: 80% partial responses, including two patients who were refractory to taxane‐ and/or platinum‐based regimens. In terms of safety, four patients who were able to continue treatment exhibited acceptable tolerability. This is the first regimen to combine taxane and anthracycline. When treating breast cancer, anthracycline is regarded as the key cytotoxic agent, and anthracycline in combination with taxane constitutes a key chemotherapeutic regimen. Given our results, we speculate both drugs are critical chemotherapeutic agents for the treatment of metastatic EMPD.

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“…The in situ VPD cases were more frequently categorized as luminal A (70%) compared with 29% invasive VPD. HER2/neu was overexpressed in 41% of cases, more commonly in the invasive ones (43% vs 30%) 56. We can conclude, after almost 30 years of fragmented and heterogeneous results, that HER2/neu overexpression characterizes at least one-third of VPD lesions, probably a subgroup with worse prognosis related to invasion, recurrence, and node metastases.…”

Section: Resultsmentioning

confidence: 73%

Reviewing vulvar Paget’s disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE

Mantovani

Fagotti

Franchi

et al. 2019

Int J Gynecol Cancer

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ObjectivesTo review the published literature on vulvar Paget’s disease (VPD) molecular bases, aiming to support the need for tailored treatment in women affected by this 'orphan' tumor.MethodsMEDLINE-PubMed and Scopus were interrogated using the following algorithm: (extramammary OR extra mammary OR vulvar) AND (paget OR pagets OR paget's) AND (molecular OR biological OR marker OR protein OR target OR expression). The inclusion criteria for papers were: peer-reviewed English-language journals, articles published in the last 30 years, studies focused on fixed research questions, quality assessment on the basis of the relevance and contribution to the selected topics.ResultsA total of 42 studies were selected, providing the following results. Molecular markers implicated in cell cycle transitions seem to be related to prognosis and could help to tailor conventional treatments. Fragmented but consistent preliminary data exist on hormonal receptor expression, ERBB2 amplification/overexpression and abnormal vascular proliferation, offering a concrete possibility for target therapy trials. Conversely, other fields linked to the possible use of immunotherapy are currently relatively unexplored, such as the tumor 'immune contexture', programmed death ligand-1 (PD-L1) expression and defects in the mismatch repair system, which is involved in genomic instability and potentially promotes a consistent response to treatment.ConclusionsAdditional effort is needed to further characterize these aspects. Centralization of patients in dedicated units would be beneficial for concentrating patient numbers, collecting valuable clinical data and conducting clinical trials. Interdisciplinary study platforms should be developed and integrated into wider multicentric networks.

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Molecular subtyping of mammary‐like adenocarcinoma of the vulva shows molecular similarity to breast carcinomas

Abstract: Breast cancer subtyping can be applied to vulvar MLAs. All four intrinsic molecular subtypes are seen, with frequencies similar to those in breast carcinoma. Our results support the potential use of breast cancer molecular profiling algorithms to guide treatment for these cancers.

Cited by 26 publications

References 40 publications

Detection and genomic characterization of a mammary-like adenocarcinoma

Detection and genomic characterization of a mammary-like adenocarcinoma

Combination Cisplatin-Epirubicin-Paclitaxel Therapy for Metastatic Extramammary Paget's Disease

Reviewing vulvar Paget’s disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE

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