Abstract:
:Male breast cancer (MBC) is extremely rare and accounts for less than 1% of all breast malignancies. Therefore, clinical management of MBC is currently guided by research on the disease in females. In this study, DNA obtained from 45 formalin-fixed paraffin-embedded (FFPE) MBCs with and 90 MBCs (52 FFPE and 38 fresh-frozen) without matched normal tissues was subjected to massively parallel sequencing targeting all exons of 1943 cancer-related genes. The landscape of mutations and copy number alterations was compared to that of publicly available estrogen receptor (ER)-positive female breast cancers (smFBCs) and correlated to prognosis. From the 135 MBCs, 90% showed ductal histology, 96% were ER-positive, 66% were progesterone receptor (PR)-positive, and 2% HER2-positive, resulting in 50, 46 and 4% luminal A-like, luminal B-like and basal-like cases, respectively. Five patients had Klinefelter syndrome (4%) and 11% of patients harbored pathogenic BRCA2 germline mutations. The genomic landscape of MBC to some extent recapitulated that of smFBC, with recurrent PIK3CA (36%) and GATA3 (15%) somatic mutations, and with 40% of the most frequently amplified genes overlapping between both sexes. TP53 (3%) somatic mutations were significantly less frequent in MBC compared to smFBC, whereas somatic mutations in genes regulating chromatin function and homologous recombination deficiency-related signatures were more prevalent. MDM2 amplifications were frequent (13%), correlated with protein overexpression (P = 0.001) and predicted poor outcome (P = 0.007). In conclusion, despite similarities in the genomic landscape between MBC and smFBC, MBC is a molecularly unique and heterogeneous disease requiring its own clinical trials and treatment guidelines.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Moelans CB,de Ligt J,van der Groep P,Prins P,Besselink NJM,Hoogstraat M,Ter Hoeve ND,Lacle MM,Kornegoor R,van der Pol CC,de Leng WWJ,Barbé E,van der Vegt B,Martens J,Bult P,Smit VTHBM,Koudijs MJ,Nijman IJ,Voest EE,Sdoi
10.1530/ERC-19-0278subject
Has Abstractpub_date
2019-10-01 00:00:00pages
779-794issue
10eissn
1351-0088issn
1479-6821pii
ERC-19-0278journal_volume
26pub_type
杂志文章abstract::Thyrotoxicosis with concomitant thyroid cancer is rare and poorly recognized, which may result in delayed diagnosis, inappropriate treatment and even poor prognosis. To provide a comprehensive guidance for clinicians, the etiology, pathogenesis, diagnosis and treatment of this challenging setting were systematically r...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0129
更新日期:2019-07-01 00:00:00
abstract::Resveratrol is a naturally occurring polyphenol that provides a number of anti-aging health benefits including improved metabolism, cardioprotection, and cancer prevention. Much of the work on resveratrol and cancer comes from in vitro studies looking at resveratrol actions on cancer cells and pathways. There are, how...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-13-0171
更新日期:2014-05-06 00:00:00
abstract::'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0059
更新日期:2009-03-01 00:00:00
abstract::Approximately 80% of human ovarian and endometrial cancers and 50% of breast cancers express GnRH and its receptor as part of an autocrine regulatory system. After binding of its ligand the tumor GnRH receptor couples to G-protein alphai and activates a variety of intracellular signaling mechanisms. (1) Through activa...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0100291
更新日期:2003-06-01 00:00:00
abstract::Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemother...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0290
更新日期:2011-04-28 00:00:00
abstract::The potential of aromatase (estrogen synthetase) within the breast to provide a significant source of estrogen mediating tumor proliferation is suggested by studies reporting 4- to 6-fold higher estrogen levels in tumors than in plasma of postmenopausal patients with breast cancer. Recent studies in our laboratory hav...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0060205
更新日期:1999-06-01 00:00:00
abstract::Apoptosis is a frequent phenomenon in breast cancer and it can be detected by light microscopy in conventional histopathological sections or by special staining techniques. The number of apoptotic cells as a percentage of cells present, or the number of apoptotic cells per square millimetre of neoplastic tissue, is us...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0060013
更新日期:1999-03-01 00:00:00
abstract::Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the p...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0078
更新日期:2016-08-01 00:00:00
abstract::Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0060333
更新日期:1999-09-01 00:00:00
abstract::Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0565
更新日期:2017-07-01 00:00:00
abstract::Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usua...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.01026
更新日期:2005-09-01 00:00:00
abstract::Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0110131
更新日期:2004-03-01 00:00:00
abstract::Recent studies have indicated that a high-fat diet (HFD) plays an important role in prostate cancer (PCa) progression. Palmitic acid (PA) is one of the most abundant saturated free fatty acids (FAs) and is associated with carcinogenesis. In this study, we investigated the mechanism underlying the association of dietar...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0227
更新日期:2013-12-16 00:00:00
abstract::Deubiquitinases (DUBs) play important roles and therefore are potential drug targets in various diseases including cancer and neurodegeneration. In this review, we recapitulate structure-function studies of the most studied DUBs including USP7, USP22, CYLD, UCHL1, BAP1, A20, as well as ataxin 3 and connect them to reg...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0516
更新日期:2015-02-01 00:00:00
abstract::Novel strategies are needed for the treatment of adrenocortical tumors that are usually resistant to chemotherapy. Hecate, a 23-amino acid lytic peptide, was conjugated to the 15-amino acid (81-95) fragment of the human chorionic gonadotropin beta (CGbeta) chain, which would selectively kill cancer cells expressing th...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0015
更新日期:2008-06-01 00:00:00
abstract::The HIV protease inhibitor Nelfinavir (NFV) inhibits PI3K/AKT and MAPK/ERK signaling pathways, emerging targets in thyroid cancers. We examined the effects of NFV on cancer cells that derived from follicular (FTC), papillary (PTC) and anaplastic (ATC) thyroid cancers. NFV (1-20 µM) was tested in FTC133, BCPAP and SW17...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0568
更新日期:2017-03-01 00:00:00
abstract::Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females pres...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0059
更新日期:2011-06-08 00:00:00
abstract::Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0555
更新日期:2016-04-01 00:00:00
abstract::Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utiliz...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01018
更新日期:2005-07-01 00:00:00
abstract::Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0538
更新日期:2019-03-01 00:00:00
abstract::Androgen deprivation therapy (ADT) is a highly effective treatment used in ∼30% of men with prostate cancer. Adverse effects of ADT on muscle are significant with consistent losses in muscle mass. However, effects of ADT on muscle strength and physical function, of most relevance to the patient, are less well understo...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0232
更新日期:2016-01-01 00:00:00
abstract::Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown hig...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0130
更新日期:2016-09-01 00:00:00
abstract::Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0267
更新日期:2014-10-01 00:00:00
abstract::Over the past years there have been significant advances in breast cancer treatment and early detection. For the first time, a decrease in cancer mortality has been observed. Recently, much progress has been made in the understanding of carcinogenesis partly due to available new technologies to detect early molecular ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0090015
更新日期:2002-03-01 00:00:00
abstract::The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this repo...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0008
更新日期:2009-06-01 00:00:00
abstract::Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options. We explored novel treatment modalities by targeting epigenetic modifications using inhibitors of BET (e.g. BRD4) activity. We evaluated the efficacy in the treatment of ATC of a novel BET inhibitor, PLX51107 (PLX), currently in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-19-0107
更新日期:2019-09-01 00:00:00
abstract::Carney triad (CT) is a rare condition with synchronous or metachronous occurrence of gastrointestinal stromal tumors (GISTs), paragangliomas (PGLs), and pulmonary chondromas in a patient. In contrast to Carney-Stratakis syndrome (CSS) and familial PGL syndromes, no germline or somatic mutations in the succinate dehydr...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0254
更新日期:2014-08-01 00:00:00
abstract::The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0538
更新日期:2017-07-01 00:00:00
abstract::The central involvement of estrogen in the development of the mammary gland and in the genesis of breast cancer has lent impetus to studies of the links between estrogen action and the cell cycle machinery. Recent studies of the estrogenic regulation of molecules with known roles in the control of G1/S phase progressi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0100179
更新日期:2003-06-01 00:00:00
abstract::It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章
doi:10.1677/erc.1.00822
更新日期:2004-12-01 00:00:00