Mammary Epithelial-Myoepithelial Carcinoma: Report of a Case With <i>HRAS</i> and <i>PIK3CA</i> Mutations by Next-Generation Sequencing

Baum, Jordan E.; Sung, Kap-Jae; Tran, Hung D.; Song, Wei; Ginter, Paula S.

doi:10.1177/1066896918821182

Cited by 25 publications

(27 citation statements)

References 16 publications

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“…This study nding is consistent with ndings by Fletcher, which reported that age may play a role in increased risk of developing triple-negative breast cancer. Premenopausal women have been found to develop triple-negative breast cancer more often than postmenopausal women [35]. In another similar study conducted in China revealed that women aged forty years and below were more likely to be PR positive compared to those aged above 40 years [36] which is in agreement with the current study.…”

Section: Discussionsupporting

confidence: 92%

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing of Women Breast Cancer in Kampala, Uganda.

Mlole

Yahaya

Othieno

et al. 2020

Preprint

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Background: The expression of estrogen and progesterone receptors and human epidermal growth factor receptor-2 has been reported to have invaluable prognostic role. This study aimed at determining the expression ER, PR and HER2 in women with breast cancer in Kampala, Uganda.Methods: Expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) was determined immunohistochemically. Logistic regression was performed to determine the effect of the independent factors in predicting the risk of not expressing the breast markers. A two-tailed p<0.05 was regarded to be statistically significant.Results: ER, PR and HER2 were expressed in 53.4%, 46.6% and 18.5%, respectively. Co-expression of ER and PR and triple negative breast cancer was present in 42.7% and 37.9%, respectively. Age was an independent predictor of expression of ER (AOR = 0.18, 95% CI: 0.062-0.541, p = 0.002), PR (AOR = 0.35, 95% CI: 0.129-0.968, p = 0.043).Conclusion: Majority of patients in this study had less than 50 years and the majority of them had infiltrating ductal carcinoma of no special type with grade 2. Age predicted independently the expression of both ER and PR in our study.

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Section: Discussionsupporting

confidence: 92%

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing of Women Breast Cancer in Kampala, Uganda.

Mlole

Yahaya

Othieno

et al. 2020

Preprint

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“…In the revised series, in addition to mutations in PIK3CA , mutations in PTEN (12.7%), PIK3R1 (11.2%), NF1 (9.8%), HRAS (8.5%), and AKT1 (3%) also occurred ( Table S1 ). Interestingly, simultaneous mutations in more than one gene of the pathway can occur, such as the simultaneous mutations in HRAS and PIK3CA , which have also been recognized as driver mutations in both benign and malignant breast adenomyoepitheliomas [ 3 , 35 ].…”

Section: Molecular Alterationsmentioning

confidence: 99%

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

González-Martínez

Pérez-Míes

Carretero‐Barrio

et al. 2020

Cancers

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Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent invasive carcinomas that display differentiation of the neoplastic epithelium towards squamous cells and/or mesenchymal-type elements. Most MBC have a triple negative phenotype and poor prognosis. Thus, MBC have worse survival rates than other invasive breast carcinomas, including other triple negative breast carcinomas (TNBC). In this study, we reviewed the molecular features of MBC, pointing out the differences among subtypes. The most frequently mutated genes in MBC were TP53 and PIK3CA. Additionally, mutations in the other genes of the PI3K/AKT pathway indicated its importance in the pathogenesis of MBC. Regarding copy number variations (CNVs), MYC was the most frequently amplified gene, and the most frequent gene loss affected the CDKN2A/CDKN2B locus. Furthermore, the pattern of mutations and CNVs of MBC differed from those reported in other TNBC. However, the molecular profile of MBC was not homogeneous among histological subtypes, being the alterations in the PI3K pathway most frequent in spindle cell carcinomas. Transcriptomic studies have demonstrated an epithelial to mesenchymal program activation and the enrichment of stemness genes in most MBC. In addition, current studies are attempting to define the immune microenvironment of these tumors. In conclusion, due to specific molecular features, MBC have a different clinical behavior from other types of TNBC, being more resistant to standard chemotherapy. For this reason, new therapeutic approaches based on tumor molecular characteristics are needed to treat MBC.

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“…2,3,10,29,30 Interestingly, co-occurring HRAS and PIK3CA mutations have recently been recognized as driver mutations in both benign and malignant adenomyoepitheliomas of the breast. 31,32 In cell culture models, the HRAS p.Q61R mutation appears to drive neoplastic transformation of breast cancer cells followed by reduced E-cadherin expression, increased myoepithelial differentiation, and activation of the Akt/PIK3CA pathway. These features, commonly seen in MBC, 32 underlie the phenotypic similarities between the 2 entities.…”

Section: Semir Vranic Et Almentioning

confidence: 99%

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

Vranić

Stafford

Palazzo

et al. 2020

Clinical Breast Cancer

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Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative phenotype. Twenty-three spindle cell carcinomas were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but, owing to the lack of uniform findings, individual patient profiling is necessary. Introduction: Spindle cell carcinoma is a rare subtype of metaplastic breast cancer, with triple-negative (TNBC: estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype. It is associated with a marked resistance to conventional chemotherapy and has an overall poor outcome. Materials and Methods: Twenty-three pure spindle cell carcinomas of the breast (18 primary and 5 recurrent/metastatic) were comprehensively explored for biomarkers of immuno-oncology and targeted therapies using immunohistochemistry and DNA/RNA sequencing. Results: The majority (21/23) of spindle cell carcinomas were TNBC. Estrogen and androgen receptor expression above the therapeutic thresholds were detected in 2 cases each. Pathogenic gene mutations were identified in 21 of 23 cases, including PIK3CA, TP53, HRAS, NF1, and PTEN. One case with matched pre-and postchemotherapy samples exhibited a consistent mutational profile (PIK3CA and HRAS mutations) in both samples. Gene amplifications were present in 5 cases, including 1 case without detectable mutations. The spindle cell carcinomas cohort had consistently low total mutational burden (all below the 80th percentile for the entire TNBC cohort). All tumors were microsatellite stable. Programmed death-ligand 1 expression was observed on both tumor cells (in 7/21 cases), and in tumor-infiltrating immune cells (2/21 cases). Conclusions: Spindle cell carcinomas are characterized by targetable molecular alterations in the majority of cases, but owing to the lack of uniform findings, individual patient profiling is necessary. Detection of individual combinations of biomarkers should improve treatment options for this rare but aggressive disease.

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Mammary Epithelial-Myoepithelial Carcinoma: Report of a Case With HRAS and PIK3CA Mutations by Next-Generation Sequencing

Cited by 25 publications

References 16 publications

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing of Women Breast Cancer in Kampala, Uganda.

Hormonal Receptors, Human Epidermal Growth Factor Receptor-2 and Triple Negative Immunohistochemical Typing of Women Breast Cancer in Kampala, Uganda.

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

Molecular Profiling of the Metaplastic Spindle Cell Carcinoma of the Breast Reveals Potentially Targetable Biomarkers

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