Breast cancer global tumor biomarkers: a quality assurance study of intratumoral heterogeneity

Clark, Beth Z.; Oniśko, Agnieszka; Assylbekova, Binara; Li, Xin; Bhargava, Rohit; Dabbs, David J.

doi:10.1038/s41379-018-0153-0

“…HER2 positive rate in the young patients with invasive carcinoma was approximately 25%, which was obviously higher than that in the whole breast cancer cohort (approximately 10%−20%) (24,25). The proportion of patients with positive Ki-67 index in young breast cancer with DCIS (57.4%) or IDC (76.2%) was much higher than that previously reported for the whole breast cancer cohort (26,27). Ki67 has been reported to be highly expressed in approximately 40% of DCIS tumors and 50%−60% of IDC tumors (27,28).…”

Section: Discussioncontrasting

confidence: 66%

Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999−2017

Guo¹,

Si²,

Xue³

et al. 2019

Chinese Journal of Cancer Research

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ObjectiveBreast cancer in young females was usually considered more aggressive and requires aggressive therapy. We investigated whether early detection and improved treatments changed the patterns of characteristics, management and outcomes of young breast cancer patients over time.MethodsFemales under 40 years of age diagnosed with breast cancer during the periods 1999−2017 and 1999−2015 were identified in the Fudan University Shanghai Cancer Center (FUSCC) and the population-based Surveillance, Epidemiology, and End Results (SEER) registry, respectively. Clinicopathologic characteristics and treatment information were collected. Patients diagnosed before 2013 were followed up.ResultsThe proportions of young breast cancer patients were 15.0% and 5.3% in the FUSCC and SEER cohorts, respectively. In the FUSCC cohort, there was a significant increase in the proportion of ductal carcinoma in situ (DCIS) (from 8.8% to 16.9%; P<0.0001) and it remained stable in SEER cohort. The proportion of T1-stage tumors increased dramatically in the FUSCC cohort (from 35.3% to 41.9%; P=0.008), whereas it decreased in SEER cohort (from 42.4% to 33.0%; P<0.0001). The percentage of estrogen receptor (ER)-positive cancers was consistently increased in both the invasive ductal carcinoma (IDC) and DCIS patients in the two cohorts. Breast-conserving surgery and immediate implant reconstruction after mastectomy both exhibited increased use over time in the FUSCC cohort. Both the FUSCC and SEER cohorts showed a significantly better prognosis in the recent time period. ConclusionsWith the increased early-stage and ER-positive diseases in young patients as well as better systemic treatment strategies, improved survival has been observed in recent years. There has been a substantial de-escalation in surgical therapies in young breast cancer patients.

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“…Similarly, molecular subtypes along with the four immunohistochemical factors are employed as a guide for targeted treatment, including hormonal therapy, anti-Her2 agent, and cytotoxic therapy [ 8 , 10 , 11 ]. Moreover, differences in prognosis among different subtypes of breast cancer also existed [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer

Zhao

¹

,

Li

²

,

Wang

³

et al. 2021

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Objectives. Molecular subtypes are employed as a guide for targeted treatment and important prognostic factors. This study focused on investigating the association of serum levels of CEA, CA15-3, and CA125 with clinicopathological characteristics of breast cancer to find prognostic markers for breast cancer and provide precise targeted therapy. Materials and Methods. In this study, 961 breast cancer patients with preoperative serum levels of CEA, CA15-3, and CA125 and molecular subtypes were analyzed. Cut-off values of 5 ng/ml, 25 U/ml, and 35 U/ml were used for CEA, CA15-3, and CA125, respectively. The χ 2 test and Fisher exact test along with logistic multivariate regression analysis were performed for investigating the correlation of CEA, CA15-3, and CA125 serum levels with molecular subtypes and associated factors. Results. An increase in the serum concentrations of CEA, CA15-3, and CA125 was discovered in 48 (4.99%), 54 (5.62%), and 55 (5.72%) breast cancer patients, respectively. Univariate analysis demonstrated that the levels of CEA ( p < 0.01 ) and CA15-3 ( p < 0.05 ) were significantly linked with molecular types of breast cancer. Moreover, patients having larger tumor size ( p < 0.01 , p < 0.0001 , and p < 0.05 , respectively) along with nodal metastasis ( p < 0.05 , p = 0.0001 , and p < 0.05 , respectively) exhibited higher rates of elevated CEA, CA15-3, and CA125 levels. Status of Her-2 positive ( p < 0.01 ) had a significant connection with elevated CEA levels. Multivariate analysis further indicated that molecular subtypes were independent factors associated with CEA and CA15-3 levels. Also, Her-2 status was significantly and independently related to CEA levels. Conclusion. Preoperative serum levels of CEA and CA15-3 were independently associated with molecular subtypes of breast cancer. CEA and CA15-3 might improve the prognostic prediction for patients with breast cancer and inform the selection of specific therapies. A further biological analysis is needed for investigating the relationship between Her-2 expression and CEA levels.

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“…At present, the genetic tests of the penetrating tumor tissues have been commonly used in the disease diagnose and prognosis prediction. However, the heterogeneity of tumor structure often interferes with the accuracy of puncture [ 9 ], and CSCs often differentiate into cells with different heterogeneities [ 10 ]. The occurrence, development and metastasis of tumors all depend on the formation of microvessels, and the heterogeneity of tumors is also reflected in the microcirculation construction [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation of breast cancer microcirculation construction with tumor stem cells (CSCs) and epithelial-mesenchymal transition (EMT) based on contrast-enhanced ultrasound (CEUS)

Leng

¹

,

Huang

²

,

Li

³

et al. 2021

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Objective This study is to explore the correlation between the contrast-enhanced ultrasound (CEUS) characteristics of breast cancer and the epithelial-mesenchyme transformation (EMT). Methods Totally 119 patients of breast cancer underwent CEUS. Tissues in the active area were collected and subjected to the immunohistochemical detection, PT-PCR and Western blot. Correlation analysis was conducted between the clinical pathological parameters and the CEUS indicators. Results The expression levels of CD44, N-cadherin, and β-catenin in breast cancer tissues were higher than those in adjacent tissues (P<0.05). However, the expression levels of CD24 and E-cadherin in breast cancer tissues were lower than those in adjacent tissues (P<0.05). There was no significant difference in E-cadherin mRNA and Vimentin levels between cancer and adjacent tissues (P>0.05). The expressions were up-regulated in the CSCs, with higher histological grade, lymph node metastasis, and negative estrogen receptor (ER) expression. Smaller breast tumors, with no lymph node metastasis, lower clinical stage, and positive ER expression, tended to exhibit the up-regulated epithelial phenotype. Breast tumors, with high histological grade, lymph node metastasis, high clinical staging grade, and negative ER expression, tended to exhibit the up-regulated interstitial phenotype. The peak intensity of the time-intensity curve (TIC) for the CEUS was positively correlated with the CSC marker CD44 and the interstitial phenotype marker N-cadherin. The starting time of enhancement was negatively correlated with the N-cadherin. Area under the curve was positively correlated with the expression of CD44 and N-cadherin, while negatively correlated with the epithelial phenotype marker β-catenin. The time to peak was negatively correlated with the interstitial phenotypes Vimentin and N-cadherin, with no correlation with the E-cadherin or β-catenin. Conclusion Breast cancers show the enlarged lesions after enlargement and perfusion defect for the CEUS. The fast-in pattern, high enhancement, and high perfusion in the TIC are correlated with the CSCs and EMT expressions, suggesting poor disease prognosis.

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Breast cancer global tumor biomarkers: a quality assurance study of intratumoral heterogeneity

Cited by 28 publications

References 40 publications

Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999−2017

Changing patterns and survival improvements of young breast cancer in China and SEER database, 1999−2017

Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer

Correlation of breast cancer microcirculation construction with tumor stem cells (CSCs) and epithelial-mesenchymal transition (EMT) based on contrast-enhanced ultrasound (CEUS)

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