Calcifications In Breast Cancer Research Articles

Radiogenomic analysis of prediction HER2 status in breast cancer by linking ultrasound radiomic feature module with biological functions

BackgroundHuman epidermal growth factor receptor 2 (HER2) overexpressed associated with poor prognosis in breast cancer and HER2 has been defined as a therapeutic target for breast cancer treatment. We aimed to explore the molecular biological information in ultrasound radiomic features (URFs) of HER2-positive breast cancer using radiogenomic analysis. Moreover, a radiomics model was developed to predict the status of HER2 in breast cancer.MethodsThis retrospective study included 489 patients who were diagnosed with breast cancer. URFs were extracted from a radiomics analysis set using PyRadiomics. The correlations between differential URFs and HER2-related genes were calculated using Pearson correlation analysis. Functional enrichment of the identified URFs-correlated HER2 positive-specific genes was performed. Lastly, the radiomics model was developed based on the URF-module mined from auxiliary differential URFs to assess the HER2 status of breast cancer.ResultsEight differential URFs (p < 0.05) were identified among the 86 URFs extracted by Pyradiomics. 25 genes that were found to be the most closely associated with URFs. Then, the relevant biological functions of each differential URF were obtained through functional enrichment analysis. Among them, Zone Entropy is related to immune cell activity, which regulate the generation of calcification in breast cancer. The radiomics model based on the Logistic classifier and URF-module showed good discriminative ability (AUC = 0.80, 95% CI).ConclusionWe searched for the URFs of HER2-positive breast cancer, and explored the underlying genes and biological functions of these URFs. Furthermore, the radiomics model based on the Logistic classifier and URF-module relatively accurately predicted the HER2 status in breast cancer.

Abstract P5-12-04: Osteogenic cocktail induces calcifications in human breast cancer cell line via placental alkaline phosphatase expression

Abstract Breast cancer is frequently characterized by calcifications in mammography. Although breast calcifications were previously thought to be produced passively as the final stage of cell regression, recent studies have shown active production. In another context, vascular smooth muscle cells have been found to produce vascular calcifications by acquiring osteoblast-like characteristics. The same mechanism has been suggested to account for breast calcifications. A report showed that breast calcifications are clearly generated by the mouse breast cancer cell line 4T1 through osteoblast-like characteristics. However, the details underlying such a mechanism of mammary calcification is unknown. Understanding this mechanism will improve diagnostic accuracy for breast cancer. We induced calcifications using osteogenic cocktail on the human breast cancer cell line MDA-MB-231. Our hypothesis was that breast cancer calcifications are generated in a process similar to that of osteoblast differentiation. By a comprehensive analysis of transcription compared with osteoblastic cell line MC3T3-E1 in a microarray, we showed that placental alkaline phosphatase (PLAP) is involved in producing calcifications through PI3K-Akt signaling pathways. Herein, we demonstrated that calcifications occur and that alkaline phosphatase enzyme activity increases in MDA-MB-231 cells cultured using an osteogenic cocktail-containing medium. Microarray transcript analysis showed that the PI3K-Akt signaling pathway was significantly involved, with recruitment of placental alkaline phosphatase. Calcifications and alkaline phosphatase enzyme activity were suppressed by silencing placental alkaline phosphatase using a small interfering RNA. Inhibition of the PI3K-Akt signaling pathway suppressed phospho-c-Jun and placental alkaline phosphatase and resulted in absence of calcifications. These findings reveal that breast cancer cells acquire alkaline phosphatase enzyme activity via placental alkaline phosphatase expression and suggest that breast calcification formation is closely associated with the PI3K-Akt signaling pathway. Our results suggest that PLAP produces ALP enzyme activity required for calcification in MDA-MB-231 cells. PLAP is clinically expressed in some breast cancers. A report showed that dexamethasone induces PLAP enzyme activity and mRNA in the human breast cancer BC-M1 cell line. Therefore, dexamethasone in osteogenic cocktail may be associated with PLAP expression in the MDA-MB-231 cells. On the other hand, c-Jun binds to the promoter region of ALPP in MDA-MB-231, and we showed that c-Jun phosphorylation appears in MDA-MB-231 cells cultured using osteogenic cocktail. We suggest that PLAP transcript would be activated when phospho-c-Jun enters the nucleus and binds to the promoter region of PLAP. Our proposed mechanism in breast calcifications is that osteogenic cocktail induces c-Jun phosphorylation via PI3K-Akt signaling pathway and that PLAP transcription would be activated when phospho-c-Jun enters the nucleus and binds to the promoter region of PLAP. Future research might assess whether increased PLAP levels are the main driver of intracellular calcifications in breast cancer, as well as whether the PI3K-Akt signaling pathway has a similar effect in vivo that we demonstrated to cause calcifications in vitro. Citation Format: Atsushi Fushimi, Hiroshi Takeyama, Toshiaki Tachibana, Yoshinobu Manome. Osteogenic cocktail induces calcifications in human breast cancer cell line via placental alkaline phosphatase expression [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-04.

Diagnostic Value of Intra - mammary Calcification in Breast Cancer

Diagnostic Value of Intra - mammary Calcification in Breast Cancer

Osteogenic cocktail induces calcifications in human breast cancer cell line via placental alkaline phosphatase expression

Breast cancer is frequently characterized by calcifications in mammography. The mechanism for calcifications in breast cancer is not completely known. Understanding this mechanism will improve diagnostic accuracy. Herein, we demonstrated that calcifications occur and that alkaline phosphatase enzyme activity increases in MDA-MB-231 cells cultured using an osteogenic cocktail-containing medium. Microarray transcript analysis showed that the PI3K-Akt signaling pathway was significantly involved, with recruitment of placental alkaline phosphatase. Calcifications and alkaline phosphatase enzyme activity were suppressed by silencing placental alkaline phosphatase using a small interfering RNA. Inhibition of the PI3K-Akt signaling pathway suppressed phospho-c-Jun and placental alkaline phosphatase and resulted in absence of calcifications. These findings reveal that breast cancer cells acquire alkaline phosphatase enzyme activity via placental alkaline phosphatase expression and suggest that breast calcification formation is closely associated with the PI3K-Akt signaling pathway.

Gene expression profiling of calcifications in breast cancer

We investigated the gene expression profiles of calcifications in breast cancer. Gene expression analysis of surgical specimen was performed using Affymetrix GeneChip® Human Gene 2.0 ST arrays in 168 breast cancer patients. The mammographic calcifications were reviewed by three radiologists and classified into three groups according to malignancy probability: breast cancers without suspicious calcifications; breast cancers with low-to-intermediate suspicious calcifications; and breast cancers with highly suspicious calcifications. To identify differentially expressed genes (DEGs) between these three groups, a one-way analysis of variance was performed with post hoc comparisons with Tukey’s honest significant difference test. To explore the biological significance of DEGs, we used DAVID for gene ontology analysis and BioLattice for clustering analysis. A total of 2551 genes showed differential expression among the three groups. ERBB2 genes are up-regulated in breast cancers with highly suspicious calcifications (fold change 2.474, p < 0.001). Gene ontology analysis revealed that the immune, defense and inflammatory responses were decreased in breast cancers with highly suspicious calcifications compared to breast cancers without suspicious calcifications (p from 10−23 to 10−8). The clustering analysis also demonstrated that the immune system is associated with mammographic calcifications (p < 0.001). Our study showed calcifications in breast cancers are associated with high levels of mRNA expression of ERBB2 and decreased immune system activity.

Dystrophic Large Calcification in Breast Cancer

There are well established diagnostic criteria for calcifications detected on mammography which allows the division into: benign intermediate concern and higher probability of malignancy according to the morphology. Large calcifications are usually associated with benign breast conditions. We report three cases of breast cancer with large dystrophic calcification on imaging studies (mammography, ultrasound, computed -tomography) and histopatology displayed into the tumor as well as into the tributaries lymph nodes.

Association between HER2/neu overexpression and calcifications in breast cancer

579 Background: HER-2/neu overexpression is an important parameter that influences prognosis and treatment for breast cancer. The purpose of this study is to explore the relationship between HER-2/neu overexpression and calcifications identified by either mammographic imaging or histologic examination. Methods: A retrospective review of the prospectively collected database was performed to evaluate the mammographic and histologic characteristics of all cases of invasive breast cancers diagnosed between 2003 and 2008. HER-2/neu positivity was defined as either overexpression by FISH analysis or 3+ staining on immunohistochemistry. Results: Of 502 invasive cancers, 165 (33%) had calcifications on mammography and 337 (67%) did not. HER-2/neu positivity was found in 63 (38%) of the calcification cases and 40 (12%) of the non-calcified cases (p &lt; 0.001). This association persisted across all age groups and races and was independent of tumor size, nodal status, or hormone receptor status. Calcifications seen histologically also correlated with HER-2/neu overexpression, but the relationship was more complex. Among 155 cases with histologic calcifications seen within a ductal intraepithelial neoplasia (DIN) component, there were 45 (29%) that were HER-2/neu positive, compared with 67/414 (16%) that did not have calcifications within DIN (p &lt; 0.001). If the calcifications were only within invasive tumor, the rate of HER-2/neu overexpression was less, 9/63 (14%). Univariate analysis demonstrated that tumor grade, necrosis, lymphovascular invasion and hormone receptor negativity were significantly associated with HER-2/neu overexpression (all p &lt; 0.01). Multivariate logistic regression showed only the following factors to be significantly associated with HER-2/neu overexpression: grade of invasive tumor, presence of necrosis, progesterone receptor negativity in either the invasive or the in situ component, and mammographic calcifications. Conclusions: Recognition of the strong association between HER-2/neu overexpression and mammographic calcifications may have clinical usefulness and could lead to a better understanding of the underlying tumor biology of this important tumor marker. [Table: see text]

Primary superficial basal cell carcinoma of the nipple

Primary superficial basal cell carcinoma of the nipple

The mammographic calcifications in breast cancer

Objective: This study was performed to exam the relativeship between mammographic calcifications and breast cancer. Methods: All of the 184 patients with breast diseases underwent mammography before either an open biopsy or a mastectomy. The presence, morphology, and distribution of calcifications visualized on mammograms for breast cancer were compared with the controls who remained cancer free. Statistical comparisons were made by using the x 2 test. Results: Of the 184 patients with breast diaeases, 93 malignant and 91 benign lesions were histologically confirmed. Calcifications were visualized on mammograms in 60 (64 %) of 93 breast cancers and 26 (28%) of 91 non breast cancers. The estimated odds ratio (OR) of breast cancer was 4.5 in women with calcifications seen on mammograms, compared with those having none (P< 0.01). Of the 60 breast carcinomas having mammographic calcifications, 28 (47%) were infiltrating ductal carcinomas. There were only 8 (24%) cases with infiltrating ductal cancers in the group of without calcifications seen on the mammograms (P<0.05). Conclusion: Our finding suggests that mammographic calcification appears to be a risk factor for breast cancer. The granular and linear cast type calcification provide clues to the presence of breast cancer, especially when the carcinomas without associated masses were seen on mammograms.

Mixed form, diffusely scattered calcifications in breast cancer with apocrine features.

HomeRadiologyVol. 179, No. 2 PreviousNext LettersMixed form, diffusely scattered calcifications in breast cancer with apocrine features.M J Homer, H SafaiiM J Homer, H SafaiiM J HomerH SafaiiPublished Online:May 1 1991https://doi.org/10.1148/radiology.179.2.2064656MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Article HistoryPublished in print: 1991 FiguresReferencesRelatedDetailsCited ByRadiologic Clinics of North America, Vol. 33, No. 6Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 179, No. 2 Metrics Downloaded 6 times Altmetric Score PDF download

Mixed form, diffusely scattered calcifications in breast cancer with apocrine features.

Diffusely scattered calcifications visible with mammography are almost always benign. Certain patterns, however, should arouse concern. For example, extensive comedocarcinoma is associated with large areas of mammographically visible calcium deposition. The authors identified 10 women in whom calcifications were visible throughout large volumes of breast tissue at mammography. The calcifications did not resemble those typical of extensive comedocarcinoma, yet they were associated with extensive breast cancer. Their mammographic pattern was characterized by a strikingly wild, chaotic appearance with profuse deposition of calcium. As in many cancers, the particles were heterogeneous, but unlike in most carcinomas, many deposits had a typically benign morphology. Histologic examination showed that even these typically benign calcifications were associated with malignant cells. The authors believe that the apocrine features displayed by many of the cancer cells in these 10 patients may explain the unusual profusion of calcium deposits.