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BMC Cancer Dec 2022Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies...
Markers associated with genomic instability, immunogenicity and immune therapy responsiveness in Metaplastic carcinoma of the breast: Expression of γH2AX, pRPA2, P53, PD-L1 and tumor infiltrating lymphocytes in 76 cases.
BACKGROUND
Metaplastic breast cancer (MpBC) is an aggressive subtype of breast carcinoma that is often resistant to conventional chemotherapy. Therefore, novel treatment strategies are urgently needed. Immune check point inhibitors have shown activity in programmed death-ligand 1 (PD-L1) - positive metastatic triple negative breast carcinoma (TNBC), which raises the possibility that immunotherapy may also be effective in MpBC as most of the MpBCs are triple negative. The aim of the present study was to assess genomic instability and immunogenicity in tumor specimens of patients with MpBC.
METHODS
A total of 76 patients diagnosed with MpBC over a 15-year period were included in the study. We performed immunohistochemical analyses for tumor cell PD-L1, immune cell PD-L1 and p53 on tissue microarrays (TMAs), analyzed stromal and intratumoral tumor infiltrating lymphocytes (TILs) from hematoxylin and eosin-stained (H&E) slides and scored gamma-H2AX (γH2AX) and phosphorylated-RPA2 (pRPA2) from whole tissue sections. We correlated marker expression with clinicopathologic features and clinical outcome.
RESULTS
All tumors expressed γH2AX and pRPA2 with median expressions of 43% and 44%. P53- (68%), tumor cell PD-L1- (59%) and immune cell PD-L1-positivity (62%) were common in MpBCs. Median stromal TIL and intratumoral TIL counts were 5% and 0. The spindle and squamous cell carcinomas expressed the highest levels of PD-L1 and TILs, and carcinoma with mesenchymal differentiation the lowest.
CONCLUSIONS
MpBC appears to be an immunogenic cancer with high genomic instability and frequent PD-L1-positivity, implying that check point inhibitors might be effective in MpBC. Expression levels of PD-L1 and TILs varied across different histologic subtypes, suggesting that immunotherapy might be less effective in carcinoma with mesenchymal differentiation.
Topics: Humans; B7-H1 Antigen; Lymphocytes, Tumor-Infiltrating; Tumor Suppressor Protein p53; Prognosis; Biomarkers, Tumor; Triple Negative Breast Neoplasms; Carcinoma, Squamous Cell
PubMed: 36503417
DOI: 10.1186/s12885-022-10408-7 -
International Journal of Molecular... Jul 2023Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates... (Review)
Review
Esophageal adenocarcinoma (EAC) is a rapidly increasing lethal tumor. It commonly arises from a metaplastic segment known as Barrett's esophagus (BE), which delineates the at-risk population. Ample research has elucidated the pathogenesis of BE and its progression from metaplasia to invasive carcinoma; and multiple molecular pathways have been implicated in this process, presenting several points of cancer interception. Here, we explore the mechanisms of action of various agents, including proton pump inhibitors, non-steroidal anti-inflammatory drugs, metformin, and statins, and explain their roles in cancer interception. Data from the recent AspECT trial are discussed to determine how viable a multipronged approach to cancer chemoprevention would be. Further, novel concepts, such as the repurposing of chemotherapeutic drugs like dasatinib and the prevention of post-ablation BE recurrence using itraconazole, are discussed.
Topics: Humans; Barrett Esophagus; Esophageal Neoplasms; Adenocarcinoma; Risk Factors; Metaplasia
PubMed: 37511077
DOI: 10.3390/ijms241411318 -
Medicine Apr 2018Metaplastic breast carcinomas are a group of breast malignancies with varying histomorphological characteristics and prognoses. The tumor composed of epithelial...
RATIONALE
Metaplastic breast carcinomas are a group of breast malignancies with varying histomorphological characteristics and prognoses. The tumor composed of epithelial -myoepithelial carcinoma and squamous cell carcinoma was not reported previously.
PATIENT CONCERNS
An 81-year-old woman presented with a palpable nodule in the left breast for 4 days. The ultrasonography showed multinodular growth and focally indistinct borders. Owing to her advanced age and possible early clinical staging, primary tumor resection was performed. One year later, a small and slow growing subcutaneous nodule was found under the incision of the left breast. Ultrasonography revealed an irregular, cystic and solid, hypoechoic mass with circumscribed borders.
DIAGNOSES
Microscopic examination of the primary tumor revealed epithelial -myoepithelial carcinoma and squamous cell carcinoma. The former had a variety of architecture patterns, including nests, lobulations, papillary and tubular structures, and the latter showed varying morphological features, from squamous pearls to spindle cells. The recurrent tumor showed only epithelial -myoepithelial carcinoma with more aggressively malignant features than those seen in the primary tumor.
INTERVENTIONS
An extensive resection of the left breast mass was performed for the recurrent tumor. The patient did not receive any adjuvant chemotherapy or radiation therapy because of the patient's advanced age.
OUTCOMES
The patient has been followed up for 1.5 years after second surgery without evidence of tumor recurrence and metastasis.
LESSONS
Wide local excision with adequate margins is recommended for elderly patients with metaplastic breast carcinoma composed of epithelial -myoepithelial carcinoma and squamous cell carcinoma.
Topics: Age Factors; Aged, 80 and over; Breast; Breast Neoplasms; Carcinoma, Squamous Cell; Female; Humans; Margins of Excision; Mastectomy, Segmental; Mastectomy, Simple; Myoepithelioma; Neoplasm Recurrence, Local; Neoplasm Staging; Reoperation; Risk Adjustment; Treatment Outcome
PubMed: 29642184
DOI: 10.1097/MD.0000000000010364 -
World Journal of Gastroenterology Feb 2016The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a... (Review)
Review
The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.
Topics: Adenocarcinoma; Adult; Aged; Alcohol Drinking; Barrett Esophagus; Comorbidity; Disease Progression; Esophageal Neoplasms; Estrogen Replacement Therapy; Estrogens; Female; Gastroesophageal Reflux; Health Status Disparities; Humans; Incidence; Life Style; Male; Middle Aged; Obesity; Prevalence; Risk Assessment; Risk Factors; Sex Distribution; Sex Factors; Smoking
PubMed: 26855539
DOI: 10.3748/wjg.v22.i5.1800 -
Archives of Pathology & Laboratory... Apr 2022Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers.
CONTEXT.—
Recurrence score (RS) testing was developed and validated in invasive ductal and rare lobular carcinomas, although it is used for all special types of breast cancers.
OBJECTIVE.—
To determine association of histologic type (HT) and RS, specifically high-risk RS.
DESIGN.—
We used RSs linked to Surveillance, Epidemiology, and End Results Program registries of invasive breast cancers diagnosed in 2004 through 2015. Multivariable logistic regression was used to evaluate association between HT and high-risk RS. Relationships between HT and low-, intermediate-, and high-risk RS were compared with χ2 test. Kaplan-Meier curves were compared using log-rank test.
RESULTS.—
A total of 110 318 patients had RS testing. Of these, 23 220 (21%) had low, 70 822 (64.2%) intermediate, and 16 276 (14.8%) high RS. Histologic types were 80 476 (73%) ductal, 12 713 (11.5%) lobular, 12 449 (11.3%) mixed, 2151 (2%) mucinous, 610 (0.6%) tubular, 382 (0.4%) micropapillary, 365 (0.3%) salivary, 208 (0.2%) papillary, 49 (0.04%) medullary, 26 (0.02%) metaplastic, 26 (0.02%) neuroendocrine, and 863 (0.8%) unknown. The distribution of low-, intermediate-, and high-risk RS was significantly different among HTs. Higher percentages of high-risk RS were identified in patients with ductal, medullary, and metaplastic types (P < .001). The odds of having high-risk RS were lower for some HTs, including micropapillary, after multivariable adjustment (P < .05). The low number of estrogen receptor-positive medullary and metaplastic carcinomas tested had higher odds of having high-risk RS. In T1 and T2 tumors, when ductal, lobular, mixed, and other types combined were compared, the mortality was different.
CONCLUSIONS.—
This population-based study of RS in HTs showed high-risk RSs are identified in traditionally good prognostic subtypes. Micropapillary carcinoma has lower odds of high-risk RS even after multivariable adjustment.
Topics: Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Papillary; Female; Humans; Prognosis; Risk Factors
PubMed: 34343231
DOI: 10.5858/arpa.2020-0837-OA -
Oncology Letters Sep 2013Metaplastic carcinoma of the breast refers to a heterogenous group of mammary carcinomas that contain a mixture of various cell types, including squamous cells, spindle...
Metaplastic carcinoma of the breast refers to a heterogenous group of mammary carcinomas that contain a mixture of various cell types, including squamous cells, spindle cells and/or a mesenchymal component, such as bone or cartilage. To the best of our knowledge, the clinical course of a tumour that has undergone a transformation from one type of metaplastic carcinoma to another subtype has not previously been reported. The present study reports the five-year clinical and pathological course of a metaplastic breast carcinoma in a 55-year-old female, who was diagnosed with a sclerosing fibroadenomatous nodule with osseous metaplasia and focal atypia. A recurrent tumour was documented four years later, showing a predominant component of osteosarcoma with adenosquamous carcinoma. Upon pathological review of the initial mass, the diagnosis was changed to low-grade adenosquamous carcinoma. The patient was treated with breast conserving therapy. However, one year later, a recurrent metaplastic carcinoma with spindle cell morphology was documented and surgically removed by mastectomy. Subsequently, pulmonary invasion of the chest wall occurred and the patient eventually succumbed due to the invasive nature of the disease.
PubMed: 24137400
DOI: 10.3892/ol.2013.1464 -
BMJ Case Reports Mar 2020Synchronous primary cancers occur in 1.7% of breast cancer cases and metaplastic breast cancer (MBC) occurs in less than 1% of breast cancer cases. We present a... (Review)
Review
Synchronous primary cancers occur in 1.7% of breast cancer cases and metaplastic breast cancer (MBC) occurs in less than 1% of breast cancer cases. We present a previously healthy 66-year-old woman diagnosed with MBC after surgical resection of a presumed cyst. A second primary cancer, multifocal lung adenocarcinoma, was discovered during the staging process for her MBC. Remarkably she had not experienced pulmonary or constitutional symptoms at the time of diagnosis. She received chemotherapy with paclitaxel and carboplatin, followed by immunotherapy with nivolumab. At 24 months of follow-up after her initial diagnosis, she was breast cancer-free with stable pulmonary nodules. This case highlights that rather than assuming multifocal lesions represent metastasis, biopsies should be considered as clinical management could be significantly altered in the presence of a synchronous cancer. Furthermore, platinum-based chemotherapy agents have potential to be considered in the treatment of MBC.
Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Lung Neoplasms; Neoplasms, Second Primary
PubMed: 32209575
DOI: 10.1136/bcr-2019-232421 -
Yonsei Medical Journal Nov 2010Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic...
PURPOSE
Metaplastic breast carcinoma (MBC) is rare. Its clinicopathologic features and prognosis are uncertain. The aim of this study was to evaluate the clinicopathologic characteristics and outcomes in comparison with invasive ductal carcinoma (IDC).
MATERIALS AND METHODS
We reviewed the data of 29 patients with MBC and 4,851 patients with IDC, who received surgery at Yonsei University Severance Hospital between 1980 and 2008. Various clinicopathologic features, recurrence free, and overall survival were investigated and compared to each other.
RESULTS
Stage IV cases at diagnosis were more common in MBC (10.3%) than in IDC (0.9%). The incidence rates of triple negative breast cancer (TNBC) were significantly higher in MBC (84.0%) than in IDC (20.1%). Larger tumors (> 2 cm) and lower tendency of axillary metastasis were frequently observed in MBC. Only one of 24 preoperative core needle biopsies (CNB) correctly diagnosed MBC. There was no significant difference in survival between the two groups.
CONCLUSION
MBC was characterized by a higher incidence of TNBC, larger tumor size, and lower tendency of axillary metastasis, and was difficult to diagnose with CNB. Although the incidence of stage IV disease at diagnosis was higher in MBC, the survival rates of stage I-III were comparable to those of IDC.
Topics: Adult; Aged; Breast Neoplasms; Carcinoma; Carcinoma, Ductal, Breast; Female; Humans; Incidence; Medical Oncology; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Recurrence; Retrospective Studies; Treatment Outcome
PubMed: 20879052
DOI: 10.3349/ymj.2010.51.6.864 -
Journal of Cell Communication and... Mar 2018Located at 6q22-23, Ccn6 (WISP3) encodes for a matrix-associated protein of the CCN family, characterized by regulatory, rather than structural, roles in development and... (Review)
Review
Located at 6q22-23, Ccn6 (WISP3) encodes for a matrix-associated protein of the CCN family, characterized by regulatory, rather than structural, roles in development and cancer. CCN6, the least studied member of the CCN family, shares the conserved multimodular structure of CCN proteins, as well as their tissue and cell-type specific functions. In the breast, CCN6 is a critical regulator of epithelial-to-mesenchymal transitions (EMT) and tumor initiating cells. Studies using human breast cancer tissue samples demonstrated that CCN6 messenger RNA and protein are expressed in normal breast epithelia but reduced or lost in aggressive breast cancer phenotypes, especially inflammatory breast cancer and metaplastic carcinomas. Metaplastic carcinomas are mesenchymal-like triple negative breast carcinomas, enriched for markers of EMT and stemness. RNAseq analyses of the TCGA Breast Cancer cohort show reduced CCN6 expression in approximately 50% of metaplastic carcinomas compared to normal breast. Our group identified frameshift mutations of Ccn6 in a subset of human metaplastic breast carcinoma. Importantly, conditional, mammary epithelial-cell specific ccn6 (wisp3) knockout mice develop invasive high-grade mammary carcinomas that recapitulate human spindle cell metaplastic carcinomas, demonstrating a tumor suppressor function for ccn6. Our studies on CCN6 functions in metaplastic carcinoma highlight the potential of CCN6 as a novel therapeutic approach for this specific type of breast cancer.
PubMed: 29357008
DOI: 10.1007/s12079-018-0451-9 -
BMC Research Notes Jul 2018The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the...
OBJECTIVES
The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS).
RESULTS
86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER negative and 86% were PR negative, respectively as compared to ductal carcinoma NOS, which were 40% ER negative and 54% were PR. Similarly, 86.7% micropapillary cancers were ER positive and 73.3% were PR positive. Moreover, 66.7% micropapillary carcinoma showed nodal metastasis and 77.8% showed lymphovascular invasion, which was significantly higher than that of IDC, NOS micropapillary and metaplastic carcinomas accounts for less than 2 and 1% of the breast cancer burden in our population and highly correlates with poor prognosis parameters therefore, require more intensive management in our population.
Topics: Adult; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Papillary; Female; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness
PubMed: 30064485
DOI: 10.1186/s13104-018-3623-z