Metaplastic Breast Cancer Treatment and Outcomes in 2500 Patients: A Retrospective Analysis of a National Oncology Database

Ong, Cecilia T.; Campbell, Brittany M.; Thomas, Samantha M.; Greenup, Rachel A.; Plichta, Jennifer K.; Rosenberger, Laura H.; Force, Jeremy; Hall, Allison; Hyslop, Terry; Hwang, E. Shelley; Fayanju, Oluwadamilola M.

doi:10.1245/s10434-018-6533-3

Cited by 89 publications

(123 citation statements)

References 31 publications

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“…It may result from the worse response to chemotherapy regimens in MBC [21,25,27,36,37]. Previous studies have concluded that radiotherapy was able to improve the survival of patients with MBC [8,28,38], and our data also demonstrated that radiation was independently prognostic factors associated with survival probability of patients with MBC. Moreover, radiotherapy was revealed to be able to reduce the risk of local recurrence [39].…”

Section: Discussionsupporting

confidence: 71%

Novel Nomograms to Predict of Overall Survival and Cancer-specific Survival of Patients of Metaplastic Breast Cancer

Chen

Xuan

et al. 2020

Preprint

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Background Metaplastic breast cancer (MBC) is a rare type of breast cancer with an increasing incidence, we aim to develop clinical nomograms to predict the overall survival and cancer-specific survival for patients with MBC.MethodsPatients data were collected from the SEER database between 1973 and 2015. All included patients were randomly assigned into the training and validation sets. Univariate and multivariate Cox analysis were performed to identify independent prognostic factors of MBC. These essential prognostic variables were combined to construct nomogram models to predict overall survival (OS) and cancer-specific survival (CSS) in patients with MBC. Model performance was evaluated by concordance index (C-index) and calibration plots.ResultsA total of 1835 patients were collected and divided into the training (1223) and validation (612) groups. The multivariate Cox model identified age, TNM stage, T stage, and N stage, chemotherapy and radiotherapy as independent covariates associated with OS, while these variables except for age and chemotherapy were independent prognostic factors of CSS. The nomogram constructed based on these covariates demonstrated excellent accuracy in estimating 3-, and 5-year OS and CSS, with a C-index of 0.759 (95% CI, 0.746-0.772) for OS and 0.766 (95% CI, 0.751-0.781) for CSS in the training cohort. In the validation cohort, the nomogram-predicted C-index was 0.754 for OS (95%CI, 0.734-0.774) and 0.752 (95%CI, 0.728-0.776) for CSS. All calibration curves exhibited good consistency between predicted and actual survival.ConclusionsThese nomogram models established in this study can help to enhance the accuracy of prognostic prediction, which may thereby improve individualized assessment of survival risks and facilitate to provide constructive therapeutic suggestions.

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Section: Discussionsupporting

confidence: 71%

Novel Nomograms to Predict of Overall Survival and Cancer-specific Survival of Patients of Metaplastic Breast Cancer

Chen

Xuan

et al. 2020

Preprint

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“…[18] However, the incidence of metaplastic BC diagnosis in the United States according to these databases is still low at less than 500 cases per year. [9,19] In our study, we found that metaplastic BC was most commonly diagnosed as a large tumor with adverse risk features such as poorly differentiated tumor grade and triple-negative receptor status. Patients with metaplastic BC had significantly worse survival regardless of stage at presentation compared with triple-negative and other BC.…”

Section: Discussionmentioning

confidence: 66%

Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes

Moreno

Bedrosian

et al. 2020

J. Cancer

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Purpose: Metaplastic breast cancer (BC) is an uncommon yet aggressive histologic subtype of BC. We sought to identify factors associated with its diagnosis and compare the management and outcomes of metaplastic BC with those of other BCs and triple negative invasive ductal carcinoma in particular given how often it has a triple negative phenotype. Patients and Methods:We identified women diagnosed with invasive BC in 2010-2014 in the National Cancer Data Base, and used univariate analysis to compare baseline patient and tumor characteristics by BC subtype. Overall survival (OS) was estimated with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to identify independent predictors of OS. Results: Of 247,355 cases, 2,084 (0.8%) were metaplastic BC, 55,998 (23%) triple negative BC, and 77% other BC. Relative to non-metaplastic BC, women with metaplastic BC were more likely to be older at diagnosis (median age, 62 vs. 59 years), have ≥1 comorbid conditions (22% vs. 18%), and be on Medicare (41% vs. 33%; P<0.001). Metaplastic BCs tended to be basal-like (77%), and relative to triple-negative or other BC, metaplastic BC was associated with higher clinical T status (cT3-4, 18% vs. 11%, 8%), no clinical nodal involvement (cN0, 86%, 77%, 80%), no lymphovascular invasion (72%, 65%, 62%), and high-grade tumors (71%, 77%, 35%) (P<0.001). Most metaplastic BCs were treated with mastectomy (58%), sentinel lymph node dissection (65%), chest wall or breast irradiation (74%), and chemotherapy (75%) as adjuvant therapy (60%). At a median follow-up time of 44.5 months, OS rates were lower for metaplastic BC than for triple-negative or other BC across all clinical stages at 5 years (stage I, 85%, 87%, 91%; II, 73%, 77%, 87%; III, 43%, 53%, 75%) and at 3 years (Stage IV, 15%, 22%, 64%; P<0.001). On multivariate analysis, increasing age, advanced clinical stage, lymphovascular invasion, axillary (vs. sentinel) node dissection, and no radiation or chemotherapy were associated with worse outcomes in metaplastic BC. Extent of surgery affected survival for triple-negative and other BC but not for metaplastic BC. Conclusion: Outcomes for metaplastic BC continue to be worse than those for other BC subtypes despite modern treatments. Optimizing systemic therapy options, which was a significant predictor of survival, should be a priority in managing metaplastic BC.

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“…7,9,[12][13][14] With rare exceptions (low-grade adenosquamous and fibromatosislike metaplastic variants), MBCs are associated with a high recurrence/metastasis risk, chemotherapy resistance, and poor outcome. 15 Mutational diversity is reflected in the morphologic heterogeneity of MBCs; PIK3CA mutations were detected in all morphologic variants of MBCs, excluding the chondroid variant, 5,6,11 whereas TERT mutations were more prevalent in spindle cell and squamous variants. 5 Microarray expression-based studies also revealed differences between the morphologic subtypes of MBC in regards to epithelial-mesenchymal transition (EMT)-related genes such as CDH1 and EPCAM.…”

Section: Introductionmentioning

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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Metaplastic Breast Cancer Treatment and Outcomes in 2500 Patients: A Retrospective Analysis of a National Oncology Database

Abstract: MBC patients had worse survival than non-MBC patients, independent of receptor status, suggesting that MBC may confer an additional survival disadvantage. Multimodal therapy was associated with improved outcomes, but ALND was not and may be overutilized in MBC.

Cited by 89 publications

References 31 publications

Novel Nomograms to Predict of Overall Survival and Cancer-specific Survival of Patients of Metaplastic Breast Cancer

Novel Nomograms to Predict of Overall Survival and Cancer-specific Survival of Patients of Metaplastic Breast Cancer

Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes

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

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