Early and Locally Advanced Metaplastic Breast Cancer: Presentation and Survival by Receptor Status in Surveillance, Epidemiology, and End Results (SEER) 2010–2014

Schroeder, Mary C.; Rastogi, Priya; Geyer, Charles E.; Miller, Lance D.; Thomas, Alexandra

doi:10.1634/theoncologist.2017-0398

Cited by 86 publications

(107 citation statements)

References 36 publications

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“…In a multivariate analysis of the SEER data, Nelson et al [3] reported a significant association between reduced survival time and LN positivity, ER and PR negativity, high grade, and tumour size. Further, in an assessment of contemporarily treated MBC, HER2 status was shown to have a significant prognostic impact, implying a responsiveness to HER2-directed therapy [29]. In contrast, our cohort demonstrates the prognostic impact of tumour size; however, we do not see significant impacts on survival made by age at diagnosis, lymph node status, grade or lymphocytic infiltrate.…”

Section: Discussioncontrasting

confidence: 71%

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

Reed

Kalaw

Nones

et al. 2018

The Journal of Pathology

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Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5‐year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology – the biological basis and clinical relevance of its seven sub‐categories are currently unclear. By establishing the Asia‐Pacific MBC (AP‐MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan‐cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for ‘mixed’ MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis‐1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed‐type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan‐cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussioncontrasting

confidence: 71%

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

Reed

Kalaw

Nones

et al. 2018

The Journal of Pathology

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“…Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype, constituting w1% of all invasive breast cancers. 1 Histologically, MBC is a highly heterogeneous disease, encompassing 6 different morphologic subtypes, including spindle, squamous, chondroid, osseous, rhabdomyoid, and mixed morphology. 1 Somatic mutations in TP53, PI3K MAPK, RB1, and Wnt pathways genes have been frequently described in MBCs.…”

Section: Introductionmentioning

confidence: 99%

“…1 Histologically, MBC is a highly heterogeneous disease, encompassing 6 different morphologic subtypes, including spindle, squamous, chondroid, osseous, rhabdomyoid, and mixed morphology. 1 Somatic mutations in TP53, PI3K MAPK, RB1, and Wnt pathways genes have been frequently described in MBCs. [2][3][4][5][6][7][8][9][10][11] MBCs are basallike and claudin-low breast cancers with a triple-negative phenotype: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu)-negative.…”

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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“…prove the outcome of LABC [21][22][23], better quality of life can be achieved with IBR. This is extremely significant for survivors of breast cancer.…”

mentioning

confidence: 97%

Immediate Breast Reconstruction vs. Mastectomy Alone in Locally Advanced Breast Cancer; Local Recurrence and Distant Recurrence

et al. 2019

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Purpose: The oncologic safety of immediate breast reconstruction (IBR) has been demonstrated. However, the outcome of IBR for locally advanced breast cancer (LABC) is still under debate. We compared the survival outcome of LABC patients who underwent IBR vs. mastectomy alone. Methods: We retrospectively analyzed a total of 248 patients with stage III breast cancer who were treated with mastectomy between 2004 and 2015. The study subjects were divided into 2 groups: patients who received IBR (n= 77) or mastectomy alone (MA) (n= 171). We compared disease-free survival (DFS) of both groups. Results: Median follow-up duration was 49 months and the mean age of patients was 49 years. Patients in the IBR group were significantly younger and had lower body mass index (BMI) than those in the MA group. In a univariate analysis, IBR group showed better DFS than the MA group (DFS 81.3 months vs. 49.8 months, p< 0.001). There was no delay in adjuvant treatment in the IBR group. In a multivariate analysis, IBR was associated with better DFS (hazard ratio (HR) for recurrence: 0.37, 95% CI 0.20-0.69, p= 0.002) when adjusted for potential prognostic factors. In a subgroup analysis performed according to disease stage (IIIA and IIIB/IIIC), DFS was significantly better in IBR than MA group in both stage subgroups (p< 0.001). Conclusion: We demonstrated that patients who underwent IBR showed better DFS outcome compared with patients who underwent mastectomy alone. Our results can help surgeons to determine if IBR is an option in patients with LABC.

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Early and Locally Advanced Metaplastic Breast Cancer: Presentation and Survival by Receptor Status in Surveillance, Epidemiology, and End Results (SEER) 2010–2014

Cited by 86 publications

References 36 publications

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

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

Immediate Breast Reconstruction vs. Mastectomy Alone in Locally Advanced Breast Cancer; Local Recurrence and Distant Recurrence

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