Outcomes after Treatment of Metaplastic Versus Other Breast Cancer Subtypes

Abstract

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.

The Role of Adjuvant Chemotherapy in Metaplastic Breast Carcinoma: A Competing Risk Analysis of the SEER Database

“…Additionally, a study based on the SEER database demonstrated that chemotherapy did not lead to improved BCSS in multivariate Cox proportional hazard models ( 23 ). On the contrary, a retrospective study of the National Cancer Data Base (NCDB) indicated that administration of chemotherapy independently improved OS for patients with MBC by using multivariate analysis ( 10 ). Another population-based research has shown that chemotherapy continued to be associated with improved OS in MBC ( 24 ).…”

“…Some MTOR inhibitors, such as temsirolimus and everolimus, have been studied in clinical trials. They seem to suppress MBC through dual anti-cancer effects (MTOR pathway inhabitation and angiogenesis suppression) ( 10 , 29 , 30 ). Also, Atezolizumab plus nab-paclitaxel has been approved as the first immunotherapy regimen for patients with locally advanced or metastatic triple-negative breast tumors expressing PD-L1 ( 31 ).…”

Metaplastic breast cancer: Prognostic and therapeutic considerations

“…Metaplastic breast carcinoma (MBC) is a rare condition accounting for 0.2-5% of all breast tumors. [1][2][3] The current World Health Organization (WHO) identifies different histological patterns of MBC: low-grade adenosquamous carcinoma, fibromatosis-like metaplastic carcinoma, squamous cell carcinoma, spindle cell carcinoma, metaplastic carcinoma with mesenchymal differentiation, mixed metaplastic carcinoma, and myoepithelial carcinoma. 4 Compared with the other histotypes of breast cancer, MBC most commonly shows a triple-negative (TN) phenotype, due to the absence of expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2.…”

“…Metaplastic breast carcinoma (MBC) is a rare condition accounting for 0.2‐5% of all breast tumors 1‐3 . The current World Health Organization (WHO) identifies different histological patterns of MBC: low‐grade adenosquamous carcinoma, fibromatosis‐like metaplastic carcinoma, squamous cell carcinoma, spindle cell carcinoma, metaplastic carcinoma with mesenchymal differentiation, mixed metaplastic carcinoma, and myoepithelial carcinoma 4 .…”

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

“…Metaplastic breast carcinoma (MBC) is a relatively rare form of breast cancer with worse clinical outcomes and resistance to neoadjuvant systemic chemotherapies [1], accounting for 0.2-5% of all breast cancers [2]. The incidence of MBC is increasing since it was recognized as a distinct pathological diagnosis in 2000 [3].. Histologically, MBC is classi ed into several subtypes, including spindle, squamous, chondroid, osseous and/or rhabdomyoid MBC [4].…”