A Case Series of Metastatic Metaplastic Breast Carcinoma Treated With Anti-PD-1 Therapy

Kim, Isaac; Bernard, Brady; Chun, Brie; Wu, Yaping; Martel, Maritza; Sun, Zhaoyu; Redmond, William L.; Sanchez, Katherine; Basho, Reva; McArthur, Heather L.; Page, David B.

doi:10.3389/fonc.2021.635237

Cited by 20 publications

(25 citation statements)

References 42 publications

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“…Our current options for MBC are far from ideal. Fortunately, immunotherapy and targeted therapy may hold promise as a new therapeutic strategy for MBC, which show e cacy in previous research [33,37,38]. Those potential treatment approach are worth exploring and studying in detail in the future.…”

Section: Discussionmentioning

confidence: 93%

“…Current chemotherapy treatment protocols for the management of MBC are not very effective, but it remains an important part of the treatment regimen for MBC. And that may be changed by immunotherapy in the future cause few previous studies found that PD-L1 was over expressed in MBC and immune checkpoint inhibitors showed good e cacy in MBC [32,33].…”

Section: Discussionmentioning

confidence: 99%

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Outcomes of metaplastic breast cancer versus triple negative breast cancer: a propensity score matching analysis

Tan

Yang

Chen

et al. 2022

Preprint

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Purpose This study aims to compare the survival outcomes of MBC with triple-negative breast cancer (TNBC) and identify prognostic factors that influence MBC survival. Methods Patients with non-metastatic MBC or TNBC were reviewed from our database from 2002 to 2021. Patient clinicopathologic features and treatment were analyzed with respect to outcomes including disease progression-free survival (DFS), and overall survival (OS). Propensity score matching (PSM) with a one-to-three matching between MBC and TNBC was performed. Results A total number of 857 female patients (76 MBC and 781 TNBC) were included in this study, with median age in 49 years (28–77 years). A subgroup of triple negative MBC (n = 60) was matched with TNBC (n = 180) cases based on patient characteristics and treatment. OS and DFS were significantly worse in the MBC group before (p = 0.0046 both) and after (p = 0.011 and p = 0.0046, respectively) PSM. Multivariable analysis revealed larger tumor size (T > 5cm) (HR = 3.797, 95%CI 1.118–12.902, p = 0.032) and lymph nodal status (N3 vs N0-2, HR = 6.149 95%CI 1.499–25.229, p = 0.012) were associated with worse OS after PSM. Among the 76 MBC patients, higher T stage and mesenchymal differentiation were associated with worse overall survival (pT1/2 vs pT3/4 and mesenchymal differentiation vs other type, p = 0.007 and p = 0.011, respectively). Lymph node positive and mesenchymal differentiation were associated with worse disease-free survival (Figs. 5 and 6, p = 0.005 and p < 0.001, respectively). Conclusions Compared with TNBC, MBC tends to have a worse OS. Mesenchymal differentiation has a worse DFS than other subtypes of MBC.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Outcomes of metaplastic breast cancer versus triple negative breast cancer: a propensity score matching analysis

Tan

Yang

Chen

et al. 2022

Preprint

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“…Previously, four case reports observed the efficacy of ICIs in advanced MBC ( Table 1 ). Six of eight patients showed a good prognosis after immunotherapy ( 18 – 21 ).…”

Section: Discussionmentioning

confidence: 99%

Partial Response After Toripalimab Plus Anlotinib for Advanced Metaplastic Breast Carcinoma: A Case Report

2022

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Metaplastic breast carcinoma (MBC) is an aggressive subtype of breast cancer, accounting for <1%. The clinical outcome is unknown due to the lack of treatment options. Here, we present the case of a 58-year-old woman with advanced MBC, in which standard adjuvant chemotherapy was unsuccessful. In the second-line therapy, she received anti-angiogenic(anlotinib) therapy plus chemotherapy. Finally, she was subsequently treated with immunotherapy (toripalimab) combined anlotinib and achieved partial response (PR); thus, immunotherapy plus anti-angiogenic therapy might be a novel option for advanced MBC patients.

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“…Additional details regarding these cases are summarized in a recently published case series. 21 Exploratory immune-based biomarker assessment Whole blood immune cell assessment Flow cytometry and TCR sequencing were used to explore univariate associations of baseline peripheral blood immune pro le with week 12 OR, the secondary outcome of the study. Clinical responses according to these biomarkers are summarized in supplemental Figs.…”

Section: Activity In Metaplastic Tnbcmentioning

confidence: 99%

A phase Ib trial evaluating the safety, efficacy, and immunologic effects of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer

Page

Pucilowska

Chun

et al. 2022

Preprint

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Background Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. Methods We report final outcomes from a phase Ib trial evaluating pembrolizumab (200mg IV every 3 weeks) with either weekly paclitaxel (80mg/m2 weekly) or flat-dose capecitabine (2000mg orally twice daily for 7 days of every 14-day cycle) in the 1st /2nd line setting. The primary endpoint was safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥ 21-day delays). The secondary endpoint was efficacy (week 12 objective response rate). Exploratory aims were to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. Results Both regimens met the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate was 29% for pembrolizumab/paclitaxel and 43% for pembrolizumab/capecitabine. Partial responses were observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens were associated with significant peripheral leukocyte contraction over time. Response was associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). Conclusions Pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens were lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. Trial registration: NCT02734290

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A Case Series of Metastatic Metaplastic Breast Carcinoma Treated With Anti-PD-1 Therapy

Cited by 20 publications

References 42 publications

Outcomes of metaplastic breast cancer versus triple negative breast cancer: a propensity score matching analysis

Outcomes of metaplastic breast cancer versus triple negative breast cancer: a propensity score matching analysis

Partial Response After Toripalimab Plus Anlotinib for Advanced Metaplastic Breast Carcinoma: A Case Report

A phase Ib trial evaluating the safety, efficacy, and immunologic effects of pembrolizumab plus paclitaxel or flat-dose capecitabine in 1st/2nd line metastatic triple-negative breast cancer

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