Effect of neoadjuvant chemotherapy and recombinant tumor necrosis factor -thymosin – α 1 (TNF-T) on overall survival in patients with triple negative breast cancer (TNBC).

AbstractBevacizumab in neoadjuvant therapy provides a new hope of improved survival for patients with triple-negative breast cancer (TNBC) by targeting vascular endothelial growth factor in combination with chemotherapy, but curative effect is limited by bevacizumab’s continuous use while mechanisms remain incompletely understood. More and more researches reported that tumor-associated macrophages mediate resistance to chemotherapy and radiotherapy in various tumors. Here we developed a TNBC model resistant to bevacizumab under bevacizumab continuous administration. It was found that proportion of a specific subset of tumor-associated macrophages characterized as M2b (CD11b+ CD86high IL10high) increased and responsible for acquired resistance to bevacizumab. Then, we showed that RAW264.7 macrophages could be polarized to M2b subtype on simultaneous exposure to bevacizumab and TLR4 ligands as occurs in the context of continuous bevacizumab treatment. Concordantly, in TLR4-deleted C57BL/10ScNJNju (TLR4lps–del) mut/mut mice with bevacizumab treatment model, it was verified that the M2b macrophage could be induced by Fc gamma receptor-TLR4 cross-talk. In MDA-MB-231-resistant tumor-bearing mice, the content of TNFα in serum kept going up consistent with CCL1, a chemokine of M2b macrophage. In vitro neutralizing tumor necrosis factor α (TNFα) could inhibit the tumor progression caused by M2b culture medium and tumor IDO1 expression. Therefore, we thought that TNFα is a key tumor-promoting effector molecule secreted by M2b macrophage. Accordingly, the curative effect of bevacizumab was proved to be significantly improved by neutralizing TNFα with anti-TNFα nanobody. This study is expected to provide theoretical and clinical evidence elucidating the drug resistance in patients receiving bevacizumab.

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Penta‐O‐Galloyl‐β‐D‐Glucose (PGG) Anti‐Proliferative and Pro‐Apoptotic Effect through Up‐Regulation of Tumor Necrosis Factor and its Receptors in Triple Negative Breast Cancer Cells

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.250.12 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Patricia Mendonca ◽

Sumaiah Alghamdy ◽

Samia S Messeha ◽

Karam F. Soliman

Keyword(s):

Breast Cancer ◽

Tumor Necrosis Factor ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Breast Cancer Cells ◽

Tumor Necrosis ◽

Triple Negative ◽

Apoptotic Effect ◽

Necrosis Factor

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Locally Advanced Breast Cancer (LABC): Real-World Outcome of Patients From Cancer Institute, Chennai

JCO Global Oncology ◽

10.1200/go.21.00001 ◽

2021 ◽

pp. 767-781

Author(s):

Manikandan Dhanushkodi ◽

Velusamy Sridevi ◽

Viswanathan Shanta ◽

Ranganathan Rama ◽

Rajaraman Swaminathan ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Tumor Size ◽

Triple Negative ◽

Locally Advanced Breast Cancer ◽

Locally Advanced

PURPOSE There are sparse data on the outcome of patients with locally advanced breast cancer (LABC). This report is on the prognostic factors and long-term outcome from Cancer Institute, Chennai. METHODS This is an analysis of untreated patients with LABC (stages IIIA-C) who were treated from January 2006 to December 2013. RESULTS Of the 4,577 patients with breast cancer who were treated, 2,137 patients (47%) with LABC were included for analysis. The median follow-up was 75 months (range, 1-170 months), and 2.3% (n = 49) were lost to follow-up at 5 years. The initial treatment was neoadjuvant concurrent chemoradiation (NACR) (77%), neoadjuvant chemotherapy (15%), or others (8%). Patients with triple-negative breast cancer had a pathologic complete response (PCR) of 41%. The 10-year overall survival was for stage IIIA (65.1%), stage IIIB (41.2%), and stage IIIC (26.7%). Recurrence of cancer was observed in 27% of patients (local 13% and distant 87%). Multivariate analysis showed that patients with a tumor size > 10 cm (hazard ratio [HR], 2.19; 95% CI, 1.62 to 2.98; P = .001), hormone receptor negativity (HR, 1.45; 95% CI, 1.22 to 1.72; P = .001), treatment modality (neoadjuvant chemotherapy, HR, 0.56; 95% CI, 0.43 to 0.73; P = .001), lack of PCR (HR, 2.36; 95% CI, 1.85 to 3.02; P = .001), and the presence of lymphovascular invasion (HR, 1.97; 95% CI, 1.60 to 2.44; P = .001) had decreased overall survival. CONCLUSION NACR was feasible in inoperable LABC and gave satisfactory long-term survival. PCR was significantly higher in patients with triple-negative breast cancer. The tumor size > 10 cm was significantly associated with inferior survival. However, this report acknowledges the limitations inherent in experience of management of LABC from a single center.

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