Antiangiogenic Agents in Breast Cancer

2007 ◽  
pp. 269-284
Author(s):  
John T. Salter ◽  
Kathy D. Miller
Keyword(s):  
Breast Cancer ◽  
Antiangiogenic Agents

Bevacizumab and oral chemotherapy for patients with lymphangitic breast cancer: A phase II randomized study of bevacizumab with sequential versus concurrent oral vinorelbine plus capecitabine

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1031-1031
Author(s):  
M. A. Locatelli ◽  
G. Curigliano ◽  
L. Fumagalli ◽  
R. Ghisini ◽  
P. Mancuso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chest Wall ◽  
Phase Ii ◽  
Biological Effects ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Antiangiogenic Agents ◽  
Surrogate Markers ◽  
Oral Vinorelbine ◽  
Antiangiogenic Activity

1031 Background: Antiangiogenic agents are most likely to be effective in patients (pts) with an extensive cutaneous neo-angiogenic trait of disease. There is a compelling need to monitor the biological activity of such agents and identify markers of efficacy. Methods: We evaluated the activity and biological effects of bevacizumab (B) (15 mg/kg, iv q 3 weeks) in a phase II randomized trial in pts with locally advanced breast cancer (BC) with lymphangitic spread to the chest wall. Primary aim was to assess activity and toxicity of B administered alone followed by sequential oral vinorelbine (V) plus capecitabine (C) (arm A) or with concurrent V plus C (arm B). Secondary aim was to evaluate predictive role of circulating progenitor cells (CECs) and progenitor endothelial cells (CEPs) as surrogate markers of antiangiogenic activity. We collected blood samples of all pts at baseline, at day 12, 42, and at progression. Results: Planned accrual was of 43 pts of whom 23 were enrolled (9 pts in arm A; 14 pts in arm B). Median age was 51 years (range 35–68). Most of the pts had a “triple negative” phenotype [19/23 (82%)]. 10/23 pts (43%) received ≥ 2 previous lines of chemotherapy. 19 pts (82 %) are evaluable for response and all 23 pts are evaluable for toxicity. We observed 5 PR (45%) and 6 SD (55%) in arm B. In arm A, while on B alone, 6 (75%) of the pts had PD and 2 (25%) had a short term SD. Adding VC to B 2 PR (25%), 3 SD (37.5%), and 3 PD (37.5%) were observed. Toxicity profile was typical for use of B (hypertension). The absolute mean number of CECs was 158/ml (range 45–461) (n = 23) at baseline, 116/ml at +12 (range 47–275), and 194/ml at +42 (range 36–891). Mean absolute value of CEPs was 270 (range 28–1060) at baseline, 245/ml at D+12 (range 14–981), and 143/ml (range 5–610) at D+42. The fraction of apoptotic/necrotic CECs was 54±19% at baseline, 64±21 at+12, and 52±18 at+42. Conclusions: Preliminary data showed that B alone is not an effective treatment in pts with lymphangitic spread of BC to the chest wall. Additional data on CECs and CEPs are needed to clarify their potential usefulness as a surrogate markers of antiangiogenic activity of B-based regimen. No significant financial relationships to disclose.

scholarly journals Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia

2012 ◽  
Vol 109 (8) ◽  
pp. 2784-2789 ◽  
Author(s):  
S. J. Conley ◽  
E. Gheordunescu ◽  
P. Kakarala ◽  
B. Newman ◽  
H. Korkaya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Hypoxia ◽  
Antiangiogenic Agents ◽  
Breast Cancer Stem Cells

Antiangiogenic Agents in Breast Cancer

2007 ◽  
Vol 25 (7) ◽  
pp. 518-526 ◽  
Author(s):  
John T. Salter ◽  
Kathy D. Miller
Keyword(s):  
Breast Cancer ◽  
Antiangiogenic Agents

Combination of famitinib with camrelizumab plus nab-paclitaxel as first-line treatment for patients with immunomodulatory advanced triple-negative breast cancer (FUTURE-C-PLUS): A prospective, single-arm, phase 2 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1007-1007
Author(s):  
Li Chen ◽  
Shao Zhimin ◽  
Zhonghua Wang ◽  
Wentao Yang ◽  
Yizhou Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Objective Response ◽  
Antiangiogenic Agents ◽  
Phase 2 ◽  
First Line ◽  
Phase 2 Study ◽  
Biomarker Analysis

1007 Background: Camrelizumab (anti-PD-1 antibody) and nab-paclitaxel (nab-P) have demonstrated promising anti-tumour activity in patients with immunomodulatory (IM) subtype metastatic triple negative breast cancer (TNBC), with 52.6% of ORR observed in heavily pretreated patients in our previous umbrella trial (FUTURE). As antiangiogenic agents were known to enhance the response to immune checkpoint inhibitors, we assessed the efficacy and safety of novel triplet combination of famitinib (tyrosine kinase inhibitor targeting VEGFR-2, PDGFR and c-kit), camrelizumab and nab-paclitaxel in patients with IM subtype advanced TNBC. Methods: In this prospective, single-arm, phase 2 study, eligible patients were 18-70 years and had treatment-naive IM subtype unresectable locally advanced or metastatic TNBC. IM subtype was defined as CD8+ by immunohistochemistry. Eligible patients received camrelizumab (200 mg iv, d1, 15, q4w) with nab-P (100 mg/m2 iv, d1, 8, 15, q4w) and famitinib (20 mg po qd, d1-28, q4w). Treatment was continued until disease progression, patient withdrawal, or unacceptable toxic effects. In the absence of intolerable toxicity, nab-P was to be administered for a minimum of 6 cycles. Primary endpoint was objective response rate according to RECIST v1.1. We explored the predictive biomarkers using targeted sequencing with a 484-gene panel. Results: From Oct 2019 to Oct 2020, 48 patients were enrolled. Confirmed objective responses were achieved in 39 (81.3%; 95% CI 70.2%-92.3%) of 48 patients in the intention-to-treat population and in 39 (84.8%; 95% CI 74.4%-95.2%) of 46 patients in the per-protocol population. Median time to response was 1.8 months (95% CI 1.8-2.0 months). With a median follow-up of 9.0 months, progression-free survival (PFS) and duration of response data were not mature. Thirty patients (62.5%) are still on the study treatment. The 9-month PFS rate was 60.2% (95% CI, 43.2% to 77.3%). Grade 3 or 4 adverse events were neutropenia (33.3%), anaemia (10.4%), febrile neutropenia (10.4%), thrombocytopenia (8.3%), hypertension (4.2%), hypothyroidism (4.2%), proteinuria (2.1%), septicemia (2.1%) and immune related myocarditis (2.1%). Adverse events that led to the discontinuation of any agent occurred in 6.3% of the patients. Two patients had treatment-related serious adverse events. No treatment-related deaths were reported. Biomarker analysis showed that somatic mutations of GSK3A may have the potential to predict immunotherapy response. Conclusions: Addition of famitinib to camrelizumab and nab-paclitaxel showed promising antitumour activity as first-line therapy with manageable toxicity profile for IM subtype advanced TNBC patients. Results from ongoing randomized controlled trial FUTURE-SUPER (NCT 04395989) are eagerly awaited. Clinical trial information: NCT04129996 .

scholarly journals Circulating endothelial-cell kinetics and viability predict survival in breast cancer patients receiving metronomic chemotherapy

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 452-459 ◽  
Author(s):  
Patrizia Mancuso ◽  
Marco Colleoni ◽  
Angelica Calleri ◽  
Laura Orlando ◽  
Patrick Maisonneuve ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Response ◽  
Cancer Patients ◽  
Clinical Benefit ◽  
Metronomic Chemotherapy ◽  
Circulating Endothelial Cells ◽  
Antiangiogenic Agents ◽  
Breast Cancer Patients ◽  
Preclinical Models ◽  
Anticancer Efficacy

Antiangiogenic agents and therapeutic strategies have entered the clinical oncology arena. The classical tumor size measurements defined to monitor efficacy of chemotherapy, however, might not be appropriate for these newer therapeutics. We previously found that circulating endothelial cells (CECs) were increased in number and more viable in cancer patients compared with control subjects. We investigated the correlation between CEC kinetics and clinical outcome in patients with advanced breast cancer receiving metronomic chemotherapy, a therapeutic strategy associated with antiangiogenic activity and anticancer efficacy. CEC number and viability were measured by flow cytometry in patients and in preclinical models. CECs were decreased in patients for whom no overall clinical benefit (defined as a clinical response or a stable disease) was observed compared with those who had a clinical benefit (P = .015). This difference was due to an increased fraction of apoptotic CECs in patients with a clinical benefit. Univariate and multivariate analyses indicated that CEC values greater than 11/μL were associated with a longer progression-free survival (P = .001) and an improved overall survival (P = .005). Preclinical models indicated that the source of apoptotic CECs was most likely the tumor vasculature. CEC kinetics and viability are very promising as predictors of clinical response in patients undergoing metronomic chemotherapy.

Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

1973 ◽  
Vol 31 ◽  
pp. 378-379
Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Human Breast Cancer ◽  
Osteogenic Sarcoma ◽  
Human Tumor ◽  
Structural Similarity ◽  
Cell Tumor ◽  
Human Breast ◽  
Human Tumor Cell ◽  
Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

Further Ultrastructural Observations on Metastatic Nodules of Human Breast Cancer

1968 ◽  
Vol 26 ◽  
pp. 224-225
Author(s):  
John L. Swedo ◽  
R. W. Talley ◽  
John H. L. Watson
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Estrogen Therapy ◽  
Specimen Preparation ◽  
Human Breast ◽  
Autophagic Vacuoles ◽  
Previous Communication ◽  
Linear Profiles ◽  
Metastatic Nodule

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.

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