T Cells Induce Pre-Metastatic Osteolytic Disease and Help Bone Metastases Establishment in a Mouse Model of Metastatic Breast Cancer

Purpose Single nucleotide polymorphisms (SNPs) in DNA repair and cell cycle control genes may alter protein function and therefore the efficacy of DNA damaging chemotherapy. We retrospectively evaluated the association of SNPs in DNA repair genes, XRCC1-01 (Arg399Gln) and XRCC3-01 (Thr241Met), and a cell cycle control gene, CCND1-02 (A870G), with progression-free survival (PFS) and breast cancer specific survival (BCSS) in patients with metastatic breast cancer (MBC). Patients and Methods SNPs in 95 patients with MBC enrolled onto one of five prospective clinical trials of high-dose chemotherapy and autologous stem-cell transplantation were evaluated using genotyping assays. Results For XRCC1-01, the hazard ratio (HR) for BCSS was 2.8 (95% CI, 1.60 to 5.00) and the HR for PFS was 2.0 (95%CI, 1.12 to 3.43). For XRCC3-01, the HR for BCSS was 2.0 (95%CI, 1.12 to 3.70) and the HR for PFS was 2.0 (95%CI, 1.09 to 3.59). For CCND1-02, the HR for BCSS was 1.8 (95%CI, 1.12 to 2.78) and the HR for PFS was 1.8 (95%CI, 1.15 to 2.85). Patients carrying one variant genotype (HR, 1.7; 95%CI, 1.07 to 2.82) or combinations of any two variant genotypes (HR, 4.7; 95% CI, 2.41 to 8.94) had significantly poorer BCSS compared with patients carrying zero variants. In multivariable analysis, XRCC1-01, presence of liver metastases, and bone metastases independently predicted BCSS. Combinations of any two variant genotypes were stronger independent predictors of BCSS and PFS than the presence of liver or bone metastases. Conclusion XRCC1-01, XRCC3-01, and CCND1-01 may be predictive of survival outcome in patients with MBC treated with DNA damaging chemotherapy.

Download Full-text

Efficacy and Safety of Intravenous Bisphosphonates in Patients with Bone Metastases Caused by Metastatic Breast Cancer

Clinical Breast Cancer ◽

10.3816/cbc.2007.s.002 ◽

2007 ◽

Vol 7 ◽

pp. S14-S20 ◽

Cited By ~ 24

Author(s):

Allan Lipton

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastases ◽

Metastatic Breast ◽

Efficacy And Safety ◽

Intravenous Bisphosphonates

Download Full-text

Bone Metastases in Patients with Metastatic Breast Cancer: Morphologic and Metabolic Monitoring of Response to Systemic Therapy with Integrated PET/CT

Radiology ◽

10.1148/radiol.2471070567 ◽

2008 ◽

Vol 247 (1) ◽

pp. 189-196 ◽

Cited By ~ 131

Author(s):

Ukihide Tateishi ◽

Cristina Gamez ◽

Shaheenah Dawood ◽

Henry W. D. Yeung ◽

Massimo Cristofanilli ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastases ◽

Systemic Therapy ◽

Metastatic Breast ◽

Metabolic Monitoring ◽

Pet Ct

Download Full-text

Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e11071 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e11071-e11071

Author(s):

Katia Cagossi ◽

Maria Grazia Lazzaretti ◽

Alessia Ferrari ◽

Giorgia Razzini ◽

Meri Leporati ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastases ◽

Kinase Inhibitor ◽

Performance Status ◽

Metastatic Breast ◽

Metronomic Chemotherapy ◽

Breast Cancer Patients ◽

Heavily Pretreated ◽

Her 2

e11071 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, measurable disease, prior systemic therapy (chemotherapy and/or hormonal therapy) for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression or unacceptable toxicity. Primary objective was time to progression (TTP) and safety. Results: Tenpatients were included. Median age was 56 years old (range 46-76). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 4 months (2-7). No complete response was observed. Six out of ten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and are still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited reduction of serum marker concentrations to normal range. No grade 3-4 toxicity was reported. There was no decline in cardiac function. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The treatment appears to be an effective and less toxic option in heavily pretreated MBC patients. Of note is the observed activity in patients with exclusive bone metastases. Monitoring of CEA and Ca15.3 during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients who are responding to the therapy. Therefore, the combination of lapatinib with metronomic chemotherapy should be explored in advance for osseous MBC.

Download Full-text

Preliminary results of the concurrent use of radiotherapy for bone metastases and trastuzumab emtansine in patients with HER2-positive metastatic breast cancer

Cancer/Radiothérapie ◽

10.1016/j.canrad.2016.03.010 ◽

2016 ◽

Vol 20 (4) ◽

pp. 312-313 ◽

Cited By ~ 1

Author(s):

A. Géraud ◽

H.P. Xu ◽

P. Beuzeboc ◽

Y.M. Kirova

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastases ◽

Metastatic Breast ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Preliminary Results ◽

Concurrent Use

Download Full-text

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.6917 ◽

2018 ◽

Vol 36 (12) ◽

pp. 1225-1231 ◽

Cited By ~ 5

Author(s):

Suparna B. Wedam ◽

Julia A. Beaver ◽

Laleh Amiri-Kordestani ◽

Erik Bloomquist ◽

Shenghui Tang ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Bone Metastases ◽

Metastatic Breast ◽

Progression Free Survival ◽

Pooled Analysis ◽

Differential Outcomes ◽

Discordance Rate ◽

Trial Outcomes ◽

The Impact

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

Download Full-text