BACKGROUND: Circulating tumor cells (CTCs) and tumor-specific alterations in cell-free plasma DNA can both be used as markers of prognosis in breast cancer. To date, there have been no studies that have compared these as markers for subclinical metastases in the follow-up of early breast cancer. In this study, we measured CTCs and plasma DNA in a published group of patients with multiple pulmonary nodules and indeterminate metastatic disease. PATIENTS & METHODS: A single blood sample for CTC and plasma DNA measurement was taken approximately 1.5 years after surgery from 19 women with histologically confirmed primary breast cancer and small pulmonary nodules. The CellSearch system was used to enrich and enumerate CTCs from peripheral blood. DNA was isolated from plasma and was analyzed by quantitative real-time PCR for DNA concentration, integrity and evidence of HER2 amplification. RESULTS: Of the 19 individuals with 'indeterminate' early or metastatic breast cancer, 17 demonstrated no evidence of CTCs, one had one CTC and one had three CTCs. The mean plasma DNA concentration was low and within the range detected in healthy female controls, as were the values for DNA integrity. HER2 amplification was detected in the plasma DNA in four of the eight patients with HER2 immunohistochemistry 3+ tumors, but there was no overlap with the two CTC-positive patients. None of the patients have relapsed thus far (median follow-up: 3.5 years). CONCLUSION: Both CTC and plasma DNA analyses together suggested that these patients had little evidence of metastatic disease. Future studies will be designed to assess the utility of these biomarkers in the follow-up of a larger number of women with breast cancer.
BACKGROUND: Circulating tumor cells (CTCs) and tumor-specific alterations in cell-free plasma DNA can both be used as markers of prognosis in breast cancer. To date, there have been no studies that have compared these as markers for subclinical metastases in the follow-up of early breast cancer. In this study, we measured CTCs and plasma DNA in a published group of patients with multiple pulmonary nodules and indeterminate metastatic disease. PATIENTS & METHODS: A single blood sample for CTC and plasma DNA measurement was taken approximately 1.5 years after surgery from 19 women with histologically confirmed primary breast cancer and small pulmonary nodules. The CellSearch system was used to enrich and enumerate CTCs from peripheral blood. DNA was isolated from plasma and was analyzed by quantitative real-time PCR for DNA concentration, integrity and evidence of HER2 amplification. RESULTS: Of the 19 individuals with 'indeterminate' early or metastatic breast cancer, 17 demonstrated no evidence of CTCs, one had one CTC and one had three CTCs. The mean plasma DNA concentration was low and within the range detected in healthy female controls, as were the values for DNA integrity. HER2 amplification was detected in the plasma DNA in four of the eight patients with HER2 immunohistochemistry 3+ tumors, but there was no overlap with the two CTC-positive patients. None of the patients have relapsed thus far (median follow-up: 3.5 years). CONCLUSION: Both CTC and plasma DNA analyses together suggested that these patients had little evidence of metastatic disease. Future studies will be designed to assess the utility of these biomarkers in the follow-up of a larger number of women with breast cancer.
Authors: Jacqueline A Shaw; Karen Page; Kevin Blighe; Natasha Hava; David Guttery; Becky Ward; James Brown; Chetana Ruangpratheep; Justin Stebbing; Rachel Payne; Carlo Palmieri; Suzy Cleator; Rosemary A Walker; R Charles Coombes Journal: Genome Res Date: 2011-10-11 Impact factor: 9.043
Authors: B Lee; L Lipton; J Cohen; J Tie; A A Javed; L Li; D Goldstein; M Burge; P Cooray; A Nagrial; N C Tebbutt; B Thomson; M Nikfarjam; M Harris; A Haydon; B Lawrence; D W M Tai; K Simons; A M Lennon; C L Wolfgang; C Tomasetti; N Papadopoulos; K W Kinzler; B Vogelstein; P Gibbs Journal: Ann Oncol Date: 2019-09-01 Impact factor: 32.976
Authors: Karen Page; David S Guttery; Nathalie Zahra; Lindsay Primrose; Shona R Elshaw; J Howard Pringle; Kevin Blighe; Stephanie D Marchese; Allison Hills; Laura Woodley; Justin Stebbing; R Charles Coombes; Jacqueline A Shaw Journal: PLoS One Date: 2013-10-18 Impact factor: 3.240
Authors: K Page; N Hava; B Ward; J Brown; D S Guttery; C Ruangpratheep; K Blighe; A Sharma; R A Walker; R C Coombes; J A Shaw Journal: Br J Cancer Date: 2011-03-22 Impact factor: 7.640
Authors: M C U Cheang; J M Bliss; G Viale; V Speirs; C Palmieri; A Shaaban; P E Lønning; J Morden; N Porta; J Jassem; C J van De Velde; B B Rasmussen; D Verhoeven; J M S Bartlett; R C Coombes Journal: Breast Cancer Res Treat Date: 2017-11-24 Impact factor: 4.872
Authors: Jonathan Krell; Adam E Frampton; Jimmy Jacob; Loredana Pellegrino; Laura Roca-Alonso; Daniel Zeloof; Costi Alifrangis; Jacqueline S Lewis; Long R Jiao; Justin Stebbing; Leandro Castellano Journal: Mol Diagn Ther Date: 2012-06-01 Impact factor: 4.074