Vascularity change and tumor response to neoadjuvant chemotherapy for advanced breast cancer.

For advanced breast cancer with severe local disease (ABC) (stage III/IV), neoadjuvant chemotherapy improves local control and surgical outcome. However, about approximately 20 to 30% of advanced cancers show either no or poor response to chemotherapy. To prevent unnecessary treatment, a capability of predicting clinical response to neoadjuvant chemotherapy of ABC is highly desirable. Vascularity index (VI) of breast cancers was derived from the quantification results in 30 ABC patients by using power Doppler sonography. Power Doppler sonography evaluation was performed every one to two weeks during chemotherapy. The overall response rate for 30 advanced patients tested was 70%, when 50% or more reduction in tumor size was the objective clinical response. Chemotherapy response was unrelated to the original tumor size (p = 0.563) or chemotherapy agents used (p = 0.657). The median VI for all 30 patients was 4.99%. The response rates for hypervascular tumors vs. hypovascular tumors, based on initial median value, were 86.7% and 53.3%, respectively (p = 0.109). The average VIs in responders and nonresponders were 7.67 +/- 4.77% and 4.01 +/- 3.82% (p = 0.052). There was a tendency for responders who have a relatively high initial vascularity. The VI change in responder group shows a pattern of initial increasing in vascularity followed by decreasing in vascularity. All patients (17/17) with a VI increment of >5% during chemotherapy had good chemotherapy response, whereas in patients with a VI increment of <5%, the response rate was 30.8% (4/13) (p < 0.001). For patients with a peak VI of >10% during chemotherapy, the response rate was 94.1% (16/17). However, in patients with a peak VI of <10%, the response rate was 38.5% (5/13) (p = 0.001). This prediction was made mostly within one month (25.47 +/- 12.96 d for VI increments >5% and 25.44 +/- 12.41 d for VI increased to >10%). In the meantime, the differences in size reduction shown in B-mode sonography were insignificant between responders and nonresponders (patient group with VI increment >5%, p = 0.308; patient group with peak VI >10%, p = 0.396). In conclusion, we propose that VI as determined by using power Doppler sonography is a good and inexpensive clinical tool for monitoring vascularity changes during neoadjuvant chemotherapy in ABC patients. Two parameters--VI increment >5% and peak VI >10%--are potential early predictors for good responses to neoadjuvant chemotherapy within one month in patients with ABC.

[1]  D. Hicklin,et al.  Therapy-Induced Acute Recruitment of Circulating Endothelial Progenitor Cells to Tumors , 2006, Science.

[2]  D O Cosgrove,et al.  Breast carcinoma: measurement of tumor response to primary medical therapy with color Doppler flow imaging. , 1994, Radiology.

[3]  U. Chetty,et al.  Colour Doppler ultrasonography studies of benign and malignant breast lesions , 1992, The British journal of surgery.

[4]  K. Miller E2100: a phase III trial of paclitaxel versus paclitaxel/bevacizumab for metastatic breast cancer. , 2003, Clinical breast cancer.

[5]  Yih-Leong Chang Vascular pathology of malignant cervical lymphadenopathy: Qualitative and quantitative assessment with power doppler ultrasound , 1998 .

[6]  Chien-Nan Lee,et al.  Vascularity index as a novel parameter for the in vivo assessment of angiogenesis in patients with cervical carcinoma , 1999, Cancer.

[7]  Fiona J Gilbert,et al.  Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  T. Delozier,et al.  Improved local control and disease-free survival after perioperative chemotherapy for early-stage breast cancer. A European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group Study. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  M. Kessler,et al.  Evaluation of breast lesions by power Doppler sonography , 2001, European Radiology.

[10]  B. Thürlimann,et al.  Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer , 2006, British Journal of Cancer.

[11]  M. Rinaldo,et al.  Color-doppler using contrast medium in evaluating the response to neoadjuvant treatment in patients with locally advanced breast carcinoma. , 2005, Anticancer research.

[12]  G. Bonadonna,et al.  Adjuvant and neoadjuvant treatment of breast cancer. , 2001, Seminars in oncology.

[13]  T. Helbich,et al.  Locally advanced breast carcinoma: computer assisted semiquantitative analysis of color Doppler ultrasonography in the evaluation of tumor response to neoadjuvant chemotherapy (work in progress). , 2000, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[14]  J B Davey,et al.  Color Doppler signals from breast tumors. Work in progress. , 1990, Radiology.

[15]  R. Lagalla,et al.  Monitoring treatment response with color and power Doppler. , 1998, European journal of radiology.

[16]  P Kelly Marcom,et al.  Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  R. Rubens,et al.  Assessment of response to therapy in advanced breast cancer. , 1977, British Journal of Cancer.

[18]  K. Chatamra,et al.  Does color Doppler ultrasound vascularity predict the response to neoadjuvant chemotherapy in breast cancer? , 2005, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[19]  J M Rubin,et al.  Power Doppler US: a potentially useful alternative to mean frequency-based color Doppler US. , 1994, Radiology.

[20]  J B Davey,et al.  Breast diseases: color Doppler US in differential diagnosis. , 1993, Radiology.

[21]  S. Kook,et al.  Evaluation of solid breast lesions with power Doppler sonography , 1999, Journal of clinical ultrasound : JCU.

[22]  R. Shukla,et al.  Color doppler ultrasound as an objective assessment tool for chemotherapeutic response in advanced breast cancer , 2005, Breast cancer.

[23]  E. Mamounas Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy studies. , 1998, Seminars in oncology.

[24]  F. Becker,et al.  Growth and metastasis of tumor in organ culture , 1963, Cancer.

[25]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[26]  Wei Tse Yang,et al.  Correlation Between Color Power Doppler Sonographic Measurement of Breast Tumor Vasculature and Immunohistochemical Analysis of Microvessel Density for the Quantitation of Angiogenesis , 2002, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[27]  M. Valle,et al.  Power Doppler sonography: clinical applications. , 1998, European journal of radiology.

[28]  Paul L Carson,et al.  Sonographic Evaluation of Early‐Stage Breast Cancers That Undergo Neoadjuvant Chemotherapy , 2005, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[29]  Shin‐Cheh Chen,et al.  Color Doppler ultrasound in benign and malignant breast tumors , 1999, Breast Cancer Research and Treatment.

[30]  R. Jain,et al.  Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions. , 1991, Cancer research.

[31]  Mamounas Ep Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy studies. , 1998 .

[32]  F. Hsieh,et al.  Color Doppler vascularity index can predict distant metastasis and survival in colon cancer patients. , 2000, Cancer research.

[33]  Correlation of Doppler US Tumor Signals with Neovascular Morphologic Features , 1988 .

[34]  F Pozza,et al.  Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. , 1992, Journal of the National Cancer Institute.

[35]  H X Chen,et al.  Bevacizumab (BV) plus 5-FU/leucovorin (FU/LV) for advanced colorectal cancer (CRC) that progressed after standard chemotherapies: An NCI Treatment Referral Center trial (TRC-0301). , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  J M Rubin,et al.  Power Doppler sonography. , 1996, Radiology.

[37]  Chiung-Nien Chen,et al.  Effect of thalidomide in hepatocellular carcinoma: assessment with power doppler US and analysis of circulating angiogenic factors. , 2005, Radiology.

[38]  S. Raza,et al.  Solid breast lesions: evaluation with power Doppler US. , 1997, Radiology.

[39]  R. Jeffrey,et al.  Preliminary experience with power Doppler imaging of solid breast masses. , 1997, AJR. American journal of roentgenology.

[40]  M. Toi,et al.  Tumor angiogenesis is an independent prognostic indicator in primary breast carcinoma , 1993, International journal of cancer.