Monitoring the Size and Response of Locally Advanced Breast Cancers to Neoadjuvant Chemotherapy (Weekly Paclitaxel and Epirubicin) with Serial Enhanced MRI

AbstractPurpose. To determine if early cancer size reduction seen on enhanced magnetic resonance imaging (MRI) can serve as a response predictor and to correlate final tumor sizes on MRI and excised gross tumor size to microscopic findings in patients with locally advanced breast cancers treated with preoperative neoadjuvant chemotherapy. Methods and materials. Thirty-three patients with advanced breast cancer entered this prospective chemotherapeutic study. Serial, dynamic, enhanced MRI was performed before chemotherapy induction, after the first course of chemotherapy and after the third course of chemotherapy prior to surgery. Responses were measured by image subtraction of tumor size on subsequent axial MRIs using the response evaluation criteria in solid tumors (RECIST). Early tumor size reduction, percentage of relative early tumor size reduction and final tumor size response were calculated and analyzed statistically. Sizes of residual tumors measured on MRI and gross tumors in excised breasts were correlated with microscopic findings. Results. Based on tumor sizes measured with enhanced MRI, four complete responders (CR), 19 partial responders (PR) and 10 non-responder were documented. Twelve (52%) of the 23 responders (CR and PR) had reached the criteria for PR (≥30% size reduction) after the first course of chemotherapy. All CR had a marked early size reduction (ESR) of more than 45%. Using the receiver operating characteristic (ROC) curve, a good cutoff point for early tumor size reduction was 7.4 cm, with a false positive rate of 0.1 and a false negative rate of 0.13. The percentage of ESR was 8.8%, with a false positive rate of 0.1 and a false negative rate of 0.09. Residual tumor size on MRI correlated well with microscopic findings (r = 0.982, p < 0.001) and gross tumor size in excised breasts correlated moderately with microscopic findings (r = 0.640, p < 0.001). Conclusion. Serial, dynamic, enhanced MRI monitoring of chemotherapeutic response in patients with locally advanced breast cancer can be used to assess early response to chemotherapy and post-chemotherapy tumor size change. Although the residual tumor size on MRI correlated well with the microscopic findings, surgical determination of residual cancer load is still recommended to avoid underestimation.

[1]  G. Hortobagyi,et al.  Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy. , 1988, Radiology.

[2]  G. Hortobagyi,et al.  Pathological assessment of response to induction chemotherapy in breast cancer. , 1986, Cancer research.

[3]  R. Gilles,et al.  Locally advanced breast cancer: contrast-enhanced subtraction MR imaging of response to preoperative chemotherapy. , 1994, Radiology.

[4]  G. Cocconi,et al.  Problems in evaluating response of primary breast cancer to systemic therapy , 2005, Breast Cancer Research and Treatment.

[5]  S E Harms,et al.  Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging , 1996, Cancer.

[6]  G. Hortobagyi,et al.  Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy , 1988, Cancer.

[7]  G. Bonadonna,et al.  Karnofsky memorial lecture. Conceptual and practical advances in the management of breast cancer. , 1989, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Padhani,et al.  The RECIST criteria: implications for diagnostic radiologists , 2001 .

[9]  J. Hanley,et al.  Statistical Approaches to the Analysis of Receiver Operating Characteristic (ROC) Curves , 1984, Medical decision making : an international journal of the Society for Medical Decision Making.

[10]  S. Steinberg,et al.  Neoadjuvant chemotherapy in the combined modality approach of locally advanced nonmetastatic breast cancer. , 1987, Cancer research.

[11]  M. Christian,et al.  Measuring response in solid tumors: unidimensional versus bidimensional measurement. , 1999, Journal of the National Cancer Institute.

[12]  G. Schwartz,et al.  Neoadjuvant chemotherapy before definitive treatment for stage III carcinoma of the breast. , 1987, Archives of surgery.

[13]  A. Giuliano,et al.  Breast conservation management of breast tumors 4 cm or larger. , 1992, Archives of surgery.

[14]  W. Kraybill,et al.  Multimodal therapy in locally advanced breast carcinoma. , 1990, American journal of surgery.

[15]  G. Hortobagyi,et al.  Feasibility of breast‐conservation surgery after induction chemotherapy for locally advanced breast carcinoma , 1992, Cancer.

[16]  P J Drew,et al.  Evaluation of response to neoadjuvant chemoradiotherapy for locally advanced breast cancer with dynamic contrast-enhanced MRI of the breast. , 2001, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[17]  C. Kuhl,et al.  Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions? , 1999, Radiology.

[18]  M D Schnall,et al.  Suspicious breast lesions: MR imaging with radiologic-pathologic correlation. , 1994, Radiology.

[19]  G. Schwartz,et al.  Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast , 1994, Cancer.

[20]  R Musumeci,et al.  Locally Advanced Breast Cancer Treated with Primary Chemotherapy: Comparison between Magnetic Resonance Imaging and Pathologic Evaluation of Residual Disease , 1999, Tumori.

[21]  Davis Pl,et al.  Technologic considerations for breast tumor size assessment. , 1994 .

[22]  Z. Baloch,et al.  Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: a determinant of outcome. , 1995, Journal of the American College of Surgeons.

[23]  G. Hortobagyi,et al.  Multimodal treatment of locoregionally advanced breast cancer , 1983, Cancer.

[24]  G Brix,et al.  MR mammography with pharmacokinetic mapping for monitoring of breast cancer treatment during neoadjuvant therapy. , 1994, Magnetic resonance imaging clinics of North America.

[25]  J. Pater Treatment of locally advanced breast cancer , 2004, Canadian Medical Association Journal.