Contrast enhanced magnetic resonance imaging underestimates residual disease following neoadjuvant docetaxel based chemotherapy for breast cancer

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Abstract

Aims

We prospectively compared the ability of magnetic resonance imaging (MRI) to measure residual breast cancer in patients treated with different neoadjuvant chemotherapy regimen.

Methods

Forty patients with locally advanced breast carcinoma underwent neoadjuvant chemotherapy. Twelve patients received 5-fluoro-uracyl-epirubicin-cyclophosphamide (FEC-group, six cycles), 28 (DXL-group) received docetaxel-based chemotherapy (six cycles DXL-epirubicin: 13 patients, eight cycles DXL alone: 15 patients). All patients had baseline and preoperative MRI. The spread of pathologic residual disease (PRd) was compared to preoperative MRI measures according to chemotherapy regimen.

Results

MRI over/underestimation of the spread of residual tumour was never superior to 15 mm in FEC group, whereas it appeared in 11/28 (39%, 30–48%—95% CI) patients in DXL group (p=0.017). Tumour shrinkage led to single nodular residual lesions in FEC group, whereas vast numerous microscopic nests were observed in docetaxel group in pathology.

Conclusion

Among tumours treated with a taxane-containing regimen, residual disease was frequently underestimated by MRI because of PRd features.

Introduction

Neoadjuvant chemotherapy is used to treat women with locally advanced breast carcinoma. It allows conservative treatment in half of patients, and may be associated with better outcome for responders.1, 2, 3 New drugs such as taxanes are often used alone or in association in this situation and seem to enhance response rate and conservative surgical treatment.4 Recent studies suggest that docetaxel may have an anti-angiogenic activity which would explain, in part, its anti-tumoural effect by reducting the synthesis of pro-angiogenic molecules (such as bFGF and VEGF) by tumour cells.5

Contrast-enhanced magnetic resonance imaging (MRI) is used to measure tumour shrinkage following neoadjuvant chemotherapy.6 Visualization of tumour by contrast-enhanced MRI is allowed by tumour vascularization. However, some studies reported that anti-angiogenic treatment may lead to vascular changes assessed by Doppler sonography7 or MRI.8, 9

Contrast enhancement may be affected by both cytotoxic and potential anti-angiogenic effects of drugs such as docetaxel, leading to over or underestimate residual tumour size, and to mislead preoperative tumour response assessment. No comparison of the accuracy of MRI for measuring residual tumour according to chemotherapy regimen has been performed yet.

This prospective study was undertaken to compare the ability of MRI to measure residual breast cancer between patients treated with or without docetaxel-based.

Section snippets

Patients and treatment

Between September 2001 and March 2004, 40 patients with histologically confirmed locally advanced breast carcinoma were treated with intravenous neoadjuvant chemotherapy. Patients with inflammatory breast cancer or synchronous metastasis were excluded. No previous treatment had been performed before chemotherapy. Twelve patients (mean age 47 years old, range 32–58) received 5 fluoro uracyl (500 mg/m2)-epirubicin (Farmorubicin® 100 mg/m2, Pharmacia and Upjohn Co)-cyclophosphamide (FEC group) and

Tumour response rates according to treatment arm

Clinical objective response rate was 82% in DXL group and 58% in FEC group (p=0.13). Radiological and histological response were also not statistically significant (p=0.45 and p=0.15, respectively) Table 1.

Tumour measurements

There were one patient with multifocal lesions in FEC group and two in DXL. Tumour MRI measurements after neoadjuvant chemotherapy were compared with histologic size for each of the 40 patients (Table 2). The average tumour size predicted by MRI was 20.3 mm (SD=17.0 mm, range 0–65 mm) compared

MRI accuracy and neoadjuvant chemotherapy

We prospectively compared accuracy of MRI to pathology to measure residual breast cancer after FEC or docetaxel preoperative chemotherapy in a homogeneous population of patient. We found a significant over/underestimation rate of tumour size by preoperative MRI and specific pathologic features were observed after docetaxel-based chemotherapy.

Neoadjuvant chemotherapy is administered to patients especially to allow breast conservation surgery in locally advanced breast cancer.1 Although, the

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