The predictive value of sentinel lymph node biopsy in locally advanced breast cancer patients who have undergone neoadjuvant chemotherapy.

With the increasing usage of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC), there is the need to investigate the routine axillary node dissections performed in this group of patients. Controversy exists about the utility of sentinel node biopsy (SNB), either before or after NAC. With the addition of trastuzumab in the treatment of Her2/neu-positive LABC patients, the validity of SNB in this subset population needs to be investigated. A retrospective study of 20 patients who underwent NAC for LABC was undertaken. The pathology of the axillary nodes, sentinel nodes, and primary tumor after neoadjuvant chemotherapy were examined. Twenty patients underwent NAC with doxorubicin and cyclophosphamide, followed sequentially by paclitaxel and carboplatin, with or without trastuzumab based on Her2/neu status. Post chemotherapy, 20 patients underwent mastectomy or lumpectomy with SNB with axillary node dissections. The overall accuracy of SNB was 95 per cent with a false-negative rate of 14 per cent (1/7). In Her2/neu-positive patients, overall accuracy was 100 per cent (8/8) and a false-negative rate of zero per cent. Sentinel node biopsy is a viable option in patients who have undergone NAC. Her2/neu-positive patients who had undergone NAC with trastuzumab had comparable accuracy for sentinel node biopsy in predicting axillary node status.

Predicting nodal status using dynamic contrast-enhanced magnetic resonance imaging in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy with and without sequential trastuzumab.

HYPOTHESIS: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a reliable and accurate method for monitoring primary tumor response in the breast and can be used as a surrogate to predict final axillary nodal status. DESIGN: Retrospective study (October 1, 2004, through February 28, 2006) of 46 patients with clinically staged locally advanced breast cancer. SETTING: Comprehensive cancer center. PATIENTS: Forty-six patients with locally advanced breast cancer. INTERVENTIONS: Neoadjuvant chemotherapy (NAC), DCE-MRI, mastectomy and lumpectomy, and axillary lymph node dissection. MAIN OUTCOME MEASURES: The DCE-MRI results and pathologic response of the breast and axillary lymph nodes. RESULTS: Forty-six patients underwent NAC with doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel and carboplatin, with or without trastuzumab based on human epidermal growth factor receptor 2 (HER2/neu) status. Twenty-one patients (46%) had a complete pathologic response. For the HER2/neu-positive patients, the complete pathologic response rate was 70% (14/20). The accuracy, sensitivity, and specificity of the primary tumor response in predicting the axillary nodal status were 78%, 88%, and 72%, respectively. The accuracy, sensitivity, and specificity of the DCE-MRI-measured response in the primary tumor in predicting axillary nodal status were 74%, 62%, and 82%, respectively. For the HER2/neu-positive patients, the accuracy, sensitivity, and specificity improved to 80%, 75%, and 82%, respectively. CONCLUSIONS: The results of DCE-MRI of the primary tumor can be predictive of axillary nodal status, especially in patients receiving trastuzumab who are HER2/neu positive. The HER2/neu-positive patients with a complete clinical response on DCE-MRI are highly unlikely to benefit from an axillary lymph node dissection. For HER2/neu-negative patients, sentinel lymph node sampling is warranted.

Measurement of volumetric and vascular changes with dynamic contrast enhanced MRI for cancer therapy monitoring.

Longitudinal dynamic contrast enhanced MRI studies were undertaken to monitor therapy induced volumetric and vascular changes. Three study components are presented in this work: one animal tumor chemotherapy study (R3230 AC adenocarcinoma treated with Taxotere), one patient with invasive lobular breast cancer undergoing neoadjuvant chemotherapy (AC regimen), and one patient with brain metastasis of primary breast cancer undergoing radiation therapy (40 Gray whole brain irradiation). In the animal study two contrast media with different molecular weights, Gadodiamide and Gadomer-17, were used. Only Gadomer-17 revealed significant changes in vascular properties. The responders showed decreased V(b) (vascular volume index) and K(2) (out-flux transport rate), which preceded tumor regression. The control tumors showed increased V(b) and K(2), before tumor growth became much faster. In the patient undergoing neoadjuvant therapy, the tumor was shrinking by 45% after 2 cycles of treatment, then again by 45% after 2 additional cycles. K(2) was decreasing over time with treatment. In the patient with brain metastasis, the 2 follow-up studies were much longer apart to monitor the regression and relapse of lesions. The pre-treatment volumes of lesions in the group without recurrence were significantly smaller compared to those with recurrence. In summary, the tumor volume was more sensitive than the vascular parameters measured by the small extracellular contrast medium for the assessment of therapy response and prediction of recurrence. The vascular properties measured by macromolecular contrast medium may have the potential to serve as early therapeutic efficacy indicators.