Magnetic Resonance Imaging Response Monitoring of Breast Cancer During Neoadjuvant Chemotherapy: Relevance of Breast Cancer Subtype
Study Design: Cohort study exploring the ability of MRI examinations to monitor response to neoadjuvant chemotherapy in different subtypes of breast cancer.
Study Eligibility: Patients with invasive breast cancer greater than 3cm and/or with at least one tumor-positive lymph node who received neoadjuvant chemotherapy (NAC) between 2000 and 2008 in two prior randomized studies. Inclusion criteria included patients who had received one MRI examination before chemotherapy and a second during, and who underwent surgery after NAC. Patients with HER2-positive tumors treated without trastuzumab were excluded.
Enrollment: 188 patients: 55% ER positive/HER2 negative, 25% triple negative and 20% HER2 positive.
Research Question: Is breast cancer subtype relevant for MRI markers of therapy response during neoadjuvant chemotherapy?
Magnetic resonance imaging (MRI) may have the ability to identify nonresponders and may be predictive of the presence of residual tumor after completion of neoadjuvant chemotherapy (NAC). Little is known about the ability of MRI to monitor response in different subtypes of breast cancer characterized by ER, PR, and HER2 status. These markers are routinely used to select therapy and predict an outcome, which led Loo et al. to investigate the ability of MRI to monitor treatment response in the different breast cancer subtypes.
Eligible patients included women with invasive breast cancer greater than 3cm and/or with at least one tumor-positive lymph node who received neoadjuvant chemotherapy between 2000 and 2008 in two prior randomized studies. Inclusion criteria included receiving one MRI examination before chemotherapy and a second during, and undergoing surgery after NAC. Patients with HER2-positive tumors treated without trastuzumab were excluded. Tumors were classified into three subgroups according to their ER, PR, and HER2 receptor status: triple negative, HER2-positive, and ER-positive/HER2-negative tumors.
MRI examinations were performed before and during NAC and included lesion morphology at baseline and changes in morphology, size, and contrast uptake kinetics. Tumor response was assessed through the presence or absence of residual tumor in the surgical specimen, and also through the breast response index (BRI), which represents the relative change in tumor stage. Multivariate analysis was used to analyze changes in MRI during NAC associated with the presence of residual disease after NAC in the three different subtypes.
Multivariate analysis of residual disease showed significant associations between breast cancer subtype and MRI. Residual tumor after NAC in the triple negative and HER2-positive group was significantly associated with the change in the largest diameter of late enhancement during NAC. However, there were no markers significantly associated with either residual disease (presence or absence) or BRI in the ER-positive/HER2-negative group. In triple negative and HER2-positive tumors, the change in largest tumor diameter at late enhancement at MRI during NAC was most predictive of outcome.
The results of this study suggest that response to NAC can be measured accurately by MRI in triple-negative or HER2-positive disease, but not in the largest subgroup: ER-positive/HER2-negative. This is because MRI of these tumors showed neither a dominant morphology at baseline nor a consistent pattern of reduction at MRI during NAC. Moreover, these tumors more often manifest as mass lesions at MRI, making an assessment of size more challenging. Limitations of this study include the use of immunohistochemistry instead of more precise techniques to create subgroups, as well as the fact that all results were assessed by one radiologist, raising questions about the validity.
Loo CE, Straver ME, Rodenhuis S, et al. “Magnetic Resonance Imaging Response Monitoring of Breast Cancer During Neoadjuvant Chemotherapy: Relevance of Breast Cancer Subtype” JCO. 2011 Jan 10.