Rationale and Objectives
The aim of this prospective study was to investigate using multiparametric and multinuclear magnetic resonance imaging during preoperative systemic therapy for locally advanced breast cancer.
Materials and Methods
Women with operable stage 2 or 3 breast cancer who received preoperative systemic therapy were studied using dynamic contrast-enhanced magnetic resonance imaging, magnetic resonance spectroscopy, and 23 Na magnetic resonance. Quantitative metrics of choline peak signal-to-noise ratio, total tissue sodium concentration, tumor volumes, and Response Evaluation Criteria in Solid Tumors were determined and compared to final pathologic results using receiver-operating characteristic analysis. Hormonal markers were investigated. Statistical significance was set at P < .05.
Results
Eighteen eligible women were studied. Fifteen responded to therapy, four (22%) with pathologic complete response and 11 (61%) with pathologic partial response. Three patients (17%) had no response. Among estrogen receptor–positive, HER2-positive, and triple-negative phenotypes, observed frequencies of pathologic complete response, pathologic partial response, and no response were 2, 5, and 0; 1, 4, and 0; and 1, 1, and 3, respectively. Responders (pathologic complete response and pathologic partial response) had the largest reductions in choline signal-to-noise ratio (35%, from 7.2 ± 2.3 to 4.6 ± 2; P < .01) compared to nonresponders (11%, from 8.4 ± 2.7 to 7.5 ± 3.6; P = .13) after the first cycle. Total tissue sodium concentration significantly decreased in responders (27%, from 66 ± 18 to 48.4 ± 8 mmol/L; P = .01), while there was little change in nonresponders (51.7 ± 7.6 to 56.5 ± 1.6 mmol/L; P = .50). Lesion volume decreased in responders (40%, from 78 ± 78 to 46 ± 51 mm 3 ; P = .01) and nonresponders (21%, from 100 ± 104 to 79.2 ± 87 mm 3 ; P = .23) after the first cycle. The largest reduction in Response Evaluation Criteria in Solid Tumors occurred after the first treatment in responders (18%, from 24.5 ± 20 to 20.2 ± 18 mm; P = .01), with a slight decrease in tumor diameter noted in nonresponders (17%, from 23 ± 19 to 19.2 ± 19.1 mm; P = .80).
Conclusions
Multiparametric and multinuclear imaging parameters were significantly reduced after the first cycle of preoperative systemic therapy in responders, specifically, choline signal-to-noise ratio and sodium. These new surrogate radiologic biomarkers maybe able to predict and provide a platform for potential adaptive therapy in patients.
Breast cancer is a potentially curable disease, and the combined effects of early detection and adjuvant systemic therapy are likely the key elements that explain the observed reduction in breast cancer mortality over the past 20 years . The currently accepted standards for the detection and diagnosis of breast abnormalities are mammography, ultrasound, and magnetic resonance (MR) imaging (MRI) . If breast lesions are detected early, adjuvant systemic therapy after primary surgery reduces the risk for systemic recurrence or death . However, not all breast cancers are detected early, and some patients may present with stage 2 or 3 disease and require multimodality therapy. Preoperative systemic therapy (PST), also referred to as primary or neoadjuvant chemotherapy, is used to potentially reduce the size of the tumor and possibly convert a mastectomy to a lumpectomy in primary operable or locally advanced breast cancer . Perhaps of greater therapeutic implications, it may allow an early assessment of disease responsiveness and an opportunity to adjust therapy on the basis of observed response .
Pathologic response following PST appears to correlate with long-term outcome. National Surgical Adjuvant Bowel and Breast Project trial protocol B18 showed that approximately 12% of patients had pathologic complete response (pCR) with an anthracycline-based regimen (eg, doxorubicin and cyclophosphamide [AC]) , while the addition of four more cycles of a taxane in National Surgical Adjuvant Bowel and Breast Project trial protocol B27 doubled the pCR rate compared to AC alone . Patients who achieved pCR in these two studies had longer disease-free and overall survival . If this is confirmed, it implies that the early identification of those likely to respond to PST is of critical importance as a prognostic marker and to potentially allow midcourse adjustments in therapy. Thus, in vivo assessment before, during, and after PST may improve decision making and outcomes. Recent studies have demonstrated that in vivo assessments of therapeutic response are possible using MRI in patients who are undergoing PST . Partridge et al demonstrated that the use of dynamic contrast-enhanced (DCE) MRI could be predictive of outcome after a reduction in the size of the tumor in a recent American College of Radiology Imaging Network multi-institutional center trial. Messiamy et al reported that the use of MR spectroscopy (MRS) within 24 to 48 hours after the first cycle of therapy could detect cellular changes in total choline concentration within the tumor, and this has been confirmed by others . In addition, recent reports have demonstrated that the use of 23 Na MRI in patients with breast and other diseases provides additional metabolic information for diagnosis .
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Materials and methods
Clinical Subjects
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Pathologic Response and Histologic Tissue Classification
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MRI Protocol
Proton MRI
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Proton MRS
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23 Na MRI
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MR Image Preprocessing and Analysis
Lesion and Volume Analysis
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MR Spectroscopic Analysis
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Quantitative 23 Na MRI
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Statistical Analysis
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Results
Clinical and Histopathologic Characteristics
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Table 1
Patient Characteristics and Treatment Response ( n = 18)
AUC, area under the receiver-operating characteristic curve; DCE, dynamic contrast-enhanced; ER, estrogen receptor; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; PR, progesterone receptor; RECIST, Response Evaluation Criteria in Solid Tumors.
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Clinical Response and Pathology Findings After PST
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Radiologic Metrics
General
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RECIST
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MRS
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23 Na MRI
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Proton DCE MR
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Subgroup Analysis Between Pathologic Response, Tumor Phenotype, and Imaging Findings
TN Phenotype
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ER-negative, Progesterone Receptor (PR)–negative, and HER2-positive Phenotype
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ER-positive, PR-positive, and HER2-negative Phenotype
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Discussion
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Conclusions
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Acknowledgments
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