title: Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI.
abstract: Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.
authors.affiliation: Screening and Test Evaluation Program (STEP), Sydney School of Public Health, A27, Edward Ford Building, The University of Sydney, NSW 2006, Australia. luke.marinovich@sydney.edu.au
authors.forename: M L
authors.initials: ML
authors.lastname: Marinovich
authors.forename: F
authors.initials: F
authors.lastname: Sardanelli
authors.forename: S
authors.initials: S
authors.lastname: Ciatto
authors.forename: E
authors.initials: E
authors.lastname: Mamounas
authors.forename: M
authors.initials: M
authors.lastname: Brennan
authors.forename: P
authors.initials: P
authors.lastname: Macaskill
authors.forename: L
authors.initials: L
authors.lastname: Irwig
authors.forename: G
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: N
authors.initials: N
authors.lastname: Houssami
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008408:Mastectomy; D020360:Neoadjuvant Therapy; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids