Diagnostic Accuracy of Magnetic Resonance Imaging Features and Tumor-to-Nipple Distance for the Nipple-Areolar Complex Involvement of Breast Cancer: A Systematic Review and Meta-Analysis

Abstract

Objective: This systematic review and meta-analysis evaluated the accuracy of preoperative breast magnetic resonance imaging (MRI) features and tumor-to-nipple distance (TND) for diagnosing occult nipple-areolar complex (NAC) involvement in breast cancer.

Materials and methods: The MEDLINE, Embase, and Cochrane databases were searched for articles published until March 20, 2022, excluding studies of patients with clinically evident NAC involvement or those treated with neoadjuvant chemotherapy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Two reviewers independently evaluated studies that reported the diagnostic performance of MRI imaging features such as continuity to the NAC, unilateral NAC enhancement, non-mass enhancement (NME) type, mass size (> 20 mm), and TND. Summary estimates of the sensitivity and specificity curves and the summary receiver operating characteristic (SROC) curve of the MRI features for NAC involvement were calculated using random-effects models. We also calculated the TND cutoffs required to achieve predetermined specificity values.

Results: Fifteen studies (n = 4002 breast lesions) were analyzed. The pooled sensitivity and specificity (with 95% confidence intervals) for NAC involvement diagnosis were 71% (58-81) and 94% (91-96), respectively, for continuity to the NAC; 58% (45-70) and 97% (95-99), respectively, for unilateral NAC enhancement; 55% (46-64) and 83% (75-88), respectively, for NME type; and 88% (68-96) and 58% (40-75), respectively, for mass size (> 20 mm). TND had an area under the SROC curve of 0.799 for NAC involvement. A TND of 11.5 mm achieved a predetermined specificity of 85% with a sensitivity of 64%, and a TND of 12.3 mm yielded a predetermined specificity of 83% with a sensitivity of 65%.

Conclusion: Continuity to the NAC and unilateral NAC enhancement may help predict occult NAC involvement in breast cancer. To achieve the desired diagnostic performance with TND, a suitable cutoff value should be considered.

Keywords: Breast cancer; Diagnostic performance; Magnetic resonance imaging; Nipple sparing mastectomy; Nipple-areolar complex.

Fig. 1. Flow diagram describing study selection process for meta-analysis. NAC = nipple-areolar complex, MRI = magnetic resonance imaging

Fig. 2. Risk of bias graph by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A: Risk of bias graph. B: Risk of bias summary for each study.

Fig. 3. Forest plots of the pooled sensitivity and specificity with 95% confidence intervals of magnetic resonance imaging features. A: Continuity to the nipple-areolar complex (NAC). B: Unilateral NAC enhancement. C: Non-mass enhancement (NME) type. D: Mass size (> 20 mm). Heterogeneity statistics are reported at the bottom left of each panel. The gray square boxes denote either sensitivity (left panel) or specificity (right panel), and the horizontal lines represent the 95% confidence interval (CI) for each study. The vertical dotted line indicates the pooled summary estimates of sensitivity or specificity, and the diamonds at the bottom indicate the 95% CI. Heterogeneity statistics (I² and Q values) for sensitivity and specificity were presented. df = degree of freedom

Fig. 4. Summary receiver operating characteristic (SROC) curve of the diagnostic performance of each magnetic resonance imaging (MRI) feature using the bivariate model. The numbers within the symbols indicate the reference study number. The dotted line represents the confidence regions of each MRI feature. SROC curves display the sensitivity and specificity of individual (represented by empty shapes) and pooled (represented by filled shapes) data points. Each MRI feature is depicted by a distinct shape. NAC = nipple-areolar complex, AUC = the area under the curves, NME = non-mass enhancement

Fig. 5. Forest plots of the sensitivity and specificty of 10 studies in tumor-to-nipple distance (TND) cutoff meta-analysis. The red square box indicates TND as 5 mm, orange one as 5.5 mm, blue one as 10 mm, green one as 15 mm, and purple one as 20 mm. CI = confidence interval

Fig. 6. Study-specific receiver operating charateristic (ROC) curves and summary receiver operating characteristic (SROC) curve from the fitted multiple threshold model. A: Study-specific ROC curves. B: Multiple thresholds of the SROC curve based on the multiple thresholds model. The point represents the pair of sensitivity and 1-specificity at a given threshold from each study. The same color points belong to the same study. Circles represent information on sensitivity and specificity.