To achieve a tumor-free margin and improve cosmetic outcome in patients with breast cancer who will undergo breast-conserving surgery (BCS), a preoperative assessment of surgical extent is essential. Although delineating the tumor border is a key step during preoperative evaluation, an optimal width of safety margin has long been debated. However, in 2014, joint panels from the Society for Surgical Oncology and the American Society for Radiation Oncology published consensus statements to guide the clinicians regarding the pathologic margin for BCS that is followed by whole-breast irradiation [1]. Based on a meta-analysis of margin width and ipsilateral breast tumor recurrence [2], the new guidelines recommend “no ink on tumor” as the standard for a negative margin. Thus, an accurate prediction of tumor extent with comprehensive breast imaging in addition to clinical examination has become more important.

The use of breast magnetic resonance imaging (MRI), in addition to standard assessment by mammography and ultrasonography (US), is increasing in newly diagnosed patients with breast cancer [345]. The role of MRI in determining the candidacy for BCS remains controversial because MRI findings have been shown to increase mastectomy rates without evidence of improved local control [267].

The accuracy of MRI compared with conventional imaging in predicting the pathologic tumor size remains controversial. Several studies reported that MRI is superior to mammography or US in preoperative assessment of the extent of the pathologic tumor, thereby suggesting the importance of MRI in surgical planning [89]. In contrast, other studies indicated that US had a better correlation with tumor size compared with MRI [1011]. Moreover, the discordance of MRI pathologic in predicting tumor size is affected by several factors, including histologic type and estrogen receptor (ER) status [1213].

In this study, to compare the ability of MRI and US in predicting the extent of the tumor, we investigated the correlation efficiency between the 2 imaging studies and pathologic examinations. Moreover, we compared the imaging-pathologic size correlation in conjunction with the intrinsic subtypes. Finally, we investigated the actual positive margin and re-excision rates in patients undergoing BCS after preoperative MRI.

Breast MRI has been used as a supplementary imaging tool in preoperative work-up. Although the sensitivity of MRI was 90%, its specificity was relatively low (75%) [15], frequently causing false-positive findings requiring additional procedures or biopsies. Previous meta-analyses showed that incorporation of MRI into surgical planning in patients with breast cancer might lead to higher mastectomy rates without lowering the re-excision rates or local recurrence [26]. However, the routine use of MRI in patients with newly diagnosed breast cancer remains a debatable topic.

For patients with lobular carcinoma and multifocal disease and for those diagnosed with occult disease using mammography or US, MRI can be beneficial [161718]. Moreover, MRI has been known to be the most accurate radiologic tool that can measure tumor diameter [1920]. In several studies, MRI measured the tumor size more accurately than US [89].

In our study, we determined whether MRI could more accurately predict the tumor extent than US and compared the accuracy between MRI and US based on the molecular subtypes of breast cancer. Moreover, we investigated whether the rate of positive margin and secondary operation differed based on the molecular subtypes using selected patients who underwent BCS based on the preoperative results of MRI and US. To this end, we selectively included patients with unifocal tumor because meticulous measurement of tumor extent is difficult in patients with multifocal disease. Moreover, patients who underwent mastectomy with futile margin assessment were excluded. In this perspective, we found that MRI superiorly predicted the pathologic tumor extent compared to US, especially in TNBC. Moreover, MRI and US did not precisely predict the pathologic size in the HER2-positive subtype, compared to that in other subtypes.

In detail, MRI was more concordant with pathologic tumor size than US in all patients (MRI, r = 0.6975 vs. US, r = 0.6211; p = 0.001). Franca et al. reported that breast MRI was more significantly correlated with the pathological examination than mammography (r = 0.872 vs. 0.710) or US (r = 0.836 vs. 0.704). Moreover, several earlier studies have shown that US underestimates the pathologic tumor size [101221]. Collectively, our finding was expected because subclinical tumor area that is invisible through US might be identified using MRI.

In further analyses of the molecular subtypes, MRI can effectively measure the pathologic extent, compared to US, in TNBC only; however, the same relationship was not found in other subtypes. The ability of MRI in estimating the tumor size based on the subtypes is not well explored. The study by Yoo et al. [13] suggested that the discordance rate between MRI and pathologic tumor size is higher in ER-negative tumors than in ER-positive tumors. Although the discordance of MRI pathology was not compared based on the ER status, our result might be consistent because ER negativity was noted as a risk factor for positive margin rate.

The poor performance of preoperative imaging in predicting tumor area in HER2-positive breast cancer may raise a question regarding the increase in positive margin rates or secondary operation for margin clearance in patients with HER2-positive breast cancer. Indeed, the relationship of imaging-pathologic size was least correlated in the HER2-positive subtype. This provided a rationale for the highest rate of positive margin as 23.2% in the HER2-positive subtype. The difference in re-excision rate was not significant between the subtypes, which might be largely attributable to the intraoperative frozen section examination that enables further resection in case of intraoperative-positive margins. If the intraoperative margin assessment is not performed, the correlation between imaging and pathologic size may result in increased secondary operation as margin clearance. In addition, our result is concordant with those of the study by Baek et al. [22] where HER2 overexpression was shown to cause inaccurate assessment of tumor size. While the mechanism in which the HER2 overexpression reduces the accuracy of breast MRI is unclear, angiogenesis may be one of causes. A hypoxic region within a tumor that stimulates the generation of new vessels is known to decrease the accuracy of contrast-enhanced MRI [2324]. HER2 expression is associated with increased angiogenesis via the modulation of pro- and anti-angiogenic factors [2526], which may hamper accurate measurement of tumor size in the HER2-positive subtype.

The major limitation of this study is its retrospective design. Particularly, since a new marginal guideline was published in February 2014, a half or our patients underwent lumpectomy under more conservative margin consensus. Thus, the results regarding the positive margin rate or re-excision rate should be carefully appraised. The role of MRI to reduce positive margin based on subtypes warrant further prospective study. Randomized trial comparing the outcome of patients with and without MRI would provide a definite conclusion. Another limitation is the small number of patients with HER2-positive cancer (82 of 516). Our finding that the positive margin rate was higher in the HER2 subtype needs to be verified in a larger cohort.

In conclusion, breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. Nevertheless, the size correlation of MRI was low and the positive margin rate was higher in the HER2 subtype than in the other subtypes. A careful approach is needed to obtain negative margin in patients with HER2-positive breast cancer undergoing BCS.