Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers

In our current study population of 36,050 Dutch patients, we found that breast MRI was performed in 29.8% of all patients. For most patients (those with IDC), the use of breast MRI increases the number of mastectomies without any improvement in surgical outcome. In contrast, we observed that breast MRI use was associated with a lower risk of primary and secondary mastectomies in patients with ILC. Although breast MRI was more often used in larger tumors, size did not seem to affect our observations, as in every sub group still a significant number of the smallest (i.e., cT1), tumors were present and the multivariable analysis takes these variations into account. We also found that patients undergoing breast MRI were four times more frequently diagnosed with contralateral breast cancers.

Our results are in line with previous results from a large meta-analysis covering nine eligible studies (3112 patients) [5]. In this study, patients were more likely to undergo mastectomy when they underwent breast MRI: adjusted OR 3.06 (95% CI 2.03–4.62, p < 0.001). However, re-excision rates were comparable for both study groups: adjusted OR 0.95 (95% CI 0.73–1.24, p = 0.71). In our study, mastectomy rates were also increased for patients that underwent breast MRI (OR 1.22), with only a slight improvement in surgical margin involvement (OR 0.84), mainly attributable to patients with ILC. The fact that breast MRI is not able to improve surgical margin involvement is poorly understood. In a recent publication, it was suggested that we might be performing breast MRI in the wrong position [8]. Tumor metrics, such as changes in volume, surface area, compactness, sphericity, and distances from key landmarks varied from 6.5 to 23.8% when standard (prone) breast MRI was compared with (supine) intraoperative breast MRI. In addition, the authors could directly assess any residual tumor tissue during surgery. These novel insights should be studied in a larger study but appear promising in achieving improved surgical outcomes when using breast MRI, maybe even regardless of tumor type.

ILCs are difficult to detect on conventional imaging [9, 10]. Sensitivity of digital mammography for detecting ILC varies from 57 to 79%, and sensitivity is only slightly better when ultrasound is used: 81–83%. ILC is reported to be associated with higher rates of surgical margin involvement than any other invasive breast cancer subtype, with reported re-excision rates varying widely from 39 to 80% [11‐15]. However, these studies have not taken preoperative breast MRI into account, which is the most accurate imaging modality to evaluate the extent of ILC. To our knowledge, only four studies evaluated the impact of preoperative breast MRI in patients with ILC on surgical outcomes [5].

Mann et al. were the first to demonstrate that preoperative breast MRI in ILC could reduce re-excision rates (9 vs. 27% in the group not receiving breast MRI) without increasing the rate of mastectomies (48 vs. 59%, p = 0.098) [16]. Conflicting results were subsequently published by McGhan et al. who did not observe any significant differences in re-excision rates in their single-center study: 9.2% for the non-MRI group versus 4.2% for the MRI group in re-excision of margins only (p = 0.202) [17]. Although their results were not statistically significant, they nevertheless showed a similar trend as the results observed by Mann et al. and our current findings. Conversion to mastectomy after primary BCT did not differ statistically significant between study groups: 7.3% for the non-MRI group versus 2.8% for the MRI group (p = 0.189). In another single-center study, the number of primary mastectomies between the MRI and the non-MRI groups was 38% versus 30%, respectively (p = 0.119), and the number of re-excision with wider margins did not differ between groups either: 11% for the MRI group and 9% for the non-MRI group (p = 0.322) [18]. The COMICE trial by Turnbull et al. was a prospective randomized controlled trial evaluating the use of preoperative breast MRI [19]. In this study, 1623 subjects were randomized between preoperative breast MRI or not. In patients with ILC (n = 133), rates of primary mastectomies appeared to be higher in those who had breast MRI as compared to those who did not (8.8 vs. 2.8%), with no clear difference between secondary mastectomy rates (19.4 vs. 15.7%).

Since ILCs only compromise 10–15% of all invasive breast cancers, the before mentioned studies all included a limited number of ILC cases, hampering us to draw definite conclusions. Our current study, although retrospective, has the advantage of having a much larger sample size of patients with ILC (n = 5135) and summarizes the results in a population-based analysis, which considers the variation in expertise that exists between breast cancer teams and hospitals, including general, teaching, and university hospitals. We demonstrated that preoperative evaluation using breast MRI of patients with ILC and treated with primary surgery is beneficial, most likely to the superior ability of breast MRI to delineate tumor extent [1]. Its use in ILC patients reduced the number of (primary and secondary) mastectomies and positive surgical margins. The results of our study show that prior European recommendations on the use of breast MRI in patients with ILC [20, 21] can indeed be translated to everyday clinical practice and different hospital subtypes. Nevertheless, one should realize that irrespective of breast MRI use, the likelihood of having positive surgical margins remains almost two times higher in patients with ILC when compared to patients with IDC (OR 1.94, 95% CI 1.64–2.28, Table 2) and patients with ILC undergo mastectomy more often than IDC patients: 31.0 versus 12.1%, respectively (Table 1).

Even though breast MRI does not seem beneficial for surgical outcomes in especially IDC patients, it might still be considered for evaluation of the contralateral breast as the likelihood of detecting contralateral breast cancer was almost fourfold higher when compared with patients that did not undergo breast MRI. Lehman et al. detected non-symptomatic, contralateral breast cancers using breast MRI in 3.1% of the cases [22], with a wide range of 4–24% reported in previous studies [23]. Previously, Houssami et al. evaluated the impact of contralateral breast cancer detection and reported a relative increase in survival due to its early detection. However, these contralateral breast cancers were detected in any kind of way [24]. In addition, studies on adjuvant systemic therapy have consistently shown to reduce the risk of contralateral breast cancer during follow-up, suggesting that already at the diagnosis of the primary breast cancer a secondary, contralateral breast cancer may be present [25, 26]. Whether knowledge of the presence of a contralateral tumor solely detected by breast MRI and its treatment ultimately improves breast cancer outcome formally remains to be proven. In our study, patients that underwent breast MRI had an almost fourfold increased risk of having contralateral breast cancer compared to those in whom breast MRI was not performed (3.9 vs. 1.3%, respectively, Table 1). From our data, contralateral breast cancers seem to be more frequently detected by breast MRI in elderly patients and patients with smaller tumor sizes, which is in line with results from the Netherlands of an older research period (1989–2009) [27]. In this latter study, it was pointed out that routine use of breast MRI in older patients is questionable, since its added value in a patient group with presumably more comorbidities might be limited. However, we might also presume that patient selection in this population-based analysis may already have accounted for performance score. Because older patients may have been treated less often with adjuvant chemotherapy, one may also argue that especially these patients may benefit from breast MRI to prevent the development of symptomatic contralateral breast cancer. Future studies should investigate the prognostic impact of these findings and the cost-effectiveness of preoperative breast MRI for detecting occult contralateral breast cancers in the elderly, perhaps in comparison to other novel imaging modalities, such as (automated) breast ultrasound [28], digital breast tomosynthesis [29], or contrast-enhanced spectral mammography [30].

The current study design resulted in several limitations. First, in this retrospective analysis, several parameters (such as breast size and density, tumor localization within the breast, patient breast cancer risk profile, and the initial surgical treatment plan based on mammographic and/or ultrasound findings) were not available since this database was primarily designed for monitoring quality of delivered health care. Hence, there is a risk of residual confounding since the motivation for performing the breast MRI exam cannot be extracted from this database. Thus, we do not have a clear idea of factors that prompted MRI. We cannot exclude that in IDC cases, the multidisciplinary tumor board requested MRI as a confirmation for mastectomies based on either tumor size or suspected multicentricity at conventional imaging. On the other hand, we cannot exclude that for ILC cases the board had more propensity to ask for breast MRI to avoid mastectomy. In short, it is important to know that ‘association is not causation.’ However, the MIPA study sheds more light on breast MRI indications [31]. As in daily practice, breast MRI is mostly used in case of doubt on feasibility of breast-conserving surgery. Therefore, we feel confident in concluding that breast MRI use in patients with ILC (in contrast to patients with IDC) protects against an overuse of mastectomy. Second, survival outcome is not (yet) available for this population, which is the most important clinical outcome in this setting of course. Although an individual patient data meta-analysis showed that there was no difference in 8-year local recurrence-free survival between breast cancer patients undergoing breast MRI and those who did not, most cases consisted of patients with IDC with only 6–8% of the cases in each study group consisting of ILC patients. Thus, to the best of our knowledge, there is currently no sound evidence on the impact of preoperative breast MRI on survival outcomes specifically for patients with ILC [32].

In conclusion, breast MRI use was associated with a reduced number of mastectomies and less positive surgical margins in invasive lobular cancer, but with an increased number of mastectomies in ductal cancers. Breast MRI use was associated with a fourfold higher incidence of CBC.