Breast Cancer 1 MRI for breast cancer screening, diagnosis, and treatment Monica Morrow, Janet Waters, Elizabeth Morris Lancet 2011; 378: 1804–11 See Editorial page 1758 This is the ﬁrst in a Series of two papers about breast cancer Breast Service, Department of Surgery (Prof M Morrow MD), Medical Library (J Waters MLS), and Department of Radiology (Prof E Morris MD), Memorial Sloan-Kettering Cancer Center, New York, NY, USA Correspondence to: Prof Monica Morrow, Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA email@example.com
See Online for webappendix
MRI is used widely both for screening women who are at increased risk of breast cancer and for treatment selection. Prospective studies conﬁrm that MRI screening of women with known or suspected genetic mutation results in a higher sensitivity for cancer detection than does mammography. However, survival data are not available. In women with breast cancer, MRI detects cancer not identiﬁed with other types of screening. In two randomised trials, this increased sensitivity did not translate into improved selection of surgical treatment or a reduction in the number of operations. Data for longer-term outcomes such as ipsilateral breast tumour recurrence rates and contralateral breast cancer incidence are scarce, but to date do not show clear beneﬁt for MRI. MRI is better than other methods of assessing the response to neoadjuvant chemotherapy, and is helpful in identifying the primary tumour in patients who present with axillary adenopathy.
Introduction Mammography is the mainstay of breast imaging, and prospective randomised trials have shown that screening mammography reduces breast cancer mortality.1 In women with breast cancer, disease burden is the main determinant of the selection of local therapy, and women selected for breast-conserving surgery with mammography successfully complete the procedure in more than 85% of cases.2 Ipsilateral breast tumour recurrence (IBTR) rates in women selected for breast-conserving surgery with mammography have fallen steadily over time, and are now less than 10% at 10 years’ follow-up.3 Also, mammography is a low-cost procedure that is widely available worldwide. Although the beneﬁts of mammography are proven, not all cancers can be visualised on screening mammograms. The sensitivity of mammography is decreased in women with dense breast tissue,4 and some women who seem to have localised cancer mammographically are found to have extensive disease necessitating mastectomy. To improve the outcomes of screening and local therapy, MRI has been widely adopted
Key messages • MRI screening in known or suspected BRCA mutation carriers, or women at a high risk of breast cancer because of their family history, has a higher sensitivity for cancer detection than mammography, and comparable speciﬁcity • The preoperative use of MRI in patients with breast cancer has not been shown to increase the likelihood of negative margins or the need to convert from lumpectomy to mastectomy • MRI is useful to identify the primary tumour in patients who present with with axillary nodal metastases and no detectable breast tumour • Identiﬁcation of the extent of residual tumour after neoadjuvant chemotherapy remains a problem, and MRI might be useful in identifying extensive residual disease
into clinical practice on the basis of the premise that an increased sensitivity for cancer detection translates into improved patient outcomes. This review will examine that premise, with a focus on outcome data obtained in the past decade.
MRI for screening Mammography is the proven standard of care for breast cancer screening throughout the world, and has been shown to decrease breast cancer mortality.1,5 But the sensitivity of mammography is lower in young women, women with dense breast tissue, and women who carry BRCA mutations,6–9 and this has led to a search for
Search strategy and selection criteria An electronic literature search of articles published between May 1, 2001, and May 25, 2011, was done in the following databases: PubMed (webappendix), Embase, and Cochrane. Limits were not placed on language. Publication types were restricted to clinical trials, retrospective studies, prospective studies, multicentre studies, meta-analyses, and systematic reviews. Controlled vocabulary (MeSH and EMTREE) and keywords were used. Two broad categories of concepts were searched, and results were combined using the Boolean operator “AND.” The broad categories included breast cancer or breast cancer risk, and magnetic resonance imaging. Each category had multiple terms that were combined using the Boolean operator “OR.” We prioritised prospective randomised trials, meta-analyses, and systematic reviews. The reference lists of articles identiﬁed in the search were examined for other relevant studies. After the elimination of duplicates, 1837 records were screened, 1575 were excluded because of lack of relevance, 262 abstracts were reviewed, and 87 papers identiﬁed. Studies with fewer than 25 patients were excluded unless a substantial number of larger studies were unavailable, and papers included in meta-analyses were not all individually cited.
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Kreige and colleagues13 Leach and colleagues14 Number of patients Risk criteria % (risk of breast cancer development)
Warner and colleagues12 Kuhl and colleagues7 Hagen and colleagues15,16 236
Proven mutation carriers
Number of cancers
BRCA carrier 100%
BRCA carrier 100%
Table 1: Summary of characteristics of the larger MRI screening studies
alternative methods of screening in women at a high-risk of breast cancer. Compared with mammography, MRI has a higher sensitivity for the detection of breast cancer and is not aﬀected by breast density.10 Screening studies to date have been done in high-risk patients: primarily those at risk because of known or suspected BRCA mutations or a family history of breast cancer. We identiﬁed no prospective randomised trials of breast cancer screening in general or high-risk populations using MRI with survival as an endpoint (see search strategy). A systematic review by Warner and colleagues11 in 2008 identiﬁed 11 prospective studies of MRI screening. Study design and entry criteria varied substantially, with the proportion of known BRCA mutation carriers ranging from 8%7 to 100%,12 and only two studies excluded women with a previous history of breast cancer.13,14 There was also variation in the number of screens and the use of other screening methods such as ultrasonography. Mammography sensitivity varied from 14% to 59% when a positive mammogram was deﬁned as a Breast Imaging-Reporting and Data System score of 4 or 5, whereas MRI sensitivity ranged from 51% to 100%.11 Characteristics of the largest studies included in the meta-analysis are summarised in table 1.7,12–15 In the systematic review,11 mammography sensitivity was 32% (95% CI 23–41) and MRI sensitivity was 75% (95% CI 62–88). Combining the two procedures increased the sensitivity to 84% (95% CI 70–97). Although all studies reported a higher sensitivity of MRI for the detection of invasive cancer, results were conﬂicting regarding its sensitivity for the detection of ductal carcinoma in situ (DCIS).13,14,16 The speciﬁcity of mammography (98·5%; 95% CI 97·8–99·2) was marginally higher than the speciﬁcity of MRI (96·1%; 95% CI 94·8–97·4). A costeﬀectiveness analysis done as part of the MRI screening trial reported by Leach and colleagues14 included 649 women screened with mammography and MRI over a 7-year period.17 The cost per cancer detected with MRI in the total study population was £28 284, and decreased to £11 731 for BRCA1 mutation carriers, leading the authors to conclude that MRI was cost eﬀective in a population at high risk because of family history. Whether MRI screening conveys a survival advantage is uncertain. Lymph node involvement was present in 14–26% of women screened with MRI, and might be a www.thelancet.com Vol 378 November 19, 2011
Panel: American Cancer Society guidelines for MRI screening Recommend annual MRI screening (on the basis of evidence from non-randomised screening trials and observational studies) BRCA mutation • Untested ﬁrst-degree relative of BRCA carrier • Lifetime breast cancer risk between 20% and 25% or greater, as deﬁned by models that are largely dependent on family history Recommend annual MRI screening (on the basis of expert consensus opinion on evidence of lifetime risk for breast cancer) • Radiation to chest between age 10 and 30 years • Li-Fraumeni syndrome and ﬁrst-degree relatives • Cowden syndrome and ﬁrst-degree relatives Insuﬃcient evidence to recommend for or against MRI screening • Lifetime risk between 15% and 20%, as deﬁned by models that are largely dependent on family history • Lobular carcinoma in situ or atypical lobular hyperplasia • Atypical ductal hyperplasia • Heterogeneously or extremely dense breast on mammography • Women with a personal history of breast cancer, including ductal carcinoma in situ Recommend against MRI screening (on the basis of expert consensus opinion) • Women at 15% or lower lifetime risk
reﬂection of the unfavourable tumours seen in women who carry BRCA1 mutations. Although a prospective randomised trial with a survival endpoint seems unlikely (since BRCA mutations are uncommon and such a trial would need to accrue large numbers of women), further follow-up of existing studies should provide additional information. There are few data for MRI screening outcomes in women who are at increased risk of breast cancer owing to factors other than family history. A review of breast cancer in women treated with chest irradiation for childhood cancer found that cancers in this cohort did not seem to be phenotypically diﬀerent from those seen 1805
in the population at large.18 However, the cumulative incidence of breast cancer was similar to that seen in BRCA mutation carriers, and the median age of onset for women irradiated before age 20 years was 35 years, supporting the idea that MRI screening should have a role in this population. Patients with diagnoses of lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia were studied retrospectively by Port and colleagues.19 The sensitivity and speciﬁcity of MRI was similar to that previously reported—at 75% and 92%, respectively—but clear evidence of MRI screening beneﬁt was not found. A
When a group of experts convened by the American Cancer Society to develop guidelines for annual MRI screening reported in 2007 (panel), the only groups for which suﬃcient evidence to justify the use of MRI screening was felt to be present were women proven to be BRCA mutation carriers, untested ﬁrst-degree relatives of mutation carriers, and women with a lifetime risk of breast cancer development of 20% or more as determined by models based on a family history of breast cancer.20 Groups for which MRI screening was recommended based on expert consensus, and the much larger group for which insuﬃcient data were available to recommend for or against MRI screening, are summarised in the panel. When screening with MRI was indicated, mammographic screening was also recommended.
MRI in the patient with cancer Selection of local therapy
Figure: Multifocal carcinoma identiﬁed on MRI A 43-year-old woman with no family history of breast cancer underwent (A) routine negative screening mammography. Because of a history of ﬁbrocystic changes, she underwent bilateral screening ultrasound, which identiﬁed a 9 mm solid mass in the upper outer quadrant of the right breast (not shown), subsequently biopsied, yielding invasive ductal carcinoma. (B) Maximum intensity projection (MIP) of the contrast-enhanced MRI identiﬁed the biopsied carcinoma in the upper outer quadrant and a second suspicious mass in the same quadrant about 1·5 cm away. The second mass was then identiﬁed on targeted ultrasound and biopsied, yielding multifocal carcinoma.
Number of patients randomly assigned Age (years) Eligibility
Median tumour size (cm) % Screen detected
Scheduled for breast-conserving surgery 1·5
BIRADS 3, 4, or 5 screen-detected lesion 1·5
COMICE=comparative eﬀectiveness of MRI in breast cancer. MONET=MR mammography of non-palpable breast tumours. *418 total patients were randomly assigned, of whom 149 had cancer. †Median. ‡Mean. BIRADS=breast imaging and reporting data system.
Table 2: Patient populations in randomised trials of MRI for selection of local therapy
COMICE MRI Initial mastectomy (%) Re-excision of margins (%) Conversion to mastectomy (%) Total mastectomy rate (%)
MONET No MRI
COMICE=comparative eﬀectiveness of MRI in breast cancer. MONET=MR mammography of non-palpable breast tumours.
Table 3: Outcomes of randomised trials of MRI for selection of local therapy
The clinical outcomes of local therapy potentially aﬀected by MRI include re-excision rates, conversion to mastectomy, local recurrence, and contralateral cancer. Studies in which the only outcome was the presence or absence of carcinoma at pathology were excluded from this review. MRI is known to identify foci of cancer that are not detectable by physical examination, mammography, or ultrasonography (ﬁgure). In a meta-analysis of 19 studies, which included 2610 patients with breast cancer, MRI identiﬁed additional disease in a median of 16% (IQR 11–24) of patients.21 Given that IBTR rates at 10 years in women selected for breast-conserving surgery without MRI are less than 10%, and as low as 3–7% in women receiving adjuvant systemic therapy,3 the identiﬁcation of additional tumour foci with MRI was not judged to be clear evidence of patient beneﬁt. Two prospective randomised trials22,23 assessed the eﬀect of MRI on short-term surgical outcomes. Reoperation rate, including both margin re-excision and conversion to mastectomy, was the primary endpoint in both studies (patient characteristics are summarised in table 2). In the Comparative Eﬀectiveness of MRI in Breast Cancer (COMICE) trial,23 7% of patients in the MRI group (n=58) were converted to mastectomy on the basis of MRI results, whereas 10 patients (1%) in the noMRI group elected for mastectomy before attempted breast-conserving surgery. Despite this, no signiﬁcant diﬀerence in reoperation rate was seen between the MRI and no-MRI groups (OR 0·96%, 95% CI 0·75–1·24; p=0·77). Rates of re-excision and conversions to mastectomy are summarised in table 3. The mastectomy rate in the MRI group was 13·0% compared with 8·8% in the no-MRI group. In the Mammography of Nonpalpable Breast Tumours (MONET) study,22 the re-excision rate was 34% in the MRI group compared with 12% in the noMRI group (p=0·008), but the number of conversions to mastectomy did not diﬀer (table 3), resulting in an overall reoperation rate of 24 (45%) of 53 patients in the MRI group and 14 (28%) of 50 patients in the no-MRI group www.thelancet.com Vol 378 November 19, 2011
(p=0·069). Thus, neither study showed that MRI signiﬁcantly reduced reoperation rates. Critics of the COMICE trial point out that many of the participating centres had little experience with MRI, and not all MRIdetected lesions were biopsied. Although this is true, the overall success rate of breast-conserving surgery in the no-MRI group was greater than 90%, and the re-excision rate was only 11%, indicating that any potential beneﬁt of MRI was likely to be quite small. The MONET trial, with only 149 cancers, was underpowered to detect anything other than extremely large diﬀerences, and the very high rate of re-excision in the MRI group is diﬃcult to understand. These randomised studies conﬁrm the ﬁndings of three single-institution, retrospective studies,24–26 including a total of 1117 patients, which also found no diﬀerence in re-excision rates among patients assessed with and without MRI. The studies of Bleicher and colleagues24 and Pengel and colleagues26 also assessed unexpected conversion to mastectomy and found no signiﬁcant diﬀerences between groups. Re-excision rates in the MRI groups of these studies ranged from 14% to 22%, and from 14% to 19% in the no-MRI groups. Eﬀorts have been made to identify subgroups of women who beneﬁt from MRI. Two retrospective studies that examined MRI in patients with inﬁltrating lobular cancer reached diﬀerent conclusions. McGhan and colleagues27 compared 72 patients with inﬁltrating lobular carcinoma undergoing MRI with 109 patients who did not, and found no signiﬁcant diﬀerence in re-excision rates. By contrast, Mann and colleagues reported on 267 patients with inﬁltrating lobular cancer treated in two Dutch centres. The use of MRI (n=99) lowered the re-excision rate by 9% (OR 3·64, 95% CI 1·30–10·20; p=0·01).28 In a single-institution, retrospective study of patients with DCIS (n=98), the incidence of positive margins was not signiﬁcantly reduced in patients who underwent MRI compared with patients who did not.29 In aggregate, the available data, both prospective and retrospective, do not support the idea that MRI improves patient selection for breast-conserving surgery or that it increases the likelihood of obtaining negative margins at the initial surgical excision.
Identiﬁcation of contralateral breast cancer Many single-institution studies in poorly characterised patient populations have suggested that MRI identiﬁes a signiﬁcant number of synchronous contralateral breast cancers not evident with conventional assessment. In a meta-analysis of 3252 women with unilateral breast cancer, 131 contralateral malignancies were detected by MRI alone;30 of these, 35·1% were DCIS. Many studies did not include consecutive patients, and selection criteria for MRI and treatment variables that aﬀect the incidence of contralateral breast cancer were not well characterised. We identiﬁed three prospective studies that assessed contralateral breast cancer: two that were limited to www.thelancet.com Vol 378 November 19, 2011
patients with breast cancer31,32 and one that included patients with both unilateral cancer and high-risk lesions (table 4).33 In the studies restricted to cancer patients, contralateral breast cancer was detected in 4% and 3% of patients when MRI was done within 6 months and 12 months of cancer diagnosis, respectively.31,32 In the third study, contralateral breast cancer was detected in 18 (15·3%) patients at the time of unilateral cancer diagnosis. Of the 18 contralateral breast cancers, ten were DCIS,33 whereas in the multi-institutional study by Lehman and colleagues,32 12 of 30 cancers were DCIS. The high contralateral breast cancer detection rates are surprising in view of large population-based studies that indicate that rates of contralateral breast cancer are decreasing.34 In the USA, rates of contralateral breast cancer since 1985 have fallen by 3·07% per year (95% CI –3·5 to –2·7). Rates of clinical contralateral breast cancer between 2001 and 2005, the period during which patients were recruited to the MRI studies, were less than 1% per year in all subgroups of patients except those aged 20–29 years with oestrogen-receptor negative cancers (a group likely to be enriched with BRCA mutation carriers). The MRI ﬁndings of much higher rates of contralateral breast cancer than are clinically observed, coupled with the high proportion of patients with DCIS, raises the possibility that lesions that would not become clinically signiﬁcant because of their biology, or that would be treated with the adjuvant systemic therapy given for the primary cancer, are being detected. The eﬀect of adjuvant systemic therapy on contralateral breast cancer incidence is well documented in the Early Breast Cancer Trialists’ Collaborative Group overview, in which patients receiving tamoxifen had a 62% reduction in contralateral breast cancer events compared with those who received placebo,35 and those who received cytotoxic chemotherapy had a 20% reduction. The concern regarding detection of lesions not destined to become clinically evident is supported by results of a single-institution retrospective study reporting the occurrence of clinically evident contralateral breast cancer 8 years after diagnosis in patients initially managed with and without MRI. Contralateral breast cancer was noted in 6% of patients in both groups.36 By contrast, in another single-institution retrospective study with a median follow-up of around 40 months, Fischer and colleagues reported contralateral breast cancer in 1·7% of 121 patients who underwent initial MRI compared with 4·9% of those (n=225) who did not (p<0·001).37 At this point, it is impossible to assess whether the high rates of Lehman and colleagues31
Lehman and colleagues32
Number of patients
Normal mammography and physical examination
Normal mammography and physical examination
Normal mammography and ultrasonography
Contralateral cancer MRI only
Pediconi and colleagues33
Table 4: MRI for contralateral cancer detection
contralateral breast cancer detection in the single-group, prospective studies of MRI are due to the selection of high-risk women for the studies and represent appropriate early detection, or whether substantial numbers of these cancers would never have become evident clinically. This question would ideally be addressed in a prospective, randomised trial stratifying for family history and the use and type of adjuvant therapy. In view of the low incidence of contralateral breast cancer, this is unlikely to be a research priority, but large multi-institutional studies in well characterised patient groups followed up for 5–10 years would help to clarify this question.
Ipsilateral breast tumour recurrence (IBTR) We identiﬁed three retrospective single-institution studies addressing the eﬀect of MRI on IBTR. Fischer and colleagues37 reported an IBTR rate of 1·2% at a mean follow-up of 40 months in 86 patients who underwent breast-conserving therapy after a pre-operative MRI compared with 6·8% in 133 patients who did not have a pre-operative MRI (p<0·001). However, in the analysis of the study data, no adjustments were made for diﬀerences in tumour characteristics between groups. Compared with patients who did not undergo MRI, patients in the MRI group had smaller tumours that were more likely to be node-negative (61% vs 54%) and less likely to be highgrade (16·9% vs 33·5%). Despite these more favourable characteristics, only 5% of patients who underwent MRI received no chemotherapy compared with 18% in the noMRI group. Adjuvant chemotherapy has been shown in randomised trials to signiﬁcantly reduce rates of IBTR,38 and the failure to adjust for diﬀerences in tumour characteristics and systemic treatment, coupled with the unusually high rate of IBTR at 40 months in the no-MRI group, makes this study diﬃcult to interpret. The retrospective studies of Solin and colleagues36 and Hwang and colleagues25 showed no diﬀerences in IBTR based on patient selection with MRI. In 756 patients reported by Solin and colleagues, rates of IBTR at 8 years were 3% in 215 patients who underwent MRI and 4% in 541 patients who went without (p=0·51). In the 463 patients reported by Hwang and colleagues, 8-year actuarial rates of IBTR were 1·8% and 2·5% (p=0·67) in women with and without MRI, respectively. Although selection bias cannot be completely excluded, statistical adjustments for diﬀerences in patient and tumour characteristics, and treatments between groups, were done. Additionally, the rates of IBTR in these studies are consistent with those noted in multiple multi-institutional prospective randomised trials,3 as opposed to the 6·8% rate of IBTR with a follow-up of only 40 months in the study of Fischer and colleagues.37
Selection of surgery after neoadjuvant therapy The eﬀectiveness of pre-operative or neoadjuvant therapy to allow breast-conserving therapy in patients who would require mastectomy if surgery were the initial treatment 1808
modality has been reported in a meta-analysis of 14 prospective randomised trials. No diﬀerence in rates of locoregional recurrence or survival based on the timing of chemotherapy were seen.39 The use of breast-conserving surgery increased by 16·6% (95% CI 15·1–18·1) in patients receiving chemotherapy ﬁrst, and this is probably an underestimation since many women in these trials were already candidates for breast-conserving surgery. The use of breast conserving surgery after neoadjuvant chemotherapy is based on the principle that a smaller volume of breast tissue than was originally occupied by the tumour is resected, making an accurate depiction of the extent of residual disease after chemotherapy essential. We identiﬁed no prospective trials, randomised or not, examining the likelihood of successful breast-conserving surgery in patients selected with and without MRI. Eight single-institution studies each including more than 25 patients, a meta-analysis of 25 studies including a total of 1212 patients,40 and a health-technology assessment were identiﬁed.41 The studies reviewed were heterogeneous in patient-inclusion criteria, type of chemotherapy used, and endpoints. The most common endpoints were the ability of MRI to predict pathological complete response (pCR), and correlation between MRI determination of residual tumour size and pathological size. The meta-analysis reported a sensitivity of MRI for predicting pCR of 63% (95% CI 56–70) and a speciﬁcity of 91% (95% CI 91–92).40 However, pCR is not necessary for successful breast-conserving surgery, so this analysis potentially underestimates the value of MRI. A prospective study of 41 women compared prediction of the degree of response by physical examination, ultrasonography, mammography, and MRI. The MRI prediction of response agreed with pathology 71% of the time, signiﬁcantly more often than physical examination, mammography, or ultrasonography (19%, 26%, and 35%, respectively).42 A retrospective study of 60 cancers in 51 patients reached similar conclusions.43 In studies that examined the correlation between MRI prediction of tumour size and pathological size,44–47 MRI was consistently more reliable than conventional assessment for predicting the amount of residual disease, but did not reliably identify scattered microscopic foci of residual tumour. In addition to predicting the amount of residual disease, MRI also helps to determine whether tumour shrinkage has been concentric or scattered (information that might be useful for the assessment of suitability for breast-conserving surgery). There is very little information addressing whether the greater accuracy of tumour size measurement and response prediction with MRI translates to an improved ability to select patients for breast-conserving therapy. Julius and colleagues48 reported 18 patients who were inoperable or required mastectomy at presentation and were thought to have responded suﬃciently to undergo breast-conserving surgery on the basis of MRI ﬁndings, and only two required a mastectomy. The issue of the www.thelancet.com Vol 378 November 19, 2011
clinical value of MRI is further complicated by studies with small numbers of patients that suggest that the accuracy of MRI in assessing response might depend on the speciﬁc therapeutic agent used for treatment.49–51 Thus, although it seems logical that MRI would improve the ability to identify candidates for breast-conserving surgery after neoadjuvant therapy, there is no evidence that this is true.
Detection of occult primary breast cancer Breast cancer that presents as axillary metastases with an occult primary tumour that cannot be detected by physical examination, mammography, or ultrasonography is seen in less than 1% of cases.52 The role of MRI in identiﬁcation of the primary tumour has been studied in a series of retrospective studies, most with fewer than 20 patients, and in a meta-analysis of eight studies including 220 patients.53 The pooled sensitivity for detection of cancer was 90% and the speciﬁcity was 31%. The mean pathological size of the occult tumours ranged from 1 mm to 50 mm, and 82% (pooled mean) were inﬁltrating ductal cancers. Because of the rarity of this condition, large studies are unlikely to ever be done. Identiﬁcation of the primary tumour allows a conventional lumpectomy and delivery of a boost dose of radiation to the primary tumour site, minimising the risk of local recurrence, and has obvious advantages compared with radiation of the intact breast without knowledge of tumour extent or characteristics.
Discussion We found limited evidence to support the idea that use of MRI improves patient outcomes. The strongest evidence of beneﬁt is in screening known BRCA mutation carriers or women who have an increased risk of breast cancer because of their family history. In all the studies reviewed, the sensitivity of MRI was better than that of mammography for the detection of invasive breast cancer, resulting in detection of smaller cancers and the occurrence of fewer interval cancers. Whether MRI screening has a survival advantage is uncertain. The cancers that occur in BRCA1 mutation carriers commonly have a poor prognostic phenotype, lacking the oestrogen and progesterone receptors and overexpressing HER2 (triplenegative), so the aﬀect of early detection on survival is uncertain.54 The beneﬁts of MRI screening in women at genetic and familial risk have been extrapolated to other high-risk women. But other high-risk groups, such as women with lobular carcinoma in situ or those at risk because of mantle irradiation, are not prone to an excess of the triple-negative phenotype seen in BRCA mutation carriers, and further studies are needed to assess MRI screening in these women. In patients with breast cancer, there is little evidence that MRI improves short-term or long-term outcomes of breast-conserving surgery. Two randomised trials22,23 do not show that the selection of patients with MRI leads to www.thelancet.com Vol 378 November 19, 2011
any decrease in surgical procedures. The data for longerterm outcomes, such as contralateral breast cancer and IBTR, are of insuﬃcient quality to draw any ﬁrm conclusions. But an increasing body of evidence shows that tumour biology and targeted therapy have a signiﬁcant eﬀect on the risk of IBTR55,56 and that patients at highest risk for IBTR are also at highest risk for chestwall recurrence after mastectomy,57 negating a beneﬁt for detecting subclinical disease with MRI to convert patients from breast-conserving surgery to mastectomy. In the absence of a signiﬁcant diﬀerence in IBTR rates in patients selected with and without MRI, there is no reason to expect that patient selection with MRI will improve survival.58 Subsets of patients with breast cancer might beneﬁt from assessment with MRI, but the low incidence of IBTR and contralateral breast cancer will make the identiﬁcation of these subsets diﬃcult. The use of MRI in problem areas of local therapy has more potential for beneﬁt. Although only retrospective data are available, it is clear that MRI identiﬁes a primary tumour in a signiﬁcant number of women who present with axillary metastases, and use of MRI in this scenario is beneﬁcial. Assessment of the extent of residual cancer after neoadjuvant chemotherapy remains a problem, as shown by the results of National Surgical Adjuvant Breast and Bowel Project (NSABP) B17,59 in which the addition of a taxane to doxorubicin and cytoxan signiﬁcantly increased the pCR rate from 14% to 26%, but the proportion of patients who underwent breast-conserving surgery did not change. The neoadjuvant model is common in clinical trials, as it aﬀords a ready opportunity for the prospective assessment of the aﬀect of MRI on selecting patients for breast-conserving surgery. Ultimately, the true value of MRI might lie in its ability to predict biological behaviour, rather than to quantitate low-volume disease. Very early changes in intracellular metabolism that are detectable by magnetic resonance spectroscopy seem to be predictive of response to treatment,60 and if validated in larger studies could avoid the toxicity and expense of continuing a chemotherapy regimen that will not be beneﬁcial. The ability to detect very low-volume disease with MRI presents an opportunity to re-examine the need to resect surgically all radiographically detected disease in the era of eﬀective multimodality therapy. The guidelines for selecting patients for breast-conserving surgery were developed more than 20 years ago, and standards of breast imaging and pathological assessment, and the eﬀectiveness of systemic therapy, have all changed considerably since then. A prospective, randomised trial has shown that macrometastases can be left behind in the axillary nodes without signiﬁcantly changing rates of local failure or survival in patients who received radiation therapy and systemic therapy,61,62 which strongly suggests that not all low-volume disease identiﬁed by MRI mandates surgical resection. This question can only be addressed in a prospective clinical 1809
trial. Future research in this ﬁeld would be most beneﬁcial if directed toward the resolution of clinical problems such as assessment of the extent of residual disease after neoadjuvant chemotherapy, or the need for some form of radiation therapy in all women who undergo breast-conserving surgery. Contributors MM planned the article, reviewed the list of articles generated from the systematic review, selected appropriate articles for further review, reviewed all abstracts, and reviewed the papers relevant to local therapy. MM also wrote the introduction, discussion, review of local therapy, neoadjuvant therapy, and occult primary cancer sections, and incorporated the contributions from the manuscript’s co-authors. JW did the search for the systematic review, eliminated duplicate records, and wrote the search strategy panel of the manuscript. EM participated in the planning of the article, reviewed the abstracts and relevant papers related to screening, wrote the section on screening, contributed the images, and wrote the ﬁgure legend.
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