Recommendation

Performing the MRI

  • Standardised reporting including BI-RADS final assessment categoriesis required.
  • Incidental, additional findings must be classified separately.
  • An incidental, additional finding must be correlated with mammography and (second-look) ultrasound, during which PA material can be obtained.
  • If an ipsilateral incidental finding is present with a preoperative patient (multifocal or multicentric) and no corresponding laesion on ultrasound or mammographyis found, a practical approach can be chosen by the breast care team and planned surgical management does not need to be amended per se.
  • The following applies to the remaining additional findings:
  • If a corresponding laesion is not found and it concerns a BI-RADS 3 laesion, a repeat MR in another phase of the menstruation or after 6 months is indicated
  • If a corresponding laesion is found and it concerns a suspicious malignant mass (BI-RADS 4 or 5), which may drastically change surgical management, this is eligible for MRI-guided      biopsy.
  • If a corresponding laesion is not found and it concerns a non-mass-like enhancement (BI-RADS 4), which may drastically change surgical management, this is eligible for MRI-guided biopsy
  • In the remaining cases, a one-off repeat of the MRI in a different phase of the cycle or in 6 months may be chosen, before proceeding to MRI-guided biopsy

 

Indications for MRI:

Screening:

  • Screening with MRI is indicated for women with a very high risk (RR 6-8)
  • There is insufficient basis to recommend annual MRI screening for women with increased risk without gene mutation, other than in a research context
  • MRI screening of women from the general population with dense breast tissue or with silicone prostheses is not recommended

 

Preoperative staging:

  • Routine preoperative MRI is not recommended.
  • Preoperative MRI is recommended for invasive carcinoma, if the woman would like to be eligible for BCT, and:
    • there is a discrepancy in size on clinical examination, mammography and ultrasound, or
    • there is invasive lobular carcinoma, unless there is a unifocal mass on a fatty mammogram

This recommendation applies especially to young women

The added value for women over 70 years of age is minor

  • Preoperative MRI is recommended with DCIS, if the woman would like to be eligible for BCT, and:
    • there is high grade DCIS, in which there is indistinctness about the tumour size
    • there is DCIS with suspicion of (micro)invasion

 

Differentiation between benign and malignant abnormalities/further characterisation:

  • MRI as additional imaging technique in the case of a problematic mammogram or ultrasound should be applied cautiously. If a punction is indicated on the basis of mammography and ultrasound, this punction indication will not be made unnecessary by MRI examination
  • MRI is recommended as additional diagnostic tool for suspicious abnormalities of the postoperative breast or positive axillary nodes and an occult primary tumour on mammogram and ultrasound

 

Determining the effect of neoadjuvant chemotherapy

  • MRI as additional imaging technique is recommended to accurately record the tumour size before and after neoadjuvant chemotherapy (unless it can be clearly determined using mammography and ultrasound)

Conclusions

 

Level 1

On average, MRI is a better approximation of the precise tumour size than clinical breast examination, mammography and ultrasound, especially with dense breast tissue.

 

A1        Houssami 2008, Brennan 2009, Mann 2008, Schouten van der Velden 2009

A2        Berg 2004, van Goethem 2004, Deurloo 2006

 

Level 2

The difference in accuracy between MRI and mammography is dependent on the density of the breast tissue. The difference is small for fatty breasts.

 

A2        Berg 2004, Sardanelli 2004,

B          Van Goethem 2004, Schnall 2005

 

Level 1

When determining the tumour size using MRI, overestimation is more common than underestimation. The percentage of overestimation in tumour size by MRI varies strongly;

it is smallest with invasive lobular carcinoma and the largest with DCIS.

 

A1        Houssami 2008, Mann 2008, Schouten van der Velden 2009

A2        Deurloo 2006, Berg 2004

 

Level 1

Compared to mammography and ultrasound, MRI has the highest accuracy in pre-operative determination of additional tumour foci and bilaterality.

This applies to invasive ductal carcinoma and invasive lobular carcinoma.

 

A1        Houssami 2008, Brennan 2009, Mann(1) 2008

 

Level 1

The sensitivity of MRI with DCIS is highly variable and there may be a substantial overestimation.

 

MRI has a higher negative predictive value than mammography in relation to multicentricity, residual tumour and detecting an invasive component.

 

MRI has the highest accuracy in determining the presence and size of high grade DCIS and an extensive intraductal component.

 

A1        Schouten van der Velden 2009

A2        Kuhl 2007, Hwang 2003

 

Level 1

Preoperative MRI may lead to a longer pre-operative process and has lead to more extensive surgery, both in terms of local excision with BCT and the percentage of mastectomies.

 

A1        Houssami 2008, Brennan 2009

B          Bleicher 2009

 

Level 1

Preoperative MRI has not lead to a significantly lower percentage of reoperations, except with ILC.

 

A1        Turnball 2010

B          Bleicher 2009, Mann (2) 2008

 

Level 1

After primary therapy (consisting of mastectomy or BCT), the chance of a local recurrence is the greatest with young women and breast-conserving therapy. These recurrences worsen the prognosis and reduce survival.

 

A1        Voogd 2005, Clarke 2005, Bartelink 2007, de Bock 2009

A2        Vrieling 2003

Literature summary

Multiple reviews are available on different subtopics. On the basis of 19 studies, Houssami (2008) has evaluated how often extra malignancy is found and what the effect is on surgical management. Brennan (2009) analysed 22 studies to determine the percentage mammographic occult contralateral malignancy. Mann ((1), 2008) evaluated 21 studies to determine the value of MRI in invasive lobular carcinoma. Schouten van der Velde (2009) determined the value of MRI for DCIS by analysing the results of 19 studies. A number of cohort studies are also cited.

 

Tumour size, multifocality, multicentricity and bilaterality

Aside from personal preference of the patient, the size of the breast cancer in relation to the size of the breast is determinant for primary treatment. The size can be determined by means of clinical breast examination, mammography, ultrasound and MRI. Berg (2004) has prospectively analysed the accuracy of mammography, ultrasound and MRI for 110 women in whom 177 malignant laesions were found. The extra laesions changed the surgical management in 30% of cases. Mammography, together with clinical examination and MRI, is the most sensitive combination. Ultrasound after MRI did not provide additional value. The sensitivity of mammography was inversely proportional to the density of breast tissue and reduced from 100 to 45% for very dense breast tissue. MRI displayed a higher sensitivity than mammography and ultrasound, both for invasive and in situ malignancy. Addition of MRI led to a false-positive finding and an overestimation of tumour size in 6%.

In the prospective study by Deurloo (2006), in which candidates for breast-conserving therapy were included, MRI was significantly more often correct in determining tumour size than conventional imaging (90% versus 70%). This was especially the case if there was an irregular shape of the tumour on the mammogram, if there was a discrepancy in size, measured on mammography and ultrasound and in younger patients. Mammographically occult laesions were detected in 13% of patients.

In the prospective multicentre trial by Schnall (2005), 414 women with proven breast cancer were examined by mammography and MRI. Mammographically occult malignant laesions that were more than two cm distance from the index laesion (and therefore usually outside the boundaries of the lumpectomy) were found in 10% of women. This especially concerned women with dense breast tissue. Half of these laesions were greater than 1 cm.

 

DCIS

The size of DCIS is usually determined by the size of the area with microcalcifications. However, this often appears to be an underestimation [Holland, 1990]. A more accurate determination of the size of DCIS by MRI is important, because complete excision means 100% curation in the case of DCIS.

In a review, Schouten van der Velden (2009) analysed 19 studies for the value of MRI with DCIS. The sensitivity varied from 38 to 100%, in which false negative findings often involved low-grade DCIS. MRI was found to be better at indicating the size of DCIS, although a lot of overestimation occurred due to the presence of enhancing benign proliferative disorders.

The publication by Kuhl (2007) is an interesting study on the value of MRI with DCIS. She studied more than 7,000 patients for different indications using both mammography and MRI. It was a double-blind study. One hundred and sixty seven cases of pure DCIS were found and these were the subject of the study. There was a moderate sensitivity (56%) for mammography and significantly higher sensitivity for MRI (96%). MRI was especially better in detecting high-grade DCIS.

MRI was also found to be more accurate in the case of an invasive carcinoma with an extensive intraductal component (EIC). There is EIC in 30 to 40% of invasive laesions. Irradically removed EIC is an important prognostic factor for the risk of a local recurrence, probably because substantially more tumour tissue remains in these patients after lumpectomy [Holland (1), 1990; Holland (2), 1990; Voogd, 2001].

 

Invasive lobular carcinoma

Invasive lobular carcinomas make up approximately 10% of all breast cancers and there are indications that the incidence is increasing [Li, 2003]. A diffuse growth, without microcalcifications, is more common than with invasive ductal carcinomas, so that the mammogram may be false negative [Arpino, 2004; Berg, 2004]. The infiltrative growing lobular carcinomas are often underestimated in size, both with mammography and ultrasound [Mann (2), 2008]. Connected to this is the fact that positive surgical margins are seen more commonly with breast-conserving treatment in the case of invasive lobular carcinoma than with invasive ductal carcinoma [Dillon 2006, de Zeeuw 2009]. However, it has never been demonstrated that ILC leads to more local recurrences, not with breast-conserving treatment, nor GRM with radiotherapy [Diepenmaat, 2009]. It appears from the review by Mann ((1), 2008) that MRI is better at indicating tumour size than mammography and ultrasound. In addition, extra ipsilateral malignant laesions were seen in 32% of patients and contralateral laesions in 7% of patients using MRI. MRI changed surgical management in 28% of cases.

 

Relation to evaluability of mammography

In the prospective trial by Sardanelli (2004), MRI was compared to mammography in 90 patients who were going to undergo a planned mastectomy. MRI was found to be more sensitive in the detection of multifocal and multicentric laesions with an overall sensitivity of 81 and 60% respectively. However, no significant difference in sensitivity was found in breasts largely composed of fat tissue. In the studies by Berg (2004) and Goethem (2004), the difference in sensitivity was also inversely proportional to the density of the breast tissue.

 

Contralateral laesions

In the multicentre study by Lehman (2007), 30 contralateral tumours (3%) were found in 969 women with a recent diagnosis of unilateral breast cancer, which were clinically and mammographically occult. The review by Brennan (2009) shows suspicious abnormalities in the contralateral breast are seen in 9.3% of women with recently diagnosed breast cancer, in which more than half are found to be false positive. A total of 131 malignant laesions were found in 3,253 women (4%). Of these laesions, 35% concerned DCIS; 65% were invasive with an average diameter of 9 mm. While the prognostic value of detecting these laesions is difficult to estimate, simultaneous detection of contralateral malignancy can spare women a second round of therapy.

 

What is the effect of preoperative MRI?

The rapid introduction of MRI is largely the result of great accuracy in relation to tumour size, multifocality and multicentricity and has lead to MRI increasingly being added to the preoperative work-up of patients eligible for BST.

This may lead to changes in surgical management, which means a mastectomy is performed instead of a lumpectomy, or a more extensive lumpectomy or an extra lumpectomy. Morrow (2004, 2006) has made critical side notes about this development. Does this more extensive surgery actually result in an improvement for the patient? Does preoperative MRI contribute to a reduction in the number of reoperations, to less recurrences or to a better prognosis?

 

Effects on the pre-operative process

In a retrospective study by Bleicher (2009) involving 577 patients, of which 130 underwent a preoperative MRI, it was noticeable that the pre-operative process with these 130 patients took more than 22 days longer (p=0.011), while there was no statistically significant difference in positive surgical margins after surgery (21.6% with MRI and 13.8 % without MRI, p=0.20). The percentage of conversions to mastectomy was higher, but this difference was also not statistically significant (9.8% with MRI and 5.9% without MRI, p=0.35). The longer duration of the pre-operative process is usually the result of the work-up of additional findings. In the study by Lehman (2007), 121 biopsies were required for the detection of 30 contralateral tumours.

 

Effect on surgical management

Berg (2004) reports that surgical management was changed in 30% of cases, Van Goethem (2004) 43%, Deurloo (2006) 22% and Mann ((2), 2008) 28% of exclusively ILC patients.

Houssami (2008) reports that the effect on surgical management is mentioned in 13 of 19 studies: mastectomy is performed instead of lumpectomy in 8% and more extensive surgery in 11% (not further specified, this concerned more ample excision, or an extra excision but also mastectomy). On the basis of false-positive findings, an unjustified mastectomy was performed in 1% of women and more extensive surgery in 5%.

 

Effect on the frequency of reoperation

Only a proportion of studies provide information about the effect of preoperative MRI on the number of irradical lumpectomies. Grobmeyer (2008) reports a low percentage (10%) of positive surgical margins. Pengel (2008) compared the number of irradical lumpectomies in a group of patients with and without preoperative MRI. This was 14% in the MRI group and 19% in the non-MRI group. Mann (2010) retrospectively evaluated the re-excision rate with ILC: this was 27% in the non-MRI group and significantly lower (9%) in the MRI group. The final mastectomy percentage was also lower in the MRI group (48% versus 59%).

Turnbull (2010) published results for the only randomised study conducted (so far) in this area. It concerns an English multicentre study in which 45 hospitals and 107 surgeons participated. The primary endpoint was the percentage of reoperations. The percentage of reoperations in 800 patients with and 800 patients without preoperative MRI were compared and were found to be practically the same: 18.7 versus 19.3%.

 

Effect on the risk of recurrence and prognosis

There is little known yet about this. There was no difference in the frequency of local recurrence in a retrospective study by Solin (2008): 3% in women with preoperative MRI and 4% in women without MRI. There was also no difference in survival: 86% in women with preoperative MRI and 86% in women without MRI. The differences in patient populations were not significantly different, the patients with MRI were a little younger (53 years versus 56 years) and had slightly more favourable tumour characteristics.

The additional tumour foci that were detected using MRI confirm what has been known for some time, namely that breast cancer is often multifocal and multicentric [Holland, 1985]. It is therefore plausible that tumour is regularly left behind during a lumpectomy. Despite this, clinical trial data show that the prognosis of patients undergoing BST is the same as patients undergoing a mastectomy [van Dongen, 2000; Fisher, 2002] and the recurrence percentage is low. Clearly, postoperative radiotherapy and chemotherapy attribute to this. Patients in these trials did not undergo preoperative MRI, from which the conclusion could be drawn that survival advantage is not gained from detecting multifocality using MRI. In relation to the risk of local recurrence, it must be noted that the risk is clearly higher for young women [Vrieling, 2003; Bartelink, 2007] and that the prognosis of patients with a local recurrence is clearly poorer than for patients who do not experience a recurrence [Voogd, 2001; Clarke, 2005]. De Bock (2009) analysed the data of 3,601 women with stage I and II breast cancer included in 3 EORTC trials. Patients with a local recurrence were found to have three times the risk of developing distant metastases than patients who did not develop a recurrence. Young age and breast-conserving therapy were the most important prognostic factors for developing a local recurrence. The expectation is that implementation of MRI specifically with young women will favourably influence survival, while in women of 70 years and older no survival advantage is expected. However this has not yet been demonstrated.

Considerations

After an enthusiastic introduction of MRI in the preoperative work-up of patients who are eligible for BCT, the added value is currently up for discussion and the indication is therefore controversial. It appears to be difficult to translate the extra information obtained by means of MRI into better surgical results. It is also possible that the role of additional radiotherapy and adjuvant chemotherapy with eradication of additional foci is being underestimated.

While sufficient information will be gained with conventional imaging for the majority of patients to perform breast-conserving treatment, it has become clear that subgroups will benefit from preoperative MRI. More randomised studies are required to define these subgroups.

If additional laesions are detected using MRI, for which PA is required, extension of the pre-operative process is sometimes unavoidable.

Authorization date and validity

Last review : 13-02-2012

Last authorization : 13-02-2012

The national Breast Cancer guideline 2012 is a living guideline, in other words there is no standard term of revision. NABON continually watches at new developments and clinical problems in the areas of screening, diagnostics, treatment and aftercare, and whether this requires an update.

Initiative and authorization

Initiative : Nationaal Borstkanker Overleg Nederland

Authorized by:
  • Nederlandse Internisten Vereniging
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Psychiatrie
  • Nederlandse Vereniging voor Radiologie
  • Nederlandse Vereniging voor Radiotherapie en Oncologie

General details

Approximately 14,000 women (and 100 men) are diagnosed with invasive breast cancer each year in the Netherlands, and about 1,900 have an in situ carcinoma. A woman's risk of having breast cancer over the course of her life is 12-13%. This means that breast cancer is the most common form of cancer in women in the Netherlands. Early detection, particularly via national breast cancer screening, combined with adjuvant therapy followed by locoregional treatment, improves the prognosis in women with breast cancer

The guideline on Breast Cancer Screening and Diagnostics, published in 2000, was updated in 2007. In 2002, the first multidisciplinary National Breast Cancer Guideline was published, it was revised in 2004, 2005 and 2006. In 2008 both guidelines were combined to Breast Cancer Guideline, which 2012 revision is now effected.

Scope and target group

This guideline is written for all the members of the professional groups that have contributed to its development.

 

This guideline is a document with recommendations and instructions to support daily practice. The guideline is based on the results of scientific research and expert opinion, with the aim of establishing good medical practice. It specifies the best general care for women with (suspected) breast cancer and for those who are eligible for screening. The guideline aims to serve as a guide for the daily practice of breast cancer screening, diagnostics, treatment and aftercare. This guideline is also used in the creation of informational materials for patients, in cooperation with the KWF (Dutch Cancer Society).

Member of workgroup

A core group consisting of a radiologist, surgeon, pathologist, medical oncologist and radiation therapist began preparing for the revision of the breast cancer practice guidelines in 2009. A multidisciplinary guideline development group was formed in early 2010 to implement the revision. This group consisted of mandated representatives from all of the relevant specialisations concerned with breast cancer, plus two delegates from the BVN (Dutch Breast Cancer Society) (see list of guideline development group members). The benefits of such a multidisciplinary approach are obvious: not only does it best reflect the care, but it offers the greatest possible expertise for the guideline. In composing the development group, geographic distribution of the members, balanced representation of the various organisations and agencies concerned, and a fair distribution in academic background were taken into account as much as possible.

 

The guideline development group received procedural and administrative support from IKNL (Comprehensive Cancer Centre for the Netherlands) and support on methodology from Bureau ME-TA. Partial funding was obtained from SKMS (Quality Funds Foundation of Dutch Medical Specialists). This subsidy would not have been possible without the extensive assistance provided by the NVvR (Radiological Society of the Netherlands).

Declaration of interest

Partial funding for the guideline revision was obtained from the Society of Dutch Medical Specialists in the framework of the SKMS. IKNL sponsored some of the cost. On two occasions, as well as at the beginning and end of the process, all of the members of the guideline development group were asked to fill out a statement of potential conflicts of interest, in which they stated their relationship with the pharmaceutical industry. A list of these statements of interest can be found in the appendices.

Patient involvement

In developing this guideline, four clinical questions were formulated. These questions emerge from an inventory of clinical problems collected in the field from professionals, patients and patient representatives.

 

Also, A multidisciplinary guideline development group was formed in early 2010 to create and implement the revision. This group consisted of mandated representatives from all of the relevant specialisations concerned with breast cancer, plus two delegates from the BVN (Dutch Breast Cancer Society).

 

Method of development

Evidence based

Implementation

Feasibility has been taken into account in developing the guideline. This included attention to factors that could promote or hinder putting the advice into practice. Examples include the implementation of an analysis of problems, the multidisciplinary composition of the guideline development group, and making active use of support from the guideline development group members. Presenting the draft guideline to the field and communicating what, if anything, is being done with the responses, also promotes implementation. In this manner, a guideline has been developed that answers current questions in the field.

The guideline is distributed widely and is available in digital form on the Dutch Guideline Database. The guideline may also be brought to the attention of a wider audience in other periodicals or continuing education sessions, for example. To promote use of the guideline, we recommend that the regional tumour working groups and group practices, as well as scientific and professional organisations, repeatedly bring the guideline to the attention of their members. Any problems that may arise in using the guidelines can then be discussed and, when appropriate, submitted to the national guideline development group, as it is a "living" guideline. If desirable, parts of the guideline can be made more explicit by formulating regional additions or translation to the local situation in departmental and/or hospital protocols.

In principle, indicators are determined during development of the guideline that can be used to monitor implementation of the recommendations. Via a documentation project, these indicators can then be used to determine the extent of compliance with the guideline. The information from the documentation project becomes input for the revision of the guideline.

Methods and proces

This module has been evidence-based revised in 2008 and consensus based updated in 2012.

 

A revision of an existing guideline consists of revised and updated text. Revised text is new text based on an evidence-based review of the medical literature; updated text is the old guideline text which has been edited by the experts without performing a review of medical literature. Each section of the guideline states what type of revision has taken place. Each chapter of the guideline is structured according to a set format, given below. The purpose of this is to make the guideline transparent, so that each user can see on what literature and considerations the recommendations are based on.

 

Description of the literature

To the greatest extent possible, the answers to the fundamental questions (and therefore the recommendations in this guideline) were based on published scientific research. The articles selected were evaluated by an expert in methodology for their research quality, and graded in proportion to evidence using the following classification system:

 

Classification of research results based on level of evidence

A1

Research   on the effects of diagnostics on clinical outcomes in a prospectively   monitored, well-defined patient group, with a predefined policy based on the   test outcomes to be investigated, or decision analysis research into the   effects of diagnostics on clinical outcomes based on results of a study of   A2-level and sufficient consideration is given to the interdependency of   diagnostic tests.

A2

Research   relative to a reference test, where criteria for the test to be investigated   and for a reference test are predefined, with a good description of the test   and the clinical population to be investigated; this must involve a large   enough series of consecutive patients; predefined upper limits must be used,   and the results of the test and the "gold standard" must be   assessed independently. Interdependence is normally a feature of situations   involving multiple diagnostic tests, and their analysis must be adjusted   accordingly, for example using logistic regression.

B

Comparison   with a reference test, description of the test and population researched, but   without the other features mentioned in level A.

C

Non-comparative   trials

D

Opinions   of experts, such as guideline development group members

 

Conclusions

Based on the medical literature, one or more relevant conclusions are made for each section. The most important literature is listed according to the level of evidential strength, allowing conclusions to be drawn based on the level of
evidence. All the medical literature included in the conclusion is described in the bibliography.

 

Classification of conclusions based on literature analysis

1

Based   on 1 systematic review (A1) or at least 2 independent A2 reviews.

2

Based   on at least 2 independent B reviews

3

Based   on 1 level A2 of B research, or any level C research

4

Opinions   of experts, such as guideline development group members

 

Other considerations

Based on the conclusion(s), recommendations are made. However, there are other considerations that contribute to formulation of the recommendation besides literature evidence, such as safety, the patients' preferences, professional expertise, cost-effectiveness, organisational aspects and social consequences. The other considerations are mentioned separately. In this manner, it is clear how the guideline development group arrived at a particular recommendation.

 

Recommendations

The final wording of the recommendation is the result of the scientific conclusion, taking into account the other considerations. The purpose of following this procedure and drawing up the guidelines  in this format is to increase transparency.

 

References

An alphabetical list of literature references can be found at the end of the guideline.

 

All draft texts have been discussed by the guideline development group.

Search strategy

Searches are available upon request. Please contact the Richtlijnendatabase.