Question

Which tool can be used for diagnosing breast cancer in symptomatic women?

Recommendation

Mammography is the basis of imaging in symptomatic women.

Conclusions

 

Level 1

The prevalence of malignancy in patients with palpable abnormalities is high, on average 9-11%. This prevalence is dependent on age.

The sensitivity of the mammogram increases with age and availability of previous imaging.

 

A1    Kerlikowske 2003

A2    Barlow 2002

 

Level 1

The negative predictive value of a normal mammogram and ultrasound in patients with a palpable abnormality that is not clinically suspect is high: 97.3–100%.

 

A1    Kerlikowske 2003

A2    Dennis 2001, Moy 2002, Shetty 2002, Soo 2003

Literature summary

The prevalence of breast cancer in a patient with a palpable abnormality lies between 9-11%. It varies strongly with age: less than 1% in women younger than 40 years, 9% in women between 41 and 55 years and 37% in women of 55 years and older [Kerlikowske, 2003].

Mammography is the basis of imaging in symptomatic women. Supplemental examination with ultrasound is indicated if thesymptoms are not adequately clarified (i.e. a negative mammogram).In a large retrospective study containing more than 40,000 mammograms, the average sensitivity of diagnostic mammography was 85.5% with a specificity of 87.7% [Barlow, 2002]. The sensitivity was higher as the breast tissue reduced in density and if there was a previous mammogram available for comparison. The sensitivity increased if the patients had reported the palpable abnormality themselves; however, the specificity decreased. A high age was associated with a higher positive predictive value, while supplemental ultrasound was found to be indicated more often in younger age groups. It was not possible to determine the sensitivity of the mammogram separately from the ultrasound in this study. In a number of smaller studies, in which this was possible, the contribution of ultrasound to a malignant diagnosis was found to be 6.5–14% [Zonderland, 1999; Flobbe, 2003; Moss, 1999]. The Sydney Breast Imaging Accuracy Study shows that knowledge of the mammogram performed prior to the ultrasound improves diagnosis [Irwig, 2006]. While the relationship between sensitivity and specificity between a mammogram, ultrasound and age is not linear in this study, the ultrasound is clearly more beneficial for women under 45 years of age.

 

A small indication area for mammography is the presence of metastases of an unknown primary tumour. The lack of a large series means there is no evidence regarding the right choice of diagnostic method. In the Guideline Primary Tumour Unknown [NVVP, 2011] and in the NICE Guideline 104 (2010), the recommendation is made that imaging of separate organ systems need to be requested on the basis of pathology results (and immunohistochemistry) and if there are clinical indications to do so. This is certainly the case with axillary lymph node metastases of an adenocarcinoma. Supplemental MRI must be considered if the resulting mammogram is negative.

 

Triple diagnostics is still the cornerstone in the diagnosis malignancy [Houssami, 2003; Houssami, 2005; Chuo, 2003], but this is changing in the case of palpable abnormalities in which malignancy is not suspected. There are an increasing number of studies in which the negative predictive value of a negative mammogram and a negative ultrasound is so high that supplemental punction is not indicated (anymore).

In four studies, with a follow-up period of at least 2 years, the negative predictive value varied from 97.3-100% [Dennis, 2001; Moy, 2002; Shetty, 2002; Soo, 2003]. Ultrasound also has a high negative predictive value as exclusive supplemental diagnostic method with palpable abnormalities not suspicious for malignancy [Cid, 2004; Whitehouse, 2001]. Authors of the abovementioned studies, even where a positive predictive value of 100% was achieved, nonetheless remain aware of the danger of delay in the diagnosis of an unjustly missed carcinoma and almost all studies also recommend clinical follow-up.

Improvement in the image quality of high resolution ultrasound has lead to a number of studies on the value of ultrasound with microcalcifications. Despite the fact that especially polymorphic, malignant microcalcification can be recognised, this does not have added value in the diagnostic process [Gufler, 2000; Yang, 2004]. 

Considerations

Mammography in symptomatic patients must at least consist of images of two views, craniocaudal and mediolateral-oblique, supplemented with local compression images or magnification views of the symptomatic area where required. Identification of the abnormality may be facilitated by use of (lead) markers. The indications for this be made by the radiologist.

Additional ultrasound should be performed directly after the mammogram. This should be performed by a radiologist that also has knowledge of the mammography findings. Images of the symptomatic area should be taken in two views. In the area around the mamilla, the scan plane radial to the nipple often provides additional information. The transducer position must be indicated on the image.

Ultrasound is the method of choice in women under 30 years of age, but also with symptomatic women who are pregnant or breastfeeding. The reason for this is the dense breast tissue, not the radiation exposure. If there is an indication for mammography, this should be performed straight after. Screening in this group of women is best delayed until a few months after childbirth or after breastfeeding has ended.

Additional techniques, such as colour Doppler, contrast ultrasound and elastography have added value with small groups, in which the operator dependency is of great importance. The reason these developments have not been implemented on a greater scale is also related to the low threshold in performing a biopsy.

Communication between the radiologist and the women should follow that, as outlined in the WGBO: it is compulsory in the WGBO for the radiologist, as a health care provider, to provide information about the results of the imaging performed, but he does not need to give a direct or definitive result (Burgerlijk Wetboek 1994 (the Dutch civil code)). The radiologist can provide the result in general terms; in the event of bad news he can indicate that the requesting physician will provide the woman with further details, given they have a better overview of all the details.

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.