For patients with an invasive breast tumour (5-30 mm) and at most 3 lymph node metastases, what new forms of risk profiling – as opposed to the traditional prognostic factors such as tumour size, lymph node status and grade of tumour differentiation – influence the choice of whether or not to start adjuvant therapy, and does this differ in patients under age 50, between ages 50 and 70, and over age 70?


Adjuvant! ( is a validated instrument for predicting the prognosis of individual patients and predicting the reduction in absolute risk of recurrence and death by adjuvant systemic therapy. For this reason, the recommendations for adjuvant systemic treatment in this guideline have been based on the tables generated with Adjuvant!.


Validated gene expression profiles may be used in individual cases with a hormone sensitive invasive ductal carcinoma, if there is doubt about the indication for adjuvant chemotherapy on the basis of traditional prognostic factors.



Level 2

It has been demonstrated for a number of gene   expression profiles in retrospective studies that they are better at distinguishing subgroups with a favourable or unfavourable prognosis than traditional risk estimations.


B          Buyse 2006, Chang 2003, Desmedt 2007, Foekens 2006,   Huang 2003, Paik 2004, Paik 2006, Sotoriou 2003, van ’t Veer 2002, van de Vijver 2002, Wang 2005, Bueno-de-Mesquita 2009, Mook 2009, Mook 2010, Dowsett 2010

Literature summary

Knauer [2010] conducted a pooled retrospective analysis of 7 studies on adjuvant therapy in 541 patients. In the high-risk group, as determined using MammaPrint, a better metastasis-free five-year survival of 88% was found in the group treated with chemotherapy followed by hormonal therapy, versus 76% in the group treated with hormonal therapy only. The predictive value of the MammaPrint for the effect of adjuvant chemotherapy has not yet been proven with this retrospective non-randomised study with different chemotherapy regimens. In a subgroup of the NSABP B20 trial, in which N0 ER+ patients were randomised between tamoxifen and tamoxifen plus chemotherapy, chemotherapy was only found to provide an advantage (by means of Oncotype DX) in patients with a high recurrence score (>30) (RR 0.26; 95%CI 0.13-0.53) [Paik, 2006]. At a low and intermediate RS, no advantage was seen with chemotherapy above tamoxifen only (RR 1.31; 95%CI 0.46-3.78 and RR 0.61; 95%CI 0.24-1.59, respectively). In a similar retrospective analysis of postmenopausal N+ ER+ patients, an advantage with adjuvant CAF chemotherapy was only seen in the group with a high RS [Albain, 2010]. While no advantage of chemotherapy could be found in the low and intermediate RS groups, a clinical advantage cannot be directly excluded given the large confidence intervals in these groups. The predictive value of the gene profile has not been prospectively researched with newer therapeutic modalities such as aromatase inhibitors, other chemotherapy agents or trastuzumab.


Of the abovementioned gene expression profiles, only the MammaPrint is currently commercially available in the Netherlands. The Food and Drug Administration approved the marketing of MammaPrint in 2008. Insurers in the United States still consider the use of MammaPrint experimental. No studies are available as yet that describe the clinical results of applying MammaPrint. The MINDACT trial is a prospective randomised multicentre study in which patients with a discordant outcome for MammaPrint and clinical risk estimation according to Adjuvant! are randomised for following the outcome of either MammaPrint or clinical risk estimation. Inclusion for this study ended on 1 July 2011. In the American TAILORx study, N0 ER+ patients and an intermediate risk according to the Recurrence Score were randomised between chemotherapy followed by hormonal therapy or hormonal therapy only. The results of these studies will  become available  in a number of years.


The St. Gallen international expert consensus panel states that validated gene expression profiles can be used as a supplement to state of the art histopathology, if there is doubt about the indication for adjuvant chemotherapy on the basis of traditional prognostic factors [Goldhirsch, 2009].

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).

Samenstelling werkgroep

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


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


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.


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.


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


Non-comparative   trials


Opinions   of experts, such as guideline development group members



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


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


Based   on at least 2 independent B reviews


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


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.



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.



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.