Neoadjuvant systemic therapy is indicated for breast cancer with locoregional metastasis (stage III).


Neoadjuvant systemic therapy may also be considered for stage II mammary tumours in which there is already an indication for systemic therapy at the time of diagnosis and in which tumour reduction is desirable in relation to a preference for BCT.


Preconditions for starting neoadjuvant therapy



  • multidisciplinary consultation
  • document cTNM and treatment plan within multidisciplinary consultation
  • clinical evaluation by the surgeon, radiotherapist and oncologist prior to starting chemotherapy


Breast diagnostics

  • histological biopsy: determination of the tumour grade, hormone receptors and HER-2 amplification
  • accurate documentation of the initial tumour size and metastasis by means of MRI (unless it can be determined well using mammography and ultrasound)
  • photograph cT4 tumours in order to record metastasis in the skin
  • placing a radio-opaque marker independent of whether mastectomy or BCT is chosen


Regional diagnostics

  • recording axillary node status clinically and via ultrasound
  • if cN1-3: cytological confirmation
  • if cN0: SWK procedure preferably prior to neoadjuvant treatment


Screening for distant metastasis

  • indicated with stage III breast cancer
  • consider for stage II clinical N+ breast cancer



Level 2

Approximately 88-89% of patients with positive lymph nodes and primary resectable breast cancer are detected with an SN procedure after neoadjuvant chemotherapy (false negative percentage 11-12%).


B          Xing 2006, Van Deurzen 2009


Level 3

An SN procedure after chemotherapy for patients with an initial T1-2N+ classification appears to be less reliable in determining downstaging.


C          Mamounas 2005, Shen 2007

Literature summary

Prior to the first treatment, each breast cancer patient should be discussed within the framework of multidisciplinary consultation. If this leads to a recommendation of neoadjuvant chemotherapy, higher demands are made of the diagnostics prior to treatment then when primary surgery is recommended. After primary surgery, tumour type, size, grade, hormone sensitivity, HER-2 amplification, angioinvasion, radicality of resection and lymph node positivity follow from histological diagnostics of the surgical tissue (mastectomy or lumpectomy and SN or ALND). Some of this information may be lost after neoadjuvant therapy. A histological diagnosis must therefore be made prior to treatment with a thick needle biopsy, in which the hormone receptors, HER-2 receptor and other prognostic characteristics may also be analysed. The location, size and metastasis of the local tumour must be documented carefully, also using clinical images, as well as any presence of additional tumour foci. This is best done using MRI, unless reliable determination is possible with mammography and/or ultrasound [Berg, 2004; Deurloo, 2005; Sardanelli, 2004]. Prior to treatment, locoregional treating physicians (surgeon, radiotherapist and oncologist) should see the clinical point of departure and preferably document the situation using clinical images, in order to adequately determine the clinical response. Given a (clinical) complete remission may occur, the location of the tumour needs to be marked with radio-opaque markers prior to neoadjuvant therapy; this is of benefit to both the surgeon and pathologist [Nadeem 2005, Oh 2007].


A good clinical and radiological determination of the axillary node status, including the level of the number of suspected lymph nodes prior to starting chemotherapy is also essential. The clinical or echographic suspicion of axillary node metastases must be confirmed before treatment using punction. An SN procedure after neoadjuvant chemotherapy appears to be less reliable. Xing (2006) performed a meta-analysis of 21 studies, in which 1,273 patients underwent an SN procedure after neoadjuvant chemotherapy, and found an identification percentage of 90% and a false negative percentage of 12%. A large proportion of patients in these studies initially had a cT1-2N0 stage. A small retrospective study in patients with axillary node metastasis cytologically documented prior to chemotherapy and clinically negative axillary after chemotherapy showed an extremely high false negative percentage of sentinel node cancer of 25% [Shen, 2007]. A more recent meta-analysis confirmed that especially the negative predictive value of an SN procedure is low after neoadjuvant chemotherapy [Van Deurzen 2009]. In contrast, no difference in reliability of the SN after neoadjuvant therapy was found in the NSABP-B27 study for patients with initial cN0 versus cN+ breast cancer [Mamounas, 2005]. An SN procedure is therefore recommended prior to chemotherapy for clinically and radiologically node-negative tumours for optimal clarity.


The chance of synchronous distant metastasis in stage III breast cancer is greater than with an early stage [Samant, 1999; Ciatto, 1988; Norum, 2000]. Staging to exclude synchronous distant metastasis is therefore recommended in this situation (stage III). Both a conventional staging procedure and FDG-PET-CT may be considered. The advantage of FDG-PET is the high specificity in staging the axillary and other regional node areas, to enable further detailing of locoregional metastasis. Given there is no information about the number of positive regional nodes prior to neoadjuvant treatment and this number also cannot be reliably determined after neoadjuvant treatment, staging via FDG-PET-CT may also be considered with stage II (especially if there are clinically positive nodes).

If there are synchronous distant metastases, multidisciplinary treatment choices must be made on an individual basis, dependent on the nature and prognostic significance of the locoregional situation and distant metastases. This chapter focuses on stage II or II breast cancer, i.e. without manifested distant metastases.

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.