When should radiotherapy of the chest wall after ablative surgery been given?


Indications for radiotherapy of the chest wall after ablative surgery:

  • a tumour-positive resection surface of the primary tumour, irradicality
  • cT4, pT4
  • pT3, depending on one or more of the following risk factors, angio-invasive growth, grade III, and/or age ≤ 40 years


Postoperative radiotherapy of the chest wall after ablative surgery may be considered in the case of:

  • 1-3 positive nodes and combination with one of the following characteristics: angio-invasive growth, grade III, age ≤ 40 years and tumour size ≥ 3 cm
  • pN0 and combination with three of the following characteristics: angio-invasive growth, grade III, age ≤ 40 years and tumour size ≥ 3 cm


Indications for locoregional postoperative radiotherapy (both after BCT and modified radical mastectomy):

  • 4 or more positive nodes
  • Tumour-positive axillary top



Level 1

Patients with large tumours (> 5 cm) and/or extensive lymph node metastases (≥ 4 positive nodes), also have an increased chance of a locoregional recurrence after radical surgery and systemic therapy.


A2        Ragaz 2005, Overgaard 1997, Overgaard 1999

C          Recht 1999, Recht 2001, Jager 1999, Katz 2001


Level 1

Postoperative locoregional radiotherapy reduces the chance of a locoregional recurrence by two-thirds and leads to an improved chance of survival [EBCTCG, 2000].


A1        EBCTCG 2000, Whelan 2000

A2        Ragaz 2005, Overgaard 1997, Overgaard 1999


Level 1

Aside from local control, locoregional radiotherapy also significantly improves overall survival after 15 years, if the locoregional recurrence risk after 5 years is 15% or more.


A1        EBCTCG 2005


Level 1

Postoperative locoregional radiotherapy improves locoregional control and overall survival with 1-3 positive nodes.


A2        Ragaz 2005, Overgaard 1997, Overgaard 1999

B          Overgaard 2007


Level 3

A combination of various tumour-related predictors for locoregional recurrence (young age, N status, vaso-invasive growth) leads to an increase in the risk of locoregional recurrence.


C          Wallgren 2003, Voogd 2005, Jagsi 2005

Literature summary

If BCT is deemed contraindicated and if preferred by the patient, mastectomy including adequate axillary staging is the appropriate treatment. The chance of a locoregional recurrence varies strongly in the different (retrospective) literature series, depending on the T and N classification [Valagussa, 1978; Ragaz, 2005; Recht, 1999; Jager, 1999]. In a recent analysis based on population in the Netherlands, 3% recurrences are seen after 5 years [van der Heiden, 2010].



On the basis of literature data there are arguments for and against considering radiotherapy after mastectomy in the case of T3 tumours [Ragaz, 2005; Jager, 1999; Overgaard, 1997; Overgaard, 1999; Recht, 2001; Taghian, 2006; Migano, 2007]. There is still insufficient data available to use extranodal growth of axillary metastases as independent criterion as indication for postoperative radiotherapy for breast cancer [Recht, 2001; Gruber, 2005; Jager, 1999]. Of course, tumour metastasis in a surgical margin is an indication for postoperative radiotherapy. There is limited literature data on the clinical significance of the width of tumour-free margin and the chance of a locoregional recurrence. A few studies state a narrow margin (< 2 mm) is a predictor of locoregional recurrence [Wallgren, 2003; Jagsi, 2005].


Postoperative radiotherapy reduces the chance of a locoregional recurrence by a factor of 3 to 4 [EBCTCG, 2000]. There is a relationship between the reduction in locoregional recurrence and long-term survival. At a five-year locoregional recurrence percentage of >15%, postoperative radiotherapy leads to a five-year survival improvement of approximately 5% [Punglia, 2005].

EBCTCG data and other studies [Darby, 2005; EBCTCG, 2005; Hooning, 2006; Hooning 2007; Taylor, 2006; Taylor, 2007] have also shown that radiotherapy in earlier times lead to higher than expected death due to cardiac morbidity. This applies especially to tumours on the left side and parasternal irradiation. It is expected that with current techniques (including Deep Inspiration Breath Hold technique) in which the heart can be spared as much as possible, the absolute effect of radiotherapy on survival is higher.


An important criterion to determine the chance of locoregional recurrence is the number of axillary node metastases. Postoperative radiotherapy is accepted for high-risk patients with ≥ 4 positive nodes. In two prospective studies, the chance of a ten-year locoregional recurrence after mastectomy including ALND and adjuvant systemic therapy was approximately 15% for patients with 1-3 axillary node metastases and approximately 30% for the 4+ patients.


These findings are confirmed by the EBCTCG (2010) meta-analysis. Aside from survival advantage and reduction in locoregional recurrences at ≥ 4 positive nodes, this has now been confirmed for 1-3 positive nodes. A point of criticism of the EBCTCG overview and abovementioned studies (especially the Danish series and British Columbia studies) is that there was an extremely high locoregional recurrence percentage (30% and 26% respectively). This may not be in line with the current situation. Approximately 30% of patients in the non-irradiated groups of the two Danish studies (with a 12 year follow-up) developed a locoregional recurrence. This suggests that surgical treatment was insufficient in many cases. No ALND’s were performed in Denmark as is common in the Netherlands, but samples of level I and II were taken. However, others reported that even after adequate ALND’s (in the case of mastectomy including ALND) and adjuvant medication-based therapy in subgroups, there was still a large chance of a locoregional recurrence if post-operative irradiation was not administered [Ragaz, 2005; Recht, 1999; Jager, 1999; Katz, 2001].

Survival advantage was originally demonstrated in the high risk groups, i.e. patients with 4 or more positive nodes. In an update of the Danish studies in the subgroup of patients in whom 8 or more nodes were removed, it appears that patients with 1-3 tumour-positive nodes had a similar survival advantage after radiotherapy than the N4+ patients (9% absolute after 15 years) [Overgaard, 2007].


It is important to select patients who have an expected locoregional recurrence percentage of ≥ 15% over 5 years, given these patients may benefit from radiotherapy, both in terms of their locoregional control and overall survival. Not only the lymph node status but also the combination with other factors may be considered here. Wallgren (2003) studied more than 5,000 patients after mastectomy including ALND who were treated in one of the seven International Breast Cancer Group randomised trials. This group consisted of lymph node positive and negative patients who did not (pN0) or did undergo systemic therapy (pN+). The factors for locoregional control were studied within this group. In addition to the number of positive nodes, tumour-related factors such as vaso-invasive growth, size of the tumour (< 2 cm) and grade III tumours were predictors of a locoregional recurrence. Especially vaso-invasive growth has been confirmed in other studies [van Tienhoven 1999, Voogd 2001]. Jagsi (2005) looked at predictive factors of locoregional recurrence after mastectomy including ALND. Three of such factors in lymph node-negative patients appeared to give a locoregional recurrence percentage of 40% after 10 years. Other studies also confirmed the possible role of radiotherapy in N1-3. Ragaz published the 20-year results of the British Columbia trial in 2005. In this study, 318 premenopausal patients with an invasive breast cancer and positive node status were randomised over two groups: radiotherapy + chemotherapy (n=164) or chemotherapy only (n=154). After 20 year follow-up, the locoregional disease-free survival was 90% in the radiotherapy group and 74% in the control group. Subdivided according to node status, this was 91% and 79% for patients with 1-3 positive nodes and 84% and 59% for patients with four or more positive node (p=0.6). The SUPREMO trial is currently underway, which studies the value of chest wall irradiation in intermediate risk patients.


In some cases it is unclear, if there is an indication for local radiotherapy, if the regional node areas (axillary, parasternal, infra and supraclavicular regions) should also be irradiated [Recht, 2001]. In trials from which the EBCTCG (2005) overview derives its data, the node areas were often routinely irradiated. However, the chance of manifestation of a recurrence in the node areas is small, so that radiotherapy of the regional node areas may be overtreated for many patients [Recht, 2001].

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

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