Question

When should regional radiotherapy be executed?

Recommendation

Pre-operative

The SN procedure is indicated for patients with a T1-2N0 breast cancer for the purpose of lymph node staging.

 

The SN procedure may also be conducted safely if multifocality at a distance of <5 cm is determined prior to surgery.

 

Relative contraindications for the SN procedure (i.e. the SN procedure may be considered, but the value is limited):

  • ³ T3 and/or multicentricity determined prior to surgery
  • earlier (recent) axillary surgery

 

Absolute contraindications for the SN procedure (i.e. axillary node dissection level I and II is indicated):

  • Axillary node metastases determined by ultrasound and punction
  • If an SN procedure cannot be performed for other reasons

 

Postoperative

Additional treatment is not recommended for patients with isolated tumour cells in the SN (on the basis of low regional recurrence percentages).

 

Patients with micrometastases in the SN have a risk of approximately 20% of non-SN involvement. The risk of non-SN involvement is additionally dependent on the primary tumour characteristics. The chance of recurrence depends on the application of radiotherapy and adjuvant systemic therapy. The best strategy for axillary treatment per patient should therefore be discussed during multidisciplinary consultation:

  • irradiation of the breast only (implicitly including a large part of level 1 and 2 of the axilla) if adjuvant systemic therapy is also administered
  • axillary radiotherapy
  • ALND

 

In the case of limited macrometastases in 2 SN’s at the most, omitting an ALND in patients who will undergo a BCT and receive adjuvant systemic therapy may be considered.

 

With more extensive macrometastasis, treatment of the axilla (ALND or radiotherapy) is indicated.

Conclusions

 


 

Level 2

With a clinically negative axilla, a sentinel node procedure can be used to determine the axillary node status in breast cancer smaller than 5 cm with a reliability of at least 95%.

 

B          de Kanter 2006, Heuts 2007, Torrenga 2004, Kuijt 2007, Straver 2010

 

Level 1

The chance of metastases in the remaining axillary nodes with a positive SN is approximately 50% when macrometases has been demonstrated and approximately 20% if micrometastases have been demonstrated.

 

A1        Cserni 2004

 

Level 3

The chance of metastasis in non-SN nodes with isolated tumours cells in an SN reduces as the primary tumour decreases in size.

 

There is currently insufficient data to indicate when this chance is < 5%.

 

C          Barranger 2005, Bolster 2007, Calhoun 2005, Cserni 2007, den Bakker 2002, Gray 2004, Lambert 2007, Rahusen 2001, Turner 2000, van Deurzen 2007

 

Level 2

The chance of an axillary recurrence with a negative SN is less than 0.5%.

 

B          Naik 2004, van der Ploeg 2008

C          Blanchard 2003, Jeruss 2005, Rosing 2006, Smidt 2005, Krag 2010

 

Level 2

Performing an ALND after a positive SN has not been demonstrated to provide survival advantage.

 

B          Bilimoria 2009, Yi 2010, Giuliano 2010

 

Level 3

Patients with a tumour-positive SN who undergo BCT and receive adjuvant systemic therapy receive no benefit from an ALND in relation to the chance of an axillary recurrence.

 

B          Giuliano 2010

 

Level 2

Axillary recurrences are extremely rare, both after ALND and primary radiotherapy.

 

Most axillary recurrences appear to occur in the first three years after primary treatment.

 

B          Louis-Sylvestre 2004, Hoebers 2007

Literature summary

There is not much literature on the relationship between the number of positive nodes and the chance of a regional recurrence. In most studies, there is an indication for postoperative radiotherapy of the high axillary and periclavicular node chain if there are ≥ 4 positive nodes. Axillary recurrences are extremely rare after level I-II ALND. The number of axillary recurrences is also extremely low with positive nodes after surgery only. This has lead to less irradiation of the axilla. Given the periclavicular node area is the most common location for recurrence growth after the breast or chest wall, this node area is usually irradiated in high-risk patients (≥ 4 positive nodes, positive axillary top).

 

Medial and central tumours give a high chance of parasternal node metastases. It has also been demonstrated that medial and central tumours are associated with a poorer prognosis [Zucali, 1998; Gaffney, 2003].Parasternal recurrences are only found in extremely rare cases.The treatment of the parasternal node chain has been a point of discussion for a long time. A patient group also cannot be defined in subgroup analyses for which this treatment would be beneficial. Given the effect of radiotherapy on survival is visible after 15 years in EBCTCG data, a longer follow-up may in fact show a difference.

Considerations

Conducting the SN procedure in patients with a status after breast augmentation with the help of intramammary prosthesis appears possible and reliable [Gray, 2004]. Peri- and intratumoural injections have been used in the Netherlands since the introduction of SN biopsy [Estourgie, 2004]. These largely follow the physiological drainage of the breast and are especially important with tumours at a deeper location and if there is attention for extra-axillary SN’s [Estourgie, 2004]. If there is only interest in the axillary lymph nodes, superficial injection techniques are a good alternative [Veronesi, 2006; Rutgers, 2004; Borgstein, 2000; Rodier, 2007]. If the radiocolloid is injected intra or peritumoural, parasternal drainage is found in almost 20% of cases using scintigraphy [van Rijk, 2006]. In old series in which surgery was expanded with a parasternal lymph node dissection, metastasis was exclusively found in these nodes in almost 10% of patients, especially in medial located tumours larger than 2 cm [Veronesi, 1983]. No univocal advice is given in literature for routine biopsy of a parasternal SN [Rutgers, 2004; Fabry, 2004; van der Ent, 2001; Lyman, 2005; Wouters, 2007]. In individual cases it can be decided to perform a biopsy of these sentinel lymph nodes. If metastases are detected, this implies a poor prognosis and parasternal radiotherapy and administering adjuvant systemic therapy is recommended.

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.