Conclusions

 

Level 1

There is no difference in survival, disease-free survival or locoregional control between   surgery or radiotherapy of the axillary and periclavicular lymph nodes with an operable breast cancer with clinical tumour-negative axilla.

 

A2        Fisher 2001, Louis-Sylvestre 2004

 

Level 3

There does not appear to be a difference in survival, disease-free survival or locoregional control between surgery or radiotherapy of the axillary lymph nodes with an operable breast cancer with a clinical tumour-positive axilla.

 

A2        Fischer 2001

 

Level 3

The chance of lymphoedema and other late morbidity is higher after ALND than after axillary   radiotherapy.

 

A2        Deutsch 2008

Literature summary

The different studies show that with the necessary experience, an SN procedure can be performed in more than 95% of patients and the procedure is reliable in predicting the presence or absence of axillary node metastases in 95% of cases (distribution 84-100%) [Sandrucci, 1999; Konstantiniuk, 2007; Straver, 2010]. For T1 tumours, phase III studies with sufficient follow-up have demonstrated that the SN procedure is a safe alternative to the ALND, if the SN is tumour-negative [Veronesi, 2006; Krag, 2010]. This is confirmed in various non-randomised studies in the Netherlands in which T2 tumours were also included (1,467 patients, median follow-up 30-65 months) [de Kanter, 2006; Heuts, 2007; Torrenga, 2004; Kuijt, 2007]. The best results are obtained with use of the combination of preoperative lymphoscintigraphy with radiocolloid, and peroperative injection with Patent Blue. The SN can then be found with the aid of a gamma probe and guided by blue-coloured afferent lymph vessels.

 

The SN procedure is indicated for patients with a T1-2N0 breast cancer. Please refer to section 3.1.1 for the SN procedure in DCIS, see Chapter 7 for the SN procedure in neoadjuvant systemic therapy and Chapter 11 for the SN procedure during pregnancy. In contrast to ALND, the SN procedure leads to substantially less functional impairments of the musculoskeletal system [Cairns, 1999; Chetty, 2000; Veronesi, 2003; Fleissig, 2006; Ashikaga, 2010].

 

Multifocal/multicentric tumours

The dilemma here is formed by uncertainty in relation to lymph drainage from the tumour. Some studies argue that each tumour has its own lymph drainage pattern, so that determination of the injection location for the radioactive substance is difficult in these patients [Estourgie, 2004] with the result that the radioactive substance does not indicate the actual drainage; the sentinel lymph nodes may be missed and the percentage of false negatives increases [Ozmen, 2002; Tousimis, 2003; Veronesi, 1999]. For this reason, it is argued that a cautious approach should be taken when performing an SN procedure in the case of multicentricity [Schule, 2007].

Other researchers argue that the lymph drainage pattern of the entire breast is uniform and the radioactive substance can be injected at many locations in the breast and that multifocality/multicentricity is not a contraindication for performing an SN procedure [Knauer, 2006].

A recent review concludes that the value of an SN procedure with large and multifocal/multicentric tumours is uncertain, especially due to the lack of randomised studies in these groups and due to the heterogenous results of non-randomised studies. On the basis of this review, it cannot be concluded in these cases that the SN procedure is automatically contraindicated. One should realise however, that there is an already greater a priori chance of lymph node metastasis with multicentricity and multifocality, as is the case with large tumours [Spillane, 2011].

 

Absolute contraindications for the SN procedure:

  • axillary node metastasis demonstrated by punction

 

Relative contraindications for the SN procedure:

  • ³ T3 and/or multicentric: Experience with the SN procedure in tumours greater than 5 cm, or multicentricity over a distance of > 5 cm is small and the benefit achieved is limited due to the large chance of axillary node metastases [Lyman, 2005; Spillane, 2011]
  • previous (recent) axillary surgery

 

Radiotherapy of the axillary region as alternative for ALND in positive SN

In the 1980’s, the NSABP trial B04 randomised 1,097 operable patients with a clinically negative axillary between mastectomy with axillary node dissection, mastectomy with locoregional radiotherapy and mastectomy without axillary treatment [Fisher, 1985; Fisher, 2001]. The 25-year follow-up data from this trial showed a better locoregional control in the node negative group was provided by mastectomy with locoregional irradiation (5%) than mastectomy with ALND (9%) or mastectomy without axillary treatment (13%) (difference between the 3 curves: p=0.002), and no difference in metastasis-free survival or total survival. In the same trial, 586 patients with clinically positive axillary nodes were randomised between mastectomy with ALND or mastectomy with locoregional radiotherapy. In this node positive group, there was no difference between axillary surgery or radiotherapy in locoregional control, metastasis-free survival or survival [Fisher, 1985; Fisher, 2001]. Deutsch (2008) studied the long-term morbidity of axillary treatment in the NSABP B04 trial. The percentage of patients with lymphoedema after mastectomy with ALND was 58%, after mastectomy only 39% and after mastectomy plus radiotherapy 38%. The morbidity of combined treatment (ALND and radiotherapy) is even higher than that of ALND only [Larson, 1986; Ryttov, 1988]. The 15-year results of another randomised comparative study with 658 patients with an N0M0 breast cancer (smaller than 3 cm) were published in 2004 [Louis-Sylvestre, 2004]. In this study, one group received ALND after surgery and the other group axillary, periclavicular and parasternal radiotherapy after surgery. Both groups received radiotherapy of the breast, in which part of the axillary is implicitly irradiated along with the rest. The ten-year disease-free survival in both groups was 72% (15 years: 64.3 vs 65.5). After 15 years, isolated axillary recurrences were found in 1% of cases in the ALND group and in 3% in the radiotherapy group (p=0.04). After a 15-year follow-up, there was no significant difference between the two groups in the occurrence of locoregional recurrences. Twenty-one percent of patients in the ALND group had lymph node metastases on surgery. The proportion in the radiotherapy group would have been comparable. In the AMAROS study, 26% of patients undergoing an ALND after a positive SN had additional positive nodes in the ALND sample [Straver, 2010]. Extrapolating this data, it appears that irradiation of the axilla is a good alternative for the treatment of the axilla in the case of a positive SN. Not only the axilla but also the periclavicular region was irradiated in the AMAROS study. This study has recently been closed and the results are awaited.

 

Axillary lymph node dissection (ALND)

Axillary node dissection is generally reserved for treatment of the axilla when lymph node metastasis has been demonstrated, such as a positive sentinel lymph node or a tumour-positive picture based on punction. ALND gives substantial morbidity, in which pain complaints, dysesthesia, functional impairments of the shoulder joint and lymphoedema of the arm are the most serious. However, a complete ALND gives a recurrence percentage of less than 3% [van der Ploeg, 2010].

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.