When are margins considered tumour-free?
The margins are tumour-free if, in an adequately processed sample, tumour does not reach into any of the surgical margins.
There is focal metastasis in a surgical margin if the tumour (invasive carcinoma and/or DCIS) reaches into a limited area (≤ 4 mm) in an inked margin.
The side with the smallest margin, or the irradicality must be specified.
Excision margin analysis with breast-conserving therapy; indications for additional surgery
Most recurrences after breast-conserving treatment develop as a result of metastasis of the residual tumour. Metastasis in surgical margins is one of the most important predictors of residual tumour [Bijker, 2006; Dunne, 2009; Scopa, 2006]. The evaluation of radicality therefore has important clinical-therapeutic consequences. The choices between breast-conserving therapy or mastectomy, for re-excision and/or adjusting the radiotherapy dose and field size, depends on the microscopic evaluation of the radicality. In doing so, it needs to be gauged if residual tumour has remained in the breast, or if it concerns an invasive carcinoma or DCIS, and/or if it involves a small or substantial amount. The distribution and density of ducts with DCIS play a role in estimating if and how much DCIS will have remained in the patient. Irradicality per se does not mean much; this should be:
- qualified: evaluate metastasis of both the invasive carcinoma and DCIS; report for both the minimum tumour-free margin in mm in various directions
- quantified: evaluate the extent of the irradicality in mm
- also localised, where possible: specify the side with the narrowest margin, or the irradicality
Naturally, surgical margin analysis is only reliable if the excision sample is submitted in toto, with markings, and adequately processed using inking of the surgical margins and samples are removed in a focused manner.
A re-excision or a mastectomy is only indicated if it is estimated on the basis of microscopic findings in the segment excision that a substantial residual tumour may have remained behind, that this will lead to an increased chance of recurrence, and that renewed surgery will reduce this chance. This is the case with:
- invasive carcinoma (or a DCIS component) that reaches more than focal into the surgical margin
- DCIS reaching into the surgical margin
- an – unsuspected – growth pattern with satellites, in which the microscopic tumour metastasis exceeds the estimated size during macroscopy and clinical imaging (especially with ILC and strongly diffuse growing IDC).
The margins are tumour-free if, in an adequately processed sample, tumour does not reach into any of the surgical margins. Unclear terms such as close to or almost at should be avoided. The chance of recurrence is only increased if there is evident metastasis in surgical margins.
There is focal metastasis in a surgical margin if the tumour (invasive carcinoma and/or DCIS) reaches into a limited area (≤ 4 mm) in an inked margin. This usually concerns one or more of the radiary extensions of a star-shaped carcinoma. In principle, this is not a requirement for renewed surgery. Local control can be achieved by adjusting radiotherapy fields and dosis.
If there is more than focal metastasis in a surgical margin, the tumour reaches into a larger area or multiple small areas in the inked resection margin. In most cases, it concerns metastatic DCIS. Metastasis of LCIS in surgical margins is not an indication for renewed surgery, given this is generally a diffuse abnormality in which radicality is difficult due to limited excision, and the risk of recurrence with LCIS is limited. An exception to this is the polymorphic or comedo-type LCIS, which has a higher chance of local recurrence and is an indication for renewed excision.
Because it is difficult to define the terms focal and more than focal in an exact manner, the following diagrams have been provided for clarification: Table
To reduce the risk of an invasive recurrence to an acceptable minimum, complete excision with a microscopically tumour-free margin is required during breast-conserving treatment of DCIS. The chance of recurrence depends on the width of the free margin [Silverstein, 1999].
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 NederlandAuthorized by:
- Nederlandse Internisten Vereniging
- Nederlandse Vereniging voor Heelkunde
- Nederlandse Vereniging voor Psychiatrie
- Nederlandse Vereniging voor Radiologie
- Nederlandse Vereniging voor Radiotherapie en Oncologie
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).
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.
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
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.
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
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.
Searches are available upon request. Please contact the Richtlijnendatabase.
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