Question

How is DCIS treated?

Recommendation

An SN procedure should be considered in the case of:

  • patients with the preoperative diagnosis DCIS, for whom a mastectomy is indicated in relation to size
  • patients with a small DCIS who are eligible for BCT, in which there are risk factors for an invasive component:
    • younger than 55 years
    • solid component on the mammogram
    • suspicion on the basis of histological biopsies
    • moderate or poorly differentiated DCIS in biopsies

 

The treatment of DCIS is mastectomy or BCT, consisting of microscopic complete tumour excision and radiotherapy, in which a boost may be considered, particularly for younger patients.

 

Contraindications for BCT:

  • Multicentricity (the presence of DCIS in multiple quadrants of the breast)
  • Residual disease: mammographic evidence or tumour-positive resection margin

 

Axillary staging is not indicated with pure DCIS in the excision sample.

 

If postoperative invasive foci are encountered that are larger than 5 mm, lymphogenous staging is recommended.

 

Adjuvant (hormonal) treatment after breast-conserving treatment (R0 resection and radiotherapy) is not recommended.

 

The same treatment recommendations apply to M. Paget of the nipple with underlying DCIS as with DCIS.

Conclusions

 

Level 1

The breast cancer-related death of patients with DCIS is relatively low (a maximum of 4.1% in 10 years). This is independent of the primary treatment: mastectomy versus breast-conserving.

 

A1        Bijker 2006, Cuzick 2011, EBCTCG 2010, Fisher 1993, Fisher 1998

 


 

Level 3

A tumour-positive resection margin is the most important predictive factor for local recurrence with BCT of DCIS.

 

C          Bijker 2001, Silverstein 1993, Silverstein 1998

 

Level 1

The addition of radiotherapy after a local excision of DCIS results in a significantly lower chance of a local recurrence.

 

A1        Bijker 2006, Fisher 1998,EBCTCG 2010, Emdin 2006, UKCCCR 2003

 


 

Level 3

The administration of a higher dose (boost), particularly in younger patients, appears to reduce the recurrence rate.

 

C          Omlin 2006

 

Level 1

Adjuvant therapy with tamoxifen in the breast-conserving treatment of DCIS, removed with tumour-free resection margins, leads to a limited improvement in local tumour control and not to a survival advantage.

 

A2        EBCTCG 2010, Fisher 1999, UKCCCR 2003, Wapnir 2011

Literature summary

Surgical treatment

Treatment of DCIS requires multidisciplinary collaboration. A decision can be made within multidisciplinary consultation if BCT or a mastectomy should be recommended, depending on whether complete excision with good cosmetic results is possible [McCormick, 1991].

In addition, the following conditions are important for optimal treatment result of breast-conserving treatment of DCIS:

  • a unifocal laesion
  • evaluable mammogram
  • the size of the laesion in relation to the size of the breast is such that a complete and cosmetically acceptable resection of the DCIS area is anticipated. This is often not possible with laesions > 4 cm. In the case of larger laesions and the wish for breast-conserving treatment, the possibility of oncoplastic techniques should be considered and discussed with the patient.

 

Removal of the entire breast (mastectomy) and breast-conserving treatment (BCT) are associated with an almost 100% chance of curation [Westenberg, 2003; Bijker, 2006; Wapnir, 2011]. Given the apparent paradox that invasive breast cancer can be treated with BCT in the majority of cases, while the pre-stage (DICS) would require removal of the entire breast, much research has been conducted on the possibilities of breast-conserving treatment.

The results of the SweDCIS, NSABP B17, EORTC 10853 and UK/ANZ studies show a high percentage of laesions detected by mammogram (40-70%). The breast cancer-related death of patients with DCIS is relatively limited and varies in studies from 1% to a maximum of 4.1% in 10 years in the EBCTCG review. Death is independent of primary treatment [Bijker, 2006; Cuzic, 2011; EBCTCG, 2010; Fisher, 1993; Fisher, 1998; Viani, 2007; Wapnir, 2011].

During BCT for DCIS, the aim must be tumour-free resection margins. With DCIS, the chance of irradicality after the diagnosis is known is approximately 30%, this is due to the fact that the tumour is often non-palpable and there is an inherent discrepancy between the mammographic and pathological dimension. If the resection margins are not tumour-free following re-excision, a re-excision or mastectomy is recommended.

 

Radiotherapy after excision of DCIS

In the meantime, 4 large randomised studies have been performed with long-term follow-up in which the role of (not) administering radiotherapy after excision of DCIS has been researched [Fisher, 1998;Emdin, 2006; Bijker, 2006,Cuzick 2011]. In all these trials together, postoperative breast irradiation halves the chance of ipsilateral recurrence, but does not improve the disease-free and total survival [EBCTCG, 2010]. Half of recurrences found in trials are again DCIS, and the other half are invasive carcinomas. The results of all DCIS trials show the same picture [EBCTCG, 2010].

No (large) subgroups can be identified from the randomised studies in which radiotherapy could have been safely omitted [Bijker, 2001; Mokbel, 2006; Viani, 2007]. Ample excision margins in combination with very extensive excision margin analysis also does not make radiotherapy unecessary per se, certainly not with grade III tumours [Hughes, 2009]. The predictive factors for locoregional recurrence after BCT for DCIS in the EORTC trial [Bijker 2001] are:

  • microscopic, small tumour-free margins
  • grading (grade II, III)
  • clinical symptoms on presentation
  • no radiotherapy (50 Gy)
  • no clinging micropapillary type
  • age £ 40 years

Others also found the margin surrounding the excised tumour tissue to be the most important predictive factor [Dunne, 2009].

 

The optimal radiotherapy dose in BCT of DCIS is not known and is currently being studied in a randomised, international trial. The locoregional recurrence rate after radiotherapy of approximately 10% after 5 years is quite high. The current locoregional recurrence rate for BCT of invasive carcinoma, in which a boost is generally administered to the tumour bed is < 5% after 5 years. The recurrence usually develops in the area of the original laesion. Administering a boost after BCT of DCIS could therefore also be worthwhile. Several authors report administration of a boost on the tumour bed [McCormick, 1991; Schwartz, 2000; Silverstein, 1999].

In a retrospective study of the Rare Cancer Network, it was concluded that the administration of a higher dose (boost) reduced the chance of a recurrence in younger patients (< 45 years; follow-up 72 months) [Omlin, 2006].It appears from retrospective and prospective studies that radiotherapy may also be effective in tumour-containing surgical margins. In the EBCTCG meta-analysis, the rate of ipsilateral recurrence in patients with an incomplete excision was also high after radiotherapy (24.2% after 10 years) [EBCTCG, 2010]. After a non-radical mastectomy, radiotherapy of the chest wall is indicated (50 Gy / 2 Gy fraction or equivalent), also with a boost, depending on the estimated amount of residual tumour.

 

Adjuvant hormonal therapy after excision of DCIS

In the NSABP B-24 and UKCCCR study (2003), it is reported that tamoxifen (administered after conserving treatment) reduces the chance of recurring DCIS [Fisher, 1999].Based on the point of departure that conserving treatment of DCIS is only indicated in tumour-negative resection margins, it is concluded that the advantage reported in the NSABP B-24 study is deemed too limited to be clinically relevant [Wapnir, 2011]. It must also be concluded on the basis of the results of the English study that there is little evidence for the use of tamoxifen in conserving treatment of DCIS after an R0 resection.

Considerations

It should be made clear to the patient with DCIS that it concerns a pre-stage of breast cancer, in which it is not yet invasive and not yet metastatic. The chance of curation is high but a complete excision of the abnormality is important. This is achieved with a great degree of certainty by mastectomy, while BCT is possible if the abnormality can be removed with free excision margins. It must also be explained that regular check-ups with mammography are indicated.

 

The same considerations apply to M. Paget of the nipple as with DCIS [Bijker, 2001; Fisher, 1993-2000].

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.