Is screening by mammography a viable way for determining breast cancer?
Screening by mammography is indicated for women in the general population between the ages of 50 and 75, with a screening interval of 2 years.
Because of the elevated risk of interval carcinoma in women between ages 30 and 50, a screening interval of one year is recommended for this group.
Because of the elevated risk of radiation-induced tumours in young women, specifically gene mutation carriers, a starting age of 30 is advised for this group.
Breast cancer screening is not advised for women over age 75.
Screening of the general population by mammography starting at age 50 reduces mortality. There is a difference in mortality between women who do participate in screening and women who do not.
One third of the proven reduction in mortality might be attributable to adjuvant systemic therapy.
Level 1: A1 Schopper 2009, Paap 2010
For a woman between the ages of 50 and 75 who participates in the national breast screening programme, the lifetime risk of getting a lethal radiation-induced breast cancer is estimated at 1.6 per 100,000 women. The lifetime risk for a woman between 25 and 30 years of age is almost twice as high.
Level 1: A1 NHSBSP 2003, de Gelder 2010
Exposure to low-dose ionizing radiation elevates the risk of tumour induction 1.3 times in women with a BRCA1 or 2 gene mutation, compared to non-exposed women with a BRCA1 or 2 gene mutation.
Level 3: B Jansen-van der Weide 2010
Mammography is the only screening method with a proven cost-effective reduction in mortality, particularly in women between the ages of 50 and 75 [de Koning 2003, Otto 2003, Groenewoud 2007].
In a review of the results of long-term screening programs in 10 countries, a 16-36% reduction in mortality was found in women who were invited and a 24-48% reduction in mortality in women who had participated at least once in the screening. Correcting for selection bias, the trend in mortality reduction remained consistent. There are as yet no screening programs with a follow-up duration of 25 years or more, as would be required to make a definitive statement on the impact of screening.
Not all the reduction in mortality can be attributed to screening; one third of the reduction may be attributable to adjuvant systemic therapy [Schopper, 2009]. Evaluation of case control studies also show a consistent decrease in mortality from participation in mammography screening, with the difference between screened and non-screened women varying between 38% and 70%. The large variation seems to be due to differences in organisational structure and level of participation [Paap, 2010].
Both the US Preventive Task Force and the national breast screening programme recommend women between the ages of 50 and 74 [USPST, 2009] or women between 50 and 75 [RIVM, 2008] undergo screening by mammogram once every 2 years. Screening women under the age of 50 is advised only in individual high risk cases, and should be done annually. The number of interval cancers would otherwise be disproportionately high because of the higher rate at which some of the cancers grow in this group [Tabar, 1995]. The disadvantages of screening increase even more with age, due to various factors. There are indications that the sojourn time (the period during which the tumour is asymptomatic, but can be detected by testing) increases with age [Fracheboud, 2006]; apart from this, additional comorbidity plays a role. This means that the negative effects of screening become increasingly relevant in older women [Mandelblatt 2009]. The number of years of life gained also decreases relatively [Kerlikowske, 1999]. This is seen as support for the decision to stop screening women in the national breast screening programme when they reach the age of 75.
Digital mammography is used in the screening practice in the Netherlands. The mean tissue dose per mammogram is highly dependent on the thickness of the breast and is about 1.66 mGy for a standard exposure of 6 cm (mGy = milliGray = common unit for radiation exposure dose). The average dose per test is about 3 times 1.66 mGy. This number varies greatly per individual; the dose can be as high as 2.12 mGy per test in women who have very thick breasts and a lot of glandular tissue. The glandular doses are monitored continuously by the LRCB (National Expert and Training Centre for Breast Cancer Screening) [LRCB, 2008]. They are below the acceptable dose limits set by the EUREF (European Reference Organisation for Quality Assured Breast Screening and Diagnostic Services) (2006).
In comparison: each resident of the Netherlands absorbs approximately 2.5 mGy annually from natural background radiation coming from space and the earth [RIVM, 2003].
Risk estimation and risk figures
The chance of radiation-induced cancer is very small and cannot be calculated; it can only be estimated based on epidemiological risk models from retrospective studies. Such cancers cannot be distinguished from "ordinary" cancers, so it is very difficult to estimate the risk accurately. Furthermore, the latency period can be very long: up to 20 years. An analysis by Preston, combining data from eight cohorts, found a linear relationship between the extra risk of breast cancer and the radiation dose [Preston, 2002].
The lifetime risk of getting radiation-induced breast cancer depends on the age at which exposure began. It is very low in women aged 50 to 65: 1 per million per mGy dose. The lifetime risk for a woman between the age of 25 and 30 is almost twice as high (1.8) [NHSBSP, 2003; Berrington de Gonzalez, 2005].
A British screening study estimates the ratio of the number of detected cancers to the number of induced cancers at 170:1. This ratio worsens where there is more glandular tissue [NHSBSP, 2003]. A Dutch study on risk models assuming a dose of 1.3 mGy per exposure found the ratio between the number of detected and the number of induced lethal cancers to be 684:1 [de Gelder, 2011].
BEIR VII (2006) provides with a model for tumour induction resulting from ionizing radiation. In this model, the additional risk of tumours resulting from ionizing radiation increases quadratically with decreasing age. Therefore, the younger a woman is when exposed to ionizing radiation and the higher the dose, the greater the chance of tumour induction.
BRCA1 and BRCA2 genes contribute to DNA repair processes. Theoretically, mutation carriers will therefore be less able to repair any damage after their exposure to ionizing radiation. On this basis it must be assumed that the chance of a radiation-induced breast cancer in this population is greater than in non-carriers. To get a sense of these risks, a systematic search was done of the medical literature over the period 1989-2009, aimed at finding studies on exposure to low-dose radiation and risk of breast cancer in women who had a higher breast cancer risk due to a family history or gene mutation [Jansen-van der Weide, 2010]. This search found 7 studies [Andrieu, 2006; Bernstein, 2006; Goldfrank, 2006; John, 2007; Ma, 2008; Millikan, 2005; Narod, 2006]. Since none of the studies provided precise information on the radiation doses to which the patients were exposed, the cumulative dose was estimated.
The odds ratios from the various studies were pooled. Low-dose radiation exposure was found to increase the risk of breast cancer by 1.3 (95% CI 0.9-1.8) in the group of women with an increased risk of breast cancer. Exposure before the age of 20 gave a higher risk of radiation-induced breast cancer (OR 2.0; 95% CI 1.3-3.1), as did an average of more than 5 screenings (OR 1.8 95% CI 1.1-3.0). Exposure between the ages of 20 and 40 also gave a higher risk, albeit not significant (OR 1.3; 95% CI 0.96-1.7).
Radiation-induced cancers cannot be distinguished from breast cancers from other causes. The risk of their occurrence is very small, and they occur only after a latency period of at least 10-20 years. Nevertheless, extra caution is advised, since this is a matter of annual radiation exams in healthy women. The LRCB therefore provides continuous monitoring and quality control.
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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