3. General – Breast Cancer
3.1 Patient information and education
Thanks to the utilization of new information technologies such as the Internet and the increasing need on the part of patients for information and involvement in decision-making about the treatment of their disease, the provision of appropriate information to patients plays a more important role than ever before. Numerous studies have confirmed the importance of this issue for the doctor-patient relationship, the course of the disease and for achieving the therapeutic aim [1], [2], [3].Non-prescriptive patient information combined with shared decision-making constitutes the basis for action by doctors. Two ethical principles are at work in this interaction: the patient’s self-determination (autonomy) and the physician’s duty of care [4]. The patient’s autonomy takes priority in this context. A decision made by a patient is always voluntary and binding for action taken by doctors. Patients can make decisions for or against diagnostic and therapeutic measures or can decide in favor of “not wanting to know”. Any existing information deficits are to be remedied by the physician so that the patient can make informed decisions (informed consent). The personal discussion between the patient and the doctor takes on special importance as the basis for an understanding based on mutual trust and respect. In this context, increased emphasis is placed on shared decision-making, i.e. enabling the patient to participate in decisions. Shared decision-making is characterized by a consultation process that follows certain rules and an intensive exchange of information between doctor and patient, and culminates in the woman making a decision both she and her doctor support as regards the performance of medical procedures [4], [5], [6].
The precondition for this is the patient-centered consultation. The patient education provided by the doctor should be comprehensive, truthful and complete as regards the type of the measure, its purpose, benefits and risks and should most importantly be plainly worded and understandable (mentioning frequencies instead of relative percentages) [7], [8] (Patientenrechtegesetz, „Gute Praxis Gesundheitsinformation“ http://www.leitlinie-gesundheitsinformation.de/ und die Leitlinie evidenzbasierte Gesundheitsinformation http://www.ebm-netzwerk.de/pdf/publikationen/gpgi2.pdf; Raodmap des Nationalen Krebsplans). (German Law on Patients’ Rights, “Good Health Information Practice” http://www.leitlinie-gesundheitsinformation.de/ http://www.leitlinie-gesundheitsinformation.de/ and the Guideline Evidence-Based Health Information http://www.ebm-netzwerk.de/pdf/publikationen/gpgi2.pdf; Roadmap of the German National Cancer Program (Roadmap des Nationalen Krebsplans]). The consultation should be conducted in a manner that takes account of the individual patient’s somatic, psychological and social situation, gender, age and any comorbidities. The doctor should directly address the patient’s anxieties and worries, any specific problems, and particularly her need for information and her expectations and preferences regarding the treatment [9], [10], [11], [12], [13]. If the patient wishes, she should be allowed to have a person of her choice (e.g. partner, family member, patient advocate) with her at this or future consultations. The information provided by the doctor should include information about the disease, results of examinations and tests, the treatment course to date, diagnostic and therapeutic options including expected side effects, as well as estimations of the respective prognoses and the influence on the patient’s life planning [14], [15], [16].
If the patient wishes, she should be allowed to have a person of her choice (e.g. partner, family member, patient advocate) with her at this or future consultations.
- Consensus
- Strong consensus
Patient information is an interdisciplinary task of all professional groups involved in oncological care. Although the doctor is primarily responsible for the information of the patient, she should be supported by other professional groups such as caregivers or psycho-oncologists for specific topics.
The doctor is primarily responsible for informing the patient about the medical aspects, but she should be supported by other professional groups such as caregivers or psycho-oncologists for specific topics.
- Consensus
- Strong consensus
Hintergrund 3.2
The Dartmouth-Hitchcock Medical Center in New Hampshire, USA is an example of how patient education can be effective as an interdisciplinary task. Since 1999, female and male patients are offered a decision coaching at the Center for Shared Decision Making to identify individual preferences and to prepare for the consultation with their doctor. During this process, decision-making aids are provided to the patients. The aim of this process is to facilitate shared decision-making and informed decisions. The role of the decision coaches is taken on mainly by caregivers (Dartmouth-Hitchcock Medical Center, 2016, [17]).
In Germany, relevant training curricula for qualified decision coaches have already been developed in the field of breast cancer [18] and multiple sclerosis [19]. These curricula should enable the caregivers to perform decision coaching including evidence-based decision-making aids.
Provision of printed material and access to such material are useful additional supportive measures to help the patient come to a decision [20], [O'connor, Annette M et al. 1999]. Such decision aids include qualified, competent, comprehensibly produced and quality-assured informational materials [20], [22].
Evidence-based health information materials (Evidenzbasierte Gesundheitsinformationen, EBGI) are intended to improve informed decision-making. Evidence-based health information materials should therefore be based on defined quality criteria. If available, they should be made available to the patient.
- Consensus
- Consent
3.1.1 Informing the patient about diagnosis
As soon as the histopathological diagnosis of breast cancer has been confirmed, the attending physician should inform the patient of her diagnosis by treating in line with the previously described criteria. It is up to the patient to decide whether her partner, a family member or a representative of a self-help group should be involved in the consultation(s). The consultation should take place in an appropriate setting and the information presented in a manner that is comprehensible to the patient and appropriate to her level of understanding[7], [8]. The doctor must inform the patient truthfully and without underplaying the gravity of the situation, but also without depriving her of the hope of recovery or relief. When presenting information, the doctor should make sure that his or her explanation follows the course of therapy.
When conveying information to the patient, doctors should observe the following basic principles of patient-centered communication, allowing the patient to share in the decision-making process:
- Display empathy and listen actively
- Address difficult topics directly and with empathy
- Whenever possible, avoid medical terminology, and if medical terms cannot be avoided, they should be explained
- Employ strategies that improve understanding (e.g. repeating, summarizing all salient points, using graphics etc.)
- Encourage the patient to ask questions.
- Allow and encourage the expression of feelings. Offer further assistance (see psycho-oncology)
3.1.2 Educating the patient about treatment
The physician informing the patient should present the rationale behind the recommendations for a special form of treatment, especially if a case-related consensus-based recommendation for treatment has been made at a multidisciplinary conference, and explain the principles of the treatment and the associated benefits and risks.
There is evidence that a repeated documentation of the patient’s wishes (decision preferences) during the treatment process is necessary to appropriately involve the patient in the decision-making process [30].
Alternative forms of treatment which can be offered to the patient within the framework of clinical trials should also be explained. The impact of the proposed treatment on the patient’s lifestyle and quality of life should be discussed.
With regard to the pharmacological therapies and regimens mentioned in the Guideline that are used outside the scope of their approved label, the patient must be informed about the “off-label-use”.
Especially in premenopausal women, the influence of treatment on fertility and aspects of contraception should be addressed. Questions relating to the treatment of therapy-related ovarian insufficiency, its symptoms and the therapeutic options should also be discussed. The women should also be informed about the possibility of fertility-conserving measures and, if needed, be referred to the appropriate experts for advice [31].
Given the importance of tumor-associated fatigue caused by adjuvant therapy and based on the evidence for preventive strategies such as physical activity and educational measures, the patients should be informed as early as possible about prevention options [32].
The patient should also be informed about measures for preventing lymphedema, about the necessity of oncological follow-up-care, about rehabilitation (see below), and about social, financial and psycho-oncological support [29] informiert werden. Für If necessary, the patient should be advised to obtain further professional advice on the topics mentioned above (rehabilitation, social counseling and psycho-oncology), and the necessary arrangements made.
Any treatment requires the patient’s cooperation. Aspects which are the patient’s own responsibility should be discussed.
During the consultation to inform the patient about treatment, the following issues should be addressed and information on the benefits and harms communicated:
- Surgical therapy: Breast-conserving therapy options with mandatory radiotherapy as equivalent to mastectomy with different variants of primary and secondary reconstruction or the provision of an external prosthesis
- Systemic therapy: Principles and desired treatment targets of (neo-)adjuvant or palliative therapy, therapy duration and mode of administration, its side effects and possible late sequelae, and the treatment options for side effects
- Radiotherapy: Principles and desired treatment targets, duration and follow-up surveillance, possible acute and late sequelae, treatment options for side effects
- Participation in clinical trials, principles behind the treatment and treatment targets, duration and mode of administration of the therapy, effects and side-effects known to date, special features (e.g. monitoring, additional measures, cooperation, data storage and processing)
- Other: Options for prevention and treatment of therapy-related side effects and sequelae (e.g. fatigue, nausea, osteoporosis, lymphedema, etc.), necessity for follow-up, possibilities for rehabilitation and psycho-oncological support as well as services offered by self-help groups, aspects that are the responsibility of the patient and cooperation (e.g. reporting symptoms and problems, treatment compliance).
- Consensus
- Strong consensus
Hintergrund 3.5
The physician must take the patient's somatic, psychological and social situation, age and any comorbidities she may have into account during the consultation. The patient’s anxieties, worries, resilience, need for information, expectations regarding treatment and preferences should be documented by the doctor at diagnosis, at the beginning of and during therapy, after completion of therapy, in the event of recurrence as well as in the event of disease progression [9], [10], [11], [13], [28]. This also includes informing patients about “normal and unremarkable” test results and the course of treatment in order to provide reassurance, while giving prognostic information to facilitate them in planning their future lives [14], [15], [16].
Breast cancer is not an emergency. The patient must always be allowed sufficient time for decision-making. She can reject a particular procedure or treatment or withdraw previously granted consent to participate in a therapeutic trial or clinical study. She has the right to review the clinical documentation at any time and to receive copies of her medical records, e.g. doctor’s letters. In principle, patients have the right to choose their doctor and hospital freely, to change doctors and/or hospitals and to obtain a second opinion
[33].
Patients should be supported in their desire for further information and for involvement and should be given direct and practical assistance [20], [O'connor, Annette M et al. 1999], [34]. Such assistance includes tips on where to obtain written information (in particular patient guidelines and decision-making aids), addresses of self-help groups, help lines and websites. Each patient should be urged to keep a file of her own medical records.
The desire to obtain information and to share in medical decision-making varies greatly from patient to patient and can change over the course of time [35], [36], [37]. Therefore the patient’s desire for and the extent of information must be documented during the entire diagnostic, therapeutic and chain of care to involve the patient in the medical decisions to be made according to her needs.
Informational and educational needs of long-term survivors should be explored and appropriate support services as well as health-promoting measures communicated when sequelae such as neurocognitive impairment, fatigue, anxiety, depression, polyneuropathy, overweight etc. are present.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 1b
- Consensus
- Strong consensus
- References
- [31]
Women and men with breast cancer are to be reassured with respect to their right to self-determination and supported by means of practical assistance.
It is at the patient’s discretion whether representatives of self-help groups should participate in medical consultations and informational sessions.
The patient should be informed about ways to contact self-help organizations. Informational material should be made available by the service providers.
- Consensus
- Strong consensus
Hintergrund 3.6 und 3.7
In Germany, self-help is considered the “fourth pillar” of the health care system. In 2000, self-help funding was declared binding under Section 20 (4) Book V of the German Social Code (Sozialgesetzbuch V, SGB V) [38].
Self-help groups have been very active for many decades especially in the field of breast cancer for those affected and their family members. Cancer self-help provides established supplementary and independent services, as partners in the spectrum of care. Cancer self-help organizations provide information and counseling on diagnostic, therapeutic and rehabilitative options from the perspective of those affected. The common ground was and still is the original desire to exchange personal experiences and knowledge and to encourage and mutually reassure each other. By offering empathic and pragmatic exchanges of experience, cancer self-help services can be very meaningful, especially, but not exclusively in those sectors where the disease has a significant impact on everyday life. This is why the involvement of self-help services in the healthcare system in general and their role as providers of information and assistance is of such inestimable value and so irreplaceable, especially to anyone seeking advice or affected by the disease.
Krebsselbsthilfeorganisationen bieten u. a. Informationen und Beratung über diagnostische, therapeutische und rehabilitative Möglichkeiten aus der Perspektive von Betroffenen an. Gemeinsam war und ist der ursprüngliche Wunsch, die persönlichen Erfahrungen und das erlebte Wissen miteinander auszutauschen, sich gegenseitig zu ermutigen und zu bestärken. Nicht nur, aber gerade in Bereichen, in denen die Krankheit erheblichen Einfluss auf das Alltagsleben nimmt, ist die Krebsselbsthilfe durch den empathischen und auch pragmatischen Erfahrungsaustausch von großer Bedeutung. Dies macht ihr Mitwirken im Gesundheitssystem generell und als Informations- und Hilfsangebot speziell für Ratsuchende und Betroffene so wertvoll und unersetzbar.
The services offered by cancer self-help groups are cross-sectoral and can be used free-of-charge whenever breast cancer is suspected, at diagnosis, during therapy and follow-up care as well. Members (and their relatives) are also offered psychosocial support and help "to help themselves" (empowerment strategies) as well as a forum sharing experiences and information aimed at sustainably improving quality of life [39]. Affected sufferers’ work for cancer self-help services is of a voluntary nature.
There is a wide range of assistance and support services offered by cancer self-help organizations. Besides local discussion groups, information is available via the various media. These include written and illustrated brochures, websites and forums that enable modern interaction by means of chats, blogs and interaction online and in real-time. State and federal cancer self-help organizations are increasingly assuming patient advocacy roles on social and healthcare policy committees.
It is recommended in the S3 Practice Guideline “Psycho-oncology" [29] to inform patients about cancer self-help services and to offer informational materials. An agreement on the cooperation between self-help and service providers should ideally be made in writing in the form of a contract of cooperation. There is a great cross-sectoral need for research of the structure and efficacy of self-help services.
Up-to-date contact details of self-help groups and other self-help providers are accessible on the website of the National Contact Point for Self-Help (Nationale Kontaktstelle für Selbsthilfe) (www.nakos.de) If and how they use the services of the offered by cancer self-help organizations is left to the discretion of each affected individual and their family members.
3.2 Early detection, mammographic screening
Breast cancer of the man is a rare disease. Asymptomatic men should not be recommended special imaging breast cancer screening measures. Diagnosis is carried out with mammography and ultrasound in case of clinical symptoms. Diagnostic clarification should be carried out according to the recommendations for women.
- Consensus
- Strong consensus
Hintergrund 3.8 und 3.9
Breast cancer occurs in both sexes. The morbidity and mortality risks, however, vary considerably. In Germany, men have a lifetime risk of 0.1% (absolute 1 out of 790) calculated across all age groups. The lifetime risk in women is 12.8% (absolute risk is 1 out of 8) [43]. No specific early detection measures are recommended for men. Please refer to Chapter 9 for detailed information about breast cancer in men. Next to the further improvement of treatment, the early detection of breast cancer in women (secondary prevention) is the most promising possibility for optimizing the diagnosis and treatment of breast cancer, for consequently reducing breast cancer mortality, and for improving the quality of life of women. The objective is to reduce the number of carcinomas detected at later stages (from UICC stage II) and hence effectively reduce breast cancer mortality. This is associated with the increased detection of carcinomas confined to the mammary gland (UICC stage I) [44], [45], [46], [47], [48], [49].
The improved prospects of a cure opened up by secondary prevention can be realized at early stages of the disease, when it is possible to employ less radical methods that place less stress on the patient, e.g. biopsy of sentinel lymph nodes (SLN) [50].
The examinations performed to achieve early breast cancer detection do not confer only benefits; they also pose risks. This fact deserves all the more attention since women who undergo examinations aimed at early detection are primarily healthy and constitute only 0.3% annually of new cases of the disease in the population (according to the prevalence round). Due to this relatively low number of newly diagnosed cases per year that add to a disease rate >12% in relation to life, the extent and burden of diagnostic investigations must be appropriate. False-positive findings must be taken into consideration as stressful components, while false-negative findings show the limits of the methods used [51], [52].
All effective early detection interventions lead to so-called overdiagnoses. These are actual breast cancers, diagnosed months to years in advance. If breast cancer would not have been detected in a woman without screening (because of slow growth or premature death of other causes) and would not have been fatal, this is referred to as overdiagnosis. This excessive detection rate also leads to additional treatments, called overtreatments, which (retrospectively) did not confer benefit on the woman. This has also to be taken into account, especially in the treatment of very early stages, e.g. DCIS (see Chapter 4.3. The precise impact of DCIS detection on the reduction of mortality is still being discussed [53], [54], [55], [56].
The early detection of breast cancer is an interdisciplinary task. There should be a quality-assured interdisciplinary combination of clinical examination, instrumental diagnostics, histological clarification and pathomorphological assessment.
- Consensus
- Strong consensus
The supply chain requires complex and quality-assured medical documentation in order to bring together the entire quality management.
- Consensus
- Strong consensus
A screening programme should be continuously evaluated with regard to relevant outcomes (e.g. incidence, mortality, morbidity and patient-related outcomes) and risks (e.g. false positive and false negative findings, overdiagnosis). For this purpose, the process data of the screening programme, the breast centres and the data of the population-based cancer registers of the Länder are to be used together after the comparison. Cancer registries should continuously provide the differentiated data for the respective federal state and the screening units, if possible before and from the start of the national screening programme in 2005. Patient lists of e.g. interval carcinomas, contralateral findings or local recurrences are part of the continuous evaluation. The independence of the evaluation should be ensured.
- Consensus
- Strong consensus
In order to ensure the best possible treatment, further therapy of breast cancer detected in screening should be carried out in certified breast centres. Continuous quality assurance is to be ensured by communication and data acquisition between the screening centre and the certified breast centre.
- Consensus
- Strong consensus
Background 3.10 to 3.13
In order to reduce mortality and benefits of early detection and therapy and to minimize the burden on healthy women, accurate monitoring, comprehensive evaluability and the highest possible quality assurance in early detection measures must be ensured [40], [57], [58].
As part of the quality assurance of mammography, independent double reporting is recommended. In screening mammograms, double reporting increases the sensitivity of carcinoma detection by 2.9 -13.7 % (median 7.8 %). The specificity can be reduced (up to 2.1 %) or increased (up to 2.8 %) [40], depending on the decision procedure after double findings. The use of computer-assisted detection systems cannot replace double findings [40], [59], [60], [61] due to the current study situation.
An individually supplementary recommendation of further early detection examinations can be useful, taking into account the individual risk-benefit ratio. In women with increased risk (usually increased familial risk, presence of histologically confirmed risk lesions, condition following malignancy of the breast or ovaries), supplementary methods or an additional examination at intervals may be considered.
Individually adapted screening tests can also be considered for women before the age of 50 and after the age of 70, depending on the individual risk. At an older age, in addition to the individual risk of breast cancer, the overall survival prognosis must be taken into account, since the risk of overdiagnosis increases significantly in the presence of competing risks, especially in older women.
Overall, it can be assumed that side effects such as overdiagnosis occur in other early detection examinations to at least a comparable extent as in quality assured screening, false positive findings to a far greater extent.
Therefore, these groups should be involved in a quality assurance programme for the implementation and evaluation of structural, process and outcome quality as well as in the diagnostic and care chain (anamnesis, risk counselling, information on health behaviour, clinical examination, instrumental diagnostics, interventional tissue removal techniques, surgical clarification and histopathological findings). In terms of age, risk and findings, management in the context of early detection of breast cancer should be based on the algorithm of the diagnostic chain (see Appendix 11.1) [40] [41], [62], [63], [64], [65].
3.2.1 Shared decision-making
Early detection examinations can lead to physical and psychological stress. This circumstance should be taken into account through careful education and an effective communication strategy.
- Consensus
- Strong consensus
In the context of breast cancer screening, information and education should not be limited to pre-formulated texts, but require a medical information interview that takes into account the preferences, needs, concerns and fears of the woman and allows for participatory decision-making. In mammography screening, information and clarification should be provided to the woman primarily in writing, with a supplementary reference to the possibility of a medical consultation in the invitation letter.
- Consensus
- Consent
Background 3.14 and 3.15
Informed self-determination and participation in medical decision-making processes is a particularly high priority for women interested in participating in screening. During the medical consultation, anamnesis, the individual risk constellation, fears and worries must be addressed and women must be supported in their decision-making processes in a participatory manner. In risk communication, absolute and relative figures and their reference periods should be included. Benefits and harms should be assessed and communicated in relation to the relevant periods. In particular, life-saving and overdiagnosis should be determined, estimated and communicated in relation to the life of the woman according to their definition [40], [66] see also Chapter 3.1: Patient information and education. In addition to the hoped-for effect, the side effects must be adequately explained according to their occurrence in any screening tests, even outside the screening programme.
For information purposes and as a decision-making aid for women, the patient information on the Oncology Guidelines Programme is available (http://www.leitlinien-programm.de) as well as the website http://www.mammo-programm.de, in accordance with the quality requirements "Good Practice Health Information" [67]. The decision support of the Joint Federal Committee of Physicians and Health Insurance Funds (GBA fact sheet updated 2017) is based on IQWIG's Rapid Review and can be accessed at http://www.mammo-programm.de The figures given there are very conservative estimates. Nevertheless, it is confirmed that mammography screening is the only imaging method with a proven reduction in breast cancer mortality and, if there is a desire for early detection, participation in the quality-assured screening programme is recommended.
3.2.2 Mammographic screening
For women between the ages of 50 and 69, participation in the National Mammography Screening Program should be recommended.
Women from the age of 70 should be offered participation in screening measures, taking into account their individual risk profile and health status and a life expectancy of more than 10 years.
The reduction in breast cancer mortality has also been demonstrated for women aged between 40 and 49 years and outweighs the risks resulting from radiation exposure. However, it is lower than in the age group of women between 50 and 69 years and results in relatively more false positive and false negative findings.
Therefore, the decision should be based on an individual risk analysis, a risk-benefit analysis and taking into account the preferences and objections of the woman.
The structural, process and result quality should be applied to the same extent to so-called curative mammography,
- Consensus
- Strong consensus
After a mammographic finding of categories 0, III, IV and V, further clarification should take place within one week in order to keep the psychological stress on the woman as low as possible.
- Consensus
- Strong consensus
Background 3.16 to 3.21
In Germany, mammography screening for women from the age of 50 until the end of the 70th year of life is part of the guideline of the Joint Federal Committee on the early detection of cancer (source: Guideline of the Joint Federal Committee on the early detection of cancer (Cancer Screening Guideline / KFE-RL) in the version of 18. June 2009 published in the Federal Gazette 2009, No. 148a entered into force on 3 October 2009 last amended on 21 April 2016, published in the Federal Gazette AT 08.07.2016 B2, entered into force on 1 January 2017 https://www.g-ba.de/informationen/richtlinien/17/).
For mammography screening, the reduction in mortality with regard to breast cancer can be regarded as assured for the group of invited versus uninvited women. The evaluations of randomized studies show a mortality reduction of 20% for all age groups from [45], [52], [68], [69], [70]. In preparing the present update of the S3 guideline recommendations, the recommendations of the American Cancer Society ACS (ACS) [41], the US Preventive Services Task Force [51], [65], [70] and the evaluation of cancer prevention and control measures by the International Agency for Research on Cancer (IARC) of WHO [42], [45], [68] have been taken into account.
The IARC assessment of the WHO will be considered in more detail below, as it is of great importance in the international context of drawing up national health measures. 29 experts from 16 countries were involved in the preparation of the comprehensive data analysis of the effects and side effects of IARC mammography screening. IARC confirms the results of the meta-analyses on the old RCTs. However, considering the considerable progress in diagnostics (mammographic technique, quality assurance of the screening chain) and therapy, the relevance of these studies, which are more than 20 years old, is questioned. Instead, IARC assesses well-controlled observational studies of modern screening programmes as better suited to assess the effectiveness of current mammography screening. Special emphasis has been placed on studies with sufficient follow-up to reduce the so-called length time bias, taking into account temporal and regional trends. Based on the available literature, approximately 20 incidence-based cohort studies and another approximately 20 case-control studies fulfilled these requirements.
The following statements were made:
For regular participants, a reduction in mortality compared to non-participants can be expected through mammography screening. It is currently assumed that in Europe up to 8 lives can be saved by screening women between 50 and 69 years of age (about 10 rounds) for every 1000 participants who are healthy today. Further data are needed to map the specific effect strength of the screening measure in the screening population.
A further reduction in mortality through continued screening up to and including the age of 74 is considered proven.
The data available for the age group between 40 and 49 years was still considered to be limited.
For none of the other imaging tests (tomosynthesis, sonography, MRI or other procedures) is there sufficient evidence for a reduction in breast cancer mortality. This applies to both complementary and substitutive use for mammography screening.
With regard to screening of BRCA1- or -2-positive women, IARC recognizes the significant increase in sensitivity in the context of intensified monitoring, but with significantly reduced specificity. For the proof of a mortality reduction the data situation was still insufficient.
Among the potential side effects, the IARC counts overdiagnosis and false positive findings in addition to the very low risk of radiation exposure.
The overdiagnosis rate was calculated only on the basis of studies that had sufficient follow-up and that sufficiently considered length time bias and other disturbing influences. (To understand: If follow-up is insufficient, early diagnoses are erroneously counted as overdiagnoses, which leads to an overestimation of the overdiagnosis rate and an underestimation of the mortality reduction). The rate of overdiagnosis after 25 years of follow-up is given as 6.5% (1%-10%) of breast cancer diagnoses. This means that out of 1000 women regularly screened over 20 years, 71 instead of 67 women learn of their actually existing breast cancer or DCIS. These 4 additionally diagnosed diseases would not have become known to women during their lifetime without screening.
In screening, false positive diagnoses are defined as findings on the basis of which a woman is again invited for additional examinations because of an ultimately benign finding. The additional examinations usually consist of imaging procedures, if necessary also histological clarifications (mostly punch or vacuum biopsies). Re-appointments for additional imaging in case of ultimately benign findings affect about 2% of the screened women per subsequent round in Europe. Histological clarifications (usually image-guided minimally invasive biopsies) with a benign result occur in up to 0.6% of screened women. Cumulated over 20 years of screening, this corresponds to a one-time order of about 20% of the participants in 20 years or biopsies in about 6% of the participants because of a finally benign finding.
Technological developments: 2D mammography and 3D mammography (digital breast tomosynthesis (DBT))
For 3D mammography (digital breast tomosynthesis (DBT)), there are very large numerical evaluations from the USA, although only retrospectively collected, as well as at least 3 prospective controlled studies from European screening programmes. The latter are based on systematic double examinations using digital full-field 2D mammography and 3D mammography. There are now 3 systematic reviews of the studies, [68], [72], [73].
The comparisons of all studies almost exclusively concern the comparison between 2D mammography and 2D + 3D mammography. However, an additional study on one type of device indicates that an "2D synthetic mammography" additionally calculated from 3D mammography should be comparable to primary 2D mammography and thus no double image (with double the radiation dose) should be necessary in the future [74]. For another type of device, wide-angle tomosynthesis, only 3D was compared with 2D (at least with regard to the first and second findings). For this device type, additional 2D mammography also did not appear necessary [75].
Data to date indicate a significant increase in detection rate for the combination of 2D + 3D mammography, which was present at all density levels, but appeared to be most pronounced at density levels ACR 2-3. This increase in the detection rate almost exclusively related to an increased detection of invasive carcinomas while maintaining the same detection at DCIS. With regard to the individual findings, 2D + 3D mammography showed an increase in specificity in most studies, but according to consensus a slight deterioration. In addition, a slight increase in the biopsy rate was observed with 3D-DBT, although the PPV remained the same. Summarizing these results, 2D + 3D mammography shows a significantly improved detection proven in prospective screening with comparable specificity and slightly increased radiation exposure.
First results show a slight reduction of the interval carcinoma rate. At present, no statements on overdiagnosis are possible. These would have to be taken into account in screening and especially in any application for early detection outside the screening program. There are still open questions regarding the comparability of the results of the device types, the quality assurance of findings and technology and logistical issues (compatibility; effects of a learning effect; fatigue in systematic reading) and require further studies. Nevertheless, due to the significant gain in sensitivity and the very good specificity, this method currently appears to be the most promising method for screening applications.
3.2.3 Measures for the early detection of breast cancer
As part of the statutory early cancer diagnosis, women should be offered an anamnesis and an explanation of possible risk factors.
- Consensus
- Consent
Through qualified information, women should be encouraged to become familiar with the normal changes in their own bodies. This includes the appearance and feel of the breasts in order to detect any deviations themselves.
- Consensus
- Strong consensus
Clinical breast examination, i.e. inspection, palpation of the breast and assessment of lymphatic drainage, should be offered to women aged 30 years and older as part of the statutory early detection examinations.
Clinical examination of the breast and axilla should not be recommended as the sole method for early detection of breast cancer.
- Consensus
- Strong consensus
3.2.3.1 Sonography
The systematic use of sonography cannot be recommended as the sole method for early detection of breast cancer.
- Consensus
- Strong consensus
Background 3.26
No studies are available on the sole use of sonography instead of mammography for the early detection of breast cancer. Sonography has not yet been recommended by the international committee for systematic screening [76], [77], [78].
In the context of complementary complementary diagnostics, the use of sonography can lead to an increase in sensitivity, especially in women with an increased risk of breast cancer,
Technological enhancements through the use of automated 3D-sonography (ABUS/AVUS) in comparison to medical 2D-sonography (HHUS) have not yet been able to identify any advantages in terms of sensitivity and specificity. Initial study data indicate that the use of automated ultrasound may be able to reduce examiner dependency. A lack of systematic quality assurance for diagnostics and screening, different device applications and availability as well as a heterogeneous study situation currently allow only limited recommendation of the method within the framework of studies [79], [80],[81], [82], [83], [84], [85], [86], [87], [88].
3.2.3.2 Complementary diagnostic imaging in high mammographic density for early detection
The evidence on the use of complementary imaging methods is limited. Outside of the high-risk situation, sonography currently appears to be the most suitable method to complement mammography. Sonography can increase the density dependent sensitivity, a reduction in mortality is not proven. In early detection it is associated with a higher rate of biopsies than the National Mammography Screening Programme.
Background 3.27 to 3.29
Increasing mammographic density is associated with a decrease in sensitivity and specificity and an increase in the risk of interval carcinoma. High mammographic density also represents an independent risk factor [89], [90], [95], which, however, is only low in relation to the risk of the normal population with a factor of approx. 1.3 [91], [96].
The data basis on which the density-related risk calculations are based has so far been based exclusively on visual density estimates using the previous density definition of classes ACR1-4 (corresponding to ACR-Lexicon, 4th ed. [D'Orsi, CJ et al. 2003]) or (semi-) quantitative density measurements. According to this previous definition, 4 density classes were defined according to the percentage of dense tissue in the mammogram (ACR1= density up to 25%, ACR2 = density of 25-50%; ACR3 = density of 50-75%; ACR4= density > 75%).
Overall, the reproducibility of the density categories is unsatisfactory (re-classification of 12.6-18.7% of mammograms) [73]. According to the updated version of the 2013 classification [98], the density is no longer given according to the percentage of density areas as ACR 1-4, but according to BIRADS density ad according to descriptive characteristics. However, objective criteria for a standardized density measurement are still missing. This limits the reliability of recommendations for the use of additional imaging for mammography screening as well as for mammography in early detection a [45], [73].
In principle, the use of additional imaging (sonography, KM-MRI, tomosynthesis) at high parenchyma density leads to the detection of additional (mostly invasive) carcinomas, but is associated with an increased false positive rate as well as increased control examination and biopsy rates. There is also a lack of long-term data on the effect on survival and overdiagnosis. When using complementary methods, data on the correlation between age and other influencing breast cancer risk factors [99] are missing.
On the basis of previous studies, medical sonography (HHUS, handheld US) performed and evaluated as a complement to mammography appears to show the best balance between benefit and risk, which is indicated by first evaluations from an Italian screening program [93].
Women should therefore be included in the decision on complementary imaging in cases of high mammographic density and negative 2D mammography and informed about the benefits and risks of such complementary imaging, taking into account the overall risk of disease.
3.2.4 Needs for research for the early detection of breast cancer
After discussion of the current data situation in the working groups as well as in the plenum of the S3 Guidelines Commission, the testing of the following topics is considered necessary:
- Optimisation of the screening programme with regard to age limits
- and the benefit/risk ratio regarding screening between 45-49 years and > 70 years
- Optimization of the screening interval, especially for younger women (
- Optimization of the investigation methodology for identified problem areas
- stratified addition of sonography (2D/3D)
- selective substitution/addition by 3D mammography (digital breast tomosynthesis (DBT))
- Optimised adaptation of therapy for prognostically favourable early breast carcinomas and pre-stages with the aim of reducing possible overtherapies without significant loss of efficancy
3.3 Women at increased risk of developing breast cancer
3.3.1 Familial breast cancer
About 30% of all women with a breast cancer in Germany have a family history of breast cancer and meet the inclusion criteria for genetic testing established and validated by the German Consortium for Familial Breast and Ovarian Cancer (see statement 3.14) [100]. These are based on a mutation detection rate of at least 10% [101].
Genetic testing should be offered if there is a familial or individual exposure that is associated with at least a 10 % probability of mutation detection.
This is the case when, in one line of the family
- at least 3 women have breast cancer
- at least 2 women suffer from breast cancer, 1 of which before the age of 51
- at least 1 woman has breast cancer and 1 woman has ovarian cancer
- at least 2 women have ovarian cancer
- at least 1 woman has breast and ovarian cancer
- at least 1 woman with 35 years or younger is suffering from breast cancer
- at least 1 woman aged 50 years or younger has bilateral breast cancer
- at least 1 man has breast cancer and 1 woman has breast or ovarian cancer
A reasonable period of reflection should be allowed before making the diagnosis.
- Recommendation grade
- B: Empfehlung für oder gegen eine Maßnahme - verwendete Ausdrucksweise = sollte/sollte nicht
- Level of evidence
- 2a
für Mutationswahrscheinlichkeit
5 - Consensus
- Consent
- References
- [102]
Background 3.30
In about 25% of these women a germline mutation can be detected in one of the known predisposing high-risk genes BRCA1 or BRCA2 [100]. Women with a BRCA1 or BRCA2 mutation fall ill about 20 years earlier than women without family risk and have a lifelong risk of developing breast cancer of on average 60%, of an average of 40% of a contralateral breast cancer and 16 - 55% of an ovarian cancer [103].
In unselected patients with a triple-negative breast carcinoma (TNBC) a mutation prevalence of BRCA1 mutations in 8.5% and of BRCA2 mutations in 2.7% could be detected [104]. However, the exact prevalence rates for gene mutations in the presence of TNBC without further familial predisposition have not yet been conclusively clarified.
In the meantime, other risk genes have also been identified, e.g. CHEK2, PALB2 and RAD51C. While CHEK2 is associated with a moderate breast cancer risk [105], PALB2 seems to be associated with a similarly high risk as BRCA1/2 [106], RAD51C is primarily associated with an increased ovarian cancer risk [107].
Even if gene panel analyses are already offered, genotype-phenotype studies should be awaited in order to recommend concrete preventive measures based on the clinical appearance [104].
The consultation should enable participatory decision-making. This requires comprehensive information for women and the clarification and inclusion of women's preferences in the decision-making process. Evidence-based decision-making aids can improve women's decisions.
In risk counselling prior to genetic testing, the following contents should be considered in particular:
- Probability for the presence of a mutation
- Disease risks in the case of positive findings
- the benefits and harms of preventive and therapeutic options, including the option of doing nothing
- Probability of false negative findings
- The importance of genetic testing for family members
After receipt of the genetic findings, the following contents in particular should be deepened in the risk consultation before offering preventive measures:
- Disease risk depending on genetic findings, age and concomitant diseases (natural course)
- Probability of false positive and false negative test results of intensified screening
- Use of preventive options (intensified early detection, prophylactic surgeries, drug therapies) with regard to mortality reduction, morbidity reduction and quality of life
- Risks of the preventive options including long-term consequences
- Competing risks, prognosis and treatability in case of disease occurrence without preventive measures taking into account the specific appearance of the genetically defined tumor subtype
- Possible risks for associated tumours,
- Psycho-oncological counselling services
Background 3.31 and 3.32
The desire of women and men for detailed information and a joint decision on prevention and treatment options has been documented several times. These findings apply, at least in Germany, largely independent of educational level, age or state of health [112]. Such so-called evidence-based health information is a prerequisite for participation and informed decisions. It has also been shown that evidence-based health information can improve decision-making [120].
Although various working groups worldwide have been working for about 20 years on the question of how information on health and disease topics can be presented in such a way that it can serve as a basis for informed decisions [114], implementation in practice and in concrete health information is currently hardly successful [118].
BRCA1-associated breast carcinomas often exhibit a characteristic histopathological and immunohistochemical phenotype:
- invasive carcinoma with medullary properties
- G3 morphology
- Estrogen receptor, progesterone receptor and HER2 negativity (triple negative)
If these characteristics are present, the pathologist should point out the possibility of a hereditary background.
- Consensus
- Strong consensus
Background 3.33 and 3.34
Breast carcinomas, which develop on the basis of a genetic disposition, can have a distinct driver gene profile, which can manifest itself in phenotypic peculiarities. This has been demonstrated for BRCA1-associated breast carcinomas. While BRCA2-associated breast carcinomas are sporadic carcinomas, BRCA1-associated carcinomas frequently exhibit a particular phenotype which shows characteristics of a medullary carcinoma without, however, forming the full picture of the classic medullary type of breast carcinoma [103], [122], [123], [124], [125]. These special features include macroscopically relatively smooth outer boundaries with displacing rather than infiltrating growth and a prominent, less coarse aspect. Also characteristic are a G3 morphology with high grade nuclear pleomorphism, high mitotic activity and lack of tubule formation with often syncytial growth as well as a lack of expression of steroid hormone receptors and HER2 (triple-negative). The Ki-67 proliferation index is usually above 30% and the tumor cells often show expression of basal cytokeratins (CK5/6, CK14). The tumour stroma shows a pronounced lymphoplasmacellular infiltration and in the neighbouring tumour-free breast tissue a so-called lymphocytic lobulitis is more frequently observed, which is a weaker indication criterion, however. The presence of these characteristics should be a reason to consider a genetic disposition and to stimulate a family anamnestic survey.
Background 3.35
On average, women with a genetic risk for breast cancer develop the disease earlier than women from the general population. Therefore, the usual early detection measures do not appear to be sufficient. The German Mammography Screening Program (MSP) according to § 25 para. 2 and 3 SGB V for the early detection of breast cancer in the general female population is aimed at asymptomatic women between the ages of 50 and 69. Special features of women from familial/hereditary high-risk collectives (including higher lifetime risks for breast cancer, mostly younger at the time of first diagnosis) are not separately considered in the MSP. Internationally, different recommendations are given on measures for intensified early detection (iFE) (including age limits, inclusion criteria and/or the scope of measures), whereby the breast MRI is included (e.g. [101], [129], [130], [132]). However, the significance of iFE with regard to patient-relevant outcomes has not been conclusively clarified.
Evaluations of the diagnostic quality of the procedures as iFE measures (e.g. for mammography or MRI, including age and/or mutation status) have been published [128].
In the systematic search for clinical studies on the significance of iFE measures in relation to outcome parameters (mortality, incidence rates, tumour stages, quality of life), which were carried out within the framework of the S3 guideline update, one prospective and two retrospective cohort studies (LoE 2a-3c) with limited significance of their results on high-risk collectives and BRCA mutation carriers were identified [123], [133], [134], which allow impressions to be made, e.g. on detection or incidence rates. For the evaluation of the benefit of the intensified early detection measures in high-risk collectives or in BRCA mutation carriers, there is no direct evidence of a reduction in mortality through intensified early detection. However, iFE can detect breast carcinomas in early stages [134]. However, intensified monitoring is also associated with an increase in the number of investigations due to false positive findings.
In addition, only a part of the family-related risk has so far been clarified. Based on new and inexpensive high-throughput methods of gene analysis, new risk genes have recently been identified, and more are to be expected. For these new genes, the clinical appearance, e.g. the age-related disease risks and the possible occurrence of special genetically defined histological tumour types with possible effects on the natural course of the disease and the effectiveness of imaging procedures, is still largely unknown. Against this background, special demands must be placed on the assurance of structural, process and result quality.
For this reason, structured measures of intensified early detection (iFE) (including MRI) were implemented within the framework of contracts pursuant to § 140a SGB V at the nationwide centers of the German Consortium for Familial Breast and Ovarian Cancer. These address women with proven pathogenic germline mutation in the genes BRCA1 and BRCA2, as well as women from negatively tested families with a lifetime disease risk of > 30% or heterozygote risk of > 20%. An essential component of this care is the recording of the quality of the iFE results on the basis of accompanying pseudonymised documentation. A mortality-based evaluation is only possible and absolutely desirable by linking to cancer registers.
Extensive measures have been established to ensure structural and process quality in breast diagnostics, e.g. within the framework of the mammography screening programme or diagnostic breast examinations. Recommendations and qualification measures of professional associations support the process of strengthening quality in the application of breast diagnostics. The German Radiological Society takes this process into account by establishing a structured continuing education program in senological radiology. A closer networking and cooperation of already established care structures with externally audited breast and screening centres should be promoted and consolidated.
Background 3.36 and 3.37
If a woman with a mutation in the BRCA1 or BRCA2 genes develops breast cancer, treatment is currently based on the recommendations for sporadic breast cancer.
However, several preclinical and retrospective studies indicate a reduced sensitivity of BRCA-incompetent cells to spindle toxins such as vinca alkaloids and taxanes [141], [142] and an increased sensitivity to DNA-intercalating substances such as platinum derivatives [137]. These observations are currently being reviewed in prospective randomized studies. However, a retrospective mutation analysis of study patients of the TNBC arm of the Geparsixto study did not show a benefit for the BRCA1/2 mutation carriers through the addition of platinum [143]. The direct comparison between platinum and taxane will be examined in the ongoing TNT study in the metastatic situation. Preliminary results here indicate a benefit of platinum [144].
Research on BRCA-deficient cell lines has led to the substance class of PARP inhibitors being used in clinical trials [145], [146]. While efficacy has already been proven in metastatic BRCA1/2-associated ovarian cancer and has already led to the approval of PARP inhibitors, final proof of efficacy for breast cancer is still pending and is currently being tested in prospective clinical trials.
Risk reducing surgery in healthy BRCA1/2 mutation carriers (IARC class 4/5): prophylactic mastectomy:
Healthy women with a BRCA1 or BRCA2 mutation have an increased lifetime risk of developing breast cancer.In healthy women with a pathogenic BRCA1 or BRCA2 gene mutation, bilateral prophylactic mastectomy leads to a reduction in the incidence of breast cancer. A reduction of breast cancer-specific mortality or total mortality by bilateral prophylactic mastectomy is not sufficiently ensured.
Background 3.38
As risk-reducing surgical procedures in healthy women affected by corresponding gene mutations, bilateral prophylactic mastectomy (BPM) and bilateral prophylactic salpingo-oophorectomy (BPSO) are available. BPM reduces the risk of breast cancer by over 95%. An effect of BPM on the reduction of breast cancer-specific mortality is not conclusively proven. Whether BPM has an influence on overall survival has not yet been sufficiently proven by 90% [147], [148], [149], [152], [153], [154], [155].
Prophylactic bilateral salpingo-oophorectomy reduces the risk of ovarian cancer by 97%. Whether this prophylactic intervention also reduces the risk of breast cancer is not clearly established at present. First retrospective examinations described a risk reduction for the first carcinoma by 50%, 30-50% for the contralateral second carcinoma [156], [157], [158]. In addition, a 75% reduction of total mortality could be shown for the prophylactic bilateral salpingo-oophorectomy [149], [158]. More recent prospective studies indicate a significantly lower effect or could not prove it at all [159], [160]. However, both studies are also subject to possible bias, so that the question is not finally clarified at present. The prophylactic bilateral salpingo-oophorectomy is recommended in women affected by BRCA mutations by laparoscopiam around the age of 40 years and after completed family planning. Hormone replacement therapy is indicated until the age of about 50 years.
The rate of metachronous ipsilateral secondary carcinomas (newly developed carcinoma of the same side) does not seem to be significantly increased in patients with proven BRCA1/2 mutation according to the current state of knowledge, so that a breast-conserving therapy is adequate [161]. However, these patients have an increased risk for a contralateral breast carcinoma of about 25-45% in 15 years [161], [162], [163], [164]. The risk depends mainly on the affected gene and the age at the time of the first disease. Bilateral or contralateral mastectomy reduces the incidence of secondary breast cancer. Studies also indicate an improvement in overall survival by contralateral mastectomy, although its significance has not yet been conclusively assessed. The prognosis of the first carcinoma must also be considered [149], [153], [165], [166].
For healthy women or women already suffering from a breast carcinoma from BRCA1/2 negatively tested risk families the benefit of prophylactic surgery is not proven [153] The indications should therefore be very strict. This also applies to women with evidence of a mutation in a non-BRCA1/2 risk gene.
Before every prophylactic surgery a comprehensive clarification with risk calculation is necessary which takes into account the affected gene and, if applicable, the age at first disease and the prognosis after first disease [162], [164]. During the preoperative consultation the possibilities for immediate reconstruction (expanders, implants, pedicled and free flap plasty) should also be discussed in detail.
A possible risk reduction through the prophylactic administration of tamoxifen has not been clearly proven. While in one study a significant reduction of the contralateral second carcinoma by 70% was described [167], another study in multivariate analysis showed no significance [157].
Risk reducing surgery in healthy BRCA1/2 mutation carriers (IARC class 4/5): prophylactic adnexectomy
Women with a pathogenic BRCA1 or BRCA2 mutation have an increased lifetime risk of ovarian cancer, tuberculosis and/or primary peritoneal carcinoma.In healthy women with a pathogenic BRCA1 or BRCA2 gene mutation, prophylactic adnexectomy leads to a reduction in ovarian cancer incidence and total mortality.
Therefore, prophylactic bilateral salpingo-oophorectomy should be discussed and recommended on a case-by-case basis in the context of a comprehensive, multidisciplinary consultation on the potential advantages and disadvantages of such an intervention, taking into account the lack of effective early detection options.
Risk reducing surgery for BRCA1/2 mutation carriers (IARC class 4/5) already unilaterally infected with breast cancer: contralateral mastectomy and prophylactic adnexectomy
Women with a pathogenic BRCA1 or BRCA2 gene mutation who already have breast cancer have an increased risk of developing contralateral breast cancer. This risk depends, among other things, on the affected gene and the age of the first disease and must be taken into account during the consultation.In patients with a pathogenic BRCA1 or BRCA2 gene mutation, prophylactic adnexectomy leads to a reduction in breast cancer-specific mortality and an increase in overall survival.
Risk reducing surgery in risk individuals without proven pathogenic (IARC class 4/5) BRCA1/2 mutation
In women without a proven BRCA1 or BRCA2 gene mutation, the benefit of prophylactic or secondary prophylactic contralateral mastectomy has not been proven.
Background 3.39 to 3.41
Bilateral prophylactic mastectomy (BPM) and bilateral prophylactic salpingo-oophorectomy (BPSO) are available as risk-reducing surgical procedures for healthy mutation carriers. The prophylactic bilateral mastectomy reduces the risk of breast cancer by more than 95%. An effect of BPM on the reduction of breast cancer-specific mortality is not conclusively proven. Whether BPM has an influence on overall survival has not yet been sufficiently proven [147], [148], [149], [152], [153], [154], [155].
Contact with cancer self-help should be offered to healthy and high-risk women and men, in order to meet their need for further information and to support their right to self-determination.
They should be supported:
- in the event of suspected family problems
- in the context of genetic testing
- before prophylactic measures
Appropriate written information material should be kept available.
- Consensus
- Strong consensus
Background 3.42
A confirmed or suspected genetic disposition leads to further burdens (genetic testing, early detection of cancer, prophylactic surgeries, desire to have children, socio-legal consequences) in addition to the actual cancer. They do not only concern concern about one's own health and/or the individual course of the disease, but also about children and grandchildren. Feelings of guilt for having inherited a predisposition are not rare. Children of mutation carriers worry about losing their mother or have already accompanied the death of close relatives and have to deal with their own potential predisposition in parallel. Partners of mutation carriers are afraid of losing their partner and having to experience a recurrence of cancer in the near future in their children. Within a relationship, women also have the fear of losing their physical integrity and attractiveness. The genetic disposition is often experienced as a flaw, as a "disability", which is perceived as a constant threat.
In addition to an interdisciplinary care structure, which also includes psycho-oncological services, the experience of those affected also offers support. Women and men who have a family disposition have an experienced, experience-based knowledge that can supplement the decision-making process with specialist medical information. The time spent at the doctor's office is often not sufficient to make decisions regarding this complex topic. Fears and worries additionally prevent the cognitive reception of all the information provided. Therefore, the processing of the information during the conversation and the exchange of experiences with people who are also affected can be helpful. In particular, descendants of confirmed mutation carriers require comprehensive information in order to be able to decide for or against the performance of a predictive genetic test and preventive measures. Persons from families with an increased risk of breast and ovarian cancer should therefore be offered contact with cancer self-help organisations. Whether and in what form this is used is at the discretion of each and every individual. Further information on cancer self-help for families with a family history of cancer can be found at https://www.brca-netzwerk.de/.
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