2008 update of the guideline: early detection of breast cancer in Germany

Abstract

Introduction

The goal of the 2008 updated guideline: early detection of breast cancer in Germany is to support physicians as well as healthy and affected women in the decision-making process involved in the diagnostic chain for the early detection of breast cancer by providing them with evidence- and consensus-based recommendations. The updated guideline replaces the guideline issued in 2003.

Materials and methods

The guideline forms the basis for developing an effective and efficient national early breast cancer detection program that meets the standards set by the Council of Europe and WHO for cancer control programs. The guideline presents the current, evidence- and consensus-based state of scientific knowledge in a multidisciplinary approach for the entire diagnostic chain, consisting of history taking and risk consultation, information on health behavior, clinical breast examination, diagnostic imaging, image-guided percutaneous tissue-acquisition techniques, open surgical excisional biopsy and pathomorphological tissue evaluation. The guideline recommends a set of quality indicators to assure resource availability, performance quality and outcomes enhancing total quality management for early breast cancer diagnosis.

Conclusion

Currently, early detection of breast cancer offers the most promising possibility to optimize the diagnosis and treatment of breast cancer and, as a result, reduce breast cancer mortality and improve health related quality of life in women.

Introduction

Rationale and goals of the updated Guideline

Despite medical advances made in the field, breast cancer in women remains a challenging problem of oncologic health and patient care in Germany. The burden of cancer can be best described by data derived from the population-based cancer registries. Breast cancer is by far the most common cancer of women in Germany, comprising 27.8% of all female cancers, with 57,230 new cases in the year 2004, mean age of the women was 63 years. The estimated age-adjusted incidence rate (European standard) is high with 104.2 per 100,000 [(Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg) 2008]. The incidence of breast cancer is rising (Ferlay et al. 2006; Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V.und das Robert Koch Institut 2006), showing a high, albeit declining, mortality rate (26.8 per 100,000 in 2004) [(Robert Koch-Institut (Hrsg) und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (Hrsg) 2008)]. The 2000–2002 period estimates of 10 years relative survival rates of breast cancer in Germany achieved 69% showing a moderate improvement of 4% when compared to the data of 1990–1992 (Brenner et al. 2005). The data on metastasized breast cancer demonstrates no improvement of life expectancy in the past 20 years (Raab-Schlesinger et al. 2005). The reason for the moderate improvements in long-term survival rates during the past decade is likely due to more effective adjuvant treatment in the absence of an early breast cancer detection program in Germany. The combination of high incidence and relatively good prognosis compared to other cancers makes breast cancer to be the most prevalent cancer. Within the German female population, we estimated that survivors of breast cancer are 1%. The negative impact that breast cancer virtually has on every aspect of the affected woman’s life describes the extent of the problem sufficiently. Currently, early detection of breast cancer offers the most promising possibility to optimize diagnosis and treatment of breast cancer and, as a result, reduce breast cancer mortality and improve the health- and disease-related quality of life in women. An increasing detection rate of non-invasive breast cancer might contribute to lowering the incidence of future invasive events by way of prevention. However, primarily the aim of secondary prevention of breast cancer is to detect the disease at an early stage without nodal or distant metastasis permitting improved chances of curing by less radical and thus less strenuous modes of treatment.

Published for the first time in 2003, the Guideline: Early Detection of Breast Cancer in Germany (Schulz et al. 2003; Albert et al. 2004), has demonstrably been integrated into new concepts of health care, which have contributed to enhancing the quality of women’s health care in Germany, as is shown by the following examples:

• monitoring of guideline adherence by certification and audit of breast cancer centers,

• integration of regulatory quality assurance standards for mammography screening and diagnosis,

• integration of guideline recommended formal measures within the mandatory quality assurance program for breast surgery in hospital care by the Federal Office for Quality Assurance (BQS),

• integration of guideline recommendations in the federal “breast cancer” disease management program (DMP) and

• a population-based cohort study on guideline implementation designated as a quality-assured breast cancer diagnosis model project in the German federal state Schleswig-Holstein called “Qualitätsgesicherte Mammadiagnostik” (QuaMaDi) (Katalinic et al. 2007).

The status analysis on the implementation of the guideline undertaken within the framework of the overall updating process shows that the application of the guideline in clinical routine leads to an improvement in breast health care (Albert et al. 2007).

However, it also pointed to existing deficits in some sectors in the country, such as:

• an imbalance between health care and patient care;

• resource shortcomings in the health care system: area-wide health care offers, trans-sectoral coordination of care, fully operative and complete cancer registers;

• performance deficits in the multidisciplinary and cross-professional networking;

• insufficiencies in safeguarding patients’ rights and inadequate guarantee of the right of informed self-determination of women;

• a lack of qualified, target group-oriented information material for women interested in secondary prevention of breast cancer especially for the mammography screening-population age 50–69 years.

Methods

Update process

The process to update the guideline started in a timely manner according to the formal standards set by the German Association of the Scientific Medical Societies (AWMF) 2006. Since there was no previous experience on the updating of such guidelines, a methodological conceptual framework was drawn up that integrates a review of the guideline according to the criteria established by AWMF and the German Agency for Quality in Medicine (ÄZQ) with all its systematic elements (Lorenz et al. 2001) into a quality management cycle (Albert et al. 2007).

The aim of the revision was fourfold: (1) to re-evaluate the guideline’s rationale, goals and scientific validity, (2) to describe and promote successful interventions in dealing with the guideline, (3) to describe and eliminate obsolete interventions and (4) to include any newly available, relevant and applicable scientific knowledge in the guideline.

The key elements of the concept are as follows:

• Assessment of the first version of the Guideline using the German Instrument for Methodological Guideline Appraisal DELBI (Encke et al. 2006; Kopp et al. 2002) to identify potential for improvement to be considered in the updated version of the guideline.

• Evaluation of the guideline implementation status and its impact on health and medical care since 2003: dissemination and recognition among physicians and the public, adoption and use in concepts of breast health care services, adherence and barriers.

• Preparation of a needs assessment, which prioritizes the issues to be updated and the methodological procedure to be applied: new evolving knowledge on specific issues including the drafting of formal evidence reports or utilization of previously processed medical knowledge by adopting international guidelines including a synopsis of current guidelines or a review of the state of the art of scientific knowledge by evaluating studies according to the criteria of evidence-based medicine by members of the guideline committee and task forces.

• Formulation of areas in need of performance improvement and reporting to enhance quality assurance across the interfaces of the diagnostic chain of breast cancer.

• Revision of the set of quality indicators derived from the finally updated practice guideline to enhance quality assurance.

This multistep process was backed by two formal consensus conferences attended by 31 contributing organizations (Table 1).

Table 1.

Contributors to the updating of the Guideline

Guideline task force	Associations and organizations
“Concerted action: early detection of breast cancer in Germany”
Coordinators	Professional associations, scientific and medical organizations
• K.-D. Schulz †, German Society of Senology	1. Task Force German Tumor Centers
• U.-S. Albert, German Society of Senology	2. Task Force Gynecological Oncology
Members of the Guideline Steering Committee	3. German Association of the Scientific Medical Societies
• H. Altland, German Professional Association of Radiologists	4. German Agency for Quality in Medicine (ÄZQ)
• V.·F. Duda, Department of Gynecology, Gynecological Endocrinology and Oncology, Giessen and Marburg, University of Marburg, Faculty of Medicine	5. German Professional Association of Radiologists
• J. Engel, Munich Tumor Register, Großhadern Medical Center, Munich	6. German Professional Association of Gynecologists
• M. Geraedts, Public Health, Medical Center of Heinrich-Heine-University of Düsseldorf	7. German Professional Association of Pathologists
• S. Heywang-Köbrunner, Munich Mammography Reference Center	8. German Federal Office for Quality Assurance
• D. Hölzel, Institute for Medical Data Processing, Biometrics and Epidemiology, Großhadern Medical Center, Munich	9. German Society of Surgery
• E. Kalbheim, German Cancer Aid	10. German Society of Gynecology and Obstetrics
• M. Koller, Center for Clinical Studies, University Hospital Regensburg	11. German Society of Hematology and Oncology
• K. König, German Professional Association of Gynecologists	12. German Society of Pathology
• R. Kreienberg, Women’s Hospital, Faculty of Medicine, University of Ulm	13. German Society of Plastic, Reconstructive and Aesthetic Surgeons
• T. Kühn, Department of Gynecology and Obstetrics, Medical Center of Esslingen	14. German Society of Psychosomatic Gynecology and Obstetrics
• A. Lebeau, Institute of Pathology, Faculty of Medicine, University of Hamburg-Eppendorf	15. German Society of Senology
• I. Naß-Griegoleit, Women’s Health Coalition	16. German Society of Social Medicine and Prevention
• W. Schlake, German Professional Association of Pathologists	17. German Society of Ultrasound in Medicine
• R. Schmutzler, Clinic and Policlinic for Gynecology and Obstetrics, Molecular Gynecological Oncology, Faculty of Medicne, University of Cologne	18. German Society of Behavioral Medicine
• I. Schreer, University Medical Center Schleswig-Holstein, Campus Kiel, Breast Center	19. German Cancer Society
• H. Schulte, German Federal Self-Help Organization for Women with Cancer	20. German Cancer Aid
• R. Schulz-Wendtland, Institute for Diagnostic Radiology and Gynecologic Radiology, University of Erlangen	21. German Menopause Society
• U. Wagner, Department of Gynecology, Gynecological Endocrinology and Oncology, Faculty of Medicine, University of Marburg	22. German Network of Research in Health Care
Chair of the Consensus Conference	23. German Society of Radiology
• I. Kopp, Association of the Scientific Medical Societies	24. Society of Epidemiologic Cancer Registers in Germany
• K.·P. Hellriegel, Berlin	25. Association for Quality Management in Health Care
	26. Austrian Society of Senology
	27. SOPHIA—Women’s Association of Breast Cancer Specialists
	Non-medical organizations
	1. Campaign Awareness of Breast Cancer
	2. German Federal Self-Help Organization for Women with Cancer
	3. Komen Germany
	4. Women’s Health Coalition

The conceptual framework and additional background information including the Evidence Report was presented in the Guideline Methods Report on the internet for public commentary ahead of the final consensus conference. May–August 2007. The final document of the Guideline Methods Report 2007 (Albert et al. 2007) and the Evidence Report 2007 (Nothacker et al. 2007) have been placed online at the German guideline registry (http://www.awmf-leitlinien.de, Reg.-Nr.: 077/001).

The final consensus conference concluded the updating process with a 92% consensus. The guideline was circulated in draft form and as final document to the task force committee and to all contributing organizations.

The Guideline Committee emphasizes that guidelines cannot always account for individual variation among patients. They are not intended to substitute physician’s judgment with respect to particular patients or special clinical situations, and cannot be considered inclusive of all proper methods of care or exclusive of other diagnostic procedures reasonably directed at obtaining the same results. Accordingly, adherence to this guideline is recommended, with the ultimate decision regarding its application to be made by the physician in light of each patient’s individual circumstances within the scope of a shared medical decision-making process. This guideline may not restrict the right of self-determination of women; their autonomy to make informed choices about any medical procedures and care. Instead, this results in the additional responsibility of the physician to provide support and offer individually tailored information for a decision-making in partnership. In addition, this guideline describes the use of procedures and quality assurance methods in clinical practice; it cannot be assumed to be applied to the use of these interventions performed in the context of clinical trials, given that clinical studies are designed to evaluate or validate innovative approaches for which improved diagnostic and staging is needed. The guideline development process includes a review and synthesis of the latest literature. It also serves to identify important questions and settings for future research which are described in the full version of the guideline (http://www.awmf-leitlinien.de, Reg.-Nr.: 077/001) (Albert 2008; Hrsg 2008).

Results

The presented 2008 Updated Guideline: Early Detection of Breast Cancer in Germany has the aim of providing interested physicians in ambulatory care and physicians in hospitals with a quick overview of the entire complex, but is not intended as a substitute for the detailed presentation of the full guideline version. This short version of the guideline contains the guideline statements and presents the most important recommended decision-making steps in the form of a clinical algorithm for the diagnostic chain (Fig. 1). Following the clinical algorithm it leads to four key results of the diagnostic chain for the early detection of breast cancer with recommended options for further action which are listed in Table 2. The underlying methodology with levels of evidence (LOE), guideline adoption (GA), good clinical practice (GCP), good epidemiological practice (GEP) and grades of recommendation (A, B, 0) of the guideline statements have been designated by way of parentheses. Tables 3 and 4 shows the criteria used to classify the level of evidence and grade of recommendation [(Ball et al. 2001; Bundesärztekammer (BÄK) 2007].

Fig. 1.

Algorithm of the diagnostic chain: guideline early detection of breast cancer (EDBC) 2008

Table 2.

Key results of the clinical algorithm and recommendation for further action

Result	Recommendations
Special strategy	Procedures according to the algorithm for the coordination of medical care in the presence of familial risk factors: referral to one of the 12 national specialized Centers for Hereditary Breast and Ovarian Cancer, for counseling and participation in a structured early cancer detection program
Individual strategy	Procedures in the case of a special risk profile: e.g., modified approaches, methods and examination intervals for the early detection of breast cancer, indications for specific diagnostic imaging methods for the detection of breast diseases, participation in clinical trials
Age-group specific approach	In the presence of normal findings continuing procedures according to the algorithm of this guideline
Histopathology of breast cancer or findings of unclear biological potential	Procedures according to the Guideline for the Diagnosis, Therapy and Follow-up Care of Breast Cancer in Women, update 2008

Table 3.

Levels of evidence according to the Oxford Classification 2001

Level	Therapy/prevention, etiology/harm	Prognosis	Diagnosis	Differential diagnosis/symptom prevalence study
1a	SR (with homogeneity*) of RCTs	SR (with homogeneity*) of inception cohort studies; CDR† validated in different populations	SR (with homogeneity*) of level 1 diagnostic studies; CDR† with 1b studies from different clinical centres	SR (with homogeneity*) of prospective cohort studies
1b	Individual RCT (with narrow Confidence Interval‡)	Individual inception cohort study with ≥ 80% follow-up; CDR† validated in a single population	Validating** cohort study with good††† reference standards; or CDR† tested within one clinical centre	Prospective cohort study with good follow-up****
1c	All or none§	All or none case-series	Absolute SpPins and SnNouts††	All or none case-series
2a	SR (with homogeneity*) of cohort studies	SR (with homogeneity*) of either retrospective cohort studies or untreated control groups in RCTs	SR (with homogeneity*) of Level >2 diagnostic studies	SR (with homogeneity*) of 2b and better studies
2b	Individual cohort study (including low quality RCT; e.g., <80% follow-up)	Retrospective cohort study or follow-up of untreated control patients in an RCT; Derivation of CDR† or validated on split-sample§§§ only	Exploratory** cohort study with good†††reference standards; CDR† after derivation, or validated only on split-sample§§§ or databases	Retrospective cohort study, or poor follow-up
2c	“Outcomes” Research; Ecological studies	“Outcomes” Research		Ecological studies
3a	SR (with homogeneity*) of case-control studies		SR (with homogeneity*) of 3b and better studies	SR (with homogeneity*) of 3b and better studies
3b	Individual Case-Control Study		Non-consecutive study; or without consistently applied reference standards	Non-consecutive cohort study, or very limited population
4	Case-series (and poor quality cohort and case-control studies§§)	Case-series (and poor quality prognostic cohort studies***)	Case-control study, poor or non-independent reference standard	Case-series or superseded reference standards
5	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”	Expert opinion without explicit critical appraisal, or based on physiology, bench research or “first principles”

For symbol explanation please refer to the original work of Ball et al. (2001)

Table 4.

Consensus criteria and grade of recommendation

Grade	Grades of recommendation according to Bundesärztekammer (2007)
A	Strong recommendation “must or should”
B	Recommendation “shall or can”
0	Recommendation open: “…” (option for action)
	Negative recommendations are expressed using the word “NOT” together with the same symbols
Consensus criteria for the grade of recommendation:	Consistency of the study results
	Clinical relevance of the end points and effect sizes
	Benefit-to-risk ratio
	Ethical obligation
	Patient preferences
	Applicability, implementability

The prioritized and formal consensus based appraised set of quality indicators to assess quality assurance and management is presented in Table 5.

Table 5.

Updated quality indicators of the diagnostic chain

Aspects of care	Quality indicators and reference range
Documentation and coordination of care	Percentage of ductal carcinoma in situ (DCIS) or invasive carcinoma of the breast reported to an epidemiologic cancer register (≥95%)
Partial aspect	Percentage of all primary DCIS or invasive breast carcinoma cases presented at a post-interventional/pre-treatment conference (>75%)
Partial aspect	Percentage of all primary DCIS or invasive breast carcinoma cases presented after primary surgery at an interdisciplinary conference (>95%)
Overall	Percentage of all primary DCIS or invasive breast carcinoma cases presented at two interdisciplinary conferences within the framework of the senologic chain of diagnosis and medical care (post-interventional/pre-therapeutic and post-surgery treatment planning) (≥95%)
	Percentage of patients with invasive breast carcinoma whose case documentation of the diagnostic chain is complete regarding the following parameters: image-guided histological confirmation of diagnosis (core needle or vacuum biopsy), post-interventional/pre-therapeutic interdisciplinary planning, tumor type according to WHO, pTNM classification, distance to the closest resection margin in metric units, tumor grade, hormone and HER2 receptor status, post-surgery interdisciplinary treatment planning and report to a cancer register (≥95%)
Resource availability	Percentage of women counseling at one of the specialized centers for hereditary breast and ovarian cancer with BRCA1, BRCA2 mutations, a high risk defined as a heterocygotic risk ≥20% or a residual life-long risk of breast cancer ≥30% (≥95%)
	Number of ambulatory care physicians (units) performing breast ultrasound meeting the required technology and performance quality standards (not known)
	Number of pathology institutes (units) performing breast pathology participating in quality assurance measures (ring trial) (not known)
	Percentage of all mammography screening units providing details regarding sensitivity and specificity of double readings (not known)
Mammography	Percentage of women between the ages of 50 and 69 who took part in the mammography screening offered (>75%)
	Percentage of age-group specific incidence and mortality rate of breast cancer in cohorts of women who accepted the offered mammography screening compared to cohorts of women who did not accept the offer (not known)
	Percentage of women obtaining a mammogram with an acceptable image quality according to the quality criteria (≥95%)
	Percentage of mammograms classified as BI-RADS™ V found to be benign following open biopsy (false positive) (<10%)
Clinical breast examination	Percentage of women with an abnormal clinical breast examination with further diagnostic assessment (diagnostic imaging and if indicated breast tissue acquisition) (≥95%)
Ultrasound	Percentage of women with a non-palpable mammographic result of BI-RADS™ 0, III, IV or V obtaining an ultrasound examination of both breasts and both axillae in accordance with the quality standards (≥95%)
	Percentage of women with high mammographic breast density (ACR 3 or 4) obtaining a supplementary ultrasound examination (≥95%)
DCE-MRI	Number of women with an elevated familial risk (carriers of BRCA1 and BRCA 2 mutations or a high risk profile defined as a heterozygotic risk of ≥20% or a residual life-long risk of ≥30%), with an offered a DCE-MRI examination (not known)
Intervention	Percentage of cases with non-palpable lesions with a mammography-, ultrasound- or MRI-guided tissue acquisition (core needle or vacuum biopsy) for histopathological pre-surgical clarification (≥70%/≥90% incl. palpable abnormalities)
Partial aspect	Percentage of cases with a mammogram result of BI-RADS™ IV and V and a correlated ultrasound lesion undergoing interventional, ultrasound-guided core needle biopsy in accordance with the quality standards (≥70%)
Partial aspect	Percentage of cases with a mammogram result of BI-RADS™ IV and V with microcalcifications without a correlated ultrasound lesion undergoing stereotactic vacuum biopsy in accordance with the quality standards (≥70%)
Partial aspect	Percentage of cases with an exclusive result of MRI-BI-RADS™ IV undergoing MRI-guided vacuum biopsy in accordance with the quality criteria (≥95%)
Overall	Percentage of all cases with a mammogram result of BI-RADS™ IV and V, ultrasound result of US-BIRADS™ IV or V and/or MRI results of MRI-BIRADS™ IV or V with tissue acquisition by the respective interventional guided technique for histopathological clarification (≥70%)
	Percentage of cases with a mammogram result of BI-RADS™ IV and V with microcalcification displaying representative microcalcifications in intra-intervention obtained specimen radiography (≥95%)
	Percentage of cases with a benign result after image-guided tissue acquisition (B-classification 1–2/WHO:ICD-0-3) subsequently proven to be malignant following open excisional biopsy (WHO:ICD-0-3) (false negative) (<10%)
Open biopsy	Percentage of cases with wire marked breast surgery, with the wire placed within a distance of ≤1 cm from the lesion (≥95%)
Partial aspect	Percentage of cases with wire marked breast surgery, with intra-operative specimen radiography following preoperative wire-marking of radiographic lesion (≥95%)
Partial aspect	Percentage of cases with wire marked breast surgery with intra-operative specimen ultrasound following preoperative wire marking of exclusively ultrasound lesions (≥95%)
Overall	Percentage of cases with wire marked breast surgery with intra-operative specimen radiography or intra-operative specimen ultrasound following preoperative marking by either method (≥95%)
	Percentage of breast surgery cases with unequivocally orientated breast tissue specimens (≥95%)
Breast pathology	Percentage of interventional guided tissue acquisition (core needle or vacuum biopsy) with categorization of the main diagnosis according to the B-classification (≥95%)
Partial aspect	Percentage of pathology reports of ductal carcinoma in situ (DCIS) with details concerning histological grade (≥95%)
Partial aspect	Percentage of pathology reports of DCIS including description tumor size in millimeter or centimeter (≥95%)
Partial aspect	Percentage of pathology reports of DCIS including description of distance to the closest resection margin in millimeter or centimeter (≥95%)
Overall	Percentage of pathology reports of DCIS with documentation of histological grade, tumor size and distance to the closest resection margin in millimeter or centimeter (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description of tumor type (WHO 2003) (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description of tumor size in millimeter or centimeter (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with documentation of pTNM classification (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description on additional tumor foci (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description of histological grade (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description of distance to the closest resection margin in millimeter or centimeter (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with data on vascular invasion (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with description of hormone receptor status (ER/PgR by immunohistochemistry) (≥95%)
Partial aspect	Percentage of pathology reports of invasive carcinoma with details on HER2-status (≥95%)
Overall	Percentage of pathology reports of invasive carcinoma with documentation regarding: histological tumor type (WHO), tumor size in millimeter or centimeter, pTNM classification, histological grade according to WHO, presence of additional tumor foci, distance to closest resection margin in millimeter or centimeter, vascular invasion, hormone receptor status (ER/PgR immunohistochemistry), HER2-status (≥95%)
	Percentage of all invasive carcinoma with a Her2- positiv status defined as immunohistochemical protein overexpression scoring 3+ or gene amplification evidenced by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) (not known)
Intermediate outcomes and evaluation	Percentage of cases of DCIS or invasive carcinoma occurring following a previous BI-RADS™ I-III mammogram within a period of 24 months (interval carcinoma rate/false negative) (<50%) (EuG)
	Percentage of cases of interval carcinomas referred and subjected to an interdisciplinary detailed analysis (≥95%)
	Percentage of DCIS among all breast cancer cases (>10%)
	Percentage of invasive breast carcinoma with ≤5 mm among all breast cancer cases (≥10%)
	Percentage of invasive breast carcinoma with ≤10 mm among all breast cancer cases (≥20%)
	Percentage of invasive breast carcinoma with ≤20 mm among all breast cancer cases (≥65%)
	Percentage of cases with lymph node negative invasive carcinoma with sentinel node biopsy (pN0sn) among all breast cancer cases (pN0) (≥75%)

Guideline recommendations

Early breast cancer detection program, coordination of care and quality management

Early detection of breast cancer is a multi-professional responsibility. It must comprise a quality-assured, multidisciplinary combination of clinical breast examination, diagnostic imaging, interventional diagnostic procedures and pathomorphological tissue evaluation. GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; World Health Organization (WHO) 2002)], GCP, A.

The diagnostic chain of breast health care requires complex and quality-assured medical documentation in order to achieve total quality management. GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; World Health Organization (WHO) 2002)], GCP, A.

Cancer registers are an equally important and necessary element for the evaluation and quality management of early breast cancer detection. All patients diagnosed with breast cancer must, therefore, be reported to a cancer register with all relevant information on the primary tumor and primary treatment being provided. By preparing population-based and regionally distributed analyses of the cancer stages and the long-term follow-up (recurrence and survival rates), the said cancer registers contribute to evaluation and quality management. When a program for early detection of breast cancer is started, baseline data for the time before should be available. GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006)], GEP (Hoffmann et al. 2004), A.

Psychological stress

Medical examinations associated with the early detection of cancer may lead to psychological stress. This aspect has to be taken into consideration by providing thorough information. GA (National Breast Cancer Center (NBCC) 2001; Smith et al. 2003), GCP, patients’ rights, A.

False positive findings cause distress and anxiety which can be counteracted by an effective communication strategy. 2a LOE, (Brett et al. 2005), GCP, A.

Women’s information

The production of qualified and competent, specialized information material (in printed form or on the Internet) should meet the quality standards of the Guideline: Women’s Information, so as to support women in their self-determined decision for or against medical intervention by providing adequate and understandable communication about the risks involved (inter alia information about natural frequencies, absolute numbers rather than relative percentages). GA (Albert et al. 2003; NHS Centre for Reviews, Dissemination 2000), GCP, A.

Shared decision-making

Within the framework of early breast cancer detection programs, information may not be reduced to pre-formulated texts alone, but must rather consist of a medical consultation addressing the preferences, the needs, the concerns and the anxieties of the woman, thus allowing a shared decision-making process and permitting informed consent to be given by the woman.

In mammography screening programs, women may receive detailed information primarily in printed form; but the written invitation must include a note that a personal consultation with a physician is an option. GA (Perry et al. 2006; Albert et al. 2003), patients’ rights, A.

Medical history taking and risk consultation

Within the framework of statutory programs for early detection and diagnosis of cancer, women should be offered a consultation in which the medical history is taken and possible risk factors are discussed. GA (Schulz et al. 2003; Albert et al. 2004), GCP, A.

Advanced age is the main demographic risk for developing breast cancer. 2a LOE, GA [(National Breast Cancer Center (NBCC) 2001; Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2006, 2007a; Calman et al. 2002)], A.

Taking the individual’s risk profile, state of health and life expectancy into consideration, participation in early breast cancer detection programs should also be offered to women above the age of 70. GA [Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2007a)], A.

Carriers of BRCA1 or BRCA2 mutations or women with a high risk profile defined as a heterozygotic risk of ≥20% or a residual life-long risk of ≥30% should be counseled and looked after in the specialized centers for hereditary breast and ovarian cancer in accordance with an early detection strategy on an individual basis. GA (NICE NCCfPC 2006c), GCP, A.

Access to programs for the early detection of breast cancer are useful for all women whose individual risk profile is defined by age and/or further risk factors (endogenous and exogenous hormone factors, mammary gland density, reproductive behavior, lifestyle, and hereditary factors). 2a LOE, GA (NCCfPC 2006c; Scottish Intecollegiate Guideline Network (SIGN) 2005, Smith et al. 2006), A.

Health behavior

Breast self-examination, even on a trained, regular basis, is in itself an insufficient method for reducing breast cancer mortality. 1a LOE, GA [(Schulz et al. 2003; Albert et al. 2004; NICE NCCfPC 2006c; Scottish Intecollegiate Guideline Network (SIGN) 2005)], A.

Women should be encouraged by qualified information to familiarize themselves with normal changes in their bodies; they should be aware of how their breasts look and feel normally in order to detect and report any new or unusual changes. GA [(National Breast Cancer Center (NBCC) 2001; Scottish Intecollegiate Guideline Network (SIGN) 2005; NICE 2005; NBCC 2006)], A.

Awareness and motivation for maintaining breast health on one’s own accord should be included in the information provided by an early breast cancer detection program. GA [(Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2007a; Calman et al. 2002; Scottish Intecollegiate Guideline Network (SIGN) 2005; NICE 2005; NBCC 2004b)], A.

Clinical breast examination

A clinical breast examination, i.e., inspection and palpation of the mammary gland and evaluation of local lymphatic drainage areas, should be offered annually to women from the age of 30 years on as a component of the statutory program for early detection and diagnosis of cancer. GA [(Perry et al. 2006; Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2007a)], A.

If the clinical breast examination reveals an abnormal finding, the diagnostic process should be completed by diagnostic imaging procedures and if indicated by histological tissue-acquisition. GA [(National Breast Cancer Center (NBCC) 2001, 2006; National Comprehensive Cancer Network (NCCN) 2007a; Calman et al. 2002; Scottish Intecollegiate Guideline Network (SIGN) 2005; NBCC 2006)], A.

The effects of endogenous and exogenous hormones have to be taken into account when performing and evaluating breast diagnostic procedures. 2b LOE, GA [Schulz et al. 2003; Albert et al. 2004; Calman et al. 2002; NBCC 2006, 2004a)], B.

Mammography

Mammography is currently the only method generally regarded as effective for the detection of non-invasive and early stages of breast cancer. 1a LOE, GA [National Comprehensive Cancer Network (NCCN) 2006, 2007a; Calman et al. 2002; Scottish Intecollegiate Guideline Network (SIGN) 2005; National Breast Cancer Centre (NBCC) 2006)], A.

The individual benefit of mammography outweighs the incumbent risks due to radiation exposure for women from the age of 40. The optimal benefit-to-risk ratio is found between the ages of 50 and 70. 5- 4 LOE, Evidence Report 2007 (Nothacker et al. 2007), GA [(Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2007a; Scottish Intecollegiate Guideline Network (SIGN) 2005; NBCC 2004b)], A.

Evidence from prospective randomized studies indicates that with the introduction of screening mammography in the form of serial X-ray examinations it is possible to reduce the age-dependent breast cancer mortality rate. 1b-1a LOE, GA (Perry et al. 2006; Smith et al. 2003; Calman et al. 2002; NBCC 2004b; Gotzsche and Nielsen 2006) A.

The reduction of breast cancer mortality has also been reported for women in the age group from 40 to 49 years, even though it is lower than in the age group of women between 50 and 69 years. Therefore, the decision for mammography should be made on the basis of an individual risk analysis, a risk-benefit assessment and taking into consideration the woman’s preferences and objections. 1b LOE, Evidence Report 2007 (Nothacker et al. 2007), GA [Smith et al. 2003; National Comprehensive Cancer Network (NCCN) 2007a)], B.

Apart from a BRCA1 or BRCA2 mutation, high mammographic breast density (ACR 3 and 4) is an important individual risk factor. Given such a situation, the limited sensitivity of mammography shall, therefore, be enhanced by a supplementary ultrasound examination. 3b LOE, Evidence Report 2007 (Nothacker et al. 2007), B.

The use of double reading in screening mammography raises the sensitivity of carcinoma detection by 2.9–13.7% (median 7.8%). Specificity may be lowered (up to 2.1%) or increased (up to 2.8%) depending on the decision-making procedure after double reading of mammograms. Unilateral recall lowers specificity, whereas consensus recall or arbitration tends to enhance specificity. 2b LOE, Evidence Report 2007 (Nothacker et al. 2007), B.

The question whether it will be possible to replace double readings by the use of CAD-systems could not be answered unequivocally until now on the basis of existing studies. 3b LOE, Evidence Report 2007 (Nothacker et al. 2007), 0.

The resource availability, the assurance of performance and result quality of mammography for women between the ages of 50 and 69 years is regulated within the framework of the mammography-screening-program. GA (Perry et al. 2006), A.

Resource availability, assurance of performance and result quality should be applied accordingly to diagnostic (“curative”) mammography. 2b LOE, (Katalinic et al. 2007; Schreer and Katalinic 2007), A.

Waiting period/psychological stress

If the mammogram revealed a BI-RADS™ [American College of Radiology (ACR) 2003] 0, III, IV or V finding, further diagnostic procedures shall be done within 5 work days helping to minimize the psychological stress for the woman. GA [(Perry et al. 2006; National Comprehensive Cancer Network (NCCN) 2007a; Scottish Intecollegiate Guideline Network (SIGN) 2005; NICE 2005; National Breast Cancer Centre (NBCC) 2006)], B.

Ultrasound

Breast ultrasound is a supplementary examination for further clarification of ambiguous findings. GA [Schulz et al. 2003; Albert et al. 2004; National Comprehensive Cancer Network (NCCN) 2007a; Calman et al. 2002; Scottish Intecollegiate Guideline Network (SIGN) 2005; NBCC 2006; National Breast Cancer Centre (NBCC) 2006 )], A.

Indications for breast ultrasound are non-palpable BI-RADS™ [American College of Radiology (ACR) 2003] 0, III, IV or V mammographic findings. 3b LOE, Evidence Report 2007 (Nothacker et al. 2007), B.

Breast ultrasound performed as a screening stand alone method cannot be recommended. 5 LoE (no trial data), O.

The aim of a standardized breast ultrasound is to perform a systematic and reproducible examination of both breasts and both axillae. GA [Schulz et al. 2003; Albert et al. 2004; National Comprehensive Cancer Network (NCCN) 2007a; Madjar et al. 2006)], GCP, B.

In symptomatic women below the age of 40 years, a breast ultrasound examination is the imaging procedure of first choice. 3b LOE, Evidence Report 2007 (Nothacker et al. 2007), GA [(National Comprehensive Cancer Network (NCCN) 2007a; NBCC 2004a)], A.

Resource availability, assurance of performance and result quality are a prerequisite for the use of breast ultrasound examinations. GCP, A.

Dynamic contrast-enhanced magnetic resonance imaging

In the presence of an elevated risk of familial breast cancer (carriers of BRCA1 or BRCA 2 mutations or a high risk defined as a heterozygotic risk of ≥20%, or a residual life-long risk of ≥30%), CE-MRI can be recommended. 2a LOE, GA (Nice NCCfPC 2006c; National Comprehensive Cancer Network (NCCN) 2007b)], B.

CE-MRI can be recommended preoperatively for local staging of lobular carcinomas and in the presence of a relevant elevated risk. 3b LOE, (Schwartz et al. 2006) GCP, B.

Except for the two indications (questions) mentioned above, no recommendation can be made for CE-MRI as a tool for early detection of breast cancer. 5 LOE (no trial data), 0.

A strict link between perfoming CE-MRI and the capability of MRI-guided interventions should be guaranteed to utilize the recommendations. GCP, A.

Intervention

The histological tissue diagnosis of ambiguous breast lesions has to be performed by imaging-guided core needle biopsy, vacuum-assisted biopsy or open biopsy. Percutaneous interventions should be performed in accordance with the quality assuring recommendations. 3a LOE, GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; National Comprehensive Cancer Network (NCCN) 2007a; NICE 2006a)], GCP, A.

Fine needle biopsy cannot be recommended as a standard method. GA [(Schulz et al. 2003; Albert et al. 2004; NICE 2006a; National Comprehensive Cancer Network (NCCN) 2007a)], B.

Interventional-guided tissue sampling for the purpose of histological clarification of diagnosis and for further treatment planning is indicated in the following situations: BI-RADS™ [American College of Radiology (ACR) 2003)] IV and V mammographic abnormalities and/or ultrasound findings classified as US-BIRADS™ [(American College of Radiology (ACR) 2003)] IV or V and/or an MRI-BIRADS™ [(American College of Radiology (ACR) 2003)] IV or V result obtained by magnetic resonance imaging. 3a LOE, GA [(Schulz et al. 2003; Albert et al. 2004; National Comprehensive Cancer Network (NCCN) 2007a)], A.

In interventional, preferably ultrasound-guided core needle biopsy ≥4 samples shall be obtained with a ≤14 G needle. 3b LOE, (Crystal et al. 2004; Fishman et al. 2003), B.

Stereotactic vacuum-assisted breast biopsy is the preferred technique to be applied for microcalcifications. 3a LOE, Evidence Report 2007 (Nothacker et al. 2007), B.

Vacuum-assisted breast biopsy shall be used for MRI-guided tissue-acquisition. GCP, B.

The performance of a stereotactic vacuum-assisted breast biopsy should follow a standardized performance protocol. Access path and the positioning of the needle (“stroke margin”) have to be documented. To document the correct position of the needle, three scouts, two pre-fire and two post-biopsy images are required. Acquisition of ≥12 cores using a 10 G needle should be routinely attempted. If other gauges are used (between 8 G and 11 G), the number of cores should produce an equivalent sample volume.

Magnification breast specimen radiography should be done to document the success of the biopsy procedure. A biopsy can be considered technically successful if representative microcalcifications can be identified. In coordination with the respective pathologist it is useful to identify the cores containing microcalcifications. After tissue removal by vacuum-assisted breast biopsy, a mammogram of the biopsied breast in two planes should be done (on the following work day at the latest). GA [(Schulz et al. 2003; Albert et al. 2004; National Comprehensive Cancer Network (NCCN) 2007a)], A.

The control of results after minimally invasive image-guided tissue-acquisition involves the correlation of the histological and imaging findings. GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; National Comprehensive Cancer Network (NCCN) 2007a; National Breast Cancer Centre (NBCC) 2006; NICE 2006b)], A.

In case of histological benign findings, a follow-up imaging examination shall be performed after 6 months. GA [National Comprehensive Cancer Network (NCCN) 2007a; NICE 2006b)], B.

Excisional biopsy

The quality assurance for an open diagnostic excision of mammographically detected lesions is based on the guidelines of the European Commission. The goal of the surgical procedure (diagnostic, therapeutic) should be clearly defined. GA (Schulz et al. 2003; Albert et al. 2004; O’Higgins et al. 2006)], A.

The pre-operative wire marking of non-palpable lesions should ensure that the wire penetrates the lesion, extending less than 1 cm beyond the lesion. If the marking wire does not penetrate the lesion, the distance between wire and lesion must be ≤1 cm. For accurate resection of certain imaging findings, it may be useful to mark the relevant volume by localization wires to be targeted in excision biopsy. 3b LOE, GA (Schulz et al. 2003; Albert et al. 2004; O’Higgins et al. 2006), A.

Pre-operative wire marking and the verification of the correct surgical excision of the lesion should be done in principle in the presence of any non-palpable imaging finding. 3b LOE, GA [(Schulz et al. 2003; Albert et al. 2004; NBCC National Breast Cancer Center 2001; O’Higgins et al. 2006), A.

The correct excision of lesions that can only be seen by ultrasound should be confirmed by intra-operative specimen ultrasound. 3b LOE, GA [(Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; National Comprehensive Cancer Network (NCCN) 2007a), A.

The breast tissue specimen should be topographically unequivocally marked in three dimensions and must be sent to the pathologist without any incision in the collected sample. GA (Schulz et al. 2003; Albert et al. 2004; Perry et al. 2006; Carlson et al. 2005), A.

Only in exceptional cases, is it justified to perform intra-operative frozen sectioning on breast tissue specimens to determine the benign or malignant nature of the lesion. Prerequisites for an intra-operative frozen sectioning of breast tissue specimens are as follows:

• the lesion is palpable both intra-operatively and in the specimen;

• the lesion is large enough (generally >10 mm).

GA (Schulz et al. 2003; Albert et al. 2004; O’Higgins et al. 2006; Amendoeira et al. 2006b), A.

Breast pathology

The histological examination of core and vacuum-assisted biopsies must assign the main diagnosis to one of the five categories of the B-classification. GA (NHSBSP 2001; Amendoeira et al. 2006a), A.

Reporting of DCIS should include the following data:

1. histological grade, based on nuclear grading, and the presence or absence of comedo-type necrosis according to WHO (WHO 2003) or Van Nuys classification (Silverstein et al. 1995);

2. tumor size: in millimeter or centimeter;

3. excision margin status: information on the distance to the closest resection margin in millimeter or centimeter;

4. oestrogene (ER) and progesterone (PgR) receptor status (in case of treatment consequences).

GA [National Comprehensive Cancer Network (NCCN) 2006; Carlson et al. 2005; Amendoeira et al. 2006b; WHO 2003], A.

Reporting of invasive carcinoma should include:

1. histological type of tumor [according to WHO (2003)];

2. histological grade according to WHO [Elston and Ellis modification of the Bloom und Richardson grading system; Elston und Ellis 1991 (Elston and Ellis 1991)];

3. tumor size in millimeter or centimeter;

4. presence of additional tumor foci;

5. excision margin status: information on the distance to the closest resection margin in millimeter or centimeter;

6. presence of peritumoral vascular invasion;

7. pTNM classification;

8. oestrogene (ER) and progesterone (PgR) receptor status;

9. HER2 status of the invasive tumor.

3b-2a LOE, GA (NBCC National Breast Cancer Center 2001), (Carlson et al. 2005), (Amendoeira et al. 2006b), (ICSI 2005), (The Association of Breast Surgery at BASO, RCoSoE 2005), (Sobin and Wittekind 2002), (Wolff et al. 2007), A.

The oestrogen and progesterone receptor status has to be determined by immunohistochemistry, preferably already on the core or vacuum needle biopsies. The respective percentage of positive tumor cell nuclei has to be stated; in doing so, summation scores can be given if the procedure applied is mentioned [Allred (Quick) score (Harvey et al. 1999)], immunoreactive score according to Remmele and Stegner (Remmele and Stegner 1987)]. GCP, A.

A tumor is defined to be HER2-positive if HER2 overexpression is demonstrated by immunohistochemistry scoring 3+ or if gene amplification is evidenced by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH). 3b LOE, Evidence Report 2007 (Nothacker et al. 2007), A.

The reliability of the procedures used to assess the status of hormone receptors and HER2 must be assured. This includes internal validation tools, the use of standardized protocols and internal controls as well as the regular, successful participation in external quality assurance schemes. GA (Carlson et al. 2005; Wolff et al. 2007), GCP, A.

Implementation and evaluation

Scientifically based change strategies are recommended for the updating and implementation process. GA (Schulz et al. 2003; Albert et al. 2004), GCP, B.

Health care outcomes including effects on quality of life should be recorded and evaluated. GA [(Schulz et al. 2003; Albert et al. 2004; World Health Organization (WHO) 2002)], GCP/GEP, A.

Quality of life parameters should primarily include physical and psychological early and late side effects of diagnostic procedures, paying special attention to any false negative and false positive results within the framework of the diagnostic chain. GA [(NHS Centre for Reviews, Dissemination 2000; Calman et al. 2002; Scottish Intecollegiate Guideline Network (SIGN) 2005; National Quality Management Committee of BreastScreen Australia 2004; NHMRC 1999)], GCP, A.

Conclusion

The updated guideline is designed to minimize existing and known deficits in nationwide, multidisciplinary and trans-sectoral health and patient care in secondary breast cancer prevention. The guideline shall enable a continuous improvement in health care, taking the particularly quality-sensitive interfaces of the diagnostic chain into consideration. The main points of the guideline update are as follows:

• emphazising quality assurance by means of cancer registers;

• definition of risk-adapted strategies and procedures for the early diagnosis of breast cancer;

• consideration of the psychological stress involved in breast cancer detection examinations;

• safeguarding the self-determination of primarily healthy women by encouraging to provide competent specialized and understandable information on health behavior, risks estimation as well as medical consultations regarding options of procedures within the chain of diagnosis;

• defining strategies of early detection and diagnosis of breast cancer in women below the age of 50 and above the age of 70;

• revision of the indications and the quality assurance for performing mammography, breast ultrasound and magnetic resonance imaging;

• update of the recommendations for multidisciplinary quality assurance across the interfaces of the diagnostic chain: e.g., discussing obsolete and indicated procedures for image-guided minimally invasive techniques and open diagnostic excision biopsy;

• update of recommendations for quality assurance of breast pathology considering new prognostic and predictive factors.

Continuing improvements in outcomes of national breast health care, however, will require economic decision-making. The guideline might help to define the challenging evidence- and consensus-based high quality assurance demands and define the areas in need of support for adequate reimbursement to make the evidence- and consensus-based options of diagnosis and treatment in Germany widely available.