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We are grateful for the contributions to the discussion, which we will briefly address. We would recommend that all interested parties refer to the long version of the S3 guideline, which has a detailed explanation of the complex evidence situation.
Mammography screening: The updated German S3 guideline has taken into account the recommendations of the American Cancer Society (1), the US Preventive Task Force (2), and the International Agency for Research on Cancer (IARC) (3). The IARC confirms the results of the meta-analyses of existing randomized controlled trials (RCTs) but considers well-controlled recent observational studies (approximately 20 incidence-based cohort and case-control studies) as more appropriate for the assessment of current screening programs.
The Cochrane analysis is based on data from older RCTs and calculates the effectiveness over a ten-year period after five rounds of screening. However, calculating screening effectiveness requires a longer observation period to exclude the length-time bias. These requirements are met by the incidence-based cohort studies. Different final outcomes can be obtained depending on the cohorts—hence the reference to “inhomogeneous evidence.”
For example, the numbers needed to screen (NNS) show the absolute effects in the different age groups: to prevent one death in the 40- to 49-year age group, the NNS is 1770 women assuming a 20% mortality reduction, or 753 women assuming a 40% mortality reduction. For the 50- to 59-year age group, the NNS is 1097 or 462 assuming a 20% or 40% mortality reduction, respectively, and for the 60- to 69-year age group, 835 or 355 women, respectively (4).
As a standard for the definition, assessment, and planning of medical services, determinants of disease clusters are used in set populations. Only using all-cause mortality (number of deaths in a given period / population size) is not helpful here. Rather, cause-specific mortality (number of deaths from a specified cause in a given period / population size) is required.
Irradiation of lymphatic drainage regions: The issue of postoperative radiotherapy of lymphatic drainage regions is complex, and the evidence is not clear. The long version of the S3 guideline explains the study situation and outlines the possible courses of action. A clinical and sonographic suspicion of lymph node involvement should be diagnostically verified before biopsy, and histopathologically verified before therapy recommendation. As part of the case report of a tumor board review, an individual recommendation for each individual patient for postoperative irradiation must be provided.
Hypofractionation: Theoretically, an influence on repopulation could indeed be expected. However, according to available studies, differences in the effects of adjuvant therapy on breast cancer at three weeks as compared to five weeks is small and not statistically significant. The guideline therefore does not describe a specific scheme but a framework. However, it can also be assumed, based on the guideline text for routine care, that the use of 40 Gy or 40.5 Gy in 15 fractions over three weeks will be favored.
Prof. Dr. med. Achim Wöckel
Frauenklinik des Universitätsklinikums Würzburg
Prof. Dr. med. Ute-Susann Albert
Prof. Dr. med. Ingrid Schreer
Prof. Dr. med. Wilfried Budach
Conflict of interest statement
Prof. Wöckel has received consultancy fees and reimbursement of participation fees from Pfizer, Novartis, Roche, Amgen, Celgene, and Eisai, and speaking honoraria from Novartis, Pfizer, Roche, Amgen, and Celgene.
Prof. Albert has received honoraria for expertise activities from Medexo, consulting honoraria from Pfizer, and study support from the WSG Study Group for conducting clinical studies.
The remaining authors declare that no conflict of interest exists.
|1.||Duke Evidence Synthesis Group: Systematic review of cancer screening literature for updating American Cancer Society breast cancer screening guidelines. 2014, Durham, North Carolina.|
|2.||Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L: Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. preventive task force recommendation. Ann Intern Med 2016, 164: 244–55 CrossRef CrossRef MEDLINE|
|3.||Breast Cancer Screening. IARC Handbook of Cancer Prevention. IARC, 2016.|
|4.||Oeffinger KC, Fontham ET, Etzioni R, et al.: Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA 2015; 314: 1599–614 CrossRef MEDLINE PubMed Central|
|5.||Wöckel A, Albert US, Janni W, Scharl A, Kreienberg R, Stüber T: Clinical practice guideline: The screening, diagnosis, treatment, and follow-up of breast cancer. Dtsch Arztebl Int 2018; 115: 316–23 VOLLTEXT|