Breast cancer screening: are we seeing the benefit?

Puliti and Zappa BMC Medicine 2012, 10:106 http://www.biomedcentral.com/1741-7015/10/106 OPINION Breast cancer screening: are we seeing the benefit? Donella Puliti and Marco Zappa* Abstract A decline in breast cancer mortality has been observed in western European Countries since the middle of the 1990s. Different methodological approaches, including case-control studies, incidence-based mortality studies, and trend studies, have been used to assess the effectiveness of mammography screening programmes in reducing breast cancer mortality. However, not all methods succeed in distinguishing the relative contributions of service screening and taking correctly into considerationthe potential source of bias that might affect the estimate. Recently, a review of six case-control studies confirmed a breast cancer mortality reduction ranging from 38% to 70% among screened women. This figure is in accordance with the estimate obtained from incidence-based mortality studies if screening compliance is taken into account. We will describe the methodological constraints of mortality trend studies in predicting the impact of screening on mortality and the necessary caution that must be applied when interpreting the results of such studies. In conclusion, when appropriate methodological approaches are used, it is evident that mammographic screening programmes have contributed substantially to the observed decline in breast cancer mortality. Keywords: Mammography screening, breast cancer mortality, case-control studies, incidence-based mortality studies, analysis of trends Introduction Screening mammography is aimed at detecting breast cancer in an early stage in women without breast symptoms. The efficacy of mammography screening programmes has been assessed in eight randomized controlled trials conducted in Sweden, Scotland, New York, and Canada in the 1970s and 1980s [1]. In 2002 an International Agency for Research of Cancer (IARC) expert group has reached a consensus, based on review of published evidence, that mammographic screening is effective in reducing mortality from breast cancer [2]. A meta-analysis indicated a 30% reduction in breast cancer (BC) mortality among women aged 50 to 74 years [3]. In December 2003 the European Council recommended the implementation of mammographic screening in all the Member States. On these bases, mammographic screening programmes have been implemented in many European countries. The extension and timing of the implementation of population-based * Correspondence: Clinical and Descriptive Epidemiology Unit, ISPO - Cancer Prevention and Research Institute, Via delle Oblate 2, 50141 Florence, Italy screening in the different countries were recently documented in the European Cancer Screening Report [4]. In 2007 about 54 million women in the age range 50 to 69 years in the European Union were targeted for breast cancer screening in the 22 Member States which had adopted policies aiming for implementation of population-based screening programmes. Now that screening is widespread, non-randomized observational studies will become the main contributors of new information on the impact of breast cancer screening as a public health policy [5]. Different statistical methods including case-control studies [6,7], incidencebased mortality studies [8,9] and trend studies [10-12] have been used to assess the effectiveness of service screening. However, not all methods succeed in distinguishing the relative contributions of service screening and taking correctly into consideration the potential sources of bias that might affect the estimate. Following, we will discuss the main methodological approaches, highlighting their strengths and weaknesses. © 2012 Puliti and Zappa; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Page 2 of 4 Puliti and Zappa BMC Medicine 2012, 10:106 http://www.biomedcentral.com/1741-7015/10/106 Case-control studies The case-control study is a traditional tool for the evaluation of the effect of screening on BC mortality. This approach has also been used extensively for evaluating the efficacy of cervical and colorectal cancer screening [13,14]. The case-control study design has been used in several studies because of its efficiency. The rationale of these studies is the comparison of the screening histories in two groups of women, namely: (1) those who have died from breast cancer (cases); and (2) women sampled from the source population from which cases were drawn (controls). The collection of screening histories of a limited number of subjects allows a more accurate and valid evaluation than it could obtain for an entire population. In 2010 a review of recent case-control studies on the effectiveness of population-based BC screening was carried out by Paap and colleagues [6]. Authors investigated the study design of six case-control studies [15-20] conducted in East Anglia (UK), Wales, Iceland, central and northern Italy, South Australia, and The Netherlands, and concluded that the design was quite similar. As shown in Table 1, the reduction of BC mortality in the different case-control studies ranged from 38% to 70% in the screened women compared with the unscreened women [15-20]. Analysis by exposure to screening measures the benefit of screening among women who agree to be screened, and therefore the result may be affected by self-selection bias. In all selected studies, a correction for self-selection bias was made using the method described by Duffy [21], and the corrected estimate was reported. Recently, a large casecontrol study [7] conducted in The Netherlands confirmed the beneficial effect of screening among women invited and participated in national mammography screening programme (OR = 0.51, 95%CI: 0.40-0.66). The validity of case-control design for evaluating screening programmes has been largely discussed [22]. One of the main potential sources of bias is the socalled ‘self-selection bias’. In other words screening participants and non-participants could present genuine differences of risk factors associated with dying from breast cancer. This reasoning is hypothetical and it is based on the argument ‘we cannot exclude’. For example, screening participants may belong to a higher educational or socioeconomical status (SES). This status can be associated with a better access to quality treatment, so that we cannot exclude that the effect of the observed lower mortality is due to better treatment of higher SES. First of all it is worth mentioning that, as far as risk factors for BC are concerned, several studies have reported an inverse pattern: excesses in BC incidence in high female socioeconomic strata were seen in most populations [23,24]. Moreover we studie (...truncated)