The Natural History of Invasive Breast Cancers Detected by Screening Mammography

VA Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, VT 05009, USA.
Archives of internal medicine (Impact Factor: 17.33). 12/2008; 168(21):2311-6. DOI: 10.1001/archinte.168.21.2311
Source: PubMed


The introduction of screening mammography has been associated with sustained increases in breast cancer incidence. The natural history of these screen-detected cancers is not well understood.
We compared cumulative breast cancer incidence in age-matched cohorts of women residing in 4 Norwegian counties before and after the initiation of biennial mammography. The screened group included all women who were invited for all 3 rounds of screening during the period 1996 through 2001 (age range in 1996, 50-64 years). The control group included all women who would have been invited for screening had there been a screening program during the period 1992 through 1997 (age range in 1992, 50-64 years). All women in the control group were invited to undergo a 1-time prevalence screen at the end of their observation period. Screening attendance was similar in both groups (screened, 78.3%, and controls, 79.5%). Counts of incident invasive breast cancers were obtained from the Norwegian Cancer Registry (in situ cancers were excluded).
As expected, before the age-matched controls were invited to be screened at the end of their observation period, the cumulative incidence of invasive breast cancer was significantly higher in the screened group than in the controls (4-year cumulative incidence: 1268 vs 810 per 100 000 population; relative rate, 1.57; 95% confidence interval, 1.44-1.70). Even after prevalence screening in controls, however, the cumulative incidence of invasive breast cancer remained 22% higher in the screened group (6-year cumulative incidence: 1909 vs 1564 per 100 000 population; relative rate, 1.22; 95% confidence interval, 1.16-1.30). Higher incidence was observed in screened women at each year of age.
Because the cumulative incidence among controls never reached that of the screened group, it appears that some breast cancers detected by repeated mammographic screening would not persist to be detectable by a single mammogram at the end of 6 years. This raises the possibility that the natural course of some screen-detected invasive breast cancers is to spontaneously regress.

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Available from: Per-Henrik Zahl, Apr 27, 2015
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    • "An independent meta-analysis of three clinical trials reported a 19% increased incidence of breast cancer among screened women during the screening period and an 11% increased incidence if the years after the active screening were included [1]. Estimates based on ecological analyses are heterogeneous [6,8,9,11-13]. A major weakness of ecological analyses is the inability to adequately [15] control for the confounding effect of hormone therapy (HT). "
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    ABSTRACT: There is increasing ambiguity towards national mammographic screening programs due to varying publicized estimates of overdiagnosis, i.e., breast cancer that would not have been diagnosed in the women's lifetime outside screening. This analysis compares the cumulative incidence of breast cancer in screened and unscreened women in Norway from the start of the fully implemented Norwegian Breast Cancer Screening Program (NBCSP) in 2005. Subjects were 53 363 women in the Norwegian Women and Cancer (NOWAC) study, aged 52-79 years, with follow-up through 2010. Mammogram and breast cancer risk factor information were taken from the most recent questionnaire (2002-07) before the start of individual follow-up. The analysis differentiated screening into incidence (52-69 years) and post screening (70-79 years). Relative risks (RR) were estimated by Poisson regression. The analysis failed to detect a significantly increased cumulative incidence rate in screened versus other women 52-79 years. RR of breast cancer among women outside the NBCSP, the "control group", was non-significantly reduced by 7% (RR = 0[bullet operator]93 ; 95% confidence interval 0[bullet operator]79 to 1[bullet operator]10) compared to those in the program. The RR was attenuated when adjusted for risk factors; RRadj = 0[bullet operator]97 (0[bullet operator]82 to 1[bullet operator]15). The control group consisted of two subpopulations, those who only had a mammogram outside the program (RRadj =1[bullet operator]04 ; 0[bullet operator]86 to 1[bullet operator]26) and those who never had a mammogram (RRadj = 0[bullet operator]77 ; 0[bullet operator]59 to 1[bullet operator]01). These groups differed significantly with respect to risk factors for breast cancer, partly as a consequence of the prescription rules for hormone therapy which indicate a mammogram. In the fully implemented NBCSP, no significant difference was found in cumulative incidence rates of breast cancer between NOWAC women screened and not screened. Naive comparisons of screened and unscreened women may be affected by important differences in risk factors. The current challenge for the screening program is to improve the diagnostics used at prevalence screenings (ages 50-51).
    BMC Cancer 12/2013; 13(1):614. DOI:10.1186/1471-2407-13-614 · 3.36 Impact Factor
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    • "However, this is never done when calculating overdiagnosis of prostate cancer (Draisma et al, 2003). Model-based lead time includes many slow-growing, dormant (Spratt et al, 1993; Draisma et al, 2003) or regressing tumours (Zahl et al, 2008, 2011), and adjustment for model-based lead time will therefore inevitably ‘adjust away' a large part of the overdiagnosis. "
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    ABSTRACT: Background: Published lead time estimates in breast cancer screening vary from 1 to 7 years and the percentages of overdiagnosis vary from 0 to 75%. The differences are usually explained as random variations. We study how much can be explained by using different definitions and methods. Methods: We estimated the clinically relevant lead time based on the observed incidence reduction after attending the last screening round in the Norwegian mammography screening programme. We compared this estimate with estimates based on models that do not take overdiagnosis into account (model-based lead times), for varying levels of overdiagnosis. Finally, we calculated overdiagnosis adjusted for clinical and model-based lead times and compared results. Results: Clinical lead time was about one year based on the reduction in incidence in women previously offered screening. When overdiagnosed tumours were included, the estimates increased to 4–9 years, depending on the age at which screening begins and the level of overdiagnosis. Including all breast cancers detected in women long after the end of the screening programme dilutes the level of overdiagnosis by a factor of 2–3. Conclusion: When overdiagnosis is not taken into account, lead time is substantially overestimated. Overdiagnosis adjusted for model-based lead time is a function tending to zero, with no simple interpretation. Furthermore, the estimates are not in general comparable, because they depend on both the duration of screening and duration of follow-up. In contrast, overdiagnosis adjusted for clinically relevant tumours is a point estimate (and interpreted as percentage), which we find is the most reasonable method.
    British Journal of Cancer 08/2013; 109(7). DOI:10.1038/bjc.2013.427 · 4.84 Impact Factor
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    • "A comparable conflict is ongoing in breast cancer screening. Recent articles usually based on cleverly designed pragmatic trials (Zahl et al. 2008; Zahl et al. 2011) express considerable doubts on the value of breast cancer screening. The details behind explanatory and pragmatic trial designs are addressed in the present paper. "
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    ABSTRACT: Rising concern for demonstrated real world comparative effectiveness has heightened interest in "pragmatic trials" design. Pragmatic trials investigate whether the efficacy, presumed or found in explanatory trials under ideal conditions, can also be detected under real world conditions, i.e. effectiveness. It is also recognized that 'real world' effects which are usually addressed in public health research gain growing interest in confirming the 'road capability' of results obtained under ideal study conditions. This paper demonstrates that studies under ideal or real world conditions use different methods, generate different information and cannot replace each other. The PCT design meets four requirements of public health and of effectiveness research. It includes all individuals who presented with the selected condition. It classifies the included individuals according to baseline risks. It enables plausibility controls. Finally, it compares the outcomes resulting from specified and not-specified interventions or treatments. We propose a pragmatic controlled trial (PCT) design in which patient preference and other co-factors crucial in determining the actual effectiveness of interventional options will not be neutralized by concealed randomization and blinding. This design is applicable to record the selected interventions and generated outcomes in day-to-day health care and is capable of incorporating preference and other participative factors into assessment of effectiveness. The PCT design is useful for public health research, e.g. the effectiveness of interventions to change smoking habits or to prevent death from breast cancer, as well as for comparative effectiveness research where it will supplement the traditional randomized controlled trial (RCT).
    Journal of Public Health 06/2013; 21(3):307-313. DOI:10.1007/s10389-012-0544-5 · 2.06 Impact Factor
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