Benefits and Harms of Mammography Screening

Abstract and Introduction

Abstract

Mammography screening for breast cancer is widely available in many countries. Initially praised as a universal achievement to improve women's health and to reduce the burden of breast cancer, the benefits and harms of mammography screening have been debated heatedly in the past years. This review discusses the benefits and harms of mammography screening in light of findings from randomized trials and from more recent observational studies performed in the era of modern diagnostics and treatment. The main benefit of mammography screening is reduction of breast-cancer related death. Relative reductions vary from about 15 to 25% in randomized trials to more recent estimates of 13 to 17% in meta-analyses of observational studies. Using UK population data of 2007, for 1,000 women invited to biennial mammography screening for 20 years from age 50, 2 to 3 women are prevented from dying of breast cancer. All-cause mortality is unchanged. Overdiagnosis of breast cancer is the main harm of mammography screening. Based on recent estimates from the United States, the relative amount of overdiagnosis (including ductal carcinoma in situ and invasive cancer) is 31%. This results in 15 women overdiagnosed for every 1,000 women invited to biennial mammography screening for 20 years from age 50. Women should be unpassionately informed about the benefits and harms of mammography screening using absolute effect sizes in a comprehensible fashion. In an era of limited health care resources, screening services need to be scrutinized and compared with each other with regard to effectiveness, cost-effectiveness and harms.

Introduction

The verb 'to screen' is defined as 'to sift by passing through a screen'.^[1] 'To 'sift'; derives from an old Dutch word ('zeef'); a 'utensil consisting of a circular frame with a finely meshed or perforated bottom, used to separate the coarser from the finer particles of any loose material'.^[1]

The definitions of screening vary among different cultures, settings, and time periods.^[2,3] In general, all definitions of screening include an identification of disease or disease precursor among presumptively healthy individuals. There are mainly two different approaches of cancer screening: prevention of disease by finding and removing premalignant precursors of cancer; and early detection of cancer where the goal is to treat the invasive cancer in an early curable stage.^[4] In 1968, the World Health Organization suggested 10 principles that should be fulfilled before implementing screening in a population (Table 1).^[5] Some of the principles regard knowledge about biologic development of cancer (principles 4 and 7).

Screening for breast cancer with mammography aims at detecting breast cancer at an early, curable stage. For early detection by screening to be beneficial, we anticipate a continuous, linear growth pattern of tumors, and that breast cancer has not spread at the time when tumors are detectable at mammography. Thus, if the assumptions of tumor growth are not correct or if growth of tumors is heterogenic, screening mammography might not be an adequate tool to reduce the burden of breast cancer.^[6]

The idea of early detection started in the US in the early 20^th century with educational mass campaigns where the message of 'do not delay' seeking medical help for a variety of cancer signs and symptoms was central.^[7] However, none of these early campaigns had an effect on the mortality of breast cancer.^[8] In 1963 the first randomized trial of mammography screening was launched within the Health Insurance Plan in New York,^[8] and several other trials followed.^[9] Most of the trials were performed before widespread use of anti-estrogens and modern chemotherapy with the exception of the Canadian National Breast Screening Study and the age trial.^[10,11]

In contrast to other cancer screening tools, mammography screening was evaluated in randomized trials before it was widely recommended and implemented. Nevertheless, there has been a continuous discussion of mammography screening, which started in full in 2000 after a Cochrane review of the randomized trials indicated little effect of screening.^[12] More recently, the effect of mammography screening outside the experimental setting, in the modern era with improvements in awareness, diagnostics, and treatment, has been discussed.^[13,14]

The mammography debate has not only been about the beneficial effects of mammography screening, but more recently also the harms. In the last 10 years increasing awareness of overdiagnosis in mammography screening has emerged. Overdiagnosis is defined as the detection of tumors at screening that might never have progressed to become symptomatic or life-threatening in the absence of screening. This is a direct harm of screening because markers to distinguish the overdiagnosed tumors from the potential life-threatening tumors are lacking and, thus, all tumors are treated. Women with overdiagnosed tumors only experience the harms and side effects of treatment, without any benefit. In this review we discuss the benefits and harms of mammography screening and give an overview of the findings from randomized trials and from more recent observational studies from the era of modern diagnostics and treatment. We aim at presenting the benefits and harms per 1,000 women invited to mammography screening who started screening at age 50 years and were screened every second year until age 69 years; screening of this age group has been shown to achieve most of the benefit with less harm.^[15,16]

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Table 1. The World Health Organization's 10 principles of screening
1.	The condition sought should be an important health problem
2.	There should be an accepted treatment for patients with recognized disease
3.	Facilities for diagnosis and treatment should be available
4.	There should be a recognizable latent or early symptomatic stage
5.	There should be a suitable test or examination
6.	The test should be acceptable to the population
7.	The natural history of the condition, including development from latent to declared disease, should be adequately understood
8.	There should be an agreed policy on whom to treat as patients
9.	The cost of case-findings (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole
10.	Case finding should be a continuing process and not a 'once and for all' project

Table 2. Different percentages of overdiagnosis and mortality reduction based on the number of cancers overdiagnosed and deaths avoided from breast cancer using different denominators (incidence/death from breast cancer in different age-groups) in Norway in 2010
Age (years)	Expected number of cancers	Percentage of overdiagnosis (n = 714.4)	Expected number of breast cancer deaths	Percentage of mortality reduction (n = 53.7)
50–99	2,208	19.4	693	7.8
50–79	1,571	27.3	506	10.6
50–69	942	45.5	334	16.1

The expected number of breast cancers and breast cancer deaths is estimated as the observed incidence and mortality rates in Norway from 1980 to 1984 multiplied by the Norwegian female population in 2010 [45–47]. The number of overdiagnosed cancers (714.4 cancers) is based on studies by Falk and coworkers [45] and Kalager and coworkers [44] and the number of reduced breast cancers (53.7 avoided deaths from breast cancer) is estimated by reducing the number of expected (358) breast cancer deaths by 15% in the age group 55 to 74 years (358 × 0.15 = 53.7).