Evidence for U . S . Preventive Services Task Force ( USPSTF ) Recommendations Against Routine Mammography for Females between 40-49 Years of Age

Breast cancer (BC) is the most common cancer among females, worldwide (DeSantis et al., 2011). It accounts for 22.9% of all cancers (excluding non-melanoma skin cancer) in females (Elmore et al., 2005). In 2008, it caused 458,503 deaths, worldwide (13.7% of cancer deaths in females and 6.0% of all cancer deaths for both males and females) (Garfinkel et al., 2009). Since 1970s, the number of cases worldwide has significantly increased that is partly attributed to the modern lifestyles (DeSantis et al., 2011). Based on current incidence rates, 12.4 percent of females born in the United States, today, will develop BC at some time during their live (Elmore et al., 2005). Recently, the World Cancer Research Fund (WCRF) indicated that females could reduce the risk of BC by a healthy weight, drinking less alcohol, being physically active and breastfeeding their children (Food). Studies suggest that these modifications might prevent 38% of BCs in the US, 42% in the UK, 28% in Brazil and 20% in China (Food). The most common early symptom of BC is typically a lump that feels different from the rest of the breast tissue (Amir et al., 2010). More than 80% of BC cases are discovered when the woman feels a lump (Skaane, 2011). This asymptomatic phase can be detected by screening methods (Lee et al., 2010). Mammography is a sensitive (77-95%) and specific (94-


Introduction
Breast cancer (BC) is the most common cancer among females, worldwide (DeSantis et al., 2011).It accounts for 22.9% of all cancers (excluding non-melanoma skin cancer) in females (Elmore et al., 2005).In 2008, it caused 458,503 deaths, worldwide (13.7% of cancer deaths in females and 6.0% of all cancer deaths for both males and females) (Garfinkel et al., 2009).Since 1970s, the number of cases worldwide has significantly increased that is partly attributed to the modern lifestyles (DeSantis et al., 2011).Based on current incidence rates, 12.4 percent of females born in the United States, today, will develop BC at some time during their live (Elmore et al., 2005).
Recently, the World Cancer Research Fund (WCRF) indicated that females could reduce the risk of BC by a healthy weight, drinking less alcohol, being physically active and breastfeeding their children (Food).Studies suggest that these modifications might prevent 38% of BCs in the US, 42% in the UK, 28% in Brazil and 20% in China (Food).The most common early symptom of BC is typically a lump that feels different from the rest of the breast tissue (Amir et al., 2010).More than 80% of BC cases are discovered when the woman feels a lump (Skaane, 2011).This asymptomatic phase can be detected by screening methods (Lee et al., 2010).Mammography is a sensitive (77-95%) and specific (94-

Evidence for U.S. Preventive Services Task Force (USPSTF) Recommendations Against Routine Mammography for Females between 40-49 Years of Age
Parisa Karimi 1 *, Armin Shahrokni 2 , Sedighe Moradi 3 97%) screening method that is performed by using either plain film or digital technologies, although the shift to digital is ongoing (Hirsch and Lyman, 2011).However, while mammography screening is the only method presently considered appropriate for mass screening of asymptomatic female (Smith et al., 2012), there are suggested potential side effects and harms, including radiation exposure, false-positive, false-negative, overdiagnosed, pain and psychological responses (Kolb et al., 2002).
In 2002, based on evidences, the U.S. Preventive Services Task Force (USPSTF) recommended mammography screening, with or without clinical breast examination, every 1-2 years for females age 40 years and older (Nelson et al., 2009).They concluded that the evidence was insufficient to recommend mammography screening for or against routine clinical breast exam alone, and insufficient to recommend for or against performing routine breast self-examination (Nelson et al., 2005).However, in 2009, the USPSTF reversed a previous recommendation that suggests females between the ages of 40 and 50 have mammograms every one to two years (Woolf, 2010).The USPSTF current recommendation states that the decision to start regular, biennial screening mammography for females younger than 50 years should be an individual decision and take patient context into account, including the patient's values regarding specific benefits and harms (Woolf, 2010).
With their grade C rating, the USPSTF recommends against routinely screening mammograms (Hendrick and Helvie, 2011).The USPSTF suggests that the net benefits of screening females between 40-49 years old are likely to be small and may be outweighed by harms such as overtreatment (DeAngelis and Fontanarosa, 2010).This decision was based on the evidence, as follows.

Radiation Exposure
Most mammographies are considered low-dose, lowenergy radiation, with the mean glandular dose of bilateral, 2-view averaging 7 mGy (Spelic, 2010).For females aged 40-49 years, yearly mammography screening for 10 years with potential additional imaging would expose an individual to approximately 60 mGy, although these levels vary (Armstrong et al., 2007).Systematic reviews that evaluate the effect of high-dose exposure of radiation exposure of radiation therapy and diagnostic radiation on BC, indicated that Relative Risks (RRs) ranged from 1.33-11.39for exposures of 0.3-43.4Gy and were worse with higher doses of exposure, younger age at exposure, and longer follow-up (Armstrong et al., 2007).
However, 10 years radiation exposure due to screening mammography and potential additional imaging much less than this amount (Armstrong et al., 2007).A recent case-control study found that females exposed to diagnostic x-rays for screening or monitoring tuberculosis or pneumonia, or therapeutic radiation for a prior cancer, had increased risks for BC (Ravdin et al., 2007).Nevertheless, no published studies have directly measured the association between radiation exposure from mammography screening and BC risk and this clearly remains a concern.

False-positives
In a meta-analysis of clinical trials, the probability of a false-positive screening mammography result was ranged 0.9-6.5% (Qaseem et al., 2007).Another systematic review reported 56% cumulative risk for falsepositive mammography results after 10 mammography examinations for females aged 40-49 years old (Hofvind et al., 2004).The Breast Cancer Surveillance Consortium (BCSC) reports indicate that for every case of invasive BC detected by mammography screening in females aged 40-49 years, 556 females have mammography, 47 have additional imaging, and 5 undergo biopsies (Nelson et al., 2009).

False-negatives
There are only few studies that evaluated the effect of negative mammography results (Drossaert et al., 2001).False-negative mammography results occur least among females 40-49 years old (1.0 per 1000 females per screening round) (Drossaert et al., 2001).However, additional studies seem necessary to understand the rate and burden of false-negative mammography findings in these females.

Over-diagnosis
False-positive results in mammography cause over-diagnosed cases that lead to additional imaging or histopathological assessment, mainly percutaneous breast biopsy (Kolb et al., 2002).It is reported that only in 2006, one-eighth of all invasive cancers detected by mammography were found over-diagnosed (Michell, 2012).About 8.7% of females attending their first screen and 3.4% of females attending for subsequent screens are recalled for further assessment, including clinical examination, imaging and in some cases needle biopsy (Elmore et al., 2005). During 2008and 2009, 2,078,195 females were screened, 91,395 (4.4%) were recalled and 16,535 (0.8%) were diagnosed with cancer (Elmore et al., 2005).A review of several randomized controlled trials show that the absolute excess cumulative incidence of over-diagnosed BC ranged from 0.07-0.73per 1000 woman-years (Moss, 2005).In these studies, total of 120,352 females, aged 40-49 years, randomly assigned to intervention (received screening mammography) and controls (did not received screening mammography) (Moss, 2005).However, a potential bias in these studies is the imbalance in socio-economic status, reflected in all-cause mortality, which is likely to have resulted in an increased risk of BC in the intervention group.Another meta-analysis of several randomized controlled trial studies suggest that rates of over-diagnosis vary from less than 1-30%, with most from 1-10% (Nelson et al., 2009).Estimates differ by outcome (invasive vs. in situ BC) and age (Nelson et al., 2009).However, this meta-analysis does not mention any statistically result since the studies were too heterogeneous to combine statistically.

Pain and Psychological Response
Pain and psychological response: To have a clear image at mammography, it is needed to compress and reduce breast thickness during imaging (Spelic, 2010).A recent systematic review of 22 surveys indicated that many females experience pain during the procedure (range, 1-77%), and 12% would consider this a deterrent from future screening (Armstrong et al., 2007).However, the scaling for measuring pain was not the same in theses studies and considered a potential bias.Also, pain could be associated with the stage of the menstrual cycle, anxiety, and the anticipation of pain that were not considered in most of theses studies.
Furthermore, the psychological responses (e.g.anxiety and distress) of females undergoing mammography were evaluated in many studies but the results were conflicting.Systematic review of cohort studies indicated that females who received clear communication of their negative mammography results had minimal anxiety (Brett et al., 2005).However, several studies reported that females had persistent anxiety, despite eventual negative results, whereas some showed only transient anxiety (Brewer et al., 2007).Further studies with more power seem necessary to evaluate pain and psychological response in these female.
In addition, the difficulties of mammography