Breast cancer is a proliferation of malignant cells that arises in the breast tissue, specifically in the terminal ductal-lobular unit. The term "breast cancer" represents a continuum of disease, ranging from noninvasive to invasive carcinoma. Screening techniques may detect any of these disease entities as well as noncancerous lesions such as benign breast cysts. This systematic evidence review is prepared for the U.S. Preventive Services Task Force (USPSTF) to update its previous recommendation on breast cancer screening for average-risk women.1 In 2002, based on results of a systematic evidence review, the USPSTF recommended screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women age 40 years and older. The USPSTF concluded that the evidence was insufficient to recommend for or against routine CBE alone to screen for breast cancer. The USPSTF also concluded that the evidence was insufficient to recommend for or against teaching or performing routine breast self examination (BSE). Breast cancer is the most frequently diagnosed non-cutaneous cancer and the second leading cause of cancer deaths after lung cancer among women in the United States. In 2008, an estimated 182,460 cases of invasive and 67,770 cases of noninvasive breast cancer were diagnosed, and 40,480 women died of breast cancer. The incidence of breast cancer increases with age. Based on Surveillance Epidemiology and End Results (SEER) data from 2002-2004, the National Cancer Institute (NCI) estimates that 14.7% of women born in the United States today will develop breast cancer in their lifetimes, 12.3% with invasive disease. The probability of a woman developing breast cancer in her forties is 1 in 69, in her fifties 1 in 38, and in her sixties 1 in 27. Although the incidence rate of breast cancer has increased since the 1970s and 1980s, recent data suggest that it may have stabilized between 2001-2003. Overall, the incidence rate declined by 6.7% between 2002-2003 from 137.3 to 124.2 per 100,000 women. Age-adjusted incidence rates for breast cancer also declined each year during 1999-2003. This trend may be attributed to discontinuation of menopausal hormone therapy, and a plateau or decline in use of screening mammography. Breast cancer mortality has decreased since 1990 at a rate of 2.3% per year overall. An evaluation of mortality trends from 1990 through 2000 from 7 studies attributed 28-65% of the decline to mammography screening, while the remainder of the decline was due to improved adjuvant treatments. The USPSTF and Agency for Healthcare Research and Quality (AHRQ) developed the key questions that guided the update. The target population includes women without preexisting breast cancer and not considered at high risk for breast cancer based on extensive family history of breast or ovarian cancer or other personal risk factors, such as abnormal breast pathology or deleterious genetic mutations. Key questions include: 1a. Does screening with mammography (film and digital) or MRI decrease breast cancer mortality among women age 40-49 years and greater than or equal to 70 years? 1b. Does CBE screening decrease breast cancer mortality? Alone or with mammography? 1c. Does BSE practice decrease breast cancer mortality? 2a. What are the harms associated with screening with mammography (film and digital) and MRI? 2b. What are the harms associated with CBE? 2c. What are the harms associated with BSE? Harms include radiation exposure, pain during procedures, patient anxiety and other psychological responses, consequences of false-positive and false-negative tests, and over diagnosis. Over diagnosis refers to women receiving a diagnosis of invasive or noninvasive breast cancer who had abnormal lesions that were unlikely to become clinically evident during their lifetimes in the absence of screening. Over diagnosis may have more effect on women with shorter life expectancies because of age or comorbid conditions.