Chapter 078. Prevention and Early Detection of Cancer (Part 9) Breast Cancer Breast self-examination, clinical breast examination by a care giver, and mammography have been advocated as useful screening tools. Only screening mammography alone and screening mammography with clinical examination have been evaluated in randomized controlled trials. MRI is being assessed and is more accurate than mammography in women at high risk due to genetic predisposition or in women with very dense breast tissue. A number of trials have suggested that annual or biennial screening with mammography or mammography plus clinical breast examination in normal-risk women over the age of 50 decreases breast cancer mortality. Each trial has been criticized for design flaws. In most trials, breast cancer mortality rate is decreased by 20–30%. Experts disagree on whether average-risk women age 40–49 should receive regular screening (Table 78-3). The significance of the screening effect in women aged 40–49 depends on the statistical test used. An analysis of eight large randomized trials showed no benefit from mammography screening for women aged 40–49 when assessed 5–7 years after trial entry. However, a small benefit emerged 10–12 years after study entry. What proportion of this benefit is due to screening after these women turned 50 is not known. In randomized screening studies of women aged 50–69, the mortality decline begins about 5 years after initiation of screening. Nearly half of women aged 40–49 screened annually will have false-positive mammograms necessitating further evaluation, often including biopsy. The risk of false-positive testing should be discussed with the patient. No study of breast self-examination has shown it to decrease mortality; however, it is recommended as prudent by many organizations. A substantial fraction of breast cancers are first detected by patients. Self-examination leads to increased biopsy rate without reducing breast cancer mortality. Genetic screening for BRCA1 and BRCA2 mutations and other markers of breast cancer risk has identified a group of women at high risk for breast cancer. Unfortunately when to begin and the optimal frequency of screening have not been defined. Mammography is less sensitive at detecting breast cancers in women carrying BRCA1 and -2 mutations, possibly because such cancers occur in younger women, in whom mammography is known to be less sensitive. MRI screening may be more effective. Cervical Cancer Screening with Papanicolaou smears decreases cervical cancer mortality. The cervical cancer mortality rate has fallen substantially since the widespread use of the Pap smear. Most screening guidelines recommend regular Pap testing for all women who are or have been sexually active for 3 years or have reached the age of 21. With the onset of sexual activity comes the risk of sexual transmission of HPV, the most common etiologic factor for cervical cancer. The recommended interval for Pap screening varies from 1–3 years. At age 30, women who have had three normal test results in a row may get screened every 2–3 years. An upper age limit at which screening ceases to be effective is not known, but women ≥70 years with no abnormal results in the previous 10 years may choose to stop screening. Colorectal Cancer Fecal occult blood testing (FOBT), digital rectal examination (DRE), rigid and flexible sigmoidoscopy, radiographic barium contrast studies, and colonoscopy have been considered for colorectal cancer screening. Annual FOBT could reduce colorectal cancer mortality by a third. The sensitivity for fecal occult blood is increased if specimens are re-hydrated before testing, but at the cost of lower specificity. The false-positive rate for rehydrated FOBT is high; 1–5% of persons tested have a positive test. Only 2–10% of those with occult blood in the stool have cancer and 20–30% have adenomas. The high false-positive rate of FOBT dramatically increases the number of colonoscopies performed. Two case-control studies suggest that regular screening of those >50 years with sigmoidoscopy decreases mortality. This type of study is prone to selection biases. A quarter to a third of polyps can be discovered with the rigid sigmoidoscope; half are found with a 35-cm flexible scope and two-thirds to three- quarters are found with a 60-cm scope. Diagnosis of adenomatous polyps by sigmoidoscopy should lead to evaluation of the entire colon with colonoscopy and/or barium enema. The most efficient interval for screening sigmoidoscopy is unknown, but 5 years is often recommended. Case-control studies suggest that intervals of up to 15 years may confer benefit. One-time colonoscopy detects ~25% more advanced lesions (polyps > 10 mm, villous adenomas, adenomatous polyps with high-grade dysplasia, invasive cancer) than one-time FOBT with sigmoidoscopy. Colonoscopy is well suited to screening subjects at high risk, such as those with ulcerative colitis or family predisposition. Perforation rates are 3/1000 for colonoscopy and 1/1000 for sigmoidoscopy. Debate continues on whether colonoscopy is too expensive and invasive for widespread use as a screening tool in standard-risk populations. DRE and barium enema are both insensitive as screening tools. . Chapter 078. Prevention and Early Detection of Cancer (Part 9) Breast Cancer Breast self-examination, clinical breast examination by a care giver, and mammography have. reducing breast cancer mortality. Genetic screening for BRCA1 and BRCA2 mutations and other markers of breast cancer risk has identified a group of women at high risk for breast cancer. Unfortunately. initiation of screening. Nearly half of women aged 40–49 screened annually will have false-positive mammograms necessitating further evaluation, often including biopsy. The risk of false-positive