Chapter 078. Prevention and Early Detection of Cancer (Part 9) potx

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.