BREAST CANCER SCREENING
Highlights from Office Gynecology/Women’s Health for Primary Care, presented by the David Geffen School of Medicine
at the University of California, Los Angeles
Jodi Friedman, MD, Associate Clinical Professor of Internal Medicine, the David Geffen School of Medicine at the
University of California, Los Angeles
| Incidence: breast cancer most prevalent cancer in women; second leading cause of cancer deaths (lung cancer leading
cause in women); lifetime risk of developing breast cancer ≈12%; lifetime risk of mortality from breast cancer
≈3.5%; 85% of breast cancer occurs in women >50 yr of age; ≈10% in women in 40s; 5% in women <40 yr of age
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| Risk factors: age—most important risk factor; prevalence increases with aging; low likelihood woman in 30s will develop
breast cancer; genetic predisposition—positive family history in 20% of women with breast cancer; lifetime
risk 50% higher than general population if woman has one first-degree relative who developed breast cancer postmenopausally;
almost 3-fold increased risk if first-degree relative developed breast cancer <30 yr of age; ≈3-fold increased
risk with 2 first-degree relatives with breast cancer; hereditary breast cancer—BRCA1 and BRCA2 mutations;
accounts for ≈5% of all breast cancers; confers 65% to 85% lifetime risk of developing breast cancer; 50% of hereditary
breast cancer occurs in women <50 yr of age; estrogen exposure—timing of exposure to high levels important
factor; 3-fold increased risk if patient has first child >30 yr of age compared to woman having first child at young age;
data show significantly increased risk for breast cancer among women in highest quartile of bone mineral density
(BMD) compared to women in lowest quartile (BMD considered marker for lifetime estrogen exposure); breast
characteristics—increased risk with history of breast biopsy, whether biopsy result benign or atypical hyperplasia
(probably related to higher breast density); women in highest quartile for breast density on mammography have 1.8- to
6-fold increased relative risk of developing breast cancer compared to women in lowest quartile (likely related to
higher endogenous estrogen states in higher density breast tissue); race and socioeconomic factors—highest in white
women; 2-fold increased risk among women of higher socioeconomic status
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| Gail model: 5-yr breast cancer risk assessment tool; does not indicate patient’s risk of carrying BRCA1 or BRCA2 mutation;
takes into account only number of first-degree relatives with breast and ovarian cancer (not multi-generational);
low–average risk—<1.66%; standard screening; moderate risk—>1.66%, unlikely BRCA1 or BRCA2; employ standard
screening; consider chemoprevention; high risk—likely BRCA1 or BRCA2; refer for genetic counseling and testing
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| Screening in women at average risk
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 | Breast self-examination (BSE): randomized controlled trials (RCTs) looked at efficacy of instructing patient how to
do monthly SBE vs no monthly SBE; 5- to 14- yr follow-up; data show no reduction in mortality from breast cancer,
or significant improvement in number or stage of cancers detected, in women doing monthly BSE vs those not
doing monthly BSE; Russian study (at 9 yr) has shown nonsignificant trend toward decreased mortality in group
doing BSE (follow-up continuing); all trials showed ≥ 2-fold increase in biopsies (benign) in BSE groups
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| Clinical breast examination (CBE): no direct evidence comparing CBE alone to no screening; reductions in mortality
observed when used with mammography; ≈10% of screen-detected cancers detected by clinicians on physical
examination and missed by mammography (majority in younger women)
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| Mammography: positive predictive value (sensitivity and specificity) increases as woman ages (breast becomes less
dense, easier to detect lesions); 8 RCTs showed results ranging from no improvement in reduction of mortality from
breast cancer to 32% improvement in women getting screened; U.S. Preventive Services Task Force (USPSTF)—
meta-analysis of 7 RCTs looking at benefit of mammography in reducing mortality from breast cancer; involved
women >50 yr of age; showed 22% reduction in breast cancer mortality in woman screened with mammography
(50% of studies included CBE as well); other studies support ≈20% decreased reduction in mortality from breast
cancer among women screened regularly by mammography; women in 40s—benefits of mammography more controversial;
study results more varied; mortality benefit often delayed; some observed benefit may be due to women
now in 50s; recent meta-analysis showed 15% reduction in mortality in women beginning screening in 40s; older
women—limited trial data; only one study included women up to 74 yr of age; increased prevalence of disease,
coupled with higher positive predictive value of mammography as woman ages, will improve reduction in mortality
from breast cancer; consider patient’s competing comorbidities when deciding whether to screen; American Geriatrics
Society (AGS) recommends screening with ≥ 4-yr life expectancy and adequate functional status
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| Screening recommendations
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| BSE: USPSTF—I (indeterminate) recommendation; American Cancer Society (ACS), American Medical Association
(AMA), American College of Obstetricians and Gynecologists (ACOG), and American Academy of Family Physicians
(AAFP)—support teaching BSE; Canadian Task Force on Preventive Health Care (CTFPHC)—recommends
against BSE because of increased false positives
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| CBE and mammography: USPSTF and AAFP—recommend screening with or without CBE every 1 or 2 yr beginning at
40 yr of age (B recommendation, reasonably good evidence); AMA, American College of Radiology (ACR), ACS, and
ACOG—recommend annual mammography and CBE beginning at 40 yr of age; ACOG—recommends CBE annually
beginning at 19 yr of age; CTFPHC and American College of Preventive Medicine (ACPM)—recommend beginning
mammography screening and CBE at 50 yr of age for average-risk woman; ACPM—recommends beginning at 40 yr
of age if woman high risk
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| Women at high risk: 2 studies published in 2004 looking at enhanced screening (usual care plus magnetic resonance
imaging [MRI]; some women also underwent ultrasonography [US]); for women at high risk for breast
cancer (carriers of BRCA1 or BRCA2 mutations), MRI detected 77% of cancers, mammography detected 36%,
US detected 33%, and CBE detected ≈10%; one interval cancer occurred (not detected by any modality); 7 cancers
detected only on MRI, 2 detected only with US, and 2 with only mammography; enhanced surveillance using
combination of modalities recommended for BRCA carriers; MRI associated with 25% false-positive rate;
combined modalities had 95% sensitivity, compared to 45% sensitivity for mammography with CBE; study not
designed to determine whether enhanced detection reduced breast cancer mortality; conclusions—women with
BRCA mutations should be enrolled in clinical trials of enhanced screening; when not possible, enhanced screening
with MRI (or perhaps US) may be of benefit; MRI and/or US not recommended for women at lower risk, including
those with family history of breast cancer; further studies needed
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| Screening for breast cancer gene mutations: BRCA1 and BRCA2 account for ≈85% of hereditary breast and
ovarian cancer, but <10% of all breast cancer; autosomal-dominant inheritance with incomplete penetrance (could
be carriers of gene mutation that do not develop cancer, but multiple generations of breast ovarian cancer seen in
family pedigree); 1 in 800 women have BRCA mutation; 2 to 3 out of 100 women of Ashkenazi Jewish ancestry
carry mutation; mutation increases risk for breast, ovarian, and prostate cancer; by 70 yr of age, female carrier has
80% risk for breast cancer; BRCA1 mutation carries 44% to 63% lifetime risk for ovarian cancer, and BRCA2 mutation
carries 27% lifetime risk; probability models exist (see Resources); important that patient receive pretest and
posttest counseling by geneticist; who to refer for testing—known family member with BRCA1 or BRCA2 mutation;
family member with both breast and ovarian cancer; 2 family members <50 yr of age with breast cancer, or one
family member <40 yr of age with breast cancer; family history of male breast cancer; 1 family member <50 yr of
age with breast cancer and Ashkenazi Jewish ancestry; 1 family member with ovarian cancer and Ashkenazi Jewish
ancestry
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| Risk reduction options for women at high risk: surgery—prophylactic oophorectomy (earlier the better) decreases
risk for breast cancer 50%; risk decreased by ≥90% with prophylactic mastectomy; tamoxifen—effective in
decreasing risk for breast cancer in high-risk women; limited data looking at BRCA carriers; effective only in decreasing
estrogen-receptor (ER)–positive tumors (most BRCA2 breast tumors ER-positive, but only small fraction
of BRCA1 tumors ER-positive); enhanced surveillance—no evidence-based guidelines; National Comprehensive
Cancer Network (NCCN) recommends monthly BSE beginning at 18 yr of age, semiannual CBE beginning at 25
yr of age, and annual mammography beginning at 25 yr of age; consider MRI beginning at 25 yr of age
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| Chemoprophylaxis for prevention of breast cancer
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| Tamoxifen: selective estrogen receptor modulator (SERM); agonist in bones, uterus, and liver; antagonist in breast
and centrally; The National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 Study —RCT; >13,000
women; 20 mg tamoxifen daily for 5 yr vs placebo; 5-yr Gail model risk >1.66%; subgroup of subjects had lobular
carcinoma in situ (LCIS; confers higher risk of developing breast cancer); data showed tamoxifen reduced
breast cancer by ≈50%; trial stopped early because of significant statistical differences between groups; effect
entirely due to decrease in ER-positive tumors (no effect on ER-negative tumors); 62% reduction in breast cancer
in women with BRCA2 mutation; older women and women with LCIS derived most benefit in reduction of
breast cancer; no difference in survival; European studies—conflicting results; did not show benefit; International
Breast Cancer Intervention Study—showed 32% reduction in breast cancer; significant number of deaths from
other causes in tamoxifen group; summary of RCT data—38% reduction in breast cancer risk; trials not designed
to assess whether reduction in breast cancer incidence leads to reduction in breast cancer mortality; effect on
overall survival unclear
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| Adverse effects of tamoxifen: estrogen-deficiency symptoms in ≤20%; 3-fold increase in thromboembolic events;
2-fold increase in stroke; 4-fold increase in endometrial cancer in women >50 yr of age; small increased risk for
cataracts
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| Recommendations: USPSTF—recommends for women at high risk (fulfill NSABP P-1 criteria); must balance
benefits against risks; eg, in woman 45 yr of age with 1.66% risk of breast cancer over next 5 yr, will prevent 3
times as many invasive cancers (8 per 1000) as number of serious thromboembolic complications caused (1
stroke and 1-2 pulmonary embolisms per 1000); benefit exceeds harm in woman 55 yr of age, only if she has no
uterus and 5-yr risk ≥4%; American Society of Clinical Oncology (ASCO)—recommends for women at high risk
based on NSABP P-1 criteria, but also suggests weighing risk/benefit ratio; Gail model criteria—consider if
woman <50 yr of age with 5-yr risk between 1.5% and 7%; or 50 to 59 yr of age, with uterus and 5-yr risk >6%,
or 50 to 59 yr of age, without urterus and 5-yr risk 3%
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| Raloxifene: Multiple Outcomes of Raloxifene Evaluation (MORE) trial—RCT; raloxifene vs placebo; women with
osteoporosis enrolled; showed significant reduction in ER-positive breast cancer tumors in women with osteoporosis;
increased thromboembolic disease and increased stroke; Study of Tamoxifen and Raloxifene (STAR)
trial—NSABP P-2; RCT of tamoxifen vs raloxifene for 5 yr; >19,000 women enrolled; similar efficacy (40%-
50%) in decreasing invasive breast cancer (raloxifene not as efficacious as tamoxifen in decreasing ductal carcinoma
in situ [DCIS]); 38% reduction in uterine cancer seen in raloxifene arm compared to tamoxifen (not statistically
significant, may be due to low number of enrollees with uterus); fewer thromboembolic events and
cataracts in raloxifene arm; no difference in stroke, ischemic heart disease, or osteoporotic fractures; no difference
in total number of deaths; quality of life issues similar in both groups
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Suggested Reading
ACOG Committee Opinion. Number 334, May 2006 (replaces No. 186, September 1997): Role of the obstetrician-gynecologist
in the screening and diagnosis of breast masses. Obstet Gynecol 107:1213, 2006; Calderon-
Margalit R et al: Prevention of breast cancer in women who carry BRCA1 or BRCA2 mutations: a critical review
of the literature. Int J Cancer 112:357, 2004; Dite GS et al: Familial risks, early-onset breast cancer, and
BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst 95:448, 2003; Rosolowich V et al: Breast self-examiantion.
J Obstet Gynaecol Can 28:728, 2006; Samuel JC et al: Prophylaxis and screening options: recommendations
for young women with BRCA mutations. Breast Dis 23:32, 2005-2006.
Resources
Breast cancer risk assessment tool: www.cancer.gov/bcrisktool
CancerGene computer program: www3.utsouthwestern.edu/cancergene
Educational Objectives
| The goal of this program is to improve and increase use of screening and preventive options in breast cancer management.
After hearing and assimilating this program, the clinician will be better able to:
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| 1. Identify women at risk of developing breast cancer.
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| 2. Summarize and evaluate trial data on the efficacy of breast cancer detection modalities.
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| 3. Select the most appropriate breast cancer screening protocol for each patient.
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| 4. Assess risk-reduction options for patients at high risk for breast cancer.
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| 5. Summarize trial data evaluating tamoxifen and raloxifene for the prevention of breast cancer.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Dr. Friedman was recorded at Office Gynecology/Women’s Health for Primary Care, sponsored by the David Geffen
School of Medicine at the University of California, Los Angeles, and held on July 27-30, 2006, in Anaheim, CA.
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