BREAST CANCER
From Scott and White’s The Adult Patient: Male and Female Issues
Anita L. Nelson, MD, Professor, Department of Obstetrics and Gynecology, David Geffen School of Medicine at the
University of California, Los Angeles
| Prevalence: breast cancer most common cancer in women; second most common cause of cancer deaths (colon
cancer third most common); >200,000 cases diagnosed in 2004; 40,000 deaths; accounts for 16% of cancers
among white women (higher for minority women); incidence of 1 in 8 based on theoretical model of woman
living to 90 yr of age; risk increases with age, peaks at 80 yr of age (85 yr of age for black women), then decreases;
breast cancer in black women <20 yr of age frequent enough to be statistically notable (pay close attention
to fibroadenomas); by time woman 25 to 30 yr of age, risk of getting breast cancer exceeds risk of sum
of all other cancers screened
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| Risk factors: most women who develop breast cancer have no family history of breast cancer; breast cancer associated
with family history no higher than 1 in 5
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 | Personal history of breast cancer: warrants close surveillance; on average, patient has 1% chance per year of
getting second primary mass
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| Long-term exposure to estrogen: issue of age, not hormones; studies show woman who goes through menopause
at 50 yr of age and uses estrogen and progestin for 5 yr has same risk of developing breast cancer as
woman who continues to menstruate and does not go through menopause until 55 yr of age; pay close attention
to patient with report of atypical hyperplasia of lobular or ductal types (precursor to breast cancer); exposure
to environmental factors
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| Factors shown to have no effect on development of breast cancer: oral contraceptives—shown to have no relationship
at all to breast cancer; breast augmentation; smoking; abortion; breast-feeding—protective with cumulative
time of 2 yr; fat intake—one study showed reduction in risk for second episode of breast cancer
with reduced fat intake, but same investigators showed no improvement in incidence of breast cancer with
reduced fat intake
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| Self breast examination (SBE): dominant masses generally found by patients before routine screening mammography;
masses found by patients larger than ones found on clinical breast examination (CBE); data show intensive
instruction in SBE did not reduce mortality from breast cancer and may increase woman’s chance of
having unnecessary intervention; American Cancer Society and American College of Obstetricians and Gynecologists
(ACOG) endorse position that SBE should be encouraged and taught only to women motivated
to practice technique; CBE detects ≈44% of masses; complements screening mammography; avoid medicolegal
risk—indistinct fullness consistent with fibrocystic changes common in luteal phase of menstrual cycle;
use crosshatches rather than circle to indicate size and location of indistinct fullness (circle denotes dominant
mass); K-Y Jelly—apply to area being examined; beneficial in distinguishing between indistinct fullness or
dominant mass
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| Mammography: 1 mm size at which mass first detectable on mammography; all forms of breast cancer treated
at systemic level because cancerous mass exists almost 7 yr before seen on mammography, providing opportunity
for hematogenous spread of cancer; mammography important screening tool, providing opportunity
to discover preinvasive cancer; however, current evidence does not show survival benefit of mass
screening for breast cancer (evidence considered inconclusive); inconclusive findings—can have psychologic
and emotional effects and can affect long-term health behaviors of woman; screening interval—unknown
whether safe to extend interval between screenings; screening nursing home patients—decision should be individualized
and based on estimated longevity; screening younger women—no data supporting screening of women
40 to 50 yr of age; decision to screen annually based on politics, not science; aggressive cancers tend to develop
in younger women, so occasional screening not appropriate; annual screening recommended for
younger women
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| Ultrasonography (US): as screening test, not as good as mammography; cannot detect calcifications; helpful
adjunct to mammography in characterizing mass as solid or cystic
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| Emerging technologies: image checker—used in conjunction with mammography; highlights suspicious areas;
improves sensitivity; does not increase false-positives; digital mammography—breast tissue seen as series of
zeros and ones; zeros and ones can be sent over telephone line, allowing for comparison of films; currently
not shown to be superior to regular screening mammography; ductal lavage and mammary aspiration specimen
cytology test (MASCT)—reserved for high-risk women
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| Identifying women at high risk: ultra high-risk—carrier of breast cancer 1 (BRCA1) gene mutation; moderate-
risk—1 or 2 relatives with breast cancer (usually postmenopausal onset); usually no other related tumors,
ie, ovarian, uterine
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| Mathematical models for calculating risk: Gail model—used in clinical trials involving tamoxifen; calculates
woman’s risk of developing breast cancer within next 5 yr and over entire lifetime; underestimates probability
of developing breast cancer if woman has never had routine screening mammography; Claus model —used
in population of women who have never undergone screening mammography, so probability number higher
than Gail model; both models based on age, age at menarche, family history of breast cancer, and findings on
breast biopsies
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| Family history: confirm that family member with breast cancer blood relative; patient has 13% to 21% risk of
developing breast cancer with mother, sister, or daughter having breast cancer at <50 yr of age; the younger
first-degree relative develops breast cancer, the more likely patient will develop it; patient’s probability of
developing breast cancer no higher with one second-degree relative developing breast cancer at >50 yr of
age; ultra high-risk—possibility patient may have genetic mutation with 2 first-degree relatives who develop
breast cancer at <50 yr of age; 50% chance with >2 breast cancers in close relative with autosomal dominant
pattern diagnosed at early age; high-risk population accounts for about one third of 1% of general population,
but responsible for 5% of all breast cancers; women of Ashkenazi Jewish descent at high risk of
carrying BRCA1 mutation; paternal side of family contributes equally to risk; 85% chance woman with
BRCA1 mutation will develop breast cancer by 70 yr of age (similar with BRCA2); mutations increase risk
for colon cancer in men and women and prostate cancer in men; BRCA gene mutation testing—should be reserved
for woman who develops breast cancer at young age, has ovarian cancer, has 3 relatives with breast
cancer, or is of Ashkenazi Jewish descent; when providing information for family members, testing should
be limited to person diagnosed with disease, and only if test positive should other family members be
tested; consider sequelae of testing family members, eg, insurance issues
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| Prophylactic interventions
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| Bilateral prophylactic mastectomy: extreme measure; 96% reduction of breast cancer in high-risk population;
requires extensive psychologic profiling; Cancer Genetic Studies Consortium states insufficient evidence
for or against mastectomy
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| Salpingooophorectomy: resultant long-term estrogen deficiency increases risk for osteoporosis; provides significant
reduction in chance of developing breast cancer; reduces, but does not eliminate, risk for ovarian cancer
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| Chemoprophylaxis: tamoxifen used in woman with history of one primary episode to arrest possibility of development
of second tumor; binds to estrogen receptor; has chemostatic effect (does not kill cancer cells, holds
them in suspended animation); should not be given to low-risk women; increases risk for endometrial cancer
and venous thromboembolism; should be given only when benefits outweigh risks; in United States, data show
50% reduction in invasive and noninvasive breast cancer; higher effectiveness in receptor-positive breast cancer;
recommended for woman with absolute risk (not relative risk) >1.77 in next 5 yr; woman with 5-yr risk >1.66
should be offered option; greatest benefit seen in premenopausal women, women without uterus, and those with
>5% risk in next 5 yr; tamoxifen acts like estrogen in clotting system, so stop medication if woman undergoing
surgery or immobilized (or initiated on antithrombotic drug); study currently investigating whether raloxifene
equally effective or superior to tamoxifen
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| Aromatase inhibitors: do not block estrogen receptors, prevent patient from making estrogen; in preliminary
studies, superior to tamoxifen in reducing risk of developing second cancer in contralateral breast; associated
with less uterine bleeding, venous thromboembolism, and hot flushes than tamoxifen, but more musculoskeletal
disorders and more fractures
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| Screening issues for high-risk women: use caution with screening tests in women with BRCA1 or BRCA2
gene mutation; woman with BRCA2 gene mutation cannot repair damage caused by radiation from mammography;
MRI more sensitive in detecting early breast cancer and does not emit radiation; good screening
tool for ultra high-risk women; US reasonable tool to use to characterize mass in younger woman; consider
chemoprevention or salpingooophorectomy if woman BRCA1 gene mutation carrier, >35 yr of age, and finished
childbearing; if woman identified as BRCA1 carrier, screen for ovarian cancer with transvaginal US
and CA125; oral contraceptives recommended if family history suggestive of mutation
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Educational Objectives
| The goal of this program is to educate the listener about screening for breast cancer and prophylactic interventions
for breast cancer in high-risk women. After hearing and assimilating this program, the clinician will be
better able to:
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| 1. List the risk factors associated with the development of breast cancer.
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| 2. Apply guidelines for breast cancer screening and recognized emerging breast cancer screening technologies.
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| 3. Discuss the importance of adhering to breast cancer interval screening guidelines in younger women.
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| 4. Identify patients at high risk of developing breast cancer and identify the appropriate mathematical model
for calculating risk in a particular woman.
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| 5. List prophylactic interventions for reducing breast cancer in high-risk women.
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Discussed on This Program
Raloxifene [Evista]
Tamoxifen citrate [Nolvadex]
Suggested Reading
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(3):357, 2004; Elmore JG et al: Screening for breast cancer. JAMA
293(10):1245, 2005; Lehman CD et al: Screening women at high risk for breast cancer with mammography and
magnetic resonance imaging. Cancer 103(9):1998, 2005; Grimes DA et al: Perspectives on the Women’s Health
Initiative trial of hormone replacement therapy. Obstet Gynecol 200(6):1344, 2002; Marshall LM et al: Risk of
breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol Biomarkers Prev
6(5):297, 1997; Rebbeck TR et al: Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and
BRCA2 mutation carriers: the PROSE study Group. J Clin Oncol 22(6):1055, 2004; Robson M: Breast cancer
surveillance in women with hereditary risk due to BRCA1 or BRCA2 mutations. Clin Breast Cancer 5(4):260,
2004; Thomas DB et al: Randomized trial of breast self-examination in Shanghai: final results. J Natl Cancer Inst
94(19):1445, 2002; Weiss NS: Breast cancer mortality in relation to clinical breast examination and breast self-
examination. Breast J 9 Suppl 2:S86-9, 2003.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed.
The following has been disclosed: Dr. Nelson has received research grants from Berlex, Organon, and Pfizer
and has served as a consultant or an advisory board member for Ascend Therapeutics, Barr, Berlex, Ortho-McNeil,
Organon, Pfizer, and Wyeth. Dr. Nelson is on the Speakers’ Bureau or has received honoraria from Barr,
Berlex, FEI Women’s Health, Merck, Organon, Ortho-McNeil, Pfizer, and Wyeth.
Dr. Nelson was recorded at The Adult Patient: Male and Female Issues, sponsored by Scott & White, and held on
June 20-24, 2005, in South Padre Island, Texas. The Audio-Digest Foundation thanks Dr. Nelson and Scott &
White for their cooperation in the production of this program.
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