Breast Cancer Diagnosis and Screening



Breast Cancer Diagnosis and Screening

|LECIA M. APANTAKU, M.D. |[pic]A patient information |

|Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois |handout on screening for |

| |breast cancer, written by the |

| |author of this article, is |

| |provided on page 605. |

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Approximately 180,000 new cases of breast cancer are diagnosed annually, accounting for about 48,000 deaths per year in the United States. The screening guidelines for the diagnosis of breast cancer are continually changing. Because of increased awareness of the signs and symptoms of breast cancer and the use of screening mammograms, breast cancers are increasingly being diagnosed at earlier stages. Annual mammograms and clinical breast examinations are recommended for women older than 40 years. Women older than 20 years should be encouraged to do monthly breast self-examinations, and women between 20 and 39 years of age should have a clinical breast examination every three years. These guidelines are modified for women with risk factors, particularly those with a strong family history of breast cancer. Ultrasonographic studies are most useful to evaluate cystic breast masses. For solid masses, diagnostic biopsy techniques include fine-needle aspiration, core biopsy and excisional biopsy. (Am Fam Physician 2000;62:596-602,605-6.)

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|See editorial |

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Breast cancer is the second most commonly diagnosed cancer among women, after skin cancer.1 Approximately 182,800 new cases of invasive breast cancer will be diagnosed among women in the United States during 2000.1 After increasing about 4 percent per year during the 1980s, breast cancer rates leveled off in the 1990s to about 110 cases per 100,000 per year.1 Breast cancer is the second leading cause of cancer death in women, after lung cancer. Approximately 48,800 American women are expected to die of breast cancer in 2000.1

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|TABLE 1 |

|Estimated New Breast Cancer Cases in Women |

|by Age |

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|The rightsholder did not grant rights to |

|reproduce this item in electronic media. For|

|the missing item, see the original print |

|version of this publication. |

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Demographics

The incidence of breast cancer increases with age (Table 1).2 White women are more likely to develop breast cancer than black women. The incidence of breast cancer in white women in 1993 was about 113 cases per 100,000 women and in black women, 100 cases per 100,000.2 However, black women younger than 50 years have a higher incidence of breast cancer than white women. In 1993, black women were more likely to die of breast cancer than white women.2 Although breast cancer usually is associated with women, 1 percent of breast cancers occur in men. Men should be aware of the relevant risk factors, including family history, and be encouraged to report any changes in their breasts to a physician.

Risk Factors

Several well-established risk factors (Table 2) are associated with the development of breast cancer,3 primarily age and female sex.4 Family history is highly significant in a first-degree relative (i.e., mother, sister, daughter) especially if the cancer has been diagnosed premenopausally.3 Women who have premenopausal first-degree relatives with breast cancer have a three- to fourfold increased risk of developing breast cancer than women who do not. Having several second-degree relatives with breast cancer may further increase the risk of developing breast cancer, but this risk has not been quantified. It is important to note that most women with breast cancer have no identifiable risk factors.

Approximately 8 percent of all cases of breast cancer are hereditary. About one half of these cases are attributed to mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2.5 Hereditary breast cancer commonly occurs in premenopausal women and is more frequently bilateral than nonhereditary breast cancer.5 Several family members are affected over three generations or more and can include women from the paternal side of the family. Screening tests are available that detect BRCA mutations.

Genetic testing is controversial and raises issues about the reliability of tests and the use made of test results. A woman who tests positive may worry about job or insurance discrimination. She may consider possible prophylactic mastectomy and oophorectomy. A woman who tests negative for a particular mutation may still be at risk for developing breast cancer from a sporadic mutation or a preexisting unidentified mutation. A false-negative test is also possible. Genetic counseling before being tested is highly recommended, and patients are required to sign a consent form.

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|TABLE 2 |

|Risk Factors for Breast Cancer |

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|Age greater than 50 years |

|Prior history of breast cancer |

|Family history |

|Early menarche, before age 12 |

|Late menopause, after age 50 |

|Nulliparity |

|Age greater than 30 at first birth |

|Obesity |

|High socioeconomic status |

|Atypical hyperplasia on biopsy |

|Ionizing radiation exposure |

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|Information from Madigan PM, Ziegler RG, Benichou J, Byrne |

|C, Hoover RN. Proportion of breast cancer cases in the |

|United States explained by well-established risk factors. J |

|Natl Cancer Inst 1987;87:1681-5. |

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Obtaining a history of previous breast biopsy is essential because a history of a proliferative abnormality such as atypical hyperplasia on biopsy may increase a woman's risk for developing breast cancer. A history of breast cancer increases the risk of developing a new breast cancer by 0.5 to 1.0 percent per year.2 Because conservative treatments are increasingly common in women with first breast cancers, many second cancers now appear in the same breast.

Early menarche and late menopause may also increase the risk of breast cancer by affecting lifetime exposure to hormones. Women who give birth to their first child after age 30 or who never become pregnant are also at an increased risk. Apparently, an increase in female reproductive hormones accelerates cell division in breast tissue, which in turn augments the risk of mutations. Use of oral contraceptives may minimally increase the risk of breast cancer, but women who have used oral contraceptives for less than 10 years have the same risk as women who never used them.6 Many studies have looked at the risk of estrogen replacement therapy (ERT). While there may be a slight increased risk with ERT, this risk is usually offset by the benefits.7 High social economic status, white race and exposure to ionizing radiation are other risk factors for developing breast cancer.1

International variations in breast cancer rates appear to correlate with variations in diet, especially fat intake. However, relevant dietary factors have not been firmly established. Other factors that may be associated with increased risk of breast cancer currently being studied include chemical exposure, alcohol consumption, weight gain, induced abortion and physical inactivity. Although women cannot change some of their inherited and personal risk factors, they can alter their diet to one that is low in fat and high in fiber, and reduce alcohol consumption. A recent study8 shows that tamoxifen, the selective estrogen receptor modulator, reduces the risk of developing breast cancer. Raloxifene, a similar compound, may also reduce the risk.9

Signs and Symptoms

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|Although breast mass is the most common presentation |

|of breast cancer, 90 percent of breast masses are |

|caused by benign lesions. |

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Detection of a breast mass is the most common breast complaint for which women seek medical advice. Approximately 90 percent of all breast masses are caused by benign lesions. Smooth and rubbery masses are usually associated with fibroadenoma in women in their 20s and 30s or cysts in women in their 30s and 40s.

Breast pain is also a common presenting problem. Mastalgia is rarely associated with breast cancer and is usually related to fibrocystic changes in premenopausal women. Postmenopausal women receiving estrogen replacement therapy may also present with breast pain caused by fibrocystic changes. The pain of fibrocystic conditions is associated with diffuse lumpy breasts.

Erythema, edema and retraction of the skin or nipple are associated with malignancies. Another common presenting problem is nipple discharge. Discharge from a breast carcinoma is usually spontaneous, bloody, associated with a mass and localized to a single duct in one breast.

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|Malignant breast masses are characteristically |

|solitary, discrete, hard and nontender. |

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Examination of the breast should be performed in the upright (sitting) and supine positions with the woman's hands behind her head. The breasts should be inspected for differences in size, retraction of the skin or nipple, prominent venous patterns and signs of inflammation. The flat surface of the fingertips should be used to palpate the breast tissue against the chest wall. The axillary and supraclavicular areas should be checked for adenopathy. The nipple should be gently squeezed to check for discharge.

A mass that is suspicious for breast cancer is usually solitary, discrete and hard. In some instances, it is fixed to the skin or the muscle. A suspicious mass is usually unilateral and nontender. Sometimes, an area of thickening that is not a discrete mass may represent cancer. Breast cancer is rarely bilateral when first diagnosed.

Diagnosis

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|TABLE 3 |

|Five-Year Survival Rates in Women with Breast Cancer* |

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|Stage at diagnosis |

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|Survival rates (%) |

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|Localized |

|96.8 |

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|Regional |

|75.9 |

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|Distant |

|20.6 |

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|*--Based on U.S. statistics from 1986 to 1993. |

|Reprinted with permission from American Cancer Society. |

|Breast cancer facts and figures. Atlanta: American Cancer |

|Society, 1997:14. |

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Mammography

Mammographic screening is appropriate for asymptomatic women. Diagnostic mammography, which may include additional views, is done for women with signs or symptoms of breast cancer. Any sign of cancer should be communicated to the radiologist with the referral for a diagnostic mammogram.

The American Cancer Society (ACS) and the National Cancer Institute recommend screening mammograms every year for asymptomatic women 40 years and older. As shown in Table 3, the survival rate for women with breast cancer is increased dramatically when diagnosed at an early stage.2 Unfortunately, only 60 percent of cancers are diagnosed at a local stage (Table 4).2 Regular screening mammography along with regular clinical breast examination offer the best opportunity to increase this percentage.

Screening women 50 to 75 years of age significantly decreases the death rate from breast cancer. Although screening women between the ages of 40 and 49 is controversial because early studies10,11 showed no improved survival rates in women who received mammograms, several studies12,13 now show a significant reduction in mortality rates in women in this age group who received mammograms.

Women between the ages of 40 and 69 have a 30 percent chance of a false-positive screening mammogram or breast examination over a 10-year period.14 False-positive results lead to additional testing, increased cost and unnecessary anxiety. The rates of false-positive screening tests are higher for younger women because fewer of their breast masses are malignant. Women need to understand the possibility of obtaining false-positive results when they have screening mammograms.

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|TABLE 4 |

|Stage of Diagnosis for Women with Breast Cancer* |

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|Stage |

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|Percentage diagnosed |

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|Localized |

|60 |

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|Regional |

|31 |

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|Distant |

|6 |

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|*--Based on U.S. statistics from 1986 to 1993. |

|Reprinted with permission from American Cancer Society. |

|Breast cancer facts and figures. Atlanta: American Cancer |

|Society, 1997:14. |

| |

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While the importance of mammography in reducing mortality in women between the ages of 40 to 75 is well documented, controversy exists as to its benefit in women older than 75 years. Screening mammograms at any age, including those in elderly patients, enable detection of tumors at a significantly earlier stage.15 Women whose life expectancy is five to 10 years should continue to undergo mammographic and clinical breast examination screening.

It is possible that annual screening of younger women and screening of older women every other year may be established as beneficial. Screening in this manner has not yet been validated.16,17

It is extremely important to remember that 10 to 15 percent of all breast cancers are not detected by a mammogram. A careful clinical breast examination is also necessary. A palpable breast mass that is not seen on a mammogram should have a thorough diagnostic work-up including ultrasound and needle biopsy and close follow-up.

The current ACS screening guidelines for detection of breast cancer in asymptomatic women with no increased risk factors are shown in Table 5.18

The U.S. Preventive Services Task Force recommends routine screening in women for breast cancer every one to two years, with mammography alone or mammography and annual clinical breast examination for women aged 50 to 69.19 Women who have a family history of BRCA mutation should begin annual mammography between 25 and 35 years of age.20

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|TABLE 5 |

|Guidelines for Early Detection of Breast Cancer in Women |

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|Age |

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|American Cancer Society guidelines |

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|20 to 39 years |

|Clinical breast examination every three years |

|Monthly self-examination of breasts |

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|Age 40 years and older |

|Annual mammogram |

|Annual clinical breast examination |

|Monthly self-examination of breasts |

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|Information from Leitch AM, Dodd GD, Costanza M, Linver M, |

|Pressman P, McGinnis L, et al. American Cancer Society |

|guidelines for the early detection of breast cancer: update |

|1997. CA Cancer J Clin 1997;47:150-3. |

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Ultrasonography

Ultrasonographic screening is useful to differentiate between solid and cystic breast masses when a palpable mass is not well seen on a mammogram. Ultrasonography is especially helpful in young women with dense breast tissue when a palpable mass is not visualized on a mammogram. Ultrasonography is not to be used for routine screening, primarily because microcalcifications are not visualized and the yield of carcinomas is negligible.21

Digital Mammography

Digital mammography is similar to standard mammography in that radiographs are used to image the breast. The advantage of digital mammography is that images are stored digitally and can be enhanced by modifying the brightness or contrast. These images can be transmitted by telephone lines for remote consultation. Computer-aided diagnosis is being applied to the digital images and is used to recognize abnormal areas found on mammogram. It may enhance the accuracy of regular mammograms. Although initial studies have demonstrated that digital mammography is as accurate as standard radiographs, this equipment has not been labeled for this purpose by the U.S. Food and Drug Administration.

Biopsy

The three breast biopsy techniques in current use are applicable to different diagnostic situations. Fine-needle aspiration (FNA) biopsy generally uses a 20-gauge needle to obtain samples from a solid mass for cytology. Ultrasound or stereotactic guidance is used to assist in collecting an FNA from a nonpalpable lump. Core biopsy uses a 14-gauge or similar needle to remove cores of tissue from a mass. This biopsy can be performed with ultrasound or stereotactic guidance and requires a small skin incision and local anesthesia. Excisional biopsy is done when needle biopsies are negative but the mass is clinically suspected of malignancy. Excision may be the initial procedure of choice if the probability of malignancy is high. If the mass is not palpable, wire localization of the mass can be done before the biopsy. These biopsies usually require only local anesthesia with intravenous sedation and may be done as an outpatient procedure.

Evaluation of Common Problems in Breast Cancer Diagnosis

Cysts

A cyst can be diagnosed by ultrasound imaging. A simple cyst is round or oval in shape with sharp margins and lacks internal echoes but has posterior acoustic enhancement. A cyst with an irregular wall may signify intracystic carcinoma or carcinoma adjacent to the cyst, both of which are rare. A simple cyst can be aspirated if it is symptomatic. Aspiration can be performed using ultrasound localization if the mass is not palpable. If the cyst reoccurs, it can be repeatedly drained if it continues to be symptomatic. Any remaining mass after cyst aspiration should be further evaluated.

Solid Masses

A clinically suspicious mass should be followed even if mammographic findings are normal. Lumpectomy should be done for suspicious masses and should include a 1-cm margin of normal tissue. FNA biopsy may be used as the initial diagnostic test. Any thickened area that does not appear clinically suspicious may undergo observation if a needle biopsy and imaging studies are negative. These masses should undergo close follow-up with repeat physical examination in two months and repeat imaging in six months.

Nipple Discharge

Nipple discharge is considered suspicious if it is associated with a mass, comes from a single duct, is spontaneous and is bloody. Discharge that is green or black and comes from more than one duct is normal. A patient with bilateral, milky nipple discharge should be evaluated for prolactinoma. Cytology of the discharge is rarely helpful. A mammogram should be obtained for a suspicious discharge even though results are usually negative. A suspicious discharge from a single duct can be evaluated with a ductogram by placing a small catheter into the duct and injecting a small amount of contrast material.22

Breast Pain

Breast pain is a common complaint usually caused by a single cyst or an area of fibrocystic change. While breast pain is rarely an indication of cancer, it does not eliminate the possibility. If mammography and physical examination are not suggestive of cancer, fibrocystic changes are the most probable cause of the pain. Explaining the cause of the pain will reassure most patients. Treatments for fibrocystic breast disease include nonnarcotic analgesia and wearing a firm support brassiere. Eliminating chocolate and caffeine23 from the diet or using vitamin E24 have not been shown to be beneficial in randomized controlled studies. Androgens should not be used in the treatment of the fibrocystic breast condition.

Pregnancy

Any mass in a pregnant or lactating woman should be thoroughly evaluated. About 2 percent of breast cancers are diagnosed in pregnant women.25 Ultrasound imaging and FNA cytology are the first steps in the evaluation of a mass in a pregnant woman.

Final Comment

A careful history of a woman's risk and symptoms and a thorough physical examination are important in the evaluation of breast problems. Appropriately timed imaging and diagnostic studies are also important. Early detection of breast cancer at a stage when it is potentially curable and there is the possibility of saving a breast should be the goal of all health care professionals.

Members of various family practice departments develop articles for "Problem-Oriented Diagnosis." This article is one in a collaborative series coordinated by David R. Rudy, M.D., M.P.H., from the Department of Family Medicine at the Chicago Medical School of Finch University of Health Sciences, and Martin Lipsky, M.D., from the Department of Family Medicine at Northwestern University Medical School, Chicago.

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The Author

LECIA M. APANTAKU, M.D.,

is an associate professor in the Division of General Surgery; director of the Surgical Undergraduate Education Program, Department of Surgery; and director of the Breast Care Center at the Robert R. McCormick University Clinics and Women's Health Center at Finch University of Health Sciences/The Chicago Medical School, North Chicago, Ill. Dr. Apantaku, an American Board of Surgery diplomate, received her medical degree and general surgery residency certificate from Finch University. She is a member of the board of directors of the American Cancer Society, Illinois Division, Inc., and a researcher in early detection of breast and cervical cancer.

Address correspondence to Lecia M. Apantaku, M.D., Department of Surgery, Finch University of Health Sciences/The Chicago Medical School at Mount Sinai Hospital Medical Center, California Avenue at 15th Street, Chicago, IL 60608. Reprints are not available from the author.

REFERENCES

1. American Cancer Society. Cancer facts and figures. Atlanta: American Cancer Society, 1999:36.

2. American Cancer Society. Breast cancer facts and figures. Atlanta: American Cancer Society, 1997:14.

3. Madigan PM, Ziegler RG, Benichou J, Byrne C, Hoover RN. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst 1987;87:1681-5.

4. Fentiman IS. The causes of breast cancer. In: Detection and treatment of early breast cancer. Philadelphia: Lippincott, 1990:11-30.

5. Krainer M, Silva-Arrieta S, FitzGerald MG, Shimada A, Ishioka C, Kanamaru R., et al. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. N Engl J Med 1997;336:1416-21.

6. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713-27.

7. Speroff L. Postmenopausal hormone therapy and breast cancer. Obstet Gynecol 1996;87:44S-54S.

8. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371-88.

9. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. JAMA 1999;281:2189-97 (published erratum appears in JAMA 1999;282:2124).

10. Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. Can Med Assoc J 1992;147:1459-74 (published erratum appears in Can Med Assoc J 1993;148:718).

11. Fletcher SW, Black W, Harris R, Rimer BK, Shapiro S. Report of the International Workshop on Screening for Breast Cancer. J Natl Cancer Inst 1993, 85:1644-56.

12. Smart CR, Hendrick RE, Rutledge JH 3d, Smith RA. Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials. Cancer 1995;75:1619-26 (published erratum appears in Cancer 1995;75).

13. Tabar L, Fagerberg G, Chen HH, Duffy SW, Smart CR, Gad A, et al. Efficacy of breast cancer screening by age. New results from the Swedish Two-county Trial. Cancer 1995;75:2507-17.

14. Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 1998;338:1089-96.

15. Wilson TE, Helvie MA, August DA. Breast cancer in the elderly patient: early detection with mammography. Radiology 1994;190:203-7.

16. Morrow M. Breast disease in elderly women. Surg Clin North Am 1994;74:145-61.

17. Cady B, Steele GD, Morrow M, Gardner B, Smith BL, Lee NC, et al. Evaluation of common breast problems: guidance for primary care providers. CA Cancer J Clin 1998;48:49-63.

18. Leitch AM, Dodd GD, Costanza M, Linver M, Pressman P, McGinnis L, Smith RA. American Cancer Society guidelines for the early detection of breast cancer: update 1997. CA Cancer J Clin 1997;47: 150-3.

19. U.S. Preventive Services Task Force. Screening for breast cancer, 2d ed. In: Guide to clinical preventive services. Baltimore: Williams & Wilkins, 1996:73-87.

20. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. JAMA 1997;277:997-1003.

21. Kolb TM, Lichy J, Newhouse JH. Occult cancer in women with dense breasts: detection with screening US--diagnostic yield and tumor characteristics. Radiology 1998;207:191-9.

22. Baker KS. Ancillary breast imaging modalities. In: The diagnosis of breast disease. Powell DE, Stelling CB, eds. St. Louis: Mosby, 1994:46-70.

23. Parazzini F, La Vecchia C, Riundi R, Pampallona S, Regallo M, Scanni A. Methylxanthine, alcohol-free diet and fibrocystic breast disease: a factorial clinical trial. Surgery 1986;99:576-81.

24. Ernster VL, Goodson WH 3d, Hunt TK, Petrakis NL, Sickles EA, Miike R. Vitamin E and benign breast "disease": a double-blind, randomized clinical trial. Surgery 1985;97:490-4.

25. Tretli G, Kvalheim G, Thoresen S, Host H. Survival of breast cancer patients diagnosed during pregnancy or lactation. Br J Cancer 1988;58:382-4.

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