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Breast cancer and pregnancy


Table of Contents

DISEASE DESCRIPTION
DIAGNOSIS
STAGING
TREATMENT OPTIONS
Early stage cancer (stages I & II)
Late stage disease (stages III & IV)
Lactation
Fetal consequences of maternal breast cancer
Consequences of pregnancy in patients with a history of breast cancer

DISEASE DESCRIPTION

Breast cancer is the most common cancer in pregnant and postpartum women occurring in about 1 in 3,000 pregnancies. The average patient is between 32 to 38 years of age and, with many women choosing to delay childbearing, it is likely that the incidence of breast cancer during pregnancy will increase.


DIAGNOSIS

The natural tenderness and engorgement of the breasts of pregnant and lactating women may hinder detection of discrete masses, and therefore, early diagnosis of breast cancer. Delays in diagnosis are common, with an average reported delay of 5 to 15 months from the onset of symptoms.[1] Because of this delay, cancers are typically detected at a later stage than in a nonpregnant, age-matched population.[2] To detect breast cancer, pregnant and lactating women should practice self-examination and undergo a breast examination as part of the routine prenatal examination by a doctor. If an abnormality is found, diagnostic approaches such as ultrasound and mammography may be used. With proper shielding, mammography poses little risk of radiation exposure to the fetus.[3] However, mammograms should only be used to evaluate dominant masses and to locate occult carcinomas in the presence of other suspicious physical findings.[3] Since 25% of mammograms in pregnancy may be negative in the presence of cancer, a biopsy is essential for the diagnosis of any palpable mass. Diagnosis may be safely accomplished with a fine-needle aspiration or excisional biopsy under local anesthesia. To avoid a false-positive diagnosis as a result of misinterpretation of pregnancy-related changes, the pathologist should be advised that the patient is pregnant.[4,5]


STAGING

Procedures used for staging of breast cancer should be modified to avoid radiation exposure to the fetus in pregnant women. Nuclear scans cause fetal radiation exposure. If such scans are essential for evaluation, hydration and Foley catheter drainage of the bladder can be used to prevent retention of radioactivity. Timing of the exposure to radiation relative to the gestational age of the fetus may be more critical than the actual dose of radiation delivered.[3] Radiation exposure during the first trimester can lead to congenital malformations, especially microcephaly. Doses greater than 100 rad may produce congenital abnormalities in 100% of cases. Doses of 10 rad may result in fewer defects. A chest x-ray delivers 0.008 rad,[6] and a bone scan delivers 0.1 rad.[1] Chest x-rays with abdominal shielding are considered safe, but as with all radiologic procedures, they should be used only when essential for making treatment decisions.[1] For the diagnosis of bone metastases, a bone scan is preferable to a skeletal series because the bone scan delivers a smaller amount of radiation and is more sensitive. Evaluation of the liver can be performed with ultrasound, and brain metastases can be diagnosed with a magentic resonance imaging (MRI) scan, both of which avoid fetal radiation exposure. However, no data evaluating the safety of MRI during pregnancy are available. Carcinogenesis in the fetus exposed to radiation is another consideration.

Breast cancer pathology is similar in age-matched pregnant and nonpregnant women. Hormone receptor assays are usually negative in pregnant breast cancer patients, but this may be the result of receptor binding by high serum estrogen levels associated with the pregnancy. However, enzyme immunocytochemical receptor assays are more sensitive than competitive binding assays. A study by Elledge et al.[7] using binding methods indicated similar receptor positivity between pregnant and nonpregnant women with breast cancer. The study concluded that increased estrogen levels during pregnancy could result in a higher incidence of receptor positivity detected with immunohistochemistry than is detected by radiolabeled ligand binding, due to competitive inhibition by high levels of endogenous estrogen.

Overall survival of pregnant women with breast cancer may be worse than in nonpregnant women at all stages.[8] However, the decreased overall survival in this patient population may be due primarily to delayed diagnosis.[9] Termination of pregnancy has not been shown to have any beneficial effect on breast cancer outcome and is not usually considered as a therapeutic option.[1,3,6] However, termination of pregnancy may be considered, based on the age of the fetus, if maternal treatment options, such as chemotherapy and radiation therapy, are significantly limited by the continuation of the pregnancy.


TREATMENT OPTIONS


Early stage cancer (stages I & II)

Surgery is recommended as the primary treatment of breast cancer in pregnant women. Since radiation in therapeutic doses may expose the fetus to potentially harmful scatter radiation, modified radical mastectomy is the treatment of choice. Conservative surgery with postpartum radiation therapy has been used for breast preservation. An analysis has been performed which helps predict the risk of waiting to have radiation.[10] If adjuvant chemotherapy is necessary, it should not be given during the first trimester to avoid the risk of teratogenicity. Chemotherapy given after the first trimester is generally not associated with a high risk of fetal malformation, but may be associated with premature labor and fetal wastage. If considered necessary, chemotherapy may be given after the first trimester. Data on the immediate and long-term effects of chemotherapy on the fetus are limited.[2]

Studies using adjuvant hormonal therapy alone or in combination with chemotherapy for breast cancer in pregnant women are also limited. Therefore, no conclusion has been reached regarding these options. Radiation therapy, if indicated, should be withheld until after delivery since it may be harmful to the fetus at any stage of development.


Late stage disease (stages III & IV)

First-trimester radiation therapy should be avoided. Chemotherapy may be given after the first trimester as discussed above. Because the mother may have a limited life span (most studies show a 5-year survival rate of 10% in pregnant patients with stages III and IV disease), and there is a risk of fetal damage with treatment during the first trimester,[1] issues regarding continuation of the pregnancy should be discussed with the patient and her family. Therapeutic abortion does not improve prognosis.[1-3]


Lactation

Suppression of lactation does not improve prognosis. However, if surgery is planned, lactation should be suppressed to decrease the size and vascularity of the breasts. It should also be suppressed if chemotherapy is to be given because many antineoplastics (specifically cyclophosphamide and methotrexate) given systemically may occur in high levels in breast milk and this would affect the nursing baby. In general, women receiving chemotherapy should not breast-feed.


Fetal consequences of maternal breast cancer

No damaging effects on the fetus from maternal breast cancer have been demonstrated, and there are no reported cases of maternal-fetal transfer of breast cancer cells.


Consequences of pregnancy in patients with a history of breast cancer

Pregnancy does not appear to compromise the survival of women with a prior history of breast cancer, based on limited retrospective data, and no deleterious effects have been demonstrated in the fetus.[2,11-15] Some physicians recommend that patients wait 2 years after diagnosis before attempting to conceive. This allows early recurrence to become manifest, which may influence the decision to become a parent. Little is known about pregnancy after bone marrow transplantation and high-dose chemotherapy with or without total-body irradiation. In one report of pregnancies after bone marrow transplant for hematologic disorders, a 25% incidence of preterm labor and low birth weight for gestational age infants was noted.[16]

References:

  1. Hoover HC: Breast cancer during pregnancy and lactation. Surgical Clinics of North America 70(5): 1151-1163, 1990.

  2. Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clinical Oncology (Royal College of Radiologists) 1(1): 11-18, 1989.

  3. Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surgery, Gynecology and Obstetrics 171(4): 347-352, 1990.

  4. Novotny DB, Maygarden SJ, Shermer RW, et al.: Fine needle aspiration of benign and malignant breast masses associated with pregnancy. Acta Cytologica 35(6): 676-686, 1991.

  5. Finley JL, Silverman JF, Lannin DR: Fine-needle aspiration cytology of breast masses in pregnant and lactating women. Diagnostic Cytopathology 5(3): 255-259, 1989.

  6. Gallenberg MM, Loprinzi CL: Breast cancer and pregnancy. Seminars in Oncology 16(5): 369-376, 1989.

  7. Elledge RM, Ciocca DR, Langone G, et al.: Estrogen receptor, progesterone receptor, and HER-2/neu protein in breast cancers from pregnant patients. Cancer 71(8): 2499-2506, 1993.

  8. Guinee VF, Olsson H, Moller T, et al.: Effect of pregnancy on prognosis for young women with breast cancer. Lancet 343(8913): 1587-1589, 1994.

  9. Petrek JA, Dukoff R, Rogatko A: Prognosis of pregnancy-associated breast cancer. Cancer 67(4): 869-872, 1991.

  10. Nettleton J, Long J, Kuban D, et al.: Breast cancer during pregnancy: quantifying the risk of treatment delay. Obstetrics and Gynecology 87(3): 414-418, 1996.

  11. Harvey JC, Rosen PP, Ashikari R, et al.: The effect of pregnancy on the prognosis of carcinoma of the breast following radical mastectomy. Surgery, Gynecology and Obstetrics 153: 723-725, 1981.

  12. Petrek JA: Pregnancy safety after breast cancer. Cancer 74(1): 528-531, 1994.

  13. von Schoultz E, Johansson H, Wilking N, et al.: Influence of prior and subsequent pregnancy on breast cancer prognosis. Journal of Clinical Oncology 13(2): 430-434, 1995.

  14. Kroman N, Jensen MB, Melbye M, et al.: Should women be advised against pregnancy after breast-cancer treatment? Lancet 350(9074): 319-322, 1997.

  15. Malamos NA, Stathopoulos GP, Keramopoulos A, et al.: Pregnancy and offspring after the appearance of breast cancer. Oncology 53(6): 471-475, 1996.

  16. Sanders JE, Hawley J, Levy W, et al.: Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation. Blood 87(7): 3045-3052, 1996.

Date Last Modified: 09/1999



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