Breast Cancer Treatment and Pregnancy (PDQ®)

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General Information About Breast Cancer Treatment and Pregnancy

Incidence

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

Pathology

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. Enzyme immunocytochemical receptor assays, however, are more sensitive than competitive binding assays. A study that used 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, which is because of competitive inhibition by high levels of endogenous estrogen.

Diagnosis

The natural tenderness and engorgement of the breasts of pregnant and lactating women may hinder detection of discrete masses and early diagnoses of breast cancer. Delays in diagnoses are common, with an average reported delay of 5 to 15 months from the onset of symptoms. Because of this delay, cancers are typically detected at a later stage than in a nonpregnant, age-matched population. 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. Mammograms should only be used, however, to evaluate dominant masses and to locate occult carcinomas in the presence of other suspicious physical findings. Since at least 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, core biopsy, 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.

Survival

Overall survival of pregnant women with breast cancer may be worse than in nonpregnant women at all stages; however, this may be primarily the result of delayed diagnoses. 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.

References:
  • 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): 2499-506, 1993.
  • Hoover HC Jr: Breast cancer during pregnancy and lactation. Surg Clin North Am 70 (5): 1151-63, 1990.
  • Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001.
  • Moore HC, Foster RS Jr: Breast cancer and pregnancy. Semin Oncol 27 (6): 646-53, 2000.
  • Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003.
  • Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989.
  • Yang WT, Dryden MJ, Gwyn K, et al.: Imaging of breast cancer diagnosed and treated with chemotherapy during pregnancy. Radiology 239 (1): 52-60, 2006.
  • Middleton LP, Amin M, Gwyn K, et al.: Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features. Cancer 98 (5): 1055-60, 2003.
  • Petrek JA, Dukoff R, Rogatko A: Prognosis of pregnancy-associated breast cancer. Cancer 67 (4): 869-72, 1991.
  • Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surg Gynecol Obstet 171 (4): 347-52, 1990.
  • Gallenberg MM, Loprinzi CL: Breast cancer and pregnancy. Semin Oncol 16 (5): 369-76, 1989.

Stage Information for Breast Cancer Treatment and Pregnancy

Procedures used for determining the stage of breast cancer should be modified for pregnant women to avoid radiation exposure to the fetus. 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. Radiation exposure during the first trimester (>0.1 Gy) may lead to congenital malformations, mental retardation, and increased relative risk of carcinogenesis. Doses greater than 1 Gy may produce congenital abnormalities. Doses of 0.1 Gy may result in fewer defects.

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. A chest x-ray delivers 0.00008 Gy.

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. A bone scan delivers 0.001 Gy. Evaluation of the liver can be performed with ultrasound, and brain metastases can be diagnosed with a magnetic resonance imaging (MRI) scan. Data on MRI during pregnancy are not yet available, but gadolinium crosses the placenta and is associated with fetal abnormalities in rats.

References:
  • Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001.
  • Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surg Gynecol Obstet 171 (4): 347-52, 1990.
  • Nicklas AH, Baker ME: Imaging strategies in the pregnant cancer patient. Semin Oncol 27 (6): 623-32, 2000.
  • Gallenberg MM, Loprinzi CL: Breast cancer and pregnancy. Semin Oncol 16 (5): 369-76, 1989.
  • Yang WT, Dryden MJ, Gwyn K, et al.: Imaging of breast cancer diagnosed and treated with chemotherapy during pregnancy. Radiology 239 (1): 52-60, 2006.

Other Considerations for Pregnancy and Breast Cancer

Lactation

Suppression of lactation does not improve prognosis. If surgery is planned, however, lactation should be suppressed to decrease the size and vascularity of the breasts. If chemotherapy is to be given, lactation should also be suppressed because many antineoplastics (i.e., cyclophosphamide and methotrexate), when given systemically, may occur in high levels in breast milk and would affect the nursing baby. In general, women receiving chemotherapy should not breastfeed.

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

Based on limited retrospective data, pregnancy does not appear to compromise the survival of women with a previous history of breast cancer, and no deleterious effects have been demonstrated in the fetus. Some physicians recommend that patients wait 2 years after diagnoses 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 transplantation for hematologic disorders, a 25% incidence of preterm labor and low birth weight for gestational-age infants was noted.

References:
  • Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989.
  • Harvey JC, Rosen PP, Ashikari R, et al.: The effect of pregnancy on the prognosis of carcinoma of the breast following radical mastectomy. Surg Gynecol Obstet 153 (5): 723-5, 1981.
  • Petrek JA: Pregnancy safety after breast cancer. Cancer 74 (1 Suppl): 528-31, 1994.
  • von Schoultz E, Johansson H, Wilking N, et al.: Influence of prior and subsequent pregnancy on breast cancer prognosis. J Clin Oncol 13 (2): 430-4, 1995.
  • Kroman N, Mouridsen HT: Prognostic influence of pregnancy before, around, and after diagnosis of breast cancer. Breast 12 (6): 516-21, 2003.
  • Malamos NA, Stathopoulos GP, Keramopoulos A, et al.: Pregnancy and offspring after the appearance of breast cancer. Oncology 53 (6): 471-5, 1996 Nov-Dec.
  • Gelber S, Coates AS, Goldhirsch A, et al.: Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer. J Clin Oncol 19 (6): 1671-5, 2001.
  • Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001.
  • Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003.
  • 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): 3045-52, 1996.

Early Stage Breast Cancer (Stage I and 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 that helps to predict the risk of waiting to have radiation.

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.

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.

References:
  • Kal HB, Struikmans H: Radiotherapy during pregnancy: fact and fiction. Lancet Oncol 6 (5): 328-33, 2005.
  • Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001.
  • Nettleton J, Long J, Kuban D, et al.: Breast cancer during pregnancy: quantifying the risk of treatment delay. Obstet Gynecol 87 (3): 414-8, 1996.
  • Kuerer HM, Gwyn K, Ames FC, et al.: Conservative surgery and chemotherapy for breast carcinoma during pregnancy. Surgery 131 (1): 108-10, 2002.
  • Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989.
  • Giacalone PL, Laffargue F, Bénos P: Chemotherapy for breast carcinoma during pregnancy: A French national survey. Cancer 86 (11): 2266-72, 1999.
  • Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003.
  • Cardonick E, Iacobucci A: Use of chemotherapy during human pregnancy. Lancet Oncol 5 (5): 283-91, 2004.
  • Berry DL, Theriault RL, Holmes FA, et al.: Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 17 (3): 855-61, 1999.
  • Isaacs RJ, Hunter W, Clark K: Tamoxifen as systemic treatment of advanced breast cancer during pregnancy--case report and literature review. Gynecol Oncol 80 (3): 405-8, 2001.

Late Stage Breast Cancer (Stage III and IV)

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

References:
  • Hoover HC Jr: Breast cancer during pregnancy and lactation. Surg Clin North Am 70 (5): 1151-63, 1990.
  • Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003.
  • Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001.
  • Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989.
  • Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surg Gynecol Obstet 171 (4): 347-52, 1990.


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