Breast Cancer Treatment and Pregnancy (PDQ®)–Health Professional Version

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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.[1] 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.[2-5] Because of this delay, cancers are typically detected at a later stage than in a nonpregnant, age-matched population.[6] 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.[7] Mammograms should only be used, however, to evaluate dominant masses and to locate occult carcinomas in the presence of other suspicious physical findings.[7] 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.[8]

Survival

Overall survival of pregnant women with breast cancer may be worse than in nonpregnant women at all stages;[7] however, this may be primarily the result of delayed diagnoses.[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.[2,3,5,10,11]

References
  1. 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. [PUBMED Abstract]
  2. Hoover HC Jr: Breast cancer during pregnancy and lactation. Surg Clin North Am 70 (5): 1151-63, 1990. [PUBMED Abstract]
  3. Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001. [PUBMED Abstract]
  4. Moore HC, Foster RS Jr: Breast cancer and pregnancy. Semin Oncol 27 (6): 646-53, 2000. [PUBMED Abstract]
  5. Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003. [PUBMED Abstract]
  6. Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989. [PUBMED Abstract]
  7. 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. [PUBMED Abstract]
  8. 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. [PUBMED Abstract]
  9. Petrek JA, Dukoff R, Rogatko A: Prognosis of pregnancy-associated breast cancer. Cancer 67 (4): 869-72, 1991. [PUBMED Abstract]
  10. Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surg Gynecol Obstet 171 (4): 347-52, 1990. [PUBMED Abstract]
  11. Gallenberg MM, Loprinzi CL: Breast cancer and pregnancy. Semin Oncol 16 (5): 369-76, 1989. [PUBMED Abstract]

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.[1] 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.[2] 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.[1,3] A chest x-ray delivers 0.00008 Gy.[4]

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.[5]

References
  1. Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001. [PUBMED Abstract]
  2. Barnavon Y, Wallack MK: Management of the pregnant patient with carcinoma of the breast. Surg Gynecol Obstet 171 (4): 347-52, 1990. [PUBMED Abstract]
  3. Nicklas AH, Baker ME: Imaging strategies in the pregnant cancer patient. Semin Oncol 27 (6): 623-32, 2000. [PUBMED Abstract]
  4. Gallenberg MM, Loprinzi CL: Breast cancer and pregnancy. Semin Oncol 16 (5): 369-76, 1989. [PUBMED Abstract]
  5. 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. [PUBMED Abstract]

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. 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.[1-9] 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.[10]

References
  1. Clark RM, Chua T: Breast cancer and pregnancy: the ultimate challenge. Clin Oncol (R Coll Radiol) 1 (1): 11-8, 1989. [PUBMED Abstract]
  2. 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. [PUBMED Abstract]
  3. Petrek JA: Pregnancy safety after breast cancer. Cancer 74 (1 Suppl): 528-31, 1994. [PUBMED Abstract]
  4. 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. [PUBMED Abstract]
  5. Kroman N, Mouridsen HT: Prognostic influence of pregnancy before, around, and after diagnosis of breast cancer. Breast 12 (6): 516-21, 2003. [PUBMED Abstract]
  6. 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. [PUBMED Abstract]
  7. 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. [PUBMED Abstract]
  8. Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001. [PUBMED Abstract]
  9. Rugo HS: Management of breast cancer diagnosed during pregnancy. Curr Treat Options Oncol 4 (2): 165-73, 2003. [PUBMED Abstract]
  10. 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. [PUBMED Abstract]

Early-Stage Breast Cancer (Stages I and II)

Generally, pregnant women with breast cancer should be treated similarly to nonpregnant patients, with some modifications to protect the fetus.

Surgery is recommended as the primary treatment of breast cancer in pregnant women. The data regarding safety of sentinel node biopsy in pregnant patients are limited to several retrospective case series. One study examined sentinel node biopsy in eight patients in the first trimester, nine patients in the second trimester, and eight patients in the third trimester. Technetium TC 99m alone was used in 16 patients, methylene blue dye alone was used in seven patients, and two patients had unknown mapping methods. All 25 patients had liveborn infants, of whom 24 were healthy, and one had a cleft palate, in the setting of other maternal risk factors.[1]

Because radiation in therapeutic doses may expose the fetus to potentially harmful scatter radiation,[2] modified radical mastectomy is the treatment of choice if the breast cancer was diagnosed early in pregnancy. If diagnosed late in pregnancy, breast-conserving surgery with postpartum radiation therapy has been used for breast preservation.[3] An analysis has been performed that helps to predict the risk of waiting to have radiation.[4,5]

Data suggest that it is safe to administer many chemotherapeutic drugs after the first trimester, with the majority of pregnancies resulting in live births with low rates of morbidity in the newborns. A multicenter case-control study compared pediatric outcomes of 129 children whose mothers had breast cancer with matched children of women without cancer. In the pregnancy study group, 96 children (74.4%) were exposed to chemotherapy, 11 (8.5%) to radiation therapy, 13 (10.1%) to surgery alone, 2 (1.7%) to other drug treatments, and 14 (10.9%) to no treatment. The study showed that there was no significant difference in birth rate below the 10th percentile (22% in the breast cancer treatment-exposed group vs. 15.2% in the control group, P = .16) or in cognitive development on the basis of the Bayley score (P = .08). The gestational age at birth was correlated with cognitive outcome in the two study groups. Evaluation of cardiac function among 47 children, who were age 36 months in the study group, showed normal cardiac findings.[6]

Anthracycline-based chemotherapy (doxorubicin plus cyclophosphamide [AC] or fluorouracil, doxorubicin, and cyclophosphamide [FAC]) appears to be safe to administer during the second and/or third trimester on the basis of limited prospective data. In a prospective single-arm study, 57 pregnant breast cancer patients were treated with FAC in the adjuvant or neoadjuvant setting.[7] Survey data collected when the children ranged from age 2 to 157 months revealed that no stillbirths, miscarriages, or perinatal deaths were observed. One child born vaginally at a gestational age of 38 weeks had a subarachnoid hemorrhage on day 2 postpartum, one child had Down syndrome, and two children had congenital anomalies (club foot and bilateral ureteral reflux). These findings were consistent with other smaller retrospective series of anthracycline-based chemotherapy.[8,9]

Safety data on the use of taxanes during pregnancy are limited. A systematic review studied 40 case reports of taxane administration during the second or third trimesters of pregnancy.[10] Minimal maternal, fetal, or neonatal toxicity were observed.

The use of trastuzumab during pregnancy is contraindicated based on results of a systematic review of 17 studies (18 pregnancies, 19 newborns).[11] Of the fetal complications noted, occurrence of oligohydramnios/anhydramnios was the most common (61.1%) adverse event. Of the pregnancies exposed to trastuzumab during the second or third trimester, 73.3% of them were complicated with oligohydramnios/anhydramnios, and the respective rate of pregnancies exposed to trastuzumab exclusively during the first trimester was 0% (P = .043). The mean gestational age at delivery was 33.8 weeks, and the mean weight of newborns at delivery was 2,261 grams or 4.984 pounds. In 52.6% of cases, a healthy neonate was born. At the long-term evaluation, all children who were without problems at birth were healthy, with a median follow-up of 9 months, and four out of nine children who faced troubles at birth had died within an interval ranging from birth to 5.25 months. All children exposed to trastuzumab in utero exclusively in the first trimester were completely healthy at birth. The data suggest that for women who become accidentally pregnant during trastuzumab administration in the first trimester and wish to continue pregnancy, trastuzumab should be stopped and pregnancy would be allowed to continue.

Endocrine therapy is generally avoided until after delivery. Case reports and literature review of tamoxifen during pregnancy shows that it is associated with vaginal bleeding, miscarriage, congenital abnormalities such as Goldenhar’s syndrome, and fetal death.[12-14] Breastfeeding is also not recommended concurrent with endocrine therapy.

References
  1. Gropper AB, Calvillo KZ, Dominici L, et al.: Sentinel lymph node biopsy in pregnant women with breast cancer. Ann Surg Oncol 21 (8): 2506-11, 2014. [PUBMED Abstract]
  2. Kal HB, Struikmans H: Radiotherapy during pregnancy: fact and fiction. Lancet Oncol 6 (5): 328-33, 2005. [PUBMED Abstract]
  3. Gwyn K, Theriault R: Breast cancer during pregnancy. Oncology (Huntingt) 15 (1): 39-46; discussion 46, 49-51, 2001. [PUBMED Abstract]
  4. 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. [PUBMED Abstract]
  5. Kuerer HM, Gwyn K, Ames FC, et al.: Conservative surgery and chemotherapy for breast carcinoma during pregnancy. Surgery 131 (1): 108-10, 2002. [PUBMED Abstract]
  6. Amant F, Vandenbroucke T, Verheecke M, et al.: Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy. N Engl J Med 373 (19): 1824-34, 2015. [PUBMED Abstract]
  7. Hahn KM, Johnson PH, Gordon N, et al.: Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer 107 (6): 1219-26, 2006. [PUBMED Abstract]
  8. Turchi JJ, Villasis C: Anthracyclines in the treatment of malignancy in pregnancy. Cancer 61 (3): 435-40, 1988. [PUBMED Abstract]
  9. Zemlickis D, Lishner M, Degendorfer P, et al.: Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med 152 (3): 573-6, 1992. [PUBMED Abstract]
  10. Mir O, Berveiller P, Goffinet F, et al.: Taxanes for breast cancer during pregnancy: a systematic review. Ann Oncol 21 (2): 425-6, 2010. [PUBMED Abstract]
  11. Zagouri F, Sergentanis TN, Chrysikos D, et al.: Trastuzumab administration during pregnancy: a systematic review and meta-analysis. Breast Cancer Res Treat 137 (2): 349-57, 2013. [PUBMED Abstract]
  12. Cullins SL, Pridjian G, Sutherland CM: Goldenhar's syndrome associated with tamoxifen given to the mother during gestation. JAMA 271 (24): 1905-6, 1994 Jun 22-29. [PUBMED Abstract]
  13. Tewari K, Bonebrake RG, Asrat T, et al.: Ambiguous genitalia in infant exposed to tamoxifen in utero. Lancet 350 (9072): 183, 1997. [PUBMED Abstract]
  14. 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. [PUBMED Abstract]

Late-Stage Breast Cancer (Stages 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,[1,2] issues regarding continuation of the pregnancy should be discussed with the patient and her family. Therapeutic abortion does not improve prognosis.[1-5]

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

Changes to This Summary (06/29/2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Early-Stage Breast Cancer (Stages I and II)

This section was extensively revised.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of breast cancer and pregnancy. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

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  • be cited with text, or
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Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Breast Cancer Treatment and Pregnancy are:

  • Beverly Moy, MD, MPH (Massachusetts General Hospital)
  • Joseph L. Pater, MD (NCIC-Clinical Trials Group)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Adult Treatment Editorial Board. PDQ Breast Cancer Treatment and Pregnancy. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/breast/hp/pregnancy-breast-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389427]

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  • Updated: June 29, 2017

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