Treatment of Early / Localized / Operable Breast Cancer During Pregnancy
Generally, pregnant women with stage I or stage II breast cancer are treated in the same way as nonpregnant patients, with some modifications to protect the fetus.
Treatment options for early/localized/operable breast cancer in pregnant women include the following:
- Surgery. Postpartum radiation therapy may also be given to women diagnosed with breast cancer late in pregnancy.
- Chemotherapy (after the first trimester).
- Endocrine therapy (after delivery).
The use of trastuzumab during pregnancy is contraindicated.
Surgery is recommended as the primary treatment of breast cancer in pregnant women.
The data regarding safety of sentinel lymph node biopsy in pregnant patients are limited to several retrospective case series. One study examined sentinel lymph 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 live-born infants, of whom 24 were healthy, and one had a cleft palate (in the setting of other maternal risk factors).
Because radiation in therapeutic doses may expose the fetus to potentially harmful scatter radiation, 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. 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 certain chemotherapeutic drugs after the first trimester, with most pregnancies resulting in live births with low rates of morbidity in the newborns.
Anthracycline-based chemotherapy (doxorubicin plus cyclophosphamide 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.[6,7,8] Safety data on the use of taxanes during pregnancy are limited.
Evidence (use of chemotherapy during the second and/or third trimester of pregnancy):
- 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 weight per ref 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 based on 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.
- In a prospective single-arm study, 57 pregnant breast cancer patients were treated with FAC in the adjuvant or neoadjuvant setting.
- Survey data collected when the children were aged 2 months to 157 months revealed that no stillbirths, miscarriages, or perinatal deaths occurred.
- 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).
- The findings of the prospective single-arm study above were consistent with other smaller retrospective series of anthracycline-based chemotherapy.[7,8]
- A systematic review studied 40 case reports of taxane administration during the second or third trimesters of pregnancy.
- Minimal maternal, fetal, or neonatal toxicity was observed.
Endocrine therapy is generally avoided until after delivery. Case reports and a literature review of tamoxifen during pregnancy show that tamoxifen administration during pregnancy is associated with vaginal bleeding, miscarriage, congenital abnormalities such as Goldenhar syndrome, and fetal death.[11,12,13] Breastfeeding is also not recommended concurrently with endocrine therapy.
The use of trastuzumab during pregnancy is contraindicated based on results of a systematic review of 17 studies (18 pregnancies, 19 newborns). 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 the pregnancies were complicated with oligohydramnios/anhydramnios. Of the pregnancies exposed to trastuzumab exclusively during the first trimester, 0% (P = .043) of the pregnancies were complicated with oligohydramnios/anhydramnios. 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 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 pregnant during trastuzumab administration and wish to continue pregnancy, trastuzumab should be stopped and pregnancy would be allowed to continue.
- 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.
- 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.
- 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.
- Turchi JJ, Villasis C: Anthracyclines in the treatment of malignancy in pregnancy. Cancer 61 (3): 435-40, 1988.
- 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.
- 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.
- Mir O, Berveiller P, Goffinet F, et al.: Taxanes for breast cancer during pregnancy: a systematic review. Ann Oncol 21 (2): 425-6, 2010.
- 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.
- Tewari K, Bonebrake RG, Asrat T, et al.: Ambiguous genitalia in infant exposed to tamoxifen in utero. Lancet 350 (9072): 183, 1997.
- 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.
- Helewa M, Lévesque P, Provencher D, et al.: Breast cancer, pregnancy, and breastfeeding. J Obstet Gynaecol Can 24 (2): 164-80; quiz 181-4, 2002.
- 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.