Pregnancy-associated breast cancer (PABC) is defined as breast cancer occurring anytime during gestation, lactation or within one year after delivery (1,2). Breast cancer is one of the most common tumor during pregnancy along with melanoma and cervical cancers and occurs in approximately one out of 3,000-10,000 pregnancies (3). Diagnosis of PABC is expected to become more frequent in the forthcoming years since there is an increasing trend for women to delay childbearing (4,5).
Significant controversy exists in the literature regarding the influence of pregnancy upon breast cancer prognosis. Some studies did not demonstrate any aggravating role (6-8), whereas other studies have reported that pregnancy itself may not represent a veritable poor prognostic factor for breast cancer, attributing any detrimental effects to the delayed diagnosis of tumours in pregnancy (9-13). On the other hand, some studies point to the opposite direction, indicating an independent, aggravating role of pregnancy (14-16). Of note, a recently published meta-analysis, including 30 studies, have shown that PABC is independently associated with poor survival particularly when diagnosed shortly post-partum (17).
In this context, it should be noted that diagnosis of breast cancer during pregnancy adds complexity to cancer treatment recommendations, taking into consideration that treatment strategies offered for pregnant women with breast cancer should not differ from their non-pregnant counterparts. Hence, the optimal management of pregnant women with breast cancer is challenging and not well established; the main concern is the effect of the drugs on the developing fetus and long-term complications after in utero exposure to anti-cancer drugs. This review, taking into consideration all available data, focuses on critical issues regarding the management of breast cancer during pregnancy, such as consultation of pregnant patients, surgical procedure, administration of chemotherapy regimens during pregnancy and lactation, radiation therapy, targeted treatment administration during pregnancy, etc.
Surgical resection is the mainstay of treatment for early breast cancer diagnosed during pregnancy (3,18). Modified radical mastectomy is standard of care in first trimester of pregnancy. Of note, breast-conserving surgery is not contraindicated per se during the first trimester, but owing to the potential impact of delaying radiotherapy; hence, mastectomy is considered in these cases. Breast-conserving surgery (lumpectomy with lymph node dissection) can be performed preferably in the second and third trimester because of the necessary ensuing radiotherapy that in any case must be delayed up until after delivery (3,18). The decision to proceed with breast-conservation or mastectomy should be based upon the clinical situation of each patient. In this context, it should be noted that surgery is a safe procedure and can be performed in all trimesters with minimal risk for the fetus; after the 12th week of gestation, in particular, the risk of abortion is minimal (19-23). Radical mastectomy may be followed by immediate breast reconstruction; however, there are no data on reconstructive breast surgery during pregnancy. Hence, reconstruction-if needed-should be better restricted to a prosthetic implant or preferably should be carried out post partum (24).
As far as sentinel lymph node biopsy (SLNB) in pregnant women is concerned, there are insufficient safety data to support this procedure during pregnancy owing to radiation concerns. However, a dosimetry study followed by a prospective trial on 12 pregnant breast cancer patients (25,26) supported the safety of SLNB, when performed with low-dose lymphoscintigraphy using 99m-Tc human serum albumin nanocolloids. In this study, eleven healthy babies were born with no malformation and with normal weight, whereas one newborn had a ventricular septal defect suspected before lymphoscintigraphy. Moreover, there was no evidence of axillary recurrence at a median follow-up of 32 months. By contrast, blue dye is associated with a risk of an anaphylactic maternal reaction, which would probably distress the fetus (27). Therefore, the use of blue dye should be avoided during pregnancy. Hence, SLNB with low-dose lymphoscintigraphy using 99m-Tc human serum albumin nanocolloids may be considered in selected cases and within centers with experience in carrying out this technique (28).
Radiation therapy is not favored during pregnancy owing to its teratogenic effects on the fetus; hence, there is a general agreement to postpone radiotherapy up until after delivery (3,18,24,29). In the first trimester (before the completion of organogenesis), radiotherapy may be related to fetal death, malformations, microcephaly, intrauterine growth retardation, mental retardation, and induction of childhood neoplasms and hematologic disorders (30,31). Adjuvant radiotherapy to the breast is never an “urgent” procedure; hence, postponing it could be better given the potential hazards of the fetus. Of note, the latter remains very low anyways during the first and second trimester with adequate shielding given that the uterus is far from the radiation field (31,32). However, in patients with brain metastases, radiotherapy to the brain is certainly given during pregnancy because there is an urgent clinical need with very low potential fetal adverse effects (31,32).
According to current clinical recommendations, tamoxifen is contraindicated during pregnancy; the agent has been associated with birth defects in up to 20% of exposures, including Goldenhar’s syndrome (33), ambiguous genitalia, vaginal bleeding, and spontaneous abortion (34-36). During pregnancy, tamoxifen and its metabolites interact with rapidly growing and developing embryonic or fetal tissues (37). Although several case reports describe tamoxifen exposure and healthy neonatal outcomes (38), there is a general agreement to postpone tamoxifen up until after delivery (29). In this context, it should be noted that aromatase inhibitors are not indicated in premenopausal women.
Chemotherapy plays a key role in improving the survival of patients with early stage breast cancer. The decision to administer chemotherapy in pregnant women with breast cancer should follow the same guidelines as applied to non-pregnant patients. Chemotherapy is generally contraindicated during the first trimester because of the possible damage to organogenesis, whereas several recent studies have shown that certain chemotherapy regimens can be relatively safely administered during the second and third trimester (39-41). Worthy of note, in the first trimester, the risk of congenital malformations ranges from 10-20%, whilst it drops to 1.3% in the third trimester of pregnancy (39).
In this context, it should be noted that although pregnancy will alter the pharmacokinetics of cytotoxic drugs, there are currently no studies justifying a change in dosage. Hence, during pregnancy, dosages should not differ from those used outside pregnancy, even if few pharmacokinetic and pharmacodynamic data are available during pregnancy (24).
Anthracyclines-based regimens are the most widely used is breast cancer treatment and were been shown to be associated with favourable safety profile when administered during pregnancy (42). More specifically, the most commonly used regimens, in the adjuvant setting, include 5-fluorouracil combined with doxorubicin (5-FU-A) and epirubicin or doxorubicin in combination with cyclophosphamide (E or A-C). Of note, no clear differences could be attributed to the aforementioned different regimens regarding maternal toxicities, short or long term fetal outcome and pregnancy outcome. Moreover, in the neo-adjuvant and in the advanced/metastatic setting, anthracyclines and anthracycline-based regimens remain the best choice (42,43).
More limited data is available on taxanes. More specifically, they have recently been incorporated in the ESMO and NCCN guidelines (3,18), as being considered relatively safe to administer beyond the first gestational trimester; the risk of abortion or congenital anomalies increases when they are administered during the first trimester. Moreover, the Food and Drug Administration classify docetaxel and paclitaxel as a category D drug (i.e., able to be administered in pregnancy if necessary).
According to a recent systematic review, a completely healthy neonate was born with a normal Apgar score, appropriate fetal growth and acceptable weight in the majority of breast cancer patients with taxanes administration during pregnancy (44). Moreover, 27 out of 30 children (90%) were completely healthy at a median follow-up of 16 months; among the remaining cases, one child with recurrent otitis media, one child with IgA deficiency and mild constipation and another child with delayed speech were reported (44,45). However, it should be underlined that there is limited information concerning the long-term consequences for the offspring. Moreover, only ex vivo data are available on the transplacental transfer of taxanes in humans, whilst in a human placental perfusion model, the transplacental transfer rate of paclitaxel was found to be low (<5%) (46).
Hence, as for taxanes, if required in the adjuvant setting, limited data is available in pregnancy (44). Still, acknowledging the limited amount of evidence, taxanes could be offered in sequence to anthracyclines following delivery (29). Regarding the metastatic setting, it seems that single agent taxane (paclitaxel or docetaxel) may represent an appealing option, especially for patients who are not suitable candidates for anthracycline-based regimens (44,47).
Targeted therapy during pregnancy
According to ESMO and NCCN guidelines (3,18), the use of trastuzumab is contraindicated during pregnancy, given the apparent risk of oligo- and/or anhydramnios as well as the unknown long-term sequelae on the fetus (48). Notably, the Food and Drug Administration classify trastuzumab as a pregnancy category B drug. While studies in cynomolgus monkeys reported no harm to the fetus, they failed to reveal placental transfer of trastuzumab in monkeys [reviewed in (48)].
A recent meta-analysis has shown that trastuzumab administration emerges as relatively safe during the first trimester of pregnancy, whereas a high incidence of oligohydramnios and/or anhydramnios is observed when this agent is used beyond the first trimester (49). An intriguing observation of this meta-analysis is that all children exposed to trastuzumab exclusively during the first trimester of pregnancy were completely healthy and showed no evidence of congenital malformations (50-52). Indeed, the occurrence of oligohydramnios/or anhydramnios was confined to pregnancies exposed during the second or third trimesters (49). A study by Pentsuk et al. concurred with this meta-analysis (53), showing that fetal exposure to trastuzumab is very low during the first trimester, and increases during the second half of gestation, to reach a drug concentration at birth similar to that of the mother.
Hence, as concerns trastuzumab administration in the adjuvant setting during pregnancy, it should be noted that there is no cause for exposing the pregnant HER2- positive woman and the fetus to the potential hazard of the agent. Mounting evidence outside pregnancy confirm the efficacy of trastuzumab even after 6 months of adjuvant chemotherapy (54), suggesting that a monoclonal antibody could be safely administered after delivery. On the other hand, as far as metastatic HER2- positive breast cancer is concerned, trastuzumab should be avoided and chemotherapy could start from the second trimester. However, in selected cases, where the agent may be urgently needed, its administration is recommended for a short period with careful control of the amniotic fluid, fetal growth and kidney function; should signs of oligohydramnios be observed, the agent should immediately be discontinued (49).
Moreover, unlike chemotherapy, trastuzumab does not induce amenorrhea (55), thus, an accidental pregnancy during its administration cannot be precluded if no adequate contraception is used. Of note, according to Azim et al. (56), patients who became pregnant after a trastuzumab-free interval of more than 3 months appeared to have normal pregnancy courses and outcomes. These data may be of particular significance to women who accidentally fall pregnant during trastuzumab administration but do not wish to terminate the pregnancy; in this setting, trastuzumab should be discontinued and pregnancy be allowed to continue without urging an abortion. However, it should be stressed that no definite conclusion can be drawn given the limited number of observations; clinicians should always advise women to use active contraception while on trastuzumab therapy and to continue doing so for up to 6 months following completion of treatment (48,49,52).
There are insufficient data on lapatinib administration during pregnancy, but its pharmacological characteristics (massive transplacental transfer) would strongly caution against its use during pregnancy; hence, lapatinib cannot be recommended during pregnancy (3,18,24). Of note, there is only one report on lapatinib exposure in a woman during the first and second trimesters; the agent was discontinued and the delivery was uncomplicated with a healthy newborn (57).
Antiemetics such as 5HT antagonists, steroids, or antihistamines are not contraindicated during pregnancy. Granulocyte-stimulating factors are considered as pregnancy category C; hence, they should be used during pregnancy by the clinical necessity (1). Concerning bisphosphonates, limited data is available for their use during pregnancy. More specifically, data on 51 pregnant women for different indications did not reveal any increase in maternal and/or fetal morbidity (58). However, given that bisphosphonates remain in mineralised bone for several years and that available data on pregnant patients are limited, it should be clearly stated that bisphosphonates should be used with caution and on personalized basis; if used, hypocalcaemia affecting the contractility of the uterus should be avoided (58,59).
Fetal and pregnancy monitoring
A multidisciplinary approach involving medical and surgical oncologists, high-risk obstetric care, genetic counsellors, pharmacists, radiation oncologists, and neonatologists is mandatory for the successful management of women with breast cancer during pregnancy (24). It is without doubt that strict fetal monitoring with morphometric ultrasound and umbilical artery Doppler should be performed at regular intervals during gestational chemotherapy (3,18,24).
The timing of delivery should be balanced according to the oncological treatment schedule and the maturation of the fetus; as in non-cancer patients, the aim of a full term delivery (>37 weeks’ gestation) is important since prematurity affects the cognitive and emotional development of children (60-62). Moreover, it is recommended that patients should not receive any chemotherapeutic agents for at least 3 weeks prior to delivery so as to avoid problems associated with haematopoeitic suppression (bleeding, infection, anaemia) in the mother and baby, and to prevent drug accumulation in the fetus (24,43,63). The mode of delivery is determined based upon the obstetrical indication (24). Although metastases to the placenta is a rare event in breast cancer patients, the placenta should always be evaluated after delivery (64,65).
In the absence of safety data, breastfeeding in the first weeks after chemotherapy is not recommended (3,18,24). Of note, primary inhibition of milk production is needed because especially lipophylic agents such as taxanes can accumulate in the milk.
In this context, it should be noted that treating cancer during pregnancy represents a relatively uncommon situation. The available data are limited and consist mainly of case reports, case series, and retrospective registries; hence, in order to provide further information for this challenging clinical situation, improved collaboration between registries and cancer centers is more than warranted given the long-term implications for both the breast cancer patient and neonate.
Moreover, it should be stressed that in all cases, a multidisciplinary therapeutic approach among obstetricians, gynaecologists, surgical oncologists, radiation oncologists, medical oncologists and hematologists is clearly warranted; the optimal therapeutic strategy in a pregnant patient with breast cancer diagnosis should take into consideration the gestational age, stage of breast cancer, treatment options, the wishes of the patient, and a host of psychological, ethical, religious, and even legal considerations.
Disclosure: The authors declare no conflict of interest.
- Viswanathan S, Ramaswamy B. Pregnancy-associated breast cancer. Clin Obstet Gynecol 2011;54:546-55. [PubMed]
- Asgeirsson KS. Pregnancy-associated breast cancer. Acta Obstet Gynecol Scand 2011;90:158-66. [PubMed]
- Pentheroudakis G, Orecchia R, Hoekstra HJ, et al. Cancer, fertility and pregnancy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21:v266-73. [PubMed]
- Mir O, Berveiller P, Ropert S, et al. Emerging therapeutic options for breast cancer chemotherapy during pregnancy. Ann Oncol 2008;19:607-13. [PubMed]
- Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda, MD. Available online: http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site, 2011.
- Ezzat A, Raja MA, Berry J, et al. Impact of pregnancy on non-metastatic breast cancer: a case control study. Clin Oncol (R Coll Radiol) 1996;8:367-70. [PubMed]
- Beadle BM, Woodward WA, Middleton LP, et al. The impact of pregnancy on breast cancer outcomes in women < or =35 years. Cancer 2009;115:1174-84. [PubMed]
- Zemlickis D, Lishner M, Degendorfer P, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obstet Gynecol 1992;166:781-7. [PubMed]
- Ishida T, Yokoe T, Kasumi F, et al. Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation: analysis of case-control study in Japan. Jpn J Cancer Res 1992;83:1143-9. [PubMed]
- Zhang J, Liu G, Wu J, et al. Pregnancy-associated breast cancer: a case control and long-term follow-up study in China. J Exp Clin Cancer Res 2003;22:23-7. [PubMed]
- Murphy C, Mallam D, Stein S, et al. Pathologic features and outcomes of pregnancy-associated breast cancer (PABC): A case control study. J Clin Oncol 2010;28:1589.
- Lethaby AE, O’Neill MA, Mason BH, et al. Overall survival from breast cancer in women pregnant or lactating at or after diagnosis. Auckland Breast Cancer Study Group. Int J Cancer 1996;67:751-5. [PubMed]
- Azim HA Jr, Botteri E, Renne G, et al. The biological features and prognosis of breast cancer diagnosed during pregnancy: a case-control study. Acta Oncol 2012;51:653-61. [PubMed]
- Rodriguez AO, Chew H, Cress R, et al. Evidence of poorer survival in pregnancy-associated breast cancer. Obstet Gynecol 2008;112:71-8. [PubMed]
- Bonnier P, Romain S, Dilhuydy JM, et al. Influence of pregnancy on the outcome of breast cancer: a case-control study. Societe Francaise de Senologie et de Pathologie Mammaire Study Group. Int J Cancer 1997;72:720-7. [PubMed]
- Moreira WB, Brandão EC, Soares AN, et al. Prognosis for patients diagnosed with pregnancy-associated breast cancer: a paired case-control study. Sao Paulo Med J 2010;128:119-24. [PubMed]
- Azim HA Jr, Santoro L, Russell-Edu W, et al. Prognosis of pregnancy-associated breast cancer: a meta-analysis of 30 studies. Cancer Treat Rev 2012;38:834-42. [PubMed]
- NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 2.2012. Available online: http://www.nccn.com
- Rovera F, Frattini F, Coglitore A, et al. Breast cancer in pregnancy. Breast J 2010;16:S22-5. [PubMed]
- Molckovsky A, Madarnas Y. Breast cancer in pregnancy: a literature review. Breast Cancer Res Treat 2008;108:333-8. [PubMed]
- Navrozoglou I, Vrekoussis T, Kontostolis E, et al. Breast cancer during pregnancy: a mini-review. Eur J Surg Oncol 2008;34:837-43. [PubMed]
- Vinatier E, Merlot B, Poncelet E, et al. Breast cancer during pregnancy. Eur J Obstet Gynecol Reprod Biol 2009;147:9-14. [PubMed]
- Amant F, Loibl S, Neven P, et al. Breast cancer in pregnancy. Lancet 2012;379:570-9. [PubMed]
- Amant F, Deckers S, Van Calsteren K, et al. Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer 2010;46:3158-68. [PubMed]
- Gentilini O, Cremonesi M, Trifirò G, et al. Safety of sentinel node biopsy in pregnant patients with breast cancer. Ann Oncol 2004;15:1348-51. [PubMed]
- Gentilini O, Cremonesi M, Toesca A, et al. Sentinel lymph node biopsy in pregnant patients with breast cancer. Eur J Nucl Med Mol Imaging 2010;37:78-83. [PubMed]
- Khera SY, Kiluk JV, Hasson DM, et al. Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J 2008;14:250-4. [PubMed]
- Azim H Jr, Gentilini O, Locatelli M, et al. Managing pregnant women with cancer: personal considerations and a review of the literature. Ecancermedicalscience 2011;5:204. [PubMed]
- Azim HA Jr, Del Mastro L, Scarfone G, et al. Treatment of breast cancer during pregnancy: regimen selection, pregnancy monitoring and more.. Breast 2011;20:1-6. [PubMed]
- Behrman RH, Homer MJ, Yang WT, et al. Mammography and fetal dose. Radiology 2007;243:605-author reply 605-6. [PubMed]
- Martin DD. Review of radiation therapy in the pregnant cancer patient. Clin Obstet Gynecol 2011;54:591-601. [PubMed]
- Guidroz JA, Scott-Conner CE, Weigel RJ. Management of pregnant women with breast cancer. J Surg Oncol 2011;103:337-40. [PubMed]
- Cullins SL, Pridjian G, Sutherland CM. Goldenhar’s syndrome associated with tamoxifen given to the mother during gestation. JAMA 1994;271:1905-6. [PubMed]
- Cunha GR, Taguchi O, Namikawa R, et al. Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract. Hum Pathol 1987;18:1132-43. [PubMed]
- Isaacs RJ, Hunter W, Clark K. Tamoxifen as systemic treatment of advanced breast cancer during pregnancy--case report and literature review. Gynecol Oncol 2001;80:405-8. [PubMed]
- Tewari K, Bonebrake RG, Asrat T, et al. Ambiguous genitalia in infant exposed to tamoxifen in utero. Lancet 1997;350:183. [PubMed]
- Braems G, Denys H, De Wever O, et al. Use of tamoxifen before and during pregnancy. Oncologist 2011;16:1547-51. [PubMed]
- Oksüzoglu B, Güler N. An infertile patient with breast cancer who delivered a healthy child under adjuvant tamoxifen therapy. Eur J Obstet Gynecol Reprod Biol 2002;104:79. [PubMed]
- Ring AE, Smith IE, Jones A, et al. Chemotherapy for breast cancer during pregnancy: an 18-year experience from five London teaching hospitals. J Clin Oncol 2005;23:4192-7. [PubMed]
- Berry DL, Theriault RL, Holmes FA, et al. Management of breast cancer during pregnancy using a standardized protocol. J Clin Oncol 1999;17:855-61. [PubMed]
- Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer 2006;107:1219-26. [PubMed]
- Azim HA Jr, Peccatori FA, Pavlidis N. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part I: Solid tumors. Cancer Treat Rev 2010;36:101-9. [PubMed]
- Loibl S, von Minckwitz G, Gwyn K, et al. Breast carcinoma during pregnancy. International recommendations from an expert meeting. Cancer 2006;106:237-46. [PubMed]
- Zagouri F, Sergentanis TN, Chrysikos D, et al. Taxanes for breast cancer during pregnancy: a systematic review. Clin Breast Cancer 2013;13:16-23. [PubMed]
- Cardonick E, Bhat A, Gilmandyar D, et al. Maternal and fetal outcomes of taxane chemotherapy in breast and ovarian cancer during pregnancy: case series and review of the literature. Ann Oncol 2012;23:3016-23. [PubMed]
- Berveiller P, Mir O. Taxanes during pregnancy: probably safe, but still to be optimized. Oncology 2012;83:239-40. [PubMed]
- Schackmuth EM, Harlow CL, Norton LW. Milk fistula: a complication after core breast biopsy. AJR Am J Roentgenol 1993;161:961-2. [PubMed]
- Azim HA Jr, Azim H, Peccatori FA. Treatment of cancer during pregnancy with monoclonal antibodies: a real challenge. Expert Rev Clin Immunol 2010;6:821-6. [PubMed]
- Zagouri F, Sergentanis TN, Chrysikos D, et al. Trastuzumab administration during pregnancy: a systematic review and meta-analysis. Breast Cancer Res Treat 2013;137:349-57. [PubMed]
- Goodyer MJ, Ismail JR, O’Reilly SP, et al. Safety of trastuzumab (Herceptin) during pregnancy: two case reports. Cases J 2009;2:9329. [PubMed]
- Waterston AM, Graham J. Effect of adjuvant trastuzumab on pregnancy. J Clin Oncol 2006;24:321-2. [PubMed]
- Azim HA Jr, Peccatori FA, Liptrott SJ, et al. Breast cancer and pregnancy: how safe is trastuzumab? Nat Rev Clin Oncol 2009;6:367-70. [PubMed]
- Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol 2009;86:328-44. [PubMed]
- Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-72. [PubMed]
- Abusief ME, Missmer SA, Ginsburg ES, et al. The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer 2010;116:791-8. [PubMed]
- Azim HA Jr, Metzger-Filho O, de Azambuja E, et al. Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01). Breast Cancer Res Treat 2012;133:387-91. [PubMed]
- Kelly H, Graham M, Humes E, et al. Delivery of a healthy baby after first-trimester maternal exposure to lapatinib. Clin Breast Cancer 2006;7:339-41. [PubMed]
- Djokanovic N, Garcia-Bournissen F, Koren G. Medications for restless legs syndrome in pregnancy. J Obstet Gynaecol Can 2008;30:505-7. [PubMed]
- Levy S, Fayez I, Taguchi N, et al. Pregnancy outcome following in utero exposure to bisphosphonates. Bone 2009;44:428-30. [PubMed]
- Amant F, Van Calsteren K, Halaska MJ, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study. Lancet Oncol 2012;13:256-64. [PubMed]
- Tamaru S, Kikuchi A, Takagi K, et al. Neurodevelopmental outcomes of very low birth weight and extremely low birth weight infants at 18 months of corrected age associated with prenatal risk factors. Early Hum Dev 2011;87:55-9. [PubMed]
- Løhaugen GC, Gramstad A, Evensen KA, et al. Cognitive profile in young adults born preterm at very low birthweight. Dev Med Child Neurol 2010;52:1133-8. [PubMed]
- Sorosky JI, Sood AK, Buekers TE. The use of chemotherapeutic agents during pregnancy. Obstet Gynecol Clin North Am 1997;24:591-9. [PubMed]
- Alexander A, Samlowski WE, Grossman D, et al. Metastatic melanoma in pregnancy: risk of transplacental metastases in the infant. J Clin Oncol 2003;21:2179-86. [PubMed]
- Dunn JS Jr, Anderson CD, Brost BC. Breast carcinoma metastatic to the placenta. Obstet Gynecol 1999;94:846. [PubMed]