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OBJECTIVE: To characterise pregnant women diagnosed with primary or recurrent cancer who died during pregnancy, during delivery or within 1 year postpartum. DESIGN: A descriptive study. SETTING: The registry of the International Network on Cancer, Infertility and Pregnancy (INCIP). POPULATION: Women diagnosed with cancer during pregnancy between 2000 and 2022. METHODS: Using the INCIP registry database, we compared the characteristics of all women with cancer who died during pregnancy, delivery or within 1 year postpartum with those of all women with cancer who survived the first year postpartum. MAIN OUTCOME MEASURES: Maternal and tumour characteristics and obstetrical and neonatal outcomes. RESULTS: Of the 2359 women registered in INCIP, there were 131 cases (5.6%) of maternal mortality. Lung cancer (9/14, 64.3% of all registered women with lung cancer), gastro-oesophageal cancer (13/21, 61.9%) and acute leukaemia (17/105, 16.2%) had the highest rates of maternal mortality. Maternal mortality was associated with fewer live births compared with the control group without maternal mortality (99/131, 75.6%, vs 1952/2163, 90.0%; P < 0.001), more elective caesarean sections (64/104, 60.4%, vs 756/1836, 41.2%; P < 0.001) and a lower gestational age at (induced) delivery (34.0 vs 37.1 weeks; P < 0.001), resulting in more preterm births. CONCLUSIONS: Maternal mortality occurred in 5.6% of cancer-in-pregnancy cases and is associated with adverse perinatal outcomes.
Assuntos
Linfoma , Recidiva Local de Neoplasia , Humanos , Gravidez , Feminino , Linfoma/diagnóstico , Linfoma/terapiaRESUMO
Data on the use of Granulocyte colony-stimulating factor (G-CSF) in pregnant cancer patients are scarce. The International Network of Cancer, Infertility and Pregnancy (INCIP) reviewed data of pregnant patients treated with chemotherapy and G-CSF, and their offspring. Among 2083 registered patients, 42 pregnant patients received G-CSF for the following indications: recent chemotherapy induced febrile neutropenia (5; 12%), dose dense chemotherapy (28, 67%), poly chemotherapy (7, 17%), or prevention of neutropenia at delivery (2; 5%). Among 24 women receiving dose dense chemotherapy, three (13%) patients recovered from asymptomatic neutropenia within 5 days. One patient developed pancytopenia following polychemotherapy after which the pregnancy was complicated by chorioamnionitis and intrauterine death. Nineteen singleton livebirths (49%) were born preterm. Sixteen neonates (41%) were admitted to the Neonatal Intensive care Unit (NICU). No neonatal neutropenia occurred. Two neonates had congenital malformations. Out of 21 children in follow-up, there were four children with a motor development delay and two premature infants had a delay in cognitive development. In conclusion, the rate of maternal and neonatal complications are similar to those described in (pregnant) women treated with chemotherapy. Due to small numbers and limited follow-up, rare or delayed effects among offspring exposed to G-CSF in utero cannot be ruled out yet.
RESUMO
OBJECTIVE: To provide contemporary gestational age-specific recommendations for management, a retrospective series of patients with renal or bladder cancer during pregnancy is reported. METHODS: Obstetric and oncological data of pregnant patients with a diagnosis of renal or bladder cancer were selected from the worldwide registry of the International Network of Cancer, Infertility and Pregnancy. In addition, the literature was reviewed for recent case reports since last reviews in 2014 for renal cancer and 2004 for bladder cancer. RESULTS: International Network of Cancer, Infertility and Pregnancy registered 22 cases (14 renal cancer and 8 bladder cancer), diagnosed between 1999 and 2017, and the literature reported 15 cases with renal cancer and 10 cases with bladder cancer between 2004 and 2019. Most common symptoms for renal and bladder cancer were pain (28%) and hematuria (66%), respectively. In more than half of the patients, surgical treatment was performed during pregnancy. Preterm deliveries were mostly medically induced (12 of 17, 71%) and all patients with a planned delivery before 34 weeks had advanced cancer. For renal and bladder cancer respectively, 79% and 87% of patients obtained complete remission. Advanced cancer stages had worse prognosis; 3 of 7 patients with known follow-up deceased within 15 months after diagnosis. CONCLUSION: Gestational age at diagnosis determines further management of renal and bladder cancers during pregnancy. Advanced stages challenge decision-making. The maternal needs for immediate treatment, and the neonatal risks including the impact of a preterm delivery should be discussed in a multidisciplinary setting while respecting the patient's autonomy.
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Neoplasias Renais , Complicações Neoplásicas na Gravidez , Neoplasias da Bexiga Urinária , Adulto , Feminino , Hematúria/etiologia , Humanos , Recém-Nascido , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Trabalho de Parto Induzido , Pessoa de Meia-Idade , Dor/etiologia , Gravidez , Complicações Neoplásicas na Gravidez/mortalidade , Complicações Neoplásicas na Gravidez/terapia , Nascimento Prematuro , Sistema de Registros , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/terapia , Adulto JovemRESUMO
BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.
Assuntos
Doença de Hodgkin/diagnóstico , Adulto , Antineoplásicos/uso terapêutico , Parto Obstétrico , Intervalo Livre de Doença , Feminino , Idade Gestacional , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Nascido Vivo , Gravidez , Cuidado Pré-Natal , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the feasibility of whole-body diffusion-weighted MRI (WB-DWI/MRI) for detecting primary tumour, nodal and distant metastases in pregnant women with cancer. METHODS: Twenty pregnant patients underwent WB-DWI/MRI in additional to conventional imaging. Reproducibility of WB-DWI/MRI between two readers was evaluated using Cohen's κ statistics and accuracy was compared to conventional imaging for assessing primary tumour site, nodal and visceral metastases. RESULTS: Both WB-DWI/MRI readers showed good-very good agreement for lesion detection (primary lesions: κ=1; lymph nodes: κ=0.89; distant metastases: κ=0.61). Eight (40 %) patients were upstaged after WB-DWI/MRI. For nodal metastases, WB-DWI/MRI showed 100 % (95 % CI: 83.2-100) sensitivity for both readers with specificity of 99.4 % (96.9-100) and 100 % (80.5-100) for readers 1 and 2, respectively. For distant metastases, WB-DWI/MRI showed 66.7 % (9.4-99.2) and 100 % (29.2-100) sensitivity and specificity of 94.1 % (71.3-99.9) and 100 % (80.5-100) for readers 1 and 2, respectively. Conventional imaging showed sensitivity of 50 % (27.2-72.8) and 33.3 % (0.8-90.6); specificity of 100 % (98-100) and 100 % (80.5-100), for nodal and distant metastases respectively. CONCLUSIONS: WB-DWI/MRI is feasible for single-step non-invasive staging of cancer during pregnancy with additional value for conventional imaging procedures. KEY POINTS: ⢠In our study, WB-DWI/MRI was more accurate than conventional imaging during pregnancy. ⢠WB-DWI/MRI improves diagnostic assessment of patients with cancer during pregnancy. ⢠Accurate imaging and oncologic staging improves treatment and outcome.
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Imagem de Difusão por Ressonância Magnética/métodos , Linfonodos/patologia , Estadiamento de Neoplasias/métodos , Neoplasias/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Imagem Corporal Total/métodos , Adulto , Feminino , Seguimentos , Humanos , Metástase Neoplásica/diagnóstico , Projetos Piloto , Gravidez , Estudos Prospectivos , Reprodutibilidade dos TestesAssuntos
Carcinoma Mucoepidermoide/cirurgia , Neoplasias Pulmonares/cirurgia , Complicações Neoplásicas na Gravidez/cirurgia , Adulto , Carcinoma Mucoepidermoide/diagnóstico por imagem , Carcinoma Mucoepidermoide/patologia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Tomografia Computadorizada por Raios X , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Data on the long-term outcome of children who are exposed to maternal cancer with or without treatment during pregnancy are lacking. METHODS: In this multicenter case-control study, we compared children whose mothers received a diagnosis of cancer during the pregnancy with matched children of women without a cancer diagnosis. We used a health questionnaire and medical files to collect data regarding neonatal and general health. All children were prospectively assessed (by means of a neurologic examination and the Bayley Scales of Infant Development) at 18 months, 36 months, or both. A cardiac assessment was performed at 36 months. RESULTS: A total of 129 children (median age, 22 months; range, 12 to 42) were included in the group whose mother had cancer (prenatal-exposure group) with a matching number in the control group. During pregnancy, 96 children (74.4%) were exposed to chemotherapy (alone or in combination with other treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment. Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the prenatal-exposure group and in 19 of 125 children (15.2%) in the control group (P=0.16). There was no significant between-group difference in cognitive development on the basis of the Bayley score (P=0.08) or in subgroup analyses. The gestational age at birth was correlated with the cognitive outcome in the two study groups. Cardiologic evaluation among 47 children at 36 months of age showed normal cardiac findings. CONCLUSIONS: Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment. (Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number, NCT00330447.).
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Antineoplásicos/efeitos adversos , Desenvolvimento Infantil , Cognição , Coração/fisiologia , Complicações Neoplásicas na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Radioterapia/efeitos adversos , Peso ao Nascer/efeitos dos fármacos , Peso ao Nascer/efeitos da radiação , Estudos de Casos e Controles , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/efeitos da radiação , Pré-Escolar , Cognição/efeitos dos fármacos , Cognição/efeitos da radiação , Feminino , Idade Gestacional , Crescimento , Coração/anatomia & histologia , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro/psicologia , Masculino , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológicoRESUMO
A multidisciplinary discussion is necessary to tackle a complex and infrequent medical problem such as cancer occurring during pregnancy. Pregnancy does not predispose to cancer, but cancers occurring in women of reproductive age are encountered during pregnancy. Ultrasonography and magnetic resonance imaging are the preferred staging examinations, but also a sentinel node staging procedure is possible during pregnancy. Standard cancer treatment is aimed for. Operations can safely be performed during pregnancy, but surgery of genital cancers can be challenging. The observation that chemotherapy administered during the second or third trimester of pregnancy, that is, after the period of organogenesis, has little effect on the long-term outcome of children adds to the therapeutic armamentarium during pregnancy. Cancer treatment during pregnancy adds in the continuation of the pregnancy and the prevention of prematurity.
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Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Efeitos Tardios da Exposição Pré-Natal , Antineoplásicos/uso terapêutico , Feminino , Humanos , Estadiamento de Neoplasias , Gravidez , Prognóstico , Radioterapia , Procedimentos Cirúrgicos OperatóriosRESUMO
The diagnosis of a gynecological malignancy during pregnancy is rare but not uncommon. Cancer treatment during pregnancy is possible, but both maternal and fetal interests need to be respected. Different treatment plans may be justifiable and multidisciplinary treatment is advised. Clinical trials are virtually impossible, and current evidence is mainly based on small case series and expert opinion. Individualization of treatment is necessary and based on tumor type, stage, and gestational age at time of diagnosis. Termination of pregnancy is not necessary in most cases. Surgery and chemotherapy (second trimester and onwards) are possible types of treatment during pregnancy. Radiotherapy of the pelvic area is not compatible with an ongoing pregnancy. This article discusses the current recommendations for the management of gynecological malignancies (cervical, ovarian, and vulvar cancers) during pregnancy.
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Antineoplásicos/administração & dosagem , Neoplasias dos Genitais Femininos/terapia , Procedimentos Cirúrgicos em Ginecologia , Complicações Neoplásicas na Gravidez/terapia , Biópsia de Linfonodo Sentinela/métodos , Antineoplásicos/efeitos adversos , Medicina Baseada em Evidências , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/patologia , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/patologia , Resultado da Gravidez , Diagnóstico Pré-Natal , Efeitos Tardios da Exposição Pré-Natal , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: The concurrence of intracranial tumours with pregnancy is rare. The purpose of this study was to describe all reported patients registered in the international Cancer in Pregnancy registration study (CIP study; http://www.cancerinpregnancy.org), and to review the literature in order to obtain better insight into outcome and possibilities of treatment in pregnancy. METHODS: We collected all intracranial tumours (primary brain tumour, cerebral metastasis, or meningioma) diagnosed during pregnancy, registered prospectively and retrospectively by international collaboration since 1973. Patients diagnosed postpartum were excluded. We summarised the demographic features, treatment decisions, obstetrical and neonatal outcomes. RESULTS: The mean age of the 27 eligible patients was 31years (range 23-41years), of which 13 and 12 patients were diagnosed in the second and third trimesters, respectively. Eight patients (30%) underwent brain surgery, seven patients (26%) had radiotherapy and in three patients (11%) chemotherapy was administered during gestation. Two patients died during pregnancy and four pregnancies were terminated. In 16 (59%) patients elective caesarean section was performed of which 14 (52%) were still preterm (range 30-36weeks, mean 33weeks). Five patients had a vaginal delivery (range 36-40weeks). Of the 21 ongoing pregnancies all children were born alive without visible congenital malformations and the available long-term follow-up data (range 2-25years) of six children were reassuring. CONCLUSION: Adherence to standard protocol for the treatment of brain tumours during pregnancy appears to allow a term delivery and a higher probability of a vaginal delivery.
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Neoplasias Encefálicas/patologia , Neoplasias Meníngeas/patologia , Meningioma/patologia , Complicações Neoplásicas na Gravidez , Adulto , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Parto Obstétrico , Feminino , Humanos , Neoplasias Meníngeas/terapia , Meningioma/terapia , Gravidez , Resultado da Gravidez , Prognóstico , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Anthracyclines are used to treat cancers during the second and third trimester of pregnancy. The chemotherapeutic effect of anthracyclines is associated with a dose- and time-dependent cardiotoxicity that is well described for infants and adults. However, data regarding fetal anthracycline-related cardiotoxicity after administration of chemotherapeutics during pregnancy are limited. In this study, we analyzed the acute effect of doxorubicin, an anthracycline derivative, on fetal and maternal rat myocardium. We injected 10 or 20 mg/kg i.v. doxorubicin to pregnant Wistar rats at day 18 of pregnancy; age-matched pregnant rats injected with physiologic saline served as controls. Maternal echocardiography and fetal Doppler scanning were performed before the injection and before sacrifice. Cesarean operation was performed at day 19 or 20, and maternal and fetal blood samples and heart biopsies were collected to measure apoptosis, the impact on cell proliferation, and structural cardiac damage. Acute maternal cardiotoxicity is associated with loss of body weight, moderately deteriorated left ventricular function, induction of apoptosis, and a decrease in cell turnover. Despite a 30% lower fetal body weight and elevated plasma B-type natriuretic peptide concentrations after doxorubicin administration, the fetal hearts had intact microstructure, an unaltered number of apoptotic cells, and preserved cell proliferation compared with controls. Our study suggests that acute treatment using anthracyclines during pregnancy impairs maternal cardiac function, whereas fetal hearts are protected.
Assuntos
Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidade , Coração Fetal/efeitos dos fármacos , Cardiopatias/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Fator Natriurético Atrial/metabolismo , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Ecocardiografia , Feminino , Cardiopatias/diagnóstico por imagem , Marcação In Situ das Extremidades Cortadas , Injeções Intravenosas , Troca Materno-Fetal , Miocárdio/metabolismo , Miosinas/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Gravidez , RNA/biossíntese , RNA/genética , Ratos , Ratos Wistar , Transcrição Gênica/efeitos dos fármacosAssuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Feminino , Humanos , Masculino , GravidezRESUMO
Chemotherapy and particularly anthracycline exposure are associated with acute and chronic cardiotoxicity. Few data exist on the effect of cardiac function after in utero exposure to maternal chemotherapy. Our recently published multicenter prospective study showed no significant changes in systolic function using conventional echocardiographic parameters. The purpose of this study was to further investigate whether early functional changes can be detected using tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE). Sixty-two children (median/range age 1.7 (1-9.8) years) exposed to chemotherapy during fetal life were enrolled and compared to 62 age- and gender-matched controls. TDI velocities were measured at the basal interventricular septum (IVS) and right and left ventricular (LV) free walls. LV global longitudinal and circumferential systolic strains were derived using 2D STE. We found small but significant differences between the groups (patients versus controls) in LV fractional shortening [35 (29-46)% versus 39 (28-53)%, p < 0.001], LV ejection fraction [66 (57-79)% versus 70 (57-83)%, p < 0.001], LV posterior wall thickness z score [-0.15 (-2.32-1.81) versus -0.10 (-1.9-2.0), p < 0.001], and IVS thickness z score [-1.06 (-2.6-1.3) versus -0.5 (-2.1-1.7), p < 0.001]. No significant differences in TDI velocities or LV global strains were observed. Within the patient group, the cardiac functional parameters did not correlate to the number of cycles of anthracycline or the cumulative anthracycline dose. Children exposed to fetal chemotherapy have a lower normal fractional shortening and mildly lower left ventricular wall thickness. Tissue Doppler and strain measurements are within normal range and not statistically different from normal controls. The long-term implications of these findings will be further studied in this prospective cohort study.
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Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Ecocardiografia/métodos , Coração/fisiologia , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Superfície Corporal , Neoplasias da Mama/tratamento farmacológico , Criança , Pré-Escolar , Técnicas de Imagem por Elasticidade , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Lactente , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnósticoRESUMO
BACKGROUND: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. METHODS: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833. FINDINGS: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539). INTERPRETATION: Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance. FUNDING: BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Peso ao Nascer/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Doenças do Recém-Nascido/induzido quimicamente , Doenças do Recém-Nascido/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , Índice de Apgar , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma Ductal/diagnóstico , Carcinoma Ductal/tratamento farmacológico , Carcinoma Ductal/patologia , Carcinoma Ductal/secundário , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Carcinoma Lobular/cirurgia , Estudos de Coortes , Parto Obstétrico/estatística & dados numéricos , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Incidência , Recém-Nascido , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Preservação de Órgãos , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
Chemotherapy and especially anthracyclines are associated to cardiotoxicity. To assess this potential risk during pregnancy a clinical case-control trial was conducted. Maternal cardiac function, fetal Doppler and fetal cardiac function were evaluated before and after chemotherapy. Maternal cardiac function was assessed by echocardiography before and after the third cycle of anthracyclines and compared with a control group of 10 non-pregnant women matched for age, type of cancer and anthracycline treatment. Ten fetuses exposed to chemotherapy were compared with 10 control fetuses matched for gestational age and gender. Biometry, amniotic fluid index, fetal Doppler and cardiac function were assessed before and after each cycle of chemotherapy. In all, 108 fetal ultrasounds scans were performed before and after 36 cycles of chemotherapy. Anthracycline exposure did not result in acute maternal and fetal cardiac dysfunction in this small cohort study.
Assuntos
Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Coração Fetal/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/induzido quimicamente , Bélgica , Estudos de Casos e Controles , Feminino , Coração Fetal/diagnóstico por imagem , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Estudos Prospectivos , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Recent insights provide support for the treatment of cancer during pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to critically review studies on the physiologic variations during pregnancy, the most common tumor markers used in diagnosis and follow-up of gynecological cancers. METHODS: We conducted a systematic review of six tumor markers during normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell carcinoma antigen (cervical cancer); and CA 125, anti-Müllerian hormone, inhibin B and lactate dehydrogenase (ovarian cancer). RESULTS: For CA 15-3, 3.3% to 20.0% of all measurements were above the cut-off (maximum 56 U/mL in the third trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and 10.5% of the measurements (maximum 4.3 µg/L in the third trimester). Up to 35% of CA 125 levels were above cut-off: levels were highest in the first trimester, with a maximum value up to 550 U/mL. Inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels were not elevated in maternal serum during normal pregnancy. CONCLUSION: During normal pregnancy, tumor markers including CA 15.3, squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels remain below normal cut-off values. Knowledge of physiological variations during pregnancy can be clinically important when managing gynecological cancers in pregnant patients.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias dos Genitais Femininos/sangue , Complicações Neoplásicas na Gravidez/sangue , Hormônio Antimülleriano/sangue , Feminino , Humanos , Inibinas/sangue , L-Lactato Desidrogenase/sangue , GravidezRESUMO
OBJECTIVE: The co-occurrence of cancer and pregnancy is more frequently diagnosed. The effects of cancer treatment on maternal and fetal outcomes are less well known. The cardiotoxic effects of chemotherapy are a specific concern for the mother and fetus. We wanted to review the existing literature, mainly consisting of case reports, case studies, and retrospective data. RESULTS: Maternal effects Overall, the published data indicate that pregnancy is not an independent risk factor influencing cancer survival. There is no indirect evidence for an increased risk for maternal chemotherapy-related cardiotoxicity. Fetal effects During the first trimester chemotherapy needs to be avoided because of teratogenic risks. The risks of chemotherapy during the second and third trimester are more controversial. It has been associated with intrauterine growth restriction and preterm delivery in some studies, while others did not find the same effect. Cardiotoxic fetal effects have been reported despite the limited transplacental passage of chemotherapy. In most patients this was transient and long-term data are generally reassuring. CONCLUSION: A specific strategy for monitoring fetal and maternal chemotherapy-induced cardiotoxicity is suggested. Prospective data are needed on the long-term effects of chemotherapy in both mother and child.