Pregnancy outcome after treatment for Wilms tumor: a report from the National Wilms Tumor Study Group.

PURPOSE: This study was undertaken to determine the effect, if any, of prior treatment with radiation therapy or chemotherapy for Wilms tumor diagnosed during childhood or adolescence on live births, birthweight, and the frequency of congenital malformations. PATIENTS AND METHODS: We reviewed pregnancy outcomes among survivors of Wilms tumor treated with or without irradiation to the flank or tumor bed on National Wilms Tumor Studies 1, 2, 3, and 4 using a maternal questionnaire and review of both maternal and offspring medical records. RESULTS: We received reports regarding 427 pregnancies with duration of 20 weeks or longer, including 409 liveborn singletons for whom 309 sets of medical records were reviewed. Malposition of the fetus and early or threatened labor were more frequent among irradiated women. Both were more frequent among women who received higher radiation therapy doses. The offspring of the irradiated female patients were more likely to weigh less than 2,500 g at birth and to be of less than 36 weeks gestation, with both being more frequent after higher doses of radiation. An increased percentage of offspring of irradiated females had one or more congenital malformations. CONCLUSION: Women who receive flank radiation therapy as part of their treatment for Wilms tumor are at increased risk of fetal malposition and premature labor. The offspring of these women are at risk for low birthweight, premature (< 36 weeks gestation) birth, and the occurrence of congenital malformations. These risks must be considered in the obstetrical management of female survivors of Wilms tumor.     

Chemotherapy for breast carcinoma during pregnancy: A French national survey

BACKGROUND: During pregnancy, the need for maternal chemotherapy for breast carcinoma must be balanced against the fetal risk because modification of cancer therapy to assure the birth of a healthy infant may affect maternal prognosis adversely. To the authors' knowledge few studies have documented the oncologic and obstetric management of this association. METHODS: A retrospective nationwide survey was used to identify women treated with chemotherapy for breast carcinoma during pregnancy. Each member of the Société Fran?aise d'Oncologie Gynécologique and the Société Fran?aise de Sénologie et de Pathologie Mammaire completed a postal questionnaire regarding cancer staging, oncologic treatment, obstetric details, pregnancy outcome, fetal behavior, and postdelivery follow-up. Twenty women were accrued to the study. RESULTS: The mean gestational age at the first cycle of treatment was 26 weeks. A total of 38 cycles were administered during pregnancy, with a median of 2 cycles. Delivery was performed at a mean of 34.7 weeks. Two pregnancies that were exposed to chemotherapy during the first trimester resulted in spontaneous abortion. One pregnancy exposed in the second trimester resulted in intrauterine death. The remaining 17 pregnancies resulted in live births, although 3 women had complications related to chemotherapy (anemia, leukopenia, and fetal growth retardation) and 1 newborn died 8 days after birth without apparent etiology. Two newborns had complications related to prematurity (transient respiratory distress). At a mean follow-up of 42.3 months, all live infants were reported to have reached normal developmental milestones. CONCLUSIONS: The current study found that even when chemotherapy was initiated after the first trimester, 95% of the pregnancies resulted in live births with low related morbidity in the newborns.     

Pregnancy outcome after diagnosis of differentiated thyroid carcinoma: no deleterious effect after radioactive iodine treatment

PURPOSE: Thyroid carcinoma is the second most common malignancy in young women, after breast cancer, aged 15-34 years in Hong Kong. Radioiodine or (131)I (RAI) has been confirmed as a useful treatment in the management of differentiated thyroid carcinoma (DTC). Serious concerns have been raised of the potential risks on subsequent pregnancies. METHODS AND MATERIALS: We conducted a single-institute, retrospective analysis of the gestational history of 104 patients who became pregnant after the diagnosis of DTC. The patients were interviewed for pregnancy outcome, and the data were supplemented by a review of the medical records in the Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong. RESULTS: Of 263 pregnancies observed, the prior RAI administration in 153 (scanning dose or ablative dose) did not adversely affect the pregnancy outcome as determined by the rate of successful delivery, mode of delivery, live birth demographics (e.g., birth weight, gender distribution). In all live births, neither congenital malformations nor first year neonatal mortality was observed. Of 116 pregnancies in 68 patients who received an ablative dose (mean, 96.6 mCi) of RAI, 78 live births were reported. The updated information on these children at age 1 month to 30.8 years (mean, 7.9 years; SD 7.3) showed that they had no abnormal development. The incidence of miscarriages was not different in those with prior RAI administration. However, the incidence of preterm delivery was greater in those with a history of RAI (p = 0.03). A higher ablative dose (>80 mCi) and shorter interval between RAI and conception (<1 year) did not significantly alter the pregnancy outcome. Two patients were inadvertently given an RAI scanning dose during pregnancy. One decided to continue the pregnancy; a healthy 6-year-old boy was reported at the last update. Fifteen patients had DTC diagnosed during pregnancy; 2 terminated the pregnancy and 13 decided to continue their pregnancy. All children were born in good health. For DTC diagnosed during the first trimester of pregnancy, the deferral of thyroid surgery to the second trimester is a good compromise for earlier treatment of the malignancy while continuing the pregnancy. CONCLUSION: Radioiodine in young women with DTC did not have deleterious effects on subsequent pregnancies. Proper education and instruction for avoiding conception within 1 year after RAI is a prudent recommendation, allowing for RAI clearance and hormonal stabilization.     

Management of gestational trophoblastic diseases: subsequent pregnancy experience

Patients with gestational trophoblastic disease (GTD) can usually achieve complete sustained remission while retaining their fertility even in the presence of wide-spread metastasis. Following complete and partial mole, our patients had 1,239 and 205 later pregnancies, respectively, which resulted in 68.6% and 74.1% term live births, respectively. Patients with either type of hydatidiform mole have, in general, a normal later pregnancy experience. After one molar pregnancy, the risk of a molar pregnancy in a later conception was about 1%. Our patients who received chemotherapy for persistent gestational trophoblastic tumor had 522 later pregnancies, which resulted in 358 (68.6%) term live births and only 10 (2.5%) major and minor congenital anomalies. Data from other centers involving 2,598 later pregnancies also indicate that after chemotherapy patients can generally anticipate a normal future reproductive outcome.     

Use of erlotinib throughout pregnancy: a case-report of a patient with metastatic lung adenocarcinoma

The use of erlotinib throughout pregnancy has not been previously reported. We present the case of a 40 year-old female patient with stage IV lung adenocarcinoma, mediastinal, bone and cerebral metastasis, a EGFR mutation and no smoking history, who had begun first line treatment with erlotinib 150 mg once daily. After two and a half months of treatment a fourteen-week pregnancy was documented, and after informing on fetal risks secondary to erlotinib use and maternal risks secondary to treatment withholding, she decided to continue with treatment under clinical surveillance by both the oncology and obstetrics clinics. At thirty-three weeks gestation a live born 1600 g female was born by caesarean section without evidence of congenital malformations. Imaging assessment after eight months of treatment showed complete bone and central nervous system response and partial lung and mediastinal response. The patient is currently undergoing the 11th month of treatment and is asymptomatic, the baby is 4 months old and is in good health.     

Pregnancy outcome in cancer patients. Experience in a large cooperative group

To evaluate the potential teratogenicity and mutagenicity of modern cancer treatment, the authors enumerated from a cooperative clinical trial group 133 pregnancies in 66 women with malignant neoplasms (53% with Hodgkin's disease, 26% with other lymphomas and leukemia, and 21% with solid tumors). The gestations were divided into the following groups: Group 1, 43 pregnancies ending before therapy; Group 2, therapy given at conception or during 32 pregnancies; and Group 3, 58 pregnancies after therapy. Although the total frequencies of abnormalities were similar in Groups 1 and 2 (23% of 35 pregnancies not electively aborted and 28% of 25, respectively), there were slightly more elective abortions and birth defects related to radiation exposure at a susceptible time of gestation in Group 2. Still, there were eight normal infants among the ten fetuses who were liveborn and had first trimester exposure to chemotherapy alone; so, drug therapy early in pregnancy is not inevitably teratogenic. The apparent and surprising excess of abnormal outcomes in Group 3, 40% of 50 pregnancies, was due to low birth weight and premature terminations of pregnancy, rather than an excess of congenital anomalies. The type of unfavorable outcomes in Group 3 and their concentration in the first year posttherapy suggested they could represent defects in factors (e.g., uterine or hormonal) that normally maintain gestations, and not genetic damage to oocytes. Limitations of the data, collected by mail from physicians and their patients, included biases of self-reporting and low statistical power. Prospective study, probably through interinstitutional collaboration, seems necessary, if accurate estimates are to be made of the frequency of certain outcomes, such as spontaneous abortion and minor anomalies.     

Tamoxifen--what next?

Most patients with advanced breast cancer (ABC) ultimately die due to disease progression. Consequently, treatments for ABC are predominantly palliative in nature and, therefore, the tolerability profile of a given treatment is particularly relevant in these patients. While cytotoxic chemotherapy and endocrine therapy exhibit efficacy in hormone-sensitive, advanced disease, it is endocrine therapy that combines efficacy with minimal acute toxicity. Tamoxifen has been the chosen endocrine therapy for postmenopausal, hormone-sensitive, ABC for over 20 years. More recently, new endocrine agents with different mechanisms of action from tamoxifen have been introduced. Evidence indicates that the aromatase inhibitors anastrozole (Arimidex; AstraZeneca; Wilmington, DE), letrozole (Femara; Novartis Pharmaceuticals Corp.; East Hanover, NJ) and exemestane (Aromasin; Pharmacia Corp.; Peapack, NJ) offer superior efficacy and tolerability to tamoxifen in the first-line treatment of postmenopausal, hormone-sensitive ABC. Similarly, after tamoxifen failure, fulvestrant (Faslodex; AstraZeneca), a new estrogen receptor (ER) antagonist that downregulates the ER, is at least as effective as anastrozole, is well tolerated, and is not cross-resistant with tamoxifen. Unlike tamoxifen, fulvestrant has no known agonist effects. The sequential use of such agents may prolong the time during which endocrine therapies can be used, thereby avoiding the more acute toxicities associated with cytotoxic chemotherapy. Indeed, a series of studies has shown that this sequential use is a relevant, active, and well-tolerated option. Establishing the comparative efficacies and optimal sequences that incorporate the newer endocrine agents will be central in determining the future role of hormonal therapy in ABC; the results of this work will determine the relative place of tamoxifen in what is a rapidly changing therapeutic environment.     

Pregnancy associated breast cancer

Background

Breast carcinoma during pregnancy put the health of the mother in conflict with that of the foetus. The aim is to give optimal treatment to the mother to maximise the chances of survival, whilst minimising the risk of harm of the foetus.We report the epidemiology, pathology, clinical picture, therapeutic management and foetal outcome of pregnant women with breast cancer treated in our institution.

Patients and methods

Twenty-two pregnant breast cancer patients were treated in our hospital from January 1996 to October 2006. Parents were surveyed by mail or telephone regarding outcomes of children exposed to chemotherapy in uterus.

Results

The treatment of breast cancer pregnancy should conform as closely as possible to standardised protocols for patients without concomitant pregnancy. Most of the patients underwent surgery during pregnancy In four cases diagnosed during the first trimester chemotherapy was initiated during the 10th week when organogenesis period was finished. None of the children exposed to chemotherapy during this trimester presented congenital malformations. All 11 cases diagnosed during second and third trimester were treated with Doxorrubicin, Fluoracil and Cyclophosphamide and four cases were treated with taxanes. No congenital malformations were detected.

Conclusion

Breast cancer can be treated with FAC chemotherapy during the second and third trimesters without significant complications for the children exposed to chemotherapy in uterus. We report four cases treated with taxanes after the first trimester and no congenital anomalies were observed.     

Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01)

Only few case reports describe the pregnancy course and outcome of breast cancer patients, who were under treatment with trastuzumab at the time of conception or who have completed trastuzumab therapy before becoming pregnant. The HERA trial is a large phase III randomized clinical trial in which patients with early HER2-positive breast cancer were randomized to receive 1 or 2 years of trastuzumab or observation following completion of primary chemotherapy. To examine the effect of trastuzumab on pregnancy outcome, we report all pregnancy events that occurred until March 2010 in patients enrolled in the study. For the sake of this analysis, patients were assigned to three groups: (1) pregnancy occurring during and up to 3 months after trastuzumab exposure (group 1); (2) pregnancy occurring >3 months of last trastuzumab dose (group 2); and (3) pregnancy occurring in patients without prior exposure to trastuzumab (group 3). Sixteen, 45 and 9 pregnancies took place in groups 1, 2, and 3, respectively. 25 and 16% of patients in groups 1 and 2 experienced spontaneous abortion, the former being higher than figures reported in the general population. However, short-term fetal outcome appeared normal across the three groups. Only 2 congenital anomalies were reported, one in group 2 and one in group 3. No congenital anomalies were reported in those exposed to trastuzumab in utero. This is the first report from a large randomized trial assessing the effect of trastuzumab on pregnancy course and outcome. Based on our results, trastuzumab does not appear to affect fetal outcome in patients who manage to complete their pregnancy. We are currently initiating a collaboration to collect similar data from the other large adjuvant trastuzumab trials to confirm these findings.     

Cancer in pregnancy: gaps, challenges and solutions

Cancer is the second leading cause of death during the reproductive years complicating between 0.02% and 0.1% of pregnancies. This incidence is expected to rise with the increase in age of childbearing. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. This article reviews the available data regarding the different aspects of the diagnosis and treatment of cancer during pregnancy as well as the effect of pregnancy on cancer prognosis. In pregnant patients diagnosed with cancer during the first trimester, treatment with multi-drug anti-cancer chemotherapy or radiotherapy (with fetal exposure >0.1-0.2 Gy) is associated with an increased risk of congenital malformations and therefore should follow a strong recommendation for pregnancy termination. The risk for malformation diminishes as pregnancy advances and when cancer is diagnosed during the second or third trimesters there is usually no clear indication for abortion. Treatment postponement, until achieving fetal maturity, while closely monitoring tumor growth may be considered in selected cases. According to the available experience it seems that non-obstetrical surgery may be performed during pregnancy without an increased risk for adverse outcomes. In most types of cancer, pregnancy has no effect on maternal prognosis when compared to non-pregnant patients matched by age, cancer stage and treatment.     

H?matologische Neoplasien in der Schwangerschaft

The management of hematologic malignancies during pregnancy presents diagnostic and therapeutic challenges requiring an interdisciplinary approach. The most common hematologic neoplasias in pregnancy include Hodgkin’s disease, aggressive non-Hodgkin’s lymphoma and acute leukemia. A cure for the mother often depends on the consistent administration of intensive chemotherapy regimens. Whenever possible, treatment should be deferred until the second trimester after the completion of organogenesis. Chemotherapy during the first trimester can induce a spontaneous abortion or significantly increase the risk of congenital malformations. During the second and third trimester chemotherapy can be administered with reasonable safety although an increased fetal risk will remain. It is important to balance the potential fetal risk against the maternal risk of an untreated neoplasia.     

Breast cancer during pregnancy

Opinion statement The concurrent diagnosis of breast cancer and pregnancy is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. Modified radical mastectomy, the preferred surgical option in women with breast cancer during pregnancy, can be accomplished with minimal fetal risk. Although breast-conserving surgery (lumpectomy or quadrantectomy) can be performed, the radiation therapy required to complete local therapy for the breast must be delayed until after delivery because of the risks associated with fetal exposure to radiation. Although much of the literature on the pharmacologic treatment of breast cancer during pregnancy is anecdotal, recently published data from our institution support the premise that breast cancer can be treated safely during the second and third trimesters of pregnancy with combination chemotherapy consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Therapeutic abortion does not appear to improve survival for the mother, but it may be an option if maternal health is jeopardized or fetal anomalies are seen or suspected.     

Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero

BACKGROUND: As women in the US delay childbearing, it has been hypothesized that the incidence of breast cancer diagnosed during pregnancy will increase. There are very little prospective data on the treatment of pregnant women with breast cancer with chemotherapy and even less data on the outcomes of their children who were exposed to chemotherapy in utero. METHODS: Fifty-seven pregnant breast cancer patients were treated on a single-arm, multidisciplinary, institutional review board-approved protocol with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant (n = 32) or neoadjuvant (n = 25) setting. Parents/guardians were surveyed by mail or telephone regarding outcomes of children exposed to chemotherapy in utero. RESULTS: Of the 57 women, 40 are alive and disease-free, 3 have recurrent breast cancer, 12 died from breast cancer, 1 died from other causes, and 1 was lost to follow-up. Of the 25 patients who received neoadjuvant FAC, 6 had a pathologic complete response, whereas 4 had no tumor response to chemotherapy and eventually died from their disease. All women who delivered had live births. One child has Down syndrome and 2 have congenital anomalies (club foot; congenital bilateral ureteral reflux). The children are healthy and those in school are doing well, although 2 have special educational needs. CONCLUSIONS: Breast cancer can be treated with FAC chemotherapy during the second and third trimesters without significant short-term complications for the majority of children exposed to chemotherapy in utero. Longer follow-up of the children is needed to evaluate possible late side effects such as impaired cardiac function and fertility.     

Weekly doxorubicin chemotherapy for breast cancer in pregnancy. A case report.

The simultaneous occurrence of breast cancer and pregnancy is rare. Little data are available about cytostatic treatment in patients with breast cancer during pregnancy. We report on a 31-year-old woman with a 28-week pregnancy and a T3 N+ Mx breast cancer treated with weekly doxorubicin chemotherapy. This was a well tolerated treatment without toxicity or complications for the mother. A partial response of the tumor was observed after 4 treatment courses. A normal baby was delivered. Doxorubicin and its metabolites were not detected in amniotic fluid collected through amniocentesis. Macroscopic and pathologic examinations of the placenta were normal. Although larger experiences are needed, weekly doxorubicin seems to yield satisfactory results without additional risks of fetal distress or malformations when given in women during the second and third trimester of pregnancy.     

Management of malignant gliomas during pregnancy: a case series

BACKGROUND.

Limited data are available on the management of glioma in pregnant women. Therefore, the aim of the current article was to describe the outcome of women with malignant gliomas who were exposed to chemotherapy early in the gestation period of their pregnancies.

METHODS.

The authors presented a case series of 6 women with malignant gliomas who during glioma‐directed treatment were discovered to have an unplanned pregnancy. All patients elected to discontinue chemotherapy and carry their pregnancy to term.

RESULTS.

All women had uneventful pregnancies with no glioma‐related complications. All women delivered healthy newborns without evidence of congenital malformations despite exposure to cytotoxic chemotherapy and anticonvulsant medications.

CONCLUSIONS.

Management of malignant glioma during pregnancy is challenging; however, normal delivery and healthy live birth is possible. Cancer 2008. © 2008 American Cancer Society.     

Interrupted pregnancy as an indicator of poor prognosis in T1, 2, N0, M0 primary breast cancer

Breast Cancer Research and Treatment - We examined the records of women with primary breast cancer for a history of pregnancy and live births. The patients were all histopathologic T1, 2, N0, M0...     

Pregnancy Outcomes after Conservative Surgery for Early-Stage Ovarian Neoplasms

Objective: This retrospective, single institute study aimed to evaluate pregnancy and oncologic outcomes in reproductive-age Thai women with early-stage ovarian neoplasms undergoing conservative surgical treatment. Methods: Medical records of 84 women of reproductive age (15-45 years) with histologically confirmed early-stage (IA-IIC) borderline ovarian tumors or cancers who had undergone conservative surgery between January 2003 and December 2012 were retrospectively reviewed. Results: The mean age of patients at diagnosis was 28.0 years (SD 7.2). Histologically, 30 (35.7%) had borderline ovarian tumors, 28 (33.3%) epithelial cancers, 22 (26.2%) malignant germ cell tumors, and 4 (4.8%) sex cord stromal tumors. Thirty-five women (41.7%) had complete surgical staging performed, whereas 49 (58.3%) underwent an incomplete staging procedure. Thirty-four patients (40.5%) received postoperative chemotherapy. Among 29 patients subsequently attempting pregnancy, 15 conceived successfully (51.7%). Pregnancy outcomes were one spontaneous abortion and 14 viable births. There were no serious adverse obstetric and neonatal outcomes among women with documented live births and no reported fetal abnormalities. Pregnancy rates were not impacted by surgical staging (53.8% vs 50.0%, p=0.837) or adjuvant chemotherapy (55.6% vs 50.0%, p=0.782). The 5-year disease-free survival was 91.0% and pregnancy after conservative surgery did not affect progression-free survival (p=0.194). Conclusion: Conservative surgery with or without appropriate adjuvant chemotherapy can be offered to young women with early-stage ovarian neoplasms who wish to preserve their fertility potential.     

Radiological abnormalities in children born as a result of assisted conception

Over 15 000 children are born each year as a result of the various techniques of assisted conception. In 1991, there were 2083 live births in Australia and New Zealand as a result of these techniques. Radiological abnormalities relating to the increased rate of prematurity, a probable increase in the risk of congenital malformations and a number of cases of neural crest tumours seen in these infants will be presented.     

Chemotherapy with taxanes in breast cancer during pregnancy: case report and review of the literature

Two patients with breast cancer received docetaxel-containing chemotherapy as adjuvant or neoadjuvant therapy during pregnancy. The first pregnant patient began neoadjuvant therapy with doxorubicin/cyclophosphamide at 14 weeks of gestation. After 4 cycles of doxorubicin/cyclophosphamide and surgery, she received adjuvant docetaxel for 4 cycles. The second patient began neoadjuvant therapy with doxorubicin/docetaxel at 14 weeks of gestation and received 6 cycles. The fetus of the first patient had hydrocephalus on ultrasound at 17 weeks of gestation (before docetaxel therapy) that persisted on serial follow-up ultrasounds and spontaneously regressed over several months after delivery. No fetal malformations were detected in the second fetus. These 2 cases add to the existing data on the use of taxanes during pregnancy. Although the data are limited with case reports, pregnant patients with cancer can be treated with chemotherapy including taxanes during the second and third trimesters without significant risks to the fetus. Taxanes should not be excluded, if indicated, in pregnant patients with cancer.     

Pregnancy outcome of partners of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

PURPOSE: This study was undertaken to determine the effect, if any, on pregnancy loss, live births, and birthweight of treatment for cancer diagnosed during childhood or adolescence. PATIENTS AND METHODS: We reviewed pregnancy outcome among sexually active male Childhood Cancer Survivor Study (CCSS) participants who responded to a questionnaire before February 3, 2000. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, volumes, and dates of administration of all radiotherapy. RESULTS: There were 4,106 sexually active males; 1,227 reported they sired 2,323 pregnancies (69% live births, 1% stillbirths, 13% miscarriages, 13% abortions, 5% unknown or in gestation). The male-to-female ratio of the offspring of the partners of the male survivors was significantly different from that of the offspring of the partners of the male siblings of the survivors (1.0:1.03 v 1.24:1.0) (P =.016). The proportion of pregnancies of the partners of male survivors that ended with a liveborn infant was significantly lower than for the partners of the male siblings of the survivors who were the control group for comparison (relative risk = 0.77, P =.007). There were no significant differences in pregnancy outcome by treatment. CONCLUSION: This large study did not identify adverse pregnancy outcomes for the partners of male survivors treated with most chemotherapeutic agents. The reversal of the sex ratio and the association observed for procarbazine warrant further investigation.