[A Case of Pregnancy-Associated Breast Cancer Which Underwent Surgical Treatment during Pregnancy and Chemotherapy after Delivery].

CASE: A 37-year-old pregnant woman arrived at our hospital with an abnormal mammogram. MEDICAL HISTORY: Mammography performed in June 2018 revealed an abnormal shadow on the left breast. Cytology from the 6-mm tumor in the left upper-outer quadrant revealed a malignancy. At the same time, a transvaginal echo revealed cysts, and the patient was diagnosed at 5 weeks gestation. Needle biopsy revealed a luminal A-like cStage Ⅰ, cT1bN0M0 invasive ductal carcinoma (IDC). Tumor resection and sentinel lymph node biopsy were performed under local anesthesia at 12 weeks gestation, and post-delivery adjuvant therapy was planned. Histologic examination of the resected tumor revealed that it was HER2-positive( immunohistochemistry score 3+); therefore, we had to reconsider the use of trastuzumab and decided to administer it to the patient after childbirth. The patient gave birth by cesarean section, and weekly paclitaxel plus trastuzumab was initiated 7 months after surgery. The patient is currently alive without recurrence. DISCUSSION: We faced several difficulties during the treatment of this patient. Postoperative adjuvant therapy is recommended to be administered 8 weeks after the surgical resection of the tumor. However, in our case, given that the tumor was HER2-positive, we could administer adjuvant therapy with trastuzumab only after delivery. Although the prevalence of breast cancer in women below the age of 40 years in Japan is currently as low as 4-6%, the incidence of pregnancy-associated breast cancer is predicted to increase as the number of elderly primigravida increases due to later marriage.

Lymphoma during pregnancy in Japan: a multicenter retrospective cohort study.

OBJECTIVE: This study was conducted to characterize lymphoma occurring during pregnancy and to investigate the outcomes of the patients and the fetuses. METHODS: Clinical data were gathered retrospectively from 29 patients at 13 participating institutions, and data from 28 eligible patients were analyzed. RESULTS: Six (21%) patients had Hodgkin lymphoma (HL) and 22 (79%) patients had non-Hodgkin lymphoma (NHL). All patients with HL presented with lymphadenopathy, but 15 (68%) of the 22 patients with NHL presented with extranodal sites only. At the median follow-up period of 1325 (range 6-4461) days, the 5-year overall survival rate was 63% for patients with NHL and 100% for patients with HL. Three of the 13 patients who received chemotherapy during pregnancy (23%) developed Pneumocystis jiroveci pneumonia (PCP). There was 1 intrauterine fetal death, 1 spontaneous abortion in the first trimester, and 15 (54%) preterm births. CONCLUSION: This study showed a higher proportion of NHL than HL during pregnancy in Japan, which was inconsistent with the proportions observed in Western countries. The high incidence of maternal PCP and preterm birth suggested the need for improvements in our management of lymphoma during pregnancy.

[Observation of Child Development in a Uterine Cervical Cancer Patient Who Received Chemotherapy during Pregnancy].

This report describes the case of a 36-year-old woman with stage ⅠB1 cervical adenocarcinoma that was diagnosed when her fetus was at 19 weeks of gestation. Both she and her family strongly hoped that her pregnancy could continue. After approval by the Ethics Committee of our hospital, she was treated with paclitaxel and carboplatin. At 32 weeks of gestation, the patient delivered a 1,518 g female newborn via cesarean section. A radical hysterectomy with pelvic lymphadenectomy was performed after delivery. The newborn had Apgar scores of 3 at 1 minute and 5 at 5 minutes. No external malformations were observed. The Kyoto Scale of Psychological Development 2001 was used for cognitive assessment. Although the Language-Social Developmental Quotient score was 65 and developmental delay was observed at 1 year 8 months, the score improved to 98 at 3 years 5 months. The child was followed up until the age of 6 years 2 months and showed no developmental delay. Presentation of this case is important because there are few reports in Japan about the development of children of cancer patients who are exposed to anticancer drugs during pregnancy.

Neoadjuvant chemotherapy with paclitaxel plus cisplatin before radical surgery for locally advanced cervical cancer during pregnancy: A case series and literature review.

RATIONALE: Despite the development of human papillomavirus vaccines and significant improvement in cervical cancer screening over the past few years, cervical cancer remains the fourth most common cancer in women of childbearing age after breast cancer, melanoma, and thyroid cancer. PATIENT CONCERNS: In this case report, the patients are all cervical cancer with stage IB2 and IB3 during pregnancy, the management constitutes a major medical challenge related to the impact of treatment on both maternal and fetal outcomes. Neoadjuvant chemotherapy (NACT) is an innovative option for cervical cancer patients with stage IB2 and IB3 before cesarean delivery and radical hysterectomy, and many chemotherapeutic agents are available, cisplatin plus paclitaxel yielded good maternal and fetal outcomes to the authors' knowledge. DIAGNOSES: Masses were discovered in the cervix of 4 pregnant women with a history of vaginal bleeding. Biopsy examination of the masses revealed cervical carcinoma, which was staged in accordance with the International Federation of Gynecology and Obstetrics (i.e., FIGO) system. INTERVENTIONS: The patients were treated with paclitaxel plus cisplatin, followed by cesarean delivery and radical hysterectomy. OUTCOMES: The 4 patients were treated successfully, with no recurrence during follow-up periods of 14 to 56 months, and all of the children were doing well with no anomalies. LESSONS: Although further data are required, in pregnant women with invasive cervical cancer, NACT with cisplatin plus paclitaxel followed by cesarean delivery and radical hysterectomy was a practical treatment option.

[Chemotherapy for breast cancer during pregnancy: about a case]. / Chimiothérapie du cancer du sein au cours de la grossesse: à propos d´un cas.

The management of breast cancer during pregnancy is a challenge for physicians due to mother´s desire to carry the pregnancy to term despite the need for chemotherapy. This study reports the case of a 37-year-old multiparous woman at 20 weeks and 4 days of amenorrhea (WA). She was hospitalized for dyspnoea (stage IV according to New York Heart Association (NYHA) classification). The patient had a syndrome of heavy left pleural effusion and bilateral mastitis. The diagnosis of metastatic breast cancer was retained based on cytological examination of pleural fluid and breast cytoponction revealing galactophoric carcinoma. The patient underwent pleural drainage with improvement of dyspnea but pleural fluid continued. After multidisciplinary consultation (MC), specific treatment of cancer was necessary. Five cycles of epirubicin- cyclophosphamide-5-FU-based chemotherapy was performed after the couple provided consent. Pleural fluid diminished significantly after the second cycle of treatment. After consultation with the obstetrician, chemotherapy was interrupted one month before the 37th week of amenorrhea. Pregnancy evolved favorable, vaginal birth was managed following rupture of membranes at term with good neonatal adaptation. After one-year follow-up, the mother was still on chemotherapy and the baby was in good health. Several parameters should be considered before the administration of antineoplastic agents, hence the role of early fetal and maternal monitoring. Multidisciplinary approach is recommended to support therapeutic decision and follow-up.

Novel agents for the treatment of lymphomas during pregnancy: A comprehensive literature review.

Lymphoproliferative diseases occurring during pregnancy present unique diagnostic and therapeutic challenges aiming to achieve maternal cure without impairing fetal health, growth, and survival. These goals are further complicated by the fast-paced emergence of novel therapies and their introduction as standard of care, even in newly diagnosed patients. Due to the rarity of hematological malignancies in pregnancy and the exclusion of pregnancy in almost all clinical trials, available data on the fetal effects of novel drugs are limited to animal models and case reports. The current review addresses the entire multidisciplinary team involved in treating pregnant patients with lymphoproliferative diseases. We describe novel agents according to their mechanism of action, and summarize our knowledge of their effects during the gestational period, particularly those associated with fetotoxicity. Therapeutic dilemmas associated with the employment of these new agents are also discussed.

Outcomes of Patients with Macroprolactinoma Desiring Pregnancy: Follow-Up to 23 Years from a Single Center.

Macroprolactinomas are rarely seen in women, and pregnancy is a risk factor for tumor growth. More studies are needed to determine appropriate management for macroprolactinoma and pregnancy. The aim of our study is to evaluate effects of treatment with dopamine agonists on macroadenoma before and during pregnancy, safety of dopamine agonists on fetus, post-pregnancy prognosis and long-term results. This is a single center retrospective study. Thirty-four pregnancies occurred in 21 patients under medical therapy. Prolactin levels, treatment results, tumor diameter changes, maternal-fetal outcomes, and disease activity were evaluated. The median tumor size at the time of diagnosis was 15 mm (10-28). Residual adenoma diameter was smaller in those receiving medical therapy longer than one year till the conception (p=0.047). Treatment was discontinued in 28 pregnancies after pregnancy confirmation, and 6 patients were exposed to bromocriptine throughout pregnancy. There was no symptomatic tumor growth during gestation. Among 27 live births, none of the fetuses developed neonatal malformation except for a case of Down syndrome. While early remission rate after pregnancy was 9.5%, this rate reached 33.3% at last follow-up visit. Lowered PRL levels at postpartum period (p=0.040), smaller tumor size at last follow-up visit (p=0.030), and total disappearance of tumor (p=0.026) were the contributor factors for remission. Use of dopamine agonist over one year may reduce the risk of symptomatic tumor growth during pregnancy in patients without invasive or large macroprolactinoma before pregnancy. Exposure to dopamine agonists seems generally safe for the fetus.

Trastuzumab administration during pregnancy: an update.

BACKGROUND: Over than one third (28-58%) of pregnancy-associated breast cancer (PABC) cases are characterized by positive epidermal growth factor receptor 2-positive (HER2) expression. Trastuzumab anti-HER2 monoclonal antibody is still the benchmark treatment of HER2-positive breast tumors. However, FDA has categorized Trastuzumab as a category D drug for pregnant patients with breast cancer. This systemic review aims to synthesize all currently available data of trastuzumab administration during pregnancy and provide an updated view of the effect of trastuzumab on fetal and maternal outcome. METHODS: Eligible articles were identified by a search of MEDLINE bibliographic database and ClinicalTrials.gov for the period up to 01/09/2020; The algorithm consisted of a predefined combination of the words "breast", "cancer", "trastuzumab" and "pregnancy". This study was performed in accordance with the PRISMA guidelines. RESULTS: A total of 28 eligible studies were identified (30 patients, 32 fetuses). In more than half of cases, trastuzumab was administered in the metastatic setting. The mean duration of trastuzumab administration during gestation was 15.7 weeks (SD: 10.8; median: 17.5; range: 1-32). Oligohydramnios or anhydramnios was the most common (58.1%) adverse event reported in all cases. There was a statistically significant decrease in oligohydramnios/anhydramnios incidence in patients receiving trastuzumab only during the first trimester (P = 0.026, Fisher's exact test). In 43.3% of cases a completely healthy neonate was born. 41.7% of fetuses exposed to trastuzumab during the second and/or third trimester were born completely healthy versus 75.0% of fetuses exposed exclusively in the first trimester. All mothers were alive at a median follow-up of 47.0 months (ranging between 9 and 100 months). Of note, there were three cases (10%) of cardiotoxicity and decreased ejection fraction during pregnancy. CONCLUSIONS: Overall, treatment with trastuzumab should be postponed until after delivery, otherwise pregnancy should be closely monitored.

Apoplexy of microprolactinomas during pregnancy: report of five cases and review of the literature.

CONTEXT: Prolactinomas frequently cause amenorrhoea, galactorrhoea and infertility and require dopamine agonist (DA) treatment to normalize prolactin levels and hence, restore ovulation. The vast majority of female patients harbour microprolactinomas in whom DA treatment is usually discontinued at the time of pregnancy diagnosis and surveillance is generally limited as the symptomatic growth is considered very rare. CASE DESCRIPTIONS: We report five cases of women harbouring a microprolactinoma in whom symptomatic pituitary apoplexy occurred during pregnancy. Only one necessitated surgery during pregnancy, while the others were treated conservatively by reintroducing DAs in three. A systematic literature review found reports of four additional cases among 20 cases of prolactinomas (both macro- and micro-prolactinomas) complicated by apoplexy during pregnancy. CONCLUSION: During pregnancy, pituitary apoplexy may occur in pre-existing microprolactinomas, causing tumour enlargement and headache, which may be self-limiting but may require intervention by re-initation of dopamine agonists or surgery. Our literature review confirms that this clinical event is rare; nevertheless, physicians managing pregnant patients with microprolactinomas must be aware that symptomatic pituitary apoplexy may incidentally occur in all trimesters of pregnancy and require prompt radiological, endocrine and ophthalmological assessment and treatment.

Use of trastuzumab in treating breast cancer during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Trastuzumab is currently the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, it is not recommended for HER2-positive breast cancer patients during pregnancy as it may jeopardize safety of the fetus. Nevertheless, there is evidence that fetuses exposed to trastuzumab in early stages of pregnancy remain healthy METHODS: To evaluate the possible effects of trastuzumab on fetus and provide evidence on the safety of trastuzumab in early pregnancy in HER2-positive breast cancer patients, we analyzed 22 studies involving 22 pregnant women and 23 fetuses. RESULTS: Based on the meta-analysis, the gestational week of exposure to trastuzumab is 0-34 weeks, the average duration of use is 17 weeks, and the average gestational week of delivery is 34.3 weeks. Complications occurred in 77.27% of patients during pregnancy and 56.52% of newborns。The main complication during pregnancy was anhydramnios (68.18%), while the main complications at birth were Respiratory distress or tachypnea (30%). After an average of 25.28 months of follow-up, 17.39% (4/23) of the children died. There was no complication during pregnancy or at birth in patients treated with trastuzumab during early pregnancy (P = 0.043). Patients older than 30 who received trastuzumab during pregnancy were more likely to have neonatal complications (OR = 7.778, 95%CI = 1.2-50.424, P = 0.04). CONCLUSION: These results suggest that trastuzumab use during pregnancy can cause pregnancy,fetal and newborn complications. However, exposed to trastuzumab only in the first trimester are less likely to have pregnancy and fetal complications. Patients with gestational age below 30 years are less likely to have neonatal complications after trastuzumab during pregnancy. Terminating pregnancy should not be the only option for such patients. But more evidence is needed to verify this conclusion.

The outcome of Ph-negative acute lymphoblastic leukemia presenting during pregnancy and treated on the Russian prospective multicenter trial RALL-2009.

We report the data on 15 women who presented with Ph-negative acute lymphoblastic leukemia (ALL) between Jan 2009 until Dec 2016 and who were treated on the prospective multicenter RALL-2009 clinical trial. A comparison of their outcome was made with 129 non-pregnant females who entered the study and were treated by the same schedule. 10-years OS for pregnant and non-pregnant women was 58.6 % (29.6 %-85.0 %) and 43.3 % (32.1 %-58.8 %), DFS was 46 % (15.2 %-78.8 %) and 51 % (39.7 %-64.6 %); probability of relapse was 49 % (16.6 %-83.3 %) and 40.3 % (27.3 %-53.4 %), respectively. Twelve born during the study children are well and alive with a median age 5 years 2 months (2 years - 9 years). Though small, our study has shown some specific features of ALL diagnosed during pregnancy (more T-cell ALL, higher initial WBC, later responses) and has shown that the long-term outcome of women with ALL treated while pregnant is equivalent to female control patients treated on the same protocol.

Mesenteric leiomyosarcoma in a pregnant woman: A case report and review of literature.

We herein describe a case of primary leiomyosarcoma of descending mesocolon mesentery in a pregnant woman. A 31-year-old woman was referred to our clinic for the presence of a suspicious mass (solid heterogenous lesion with lobulated margins) detected during routine obstetric ultrasonography (USG), growing throughout her term. Imaging in her third trimester showed a considerable increase in the size of the mass and was suspected to be malignancy of uterine origin. Tru-cut biopsy performed post-partum indicated leiomyosarcoma. She underwent neoadjuvant chemotherapy with six cycles of dacarbazine and doxorubicin with partial response. Subsequently, she underwent surgery, and the tumor was found to be present in sigmoid colon mesentery extending in retroperitoneum involving 5 cm of ureter. The mass was resected along with part of the colon and ureter that was involved by disease. Patient had uneventful recovery post-surgery. Considering moderate response to chemotherapy and discussion in tumor board, she was not given adjuvant chemotherapy. At follow-up of 15 months, the patient is disease-free with a normal, healthy baby.

Imaging modalities in pregnant cancer patients.

Cancer during pregnancy is increasingly diagnosed due to the trend of delaying pregnancy to a later age and probably also because of increased use of non-invasive prenatal testing for fetal aneuploidy screening with incidental finding of maternal cancer. Pregnant women pose higher challenges in imaging, diagnosis, and staging of cancer. Physiological tissue changes related to pregnancy makes image interpretation more difficult. Moreover, uncertainty about the safety of imaging modalities, fear of (unnecessary) fetal radiation, and lack of standardized imaging protocols may result in underutilization of the necessary imaging tests resulting in suboptimal staging. Due to the absence of radiation exposure, ultrasound and MRI are obvious first-line imaging modalities for detailed locoregional disease assessment. MRI has the added advantage of a more reproducible comprehensive organ or body region assessment, the ability of distant staging through whole-body evaluation, and the combination of anatomical and functional information by diffusion-weighted imaging which obviates the need for a gadolinium-based contrast-agent. Imaging modalities with inherent radiation exposure such as CT and nuclear imaging should only be performed when the maternal benefit outweighs fetal risk. The cumulative radiation exposure should not exceed the fetal radiation threshold of 100 mGy. Imaging should only be performed when necessary for diagnosis and likely to guide or change management. Radiologists play an important role in the multidisciplinary team in order to select the most optimal imaging strategies that balance maternal benefit with fetal risk and that are most likely to guide treatment decisions. Our aim is to provide an overview of possibilities and concerns in current clinical applications and developments in the imaging of patients with cancer during pregnancy.

Neoadjuvant chemotherapy in pregnant patients with cervical cancer: a Latin-American multicenter study.

OBJECTIVE: To describe oncologic and obstetric outcomes in patients diagnosed with cervical cancer during pregnancy who had a successful delivery after neoadjuvant chemotherapy. METHODS: A multicenter retrospective review was conducted in 12 institutions from six Latin American countries, between January 2007 and December 2018. Data collected included clinical characteristics, neoadjuvant chemotherapy agents, treatment, obstetric and oncologic outcomes. RESULTS: Thirty-three patients were included. Median age was 34 years (range 31-36). Twenty (60.6%) women were diagnosed at early stage (IB), and 13 (39.4%) with locally advanced stage (IIA-IIIB) according to FIGO 2009 classification. Carboplatin and paclitaxel was the most frequent combination used (60.6%). Partial and complete response rates were 27.3% and 9.1%, respectively. Median gestational age at delivery was 35 weeks (range 34-36). All patients had live births delivered by cesarean section. Obstetric pathology: pre-term labor, placenta percreta or intra-uterine growth restriction, was documented in seven patients (21.2%). Two (6.1%) neonates had low birth weight. Definitive treatment was primary chemo-radiation in 19 (57.6%) patients, radical hysterectomy in 11 (33.3%), abandoned radical hysterectomy with para-aortic lymphadenectomy and ovarian transposition in 1 patient (3.0%), and no further treatment in 2 (6.1%) patients. After a median follow-up of 16.3 months (range 2.0-36.9), 8 (26.7%) patients had recurrent disease. Of these, four (13.3%) died due to disease. CONCLUSION: Neoadjuvant chemotherapy may be offered to patients wishing to preserve an ongoing pregnancy in order to achieve fetal maturity. Long-term consequences of chemotherapy in the child are yet to be determined.

Advanced Hodgkin lymphoma in the East of England: a 10-year comparative analysis of outcomes for real-world patients treated with ABVD or escalated-BEACOPP, aged less than 60 years, compared with 5-year extended follow-up from the RATHL trial.

Treatment with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) or escalated(e)-BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) remains the international standard of care for advanced-stage classical Hodgkin lymphoma (HL). We performed a retrospective, multicentre analysis of 221 non-trial ("real-world") patients, aged 16-59 years, diagnosed with advanced-stage HL in the Anglia Cancer Network between 2004 and 2014, treated with ABVD or eBEACOPP, and compared outcomes with 1088 patients in the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial, aged 18-59 years, with median follow-up of 87.0 and 69.5 months, respectively. Real-world ABVD patients (n=177) had highly similar 5-year progression-free survival (PFS) and overall survival (OS) compared with RATHL (PFS 79.2% vs 81.4%; OS 92.9% vs 95.2%), despite interim positron-emission tomography-computed tomography (PET/CT)-guided dose-escalation being predominantly restricted to trial patients. Real-world eBEACOPP patients (n=44) had superior PFS (95.5%) compared with real-world ABVD (HR 0.20, p=0.027) and RATHL (HR 0.21, p=0.015), and superior OS for higher-risk (international prognostic score ≥3 [IPS 3+]) patients compared with real-world IPS 3+ ABVD (100% vs 84.5%, p=0.045), but not IPS 3+ RATHL patients. Our data support a PFS, but not OS, advantage for patients with advanced-stage HL treated with eBEACOPP compared with ABVD and suggest higher-risk patients may benefit disproportionately from more intensive therapy. However, increased access to effective salvage therapies might minimise any OS benefit from reduced relapse rates after frontline therapy.

Risks of molecular targeted therapies to fertility and safety during pregnancy: a review of current knowledge and future needs.

INTRODUCTION: As the population of young cancer survivors is increasing and a trend toward postponing pregnancy later in life is reported, more efforts are focused toward understanding treatment-induced sequelae, in particular, the effects of cancer and/or treatment on fertility. AREA COVERED: Whereas the fertility risk of cytotoxic agents for both men and women is well recognized, the impact of molecular-targeted therapy (MTT) on fertility parameters, their teratogenic potential and pregnancy outcome/management in case of an accidental exposure are not established. We update available clinical data on the impact of new MTTs on fertility in both sexes, their potential teratogenic effects and the outcome of pregnancy during accidental exposure. Agents are categorized by class and the potential relevance of their target signaling pathways to gonadal maturation. EXPERT OPINION: The majority of MTTs have worrying preclinical data discouraging their use during pregnancy and reinforcing the idea that they can induce impairment in gonadal function. However, it does not mean that all MTTs result in permanent infertility and that they should be completely avoided during pregnancy. The current review provides a critical evaluation on the most commonly used MTTs, offering a possible guide for clinicians.

Prolapsed submucosal pyomyoma postpartum, a rare complication of fibroids.

BACKGROUND: Pyomyoma is an unusual fibroid that usually develops during the puerperal or postmenopausal period. If not promptly diagnosed and treated, it can become life threatening. Although various conservative and surgical therapies have been discussed in the literature for this condition, there are very few reports related to the management of prolapsed pedunculated submucosal myoma. CASE PRESENTATION: In this case report, an intramural fibroid transformed into a pedunculated submucosal pyomyoma, which prolapsed into the vagina after a miscarriage and caused life-threatening toxic shock. Apart from prompt antibiotic treatment, a transabdominal myomectomy rather than hysterectomy was performed due to the very large diameter of the pyomyoma. As a result, fertility was preserved, and the patient conceived naturally and delivered a healthy baby two years later. DISCUSSION AND CONCLUSIONS: It is important to maintain strong clinical suspicion for pregnant or postpartum women with a triad of pain, sepsis without an obvious source and a known diagnosis of leiomyoma. Timely recognition and prompt surgical treatment with antibiotics are necessary and could conserve the uterus for future fertility.