LETTER TO THE EDITOR—BRIEF COMMUNICATION

Chemotherapy for breast cancer during pregnancy

Metastatic cancers during pregnancy have historically been associated with dismal outcomes, with greater rates of tumor progression in part because of diminished treatment alternatives. Immunotherapy with T-cell checkpoint inhibitors has significantly impacted the survival of several metastatic tumors. However, given their mechanism of action, immune-related adverse events can occur, especially with combined immunotherapy treatments. During pregnancy, checkpoint pathways have a major role, providing immune tolerance to the fetal allograft. Furthermore, evidence suggests that inhibition of this pathway may be associated with an increased risk of miscarriage. We describe, to our knowledge, the first case reported in the literature of a patient 7 weeks pregnant, diagnosed with metastatic melanoma and treated with nivolumab plus ipilimumab. We also present the associated immune-related side effects and their treatment, as well as the oncologic results that lead to favorable pregnancy outcome.

O objetivo do estudo é estabelecer a segurança do uso da quimioterapia na gestante portadora de câncer de mama e verificar as possíveis intercorrências no feto. Para identificação de publicações foi realizada pesquisa bibliográfica nas bases de dados: MEDLINE/PubMed, LILACS, SciELO, Cochrane, Uptodate e Google acadêmico. A busca totalizou 86 artigos publicados de 2001 a 2012, que foram avaliados por dois revisores obedecendo aos critérios de exclusão e inclusão pré-estabelecidos, sendo selecionados 39 artigos para a elaboração deste estudo. Todos os quimioterápicos utilizados no tratamento do câncer de mama na gravidez pertencem à categoria D, consistindo no uso de 5-fluorouracil (F), doxorrubicina (A) ou epirrubicina (E) e ciclofosfamida (C) ou na combinação de doxorrubicina e ciclofosfamida (AC), método seguro quando utilizado após o primeiro trimestre da gestação. Poucos estudos avaliaram o uso de taxanos (T) como docetaxel (D) e paclitaxel (P), não sendo demonstrado aumento da ocorrência de malformações fetais e outras complicações maternas quando utilizados no segundo e terceiro trimestres da gestação. O uso do trastuzumabe em gestantes encontra-se associado à oligodramnia e adramnia, não sendo recomendado na gravidez. Em função da quase totalidade dos estudos serem observacionais e retrospectivos, torna-se necessário a confecção de novos estudos prospectivos sobre o tema.

This study aimed to establish the safety of chemotherapy use in pregnant women with breast cancer, and to find possible effects in the fetus. A search of MEDLINE/PubMed, LILACS, SciELO, Cochrane, UpToDate, and Google Scholar databases was performed to identify publications, 86 articles published from 2001 to 2012 were retrieved and evaluated by two readers in accordance predetermined exclusion and inclusion criteria; 39 articles were selected. All the chemotherapy drugs used to treat breast cancer during pregnancy belonged to class D, and consisted of 5-fluorouracil (F), doxorubicin (A) or epirubicin (E) and cyclophosphamide (C), or the combination doxorubicin and cyclophosphamide (AC), a safe regimen when used after the first trimester of pregnancy. Few studies evaluated the use of taxanes (T), such as docetaxel (D) and paclitaxel (P), with no increase in the occurrence of fetal defects and other maternal complications when used in the second and third trimesters of pregnancy. The use of trastuzumab in pregnant women is associated with oligohydramnios and anhydramnios; thus, it is not recommended during pregnancy. As almost all studies were observational and retrospective, new prospective studies on the subject are needed.

The association of cancer and pregnancy is increasingly encountered nowadays in clinical practice. Due to the relative rarity of the situation, it lacks a systematized approach. Different systemic therapies are used in managing cancer with uncertainty regarding the potential hazards they could pose on the pregnancy and/or the fetus.

We have performed a systematic review of literature to identify all reports addressing cancer patients who were exposed to any of the known systemic therapies during the course of the pregnancy. The results were discussed in two parts; part I addresses pregnant patients with solid tumors while part I for those with hematological malignancies.

In part I, we identified different solid tumors diagnosed and treated during the course of pregnancy. Breast cancer was the most commonly treated followed by ovarian cancer. Other tumors were treated as well including lung cancer, cervical cancer, sarcoma and melanomas. It is important to acknowledge the intent of therapy (palliative vs. curative) and the patients has to be properly counseled to reach an informed decision.

We aim to provide a more robust consensus on how to approach these cases and provide a higher degree of evidence to support the safety of applying certain management strategies over the other.