Chapter 1 - Cancer Treatment during Pregnancy
Breast cancer is the most commonly diagnosed cancer during pregnancy. Once a patient is diagnosed, she should be approached in a similar way as young breast cancer patients, taking into consideration the gestational age at diagnosis. Patients with small locally-confined tumours should be considered for primary surgery. In general, surgery could be performed any time during pregnancy, but a careful monitoring of maternal and foetal conditions is advised, particularly after the 25th week of gestation. The choice of surgery is the same as in the non-pregnant setting. Patients subjected to conservative breast surgery should receive adjuvant radiation therapy, which in general should be postponed until after delivery. In patients requiring surgery early during the first trimester, the expected delay in receiving radiotherapy could favour performing mastectomy in some of these cases, particularly those who are at a high risk of developing local recurrence. No foetal defects secondary to sentinel lymph node biopsy (SLNB) have been observed, acknowledging the limited published data in this regard. Hence, it could be considered in centres in which SLNB is routine practice in the non-pregnant setting.
Chemotherapy should be considered in patients with (1) metastatic disease at presentation, (2) large tumours requiring neoadjuvant therapy and (3) adverse prognostic features at surgery necessitating adjuvant therapy. Anthracycline-based regimens remain the chemotherapy of choice during pregnancy. Both epirubicin and doxorubicin can be safely administered. As for taxanes, transplacental transfer is very low and emerging clinical data are rather reassuring regarding their safety. Weekly paclitaxel does not require high-dose steroid preparation and is less toxic compared to 3-weekly docetaxel, and hence is preferred in pregnant breast cancer patients. On the other hand, regimens such as cyclophosphamide, methotrexate and fluorouracil (5-FU) (CMF) should be completely avoided, given the high abortive properties of methotrexate and the lack of particular importance of such a regimen in current breast cancer management.
Patients with HER2-positive breast cancer are candidates for treatment with anti-HER2 targeted agents. Trastuzumab increases the risk of developing oligohydramnios, a condition that can lead to premature delivery, foetal morbidity and mortality. This is believed to be secondary to the effect of trastuzumab on the foetal kidney, which expresses HER2 and is responsible for the amniotic fluid production. Currently, we lack any data on the safety of other HER2-targeted agents. Hence, all anti-HER2 targeted agents should be avoided during pregnancy.
Occasionally, pregnant breast cancer patients are diagnosed with small (e.g. pT1), node-negative, low-grade endocrine-sensitive tumours (i.e. luminal-A breast cancer). Outside pregnancy, chemotherapy is often not offered to these patients. Given that hormonal agents are contraindicated during pregnancy, these patients could be offered only surgery during pregnancy, postponing hormonal therapy along with radiation therapy, if indicated, following delivery.
Pregnant patients diagnosed with acute leukaemias or aggressive lymphomas often require the prompt initiation of chemotherapy. Hence, in the majority of cases diagnosed during the first few weeks of pregnancy, abortion should be considered, as a delay in the initiation of therapy could significantly hamper the patient’s prognosis.
In lymphomas, the standard ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) regimens can be safely administered following the first trimester in patients with Hodgkin’s and non-Hodgkin’s lymphoma, respectively, with no obvious increase in foetal or pregnancy-related complications. The use of rituximab in pregnant patients with B-cell lymphomas has been shown to be associated with foetal B-cell depletion at delivery, which is generally reversible. Hence, in patients in whom the use of rituximab during pregnancy is deemed necessary, the drug could be administered, acknowledging that this might have a transient effect on foetal immunity at delivery.
Managing acute leukaemias during pregnancy is very challenging. The use of anthracycline analogues, such as daunorubicin and idarubicin, is preferably avoided during pregnancy, even following the first trimester. They are highly lipophilic, resulting in high placental crossing and serious foetal complications irrespective of the timing of exposure. An alternative could be doxorubicin, which is safer during pregnancy and has considerable activity in acute leukaemia as well. Patients with promyelocytic leukaemia require treatment with all-trans-retinoic acid as well, which can be safely administered starting from the second trimester.
The use of imatinib in patients with chronic myeloid leukaemia has been shown to be safe following the first trimester. When treatment is required during the first trimester, interferon could be used as an alternative, as it is a large molecule and does not cross the placenta. In addition, clinical data clearly support its safety when administered during the first trimester.
Cervical cancer is the second most common tumour diagnosed during pregnancy. Radiation therapy is the standard of care in early stages but this would compromise the continuation of pregnancy and hence should be avoided. Otherwise, abortion should be considered. Lymphadenectomy should be considered in patients with positive lymph nodes and neoadjuvant chemotherapy with a cisplatin-based regimen could be considered until delivery.
Patients with epithelial ovarian cancer are often diagnosed at an advanced stage and require systemic chemotherapy. The combination of weekly paclitaxel and carboplatin is the preferred option until delivery. Radical surgery could be considered at the time of delivery. No clinical data are available on the safety of bevacizumab during pregnancy. However, preclinical data have shown developmental anomalies and interference with embryonic development. Hence, bevacizumab presently should not be used during pregnancy.
The use of standard BEP (bleomycin, etoposide and cisplatin) or EP (etoposide and cisplatin) regimens during gestation seems feasible, although the use of etoposide during pregnancy has been shown to be associated with relatively high risk of pregnancy and foetal complications. An alternative could be paclitaxel and cisplatin. No apparent increases in foetal toxicities have been reported using these regimens.