17th International Meeting of the European Society of Gynaecological Oncology (ESGO 2011) 11—14 September 2011, Milan, Italy

Treating cancer during pregnancy

Dr Frederic Amant – Katholieke Universiteit, Leuven, Belgium

The updates are basically a result of the first prospective study that we conducted since 2004. There was one patient with cervical cancer during pregnancy and she really was motivated to continue the pregnancy. At that stage we didn’t know too much about the pathology, the entity, and how to treat this case. Looking into the literature we noticed that there is a big lack of information at that stage and so we treated her with chemotherapy during pregnancy and everything was successful.

Afterwards, looking into the gaps of scientific knowledge, we decided to start with a prospective study. Let’s say we got several parts of the study, and I will maybe give a short overview of each part and the innovative aspects of each part. The registration study, it’s a pan-European registration study, shows that in 503 cases, all types of cancer, all types of treatment, shows that breast cancer is definitely the most common entity and that 42% of cases, cancers diagnosed, during pregnancy are breast cancer. Second is hematologic tumours, 18%, and third cervical cancer with 10%. So that is one of the new results.

We did present the results of a survey, these are unpublished data, and they show that actually more than 50% of specialists actually would prefer to terminate the pregnancy rather than treat with chemotherapy. More than 50% would delay maternal treatment because of the fear of chemotherapy and the majority also would consider pre-term delivery of the baby in order to be able to treat the mother without taking the long-term consequences of pre-term delivery into consideration. So the results of this survey show that there is still a way to go and that we need to have more research data but also to convince people that cancer treatment during pregnancy is possible.

There are new data on the trans-placental passage of chemotherapy because the issue on chemotherapy is really a sensitive one and many clinicians and patients fear for the long-term consequences of chemotherapy for the children. But our data show that the placenta is a filter function and that not all chemotherapy reaches the foetus. We did this in animals and the results can be compared to the human setting; we know that because the placenta is more or less the same. We see that in many cases we cannot detect any level of chemotherapy in the foetus and, if it is detectable, these are low levels, especially for drugs that are used for breast cancer, so epirubicin, doxorubicin, taxanes, it’s very low levels that we can find with the foetus. And the most important, or the most vulnerable, period of pregnancy is the first trimester because then all the organs are formed. So our point is that if you give chemotherapy after the first trimester, taking into consideration that the placenta is a filter, then we think that it’s safe to treat pregnant women with chemotherapy.

But we acknowledge that in the long run we need more data. So preliminary data show that the children do well, that there is no increase on congenital malformations, but we definitely need more data on the long-term of these children. That includes, of course, the heart of the baby, of the children, that we also have to examine because many of these women receive doxorubicin and doxorubicin is one of the most important drugs in the adjuvant treatment of chemotherapy. It’s also one of the standard drugs in hematologic cancers, which was the second most common. So approximately, of pregnant women with chemotherapy, 70% receive doxorubicin so we think it’s also necessary to look to the foetal heart. But preliminary data suggests that is also safe for the foetal heart.

I think this is already very important and that this may add to convince clinicians to treat cancer during pregnancy with chemotherapy. With regard to radiotherapy, we think radiotherapy of the upper parts of the body is possible as well because the abdomen, the pregnant uterus, the baby is protected with a lead skirt and there is always a distance from the pregnant womb to the field of radiation. Actually in the third trimester of pregnancy, the womb is becoming larger and the foetus is becoming closer to the upper part of the abdomen and then the distance becomes too close so there radiotherapy is not possible. But in the second and first trimester, especially for the breast, Hodgkin’s disease, tongue cancer or brain tumours, thyroid tumours, it’s possible to irradiate during pregnancy.

We started this study in Leuven, we have a collaboration with Prague and with Nijmegen in the Netherlands. As a council member I now initiated a task force to get better data in more patients and to start new initiatives on a European level. So the survey was actually the first result of this task force and we are now in the process of looking for new projects, better collaboration, in order to get better information to treat these patients as non-pregnant patients because that’s what we think. We have to look for the prognosis of the mother, also for the child and we think that the maternal prognosis will be best preserved if we treat them as much as possible as non-pregnant women. That is the best guarantee that we have the same prognosis for the mother.

Is there any danger in treating cervical cancer during pregnancy?

Cervical cancer is very difficult because in contrast to breast cancer it’s the organ where the foetus itself is involved. So in fact you should remove the pregnancy as part of the treatment so it’s really challenging. The treatment of cervical cancer during pregnancy depends definitely on the wish of the patient to continue; it depends on the stage of the treatment and it depends on the stage of the pregnancy. And it’s this mixture or this combination that actually shows clinicians how best to treat cervical cancer during pregnancy. But it is possible and it can be a conization it can be trachelectomy or you can give neo-adjuvant chemotherapy followed by a surgical resection or you can give neo-adjuvant chemotherapy, do a caesarean section followed by Wertheim resection or followed by chemoradiation. So you immediately feel that there are different options and I think cervical cancer is the cancer during pregnancy where there is most discussion and where there are the most different options.