Reconciling cancer and pregnancy

In the fifth month of her pregnancy, a 32-year-old woman, expecting her first child, notices a lump in her right breast. Worried, she consults. After ultrasound and a biopsy, her gynecologist diagnosed her with cancer and offered her a termination of pregnancy. “This person asked for another medical opinion, and she arrived in our department, testifies Dr. Roman Rouzier, gynecological surgeon in the department of Pr Serge Uzan at Tenon hospital (AP-HP). We did chemotherapy, and the pregnancy was carried to term. The patient was Caesarized because the baby was breech, but he is doing very well, the treatment has not affected him, and the tumor has been eradicated ”.

Cancer discovered during pregnancy? Compared to the 800,000 births per year, this type of event is rare in France. It concerns between 1/1000 and 1/6000 patients. According to the medical literature, its incidence is estimated at 450 – 500 cases per year. “However, their frequency is increasing, especially breast cancer cases, because women have their first child later and later,” says Dr Rouzier. The average age is approaching thirty. Cancer is the second leading cause of death in women aged 25 to 44. “Breast cancer associated with pregnancy represents the most common situation followed by cervical cancer; then come lymphomas and leukemias, ”notes Dr Rouzier.

“But we are also seeing the emergence of other cancers, such as lung cancer,” adds Dr Olivier Mir, oncologist and pharmacologist at Cochin / St Vincent de Paul hospital. In the international literature, in 50 years, only 10 cases of lung cancer associated with pregnancy have been identified, but between 2006 and 2007, 12 cases were studied and published. It is a generational phenomenon, it corresponds to that of women aged 25-35 who smoke two packs of blondes since the age of 16… ”

Faced with these complex and distressing situations, both for the patients and for the caregivers, medical teams (1) from the Public Assistance-Hospitals of Paris (Tenon, Béclère, Cochin / St Vincent de Paul) and the Gustave Institute Roussy organized a network dedicated to the management of cancer during pregnancy. This is a first in France and in Europe. Funded by the National Cancer Institute (INCa) to the tune of 150,000 euros for two years as part of the treatment of rare cancers in adults (see document), this network will help to disseminate homogeneous and optimal practices for the patients, and will allow the obtaining of epidemiological and pharmacological data. The network also benefits from the support of the National College of French Obstetrician Gynecologists (CNGOF) and the intermediary of hospital centers in the provinces.
“The actions to be taken have so far been fairly empirical. Through this network, we are going to rationalize treatment, announces Dr Philippe Morice, gynecological surgeon at IGR, specialist in cervical cancer. “Often an interruption of pregnancy is proposed, this is debatable, develops Dr. Rouzier who has developed a framework for the management of breast cancer. Today, we are starting to have some data and a little perspective ”. For these cancers which occur during pregnancy, the question of the treatments to be implemented is complex. These situations bring into play the maternal prognosis and that of the unborn child. In general, the therapeutic attitude depends on the progress of the pregnancy, the histological type and the extension of the tumor. »And the side effects of the treatments on the child.
Based on existing data, surgery is possible during pregnancy. “It remains the treatment of choice for breast cancer, including during pregnancy,” explains Dr Rouzier.
Chemotherapy is also possible. “Despite the toxicity of antineoplastic agents, chemotherapy can be considered during pregnancy. The treatments used are antimetabolites, anthracyclines (doxorubicin), alkylating agents (cyclophosphamide) and periwinkle alkaloids, describes Dr Rouzier. In general, chemotherapy is avoided in the 1st trimester of pregnancy. If treatment must be initiated, doxorubicin is preferred over other treatments. During the 2nd and 3rd trimesters, the therapeutic possibilities are wider, subject to strict fetal monitoring. “

However, studies must be continued because the patient cohorts are quite small, only 200 cases treated with endoxan, and for more recent molecules, such as taxotere, there are around ten cases, specifies Dr Olivier Mir. Chemotherapy can have serious consequences on the health of the fetus: risk of malformation, abortion. And the harmful effects can occur long after birth. Dr Olivier Mir cites the case of a child born normally after his mother was treated. “At 14, the boy developed lymphoma, and at 17, thyroid cancer…” The network will set up, thanks to unit 149 of Inserm, a follow-up register for patients and children.

The monitoring of the dosage is essential. This is because the pharmacokinetics of drugs are altered by physiological changes that occur during pregnancy. “Stomach filling is slower and gastrointestinal motility is reduced, which affects the rate of absorption of oral medications,” explains Dr. Rouzier. And during pregnancy, the total amount of water in the body is dramatically increased. The plasma volume increases by approximately 50%, which induces an increased volume of distribution for water-soluble drugs. ”
To limit these toxic effects, a great deal of clinical pharmacology work is necessary, we must make occasional measurements in the blood of the mother, the cord, and the child. “We are also studying the possible passage of the drug through the placenta. For that we collect placentas and we infuse them to see if there is passage or not. But this type of study is only valid for the late stage of pregnancy not for the beginning, explains Dr Olivier Mir.

The data collected by the network also shows that radiotherapy is possible “for cancers remote from the pelvis, but the precautions to be taken are important (irradiating doses, fetal protection)”. In practice, radiotherapy is avoided in the 1st trimester. It is possible during the 2nd and 3rd trimesters, but it is preferable to schedule it after childbirth.

Thus, alternatives to the termination of pregnancy exist to resolve this double problem posed by the occurrence of cancer during pregnancy. Nevertheless, in this delicate equation, it is also necessary to take into account the opinion and the plan of the parents. “Our objective will be to provide honest and intelligible information for the patients”, adds Dr Olivier Mir. “These questions are not decided within the framework of the multidisciplinary meetings of the network but with the patient,” explains Dr Roman Rouzier. Our role of the network will be to provide the medical team and the couple with all the reliable knowledge at their disposal ”.

(1) At Tenon hospital where the network secretariat is located: Pr Serge Uzan and Dr Roman Rouzier. At the Institut Gustave Roussy, Dr Philippe Morice and Catherine Uzan. At the Béclère hospital, Professor René Frydman and Dr Aurélia Chauveaud. In Cochin / St Vincent de Paul, Prof. Jean-Marc Treluyer and Dr Olivier Mir. As well as Unit 149 of Inserm specializing in epidemiological research in perinatal health and women’s health.