Comment by ecancermedicalscience Scientific Editor Dr Linda Cairns and Dr Fedro Peccatori of the European Institute of Oncology
Cancer during pregnancy occurs in approximately one in every thousand pregnancies, although the number of cases globally is increasing.
The tumour is often diagnosed late influencing both the survival of the woman and the foetus.
Often the decision to terminate the pregnancy or to induce a preterm delivery is taken without a valid medical reason despite the availability of effective treatments to save both the life of mother and child.
‘Pregnancy and cancer’ are two words that in the minds of many cannot coexist, as one represents the beginning of a life, the other, for many, the possible end.
However ‘Cancer and Pregnancy was the title of a meeting held in Milan, April 12th 2012, that brought together physicians and researchers, with a vested interest in this subject, with the aim of offering pregnant patients the same optimum management as non-pregnant patients.
The discovery of a tumour during pregnancy is thought to be on the increase because women are leaving it later to start a family, and the incidence of cancer increases with their age.
Fortunately progress in recent decades has overturned old misconceptions and taught doctors to address this situation in a rational and safe manner.
"The most common cancers in pregnancy are breast, gynaecological (mainly ovarian and uterine cervix), haematological (leukaemia and lymphoma) and melanoma", reported Dr Alessandro Phaedrus Sinners from the Fertility and Reproductive Oncology Unit at the European Institute of Oncology in Milan. "A decrease in the number of girls who conceive before the age of twenty and less breastfeeding, two factors known to protect against breast cancer, have not surprisingly led to an increase of this disease in young women. We therefore need better surveillance during pregnancy: early diagnosis of any cancer can significantly improve survival. Simple screening programs should be introduced during pregnancy, and women should be encouraged to discuss any concern with their physician."
Cancer occurring during pregnancy is at risk of being misdiagnosed so allowing tumour progression and a delay, or a reduction, in the intensity of the treatment due to the concomitant pregnancy.
"The decisions regarding oncological treatment during pregnancy are often difficult due to the conflict between the health of the mother and the affect on the foetus” added Giovanna Scarfone, Division of Obstetrics and Gynaecology, IRCCS Fondazione Ca' Granda Hospital Maggiore Polyclinic of Milan. “The physician must provide the patient with the most accurate and up to date information on their treatment options. Their choice may be influenced by ethical, legal, personal and religious beliefs and the physician must be prepared to answer any questions that the patient may have regarding the timing of treatment and the fear of progression.
"The treatment of tumours in pregnancy can be associated with unacceptable errors e.g. unjustified termination of pregnancies or the choice of an inadequate strategy for treatment of a tumour with the risk of compromised survival" added Scarfone.
First, when a pregnant woman is diagnosed with cancer, doctors and patients must weigh the risk of the effects of treatment on the foetus and newborn with the risks involved in the decision to defer therapy until after delivery. "Today there are many more treatment options than a few years ago, and even cancer in pregnancy can be treated with surgical and pharmacological techniques that previously were thought to be contraindicated" emphasized Oreste Gentilini, deputy director of the Surgical Senology Division, European Institute of Oncology in Milan.
ESGO (The European Society of Gynecological Oncology) has formed a task force for ‘Cancer in Pregnancy’, to develop consensus documents on the diagnosis and treatment of gynaecologic and breast cancers during pregnancy.
"There is agreement that chemotherapy should be avoided during the first 3-10 weeks after conception when organogenesis is occurring” continued Gentilini. "Even beyond this gestational period, the central nervous system, ears, eyes, teeth and external genitalia continue to grow and exposure could potentially lead to functional defects, although a recent study (2) published in the journal Lancet Oncology and conducted by Frederic Amant on 8-25 week foetuses undergoing cancer treatment in utero reported encouraging findings. Amant in fact observed normal cardiac development and cognitive development in most of the children followed, with the exception of some preterm infants. The study should reassure women and their doctors about cancer treatment during pregnancy. "
The influence of the pregnancy on the effectiveness of the treatment is unclear. It’s known that the metabolism of several drugs are modified during pregnancy but the limited number of studies involving pregnant women means that the effect of the pregnancy on survival is still uncertain.
"In general, chemotherapy should be postponed until at least the second trimester, i.e. after the sixteenth week," confirmed Gentilini. "Methotrexate is one of the most dangerous drugs and is not recommended even in the later stages of pregnancy for the risk of accumulating in the amniotic fluid. The anthracyclines and therapeutic antibodies were the most safe in our series of 20 patients who did not show any increase in the incidence of congenital malformations or foetal growth retardation (3). It is important that the pregnancy is carefully monitored by specialists"
Cervical and ovarian cancers are the most common gynaecological cancers diagnosed during pregnancy.
Endometrial and vulvar cancers are less common and are generally treated as in non-pregnant women with limited effects on the course of the pregnancy.
Treatment strategies for ovarian and cervical tumours should be decided by a multidisciplinary team comprising oncologists, psychologists, obstetricians, paediatricians and neonatologists.
In early stage disease, during the first and at the beginning of the second trimester, the two main considerations for management of the patient are the tumour size (and stage) and nodal staging.
MRI and laparoscopic lymphadenectomy are useful for clinicians planning a potentially conservative approach. The management of patients with locally advanced disease is controversial and should be discussed on a case-by-case basis.
The current trend is to preserve pregnancy in patients diagnosed with cervical or ovarian cancer, whenever feasible. Clinical studies are needed, particularly for key issues in clinical management such as an intentional delay in early-stage cervical cancer or radical trachelectomy and neoadjuvant chemotherapy, to establish a balance between curing for the patient and safeguarding the foetus.
With breast cancer, the most frequent tumour encountered during pregnancy, no specific risk factors have been identified when the genetic and environmental conditions are similar to those of the general population.
Delayed diagnosis is common and results in more advanced disease, an increased risk of metastasis and worse outcome.
Tumours diagnosed in pregnant women are 2.5 times more likely to be diagnosed with advanced cancer compared to non-pregnant women (4).
A swollen or inflamed breast or a suspicious mass should be given due attention, even if 80% of lumps during pregnancy are benign. "Any breast lump with suspicious characteristics should be investigated by the breast specialist during pregnancy, and if the nodule is malignant, the patient should be referred to a specialized centre for treatment emphasized Dr. Sinners.
In general, surgery can be performed safely during most stages of pregnancy and most of anaesthetics do not appear to harm the foetus. Trastuzumab treatment or HER2-positive tumours is at present not recommended in pregnant women as it may lead to kidney damage of the foetus. New drugs such as bevacizumab and inhibitors of tyrosine kinases have not yet been tested in this group of patients.
on the long term cognitive and cardiac outcome after prenatal exposure to chemotherapy in children 18 months or older. Lancet Oncol 2012; published online Feb 10. DOI:10.1016/S1470- 2045(11)70363-1.
(3) Peccatori F, Azim HAJr, Scarfone G et al Weekly epirubicin in the treatment of gestational breast cancer (GBC).Breast Cancer Res Treat. 2009 Jun;115(3):591-4.
(4) Azim H Jr, Gentilini O, Locatelli M et al. Managing pregnant women with cancer: personal considerations and review of the literature. Ecancermedicalscience. 2011;5:204. Epub 2011 Feb 14.
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