ANTI-TUMOUR TREATMENTThe pregnant mother with breast cancer: Diagnostic and therapeutic management
Introduction
Cancer complicates approximately 1 per 1.000 pregnancies and accounts for one-third of maternal deaths during gestation.[1], [2] The malignant tumours most commonly diagnosed in pregnancy are those with a peak incidence during the woman’s reproductive period such as breast, cervical, melanoma, thyroid cancer as well as lymphomas and leukemias. As the trend for delaying pregnancy into the later reproductive years continues, other malignancies may occur, i.e., colorectal or lung cancers.
The reproductive system is affected by malignant growth more frequently than other systems during pregnancy. Breast and cervix are the most predominant sites followed by ovarian, endometrial and vulvar carcinoma or trophoblastic tumours. Approximately 3% of women detected with cancer of the reproductive system will have a coexisting pregnancy. Diagnostic delay of those tumours is not a rare phenomenon due to masking of symptoms and signs by the normal changes associated with pregnancy.3
The management of a pregnant mother with cancer is difficult and emotionally driven and often requires the participation of the doctor, the patient and her family. The main concerns of both the obstetrician and the oncologist are to save mother’s life, to protect the fetus and to keep the woman’s reproductive system intact. The ideal combination is to cure the mother from breast cancer and to deliver a healthy baby. In addition, difficult ethical and religious issues complicate the final decision when the management of the pregnant patient with breast cancer is incompatible with continuation of the gestation.[4], [5]
Section snippets
Incidence
In 1955 White reviewed 45,881 cases of breast cancer treated between 1850 and 1950, from whom 1296 women (2.8%) had a coexistent pregnancy.6
There is evidence that the risk of pregnancy-associated breast cancer is age related. From the SEER Cancer Statistics data it becomes evident that women who have their first pregnancy before the age of 20 years have a 2–3 times less risk of developing breast cancer than women who have their first term pregnancy after the age of 30 years.7
The prevalence of
Pathology
In pregnancy the pathology profile of benign lesions is the same as in non-pregnant women. Almost 70% of them are fibroadenomas, lipomas or papillomas and the rest are lesions related to pregnancy, such as galactoceles, lactating adenomas, mastitis, or infarcts.[13], [14], [15], [16], [17]
The various histological types of breast cancer occur with similar frequencies in pregnant and non-pregnant women. In most of the reported series the predominant histological type is invasive ductal carcinoma
Clinical picture
The most common clinical presentation is a painless mass usually detected by breast self-examination. Bloody nipple discharge during pregnancy or lactation is a less common presenting symptom and should always be associated with a palpable mass. More rarely pregnant women are presented with typical clinical picture of inflammatory breast cancer. The “milk rejection sign” refers to the unexplained refusal of an infant to nurse from a carcinomatous breast.[3], [6], [9], [13], [21]
During pregnancy
Radiodiagnostic work-up
Imaging techniques used for staging breast cancer in a pregnant woman should be modified to avoid radiation exposure to the fetus.
Ionizing radiation (gamma rays, X-rays, particulate radiation) can potentially induce leukemia and solid tumours in children and adults. The radiation effect on fetal life seems to be dose dependent. Doses of less than 0.1 Gy have no effect on the fetus, whereas doses of 2.5 Gy and more than 3.0 Gy are associated with fetal malformations and abortion, respectively.
In
Therapeutic management
The management of breast cancer during pregnancy should follow the same criteria as their non-pregnant counterparts, should mainly be dependent on the disease stage and should be modified according to the needs of the mother and fetus.
Mother and fetal outcome
Since not adequate information is available from prospective studies, the knowledge of the effect of local or systemic treatment in pregnant mothers with breast cancer and the fetuses is mainly collected from retrospective reports.
The methods of deliveries applied vary in the largest series, although it seems that vaginal delivery is practically feasible. In some studies the gestational age at delivery was around 34–35 weeks. Delivery should be avoided during the maternal nadir, usually 2–3
The safety of chemotherapy and associated medical treatment during pregnancy
All chemotherapy drugs are capable of crossing the placenta. However, the first trimester is the most critical period, during which severe damage leads to spontaneous abortion. However, if sublethal damages happen chemotherapy may have detrimental effects on the fetus by inducing malformations, teratogenesis, mutations, carcinogenesis, organ toxicity or mental retardation. The rate of chemotherapy-associated fetal malformations is 12.7–17%, and that of low birth weight is 40%. In contrast, the
When termination of pregnancy is indicated?
In the 1950s and 1960s therapeutic abortion was a recommendation for pregnant women with breast cancer. Twenty years later it was observed that abortion does not prolong survival of patients, since pregnancy has no influence on the disease course.[21], [45]
Nowadays, a recommendation to terminate pregnancy has only room when pregnancy itself is an obstacle to drastic treatment. The main reasons to advocate therapeutic abortions are the following: (a) pregnant women requiring systemic treatment
Metastatic spread to the placenta and/or fetus
Metastatic spread of breast cancer cells to the placenta is extremely rare. Metastatic lesions to the placenta have been described in approximately 60 cases worldwide. Melanoma and hematologic malignancies are the commonest tumors that may invade placenta. Sporadic cases with fetal metastases have also been observed.
Up to 2001 nine cases of pregnant women with breast cancer with placental involvement have been reported, while no case with metastatic lesions to the fetus was found.[2], [3], [76]
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