ReviewPregnancy after breast cancer
Introduction
Recent figures from the Office for National Statistics have shown that the average age of women at birth has gradually increased from 26.2 years in 1972 to 29.1 in 2000 [1]. With this shift, there may be a larger proportion of premenopausal patients with breast cancer who are yet to have a pregnancy in future decades. Only 6.5% of all breast cancers are diagnosed in women under 40 years and 21.8% diagnosed in those under 50 years [2]. Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile [3]. However, poorer survival previously seen in premenopausal women with breast cancer has improved with the use of better treatments in specialist centres by multidisciplinary teams [4]. It is therefore important to have an evidence base on which to provide information regarding the potential risks of pregnancy after a diagnosis of breast cancer.
This paper reviews the literature regarding the effect of a pregnancy subsequent to a diagnosis of breast cancer. It also assesses the influence of breast cancer treatment on subsequent pregnancies. Medline and Embase databases were searched to identify all published research between 1954 and 2002 relating to pregnancy after a diagnosis of breast cancer excluding all those regarding pregnancy-associated breast cancer. The literature regarding pregnancy in breast cancer survivors is limited to case series and case control studies. The primary outcome measure in the majority of these studies is survival.
Section snippets
Influence of subsequent pregnancy on survival
Many studies have shown that pregnancy following a diagnosis of breast cancer is not detrimental to survival. These studies are predominantly case control studies where cases are defined as women treated for breast cancer who subsequently become pregnant and controls are women treated for breast cancer who do not subsequently become pregnant. Population-based studies reporting relative risks are presented in Table 1. These studies have in fact shown that a subsequent pregnancy results in an
Influence of pregnancy on recurrence and distant metastasis
Other outcome measures include recurrence and incidence of distant metatasis. However, the lack of data is due to the fact that the studies are retrospective with incomplete data. Malamos and colleagues [10] present a rate of local recurrence of 14% in the pregnant group and 39% in the non-pregnant group. Sutton and colleagues [27] in 1989 also reported a recurrence rate of 28% in the pregnancy group and 46% in the non-pregnant group. In these studies, however, the site of recurrence is not
‘Healthy mother effect’ [8]
Interpretation of data can also be problematic due to the population under study.
Women who become pregnant following treatment for breast cancer are thought to have different characteristics to women who do not become pregnant. This results in a ‘healthy mother’ bias: those who feel well have children and those who are affected by the disease do not [8]. Sankila and colleagues suggest that even when cases and controls are matched at the time of diagnosis, their prognosis may not be the same at
Methodology of studies
Studies of pregnancy after breast cancer are predominantly retrospective case control studies or case series. This introduces a number of issues regarding methodology. The denominator population of women undergoing pregnancy does not always include all those who become pregnant due to the difficulty in identifying cases in retrospective studies. The definition of ‘pregnancy’ also varies between studies with some using all pregnancies as a baseline including those that result in a spontaneous
Length of time from diagnosis of breast cancer to pregnancy
When looking at the length of time from diagnosis of breast cancer to pregnancy and whether this affects survival, it is again difficult as the numbers are small and stratifying for different time bands makes the analysis less valid. Clark and Reid [28] found that survival was better with a longer time interval between cancer diagnosis and conception. They reported a 5-year survival rate of 54% in those who became pregnant within 6 months of a diagnosis and 78% in those who waited between 6
Hypothesis regarding survival
The survival advantage for those patients who become pregnant subsequent to a diagnosis of breast cancer may in part be due to the bias of retrospective studies. A foetal antigen hypothesis has, however, been proposed [29] to account for a causal effect of pregnancy on survival of women who have had a diagnosis of breast cancer. This suggests that during pregnancy, isoimmunisation occurs due to breast carcinoma cells and foetal cells sharing common antigens. It is postulated that foetal
Effect of chemotherapy on ovarian function
Chemotherapeutic agents affect follicular growth and maturation resulting in ovarian failure. This results in irregular menses and amenorrhoea. Cyclophosphamide causes fibrosis of ova causing a reduction in oestrogen and disruption of the normal menstrual cycle. Methotrexate and 5-fluorouracil also induce amenorrhoea. However, the effects of other agents including doxorubicin and anthracyclines are unclear. Alkylating agents are more likely to cause infertility than non-alkylating agents [32].
Teratogenicity of adjuvant systemic therapy
The incidence of teratogenesis in the general population is 3%. Little is known about foetal outcome following treatment of a pregnant patient with tamoxifen. However, adverse effects of tamoxifen in animal studies have been demonstrated [38]. With regard to chemotherapy, Doll and colleagues [39] have shown that if chemotherapy is administered during pregnancy, there is a 16% incidence of foetal malformation if used in the first trimester, but no increase in the incidence of teratogenesis if
Quality of life (QOL)
There have been few qualitative studies on a women's adjustment to breast cancer and, as a result, little understanding of the concerns of younger women following a diagnosis of breast cancer [40]. Few papers assess quality of life with regard to a subsequent pregnancy. Dow [12] states that in addition to prognostic indicators after breast cancer, perceived quality of life, desire for children and the degree of support for or from one's spouse and family were also highly important
Conclusion
Based on available data, the effect of a subsequent pregnancy on patients who have had breast cancer with regard to local recurrence, distant metastasis and survival remains debatable. Current evidence is difficult to interpret due to differing populations and the techniques of data collection. Only large prospective studies may answer these questions. Within prospective studies, analysis using a nested case control approach could be used. Until these data are available, advice to women
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