More on Pregnancy in Breast Cancer Survivors
July 1, 1999 5 minutes read
More on Pregnancy in Breast Cancer Survivors
abstract & commentary
Synopsis: Premenopausal women diagnosed with invasive breast cancer between 1983-1992 were interviewed or responded to a questionnaire. By establishing appropriate controls, investigators concluded that the risk of death from breast cancer was not adversely affected by pregnancy. However, spontaneous abortions were more frequent in breast cancer survivors than in age-matched controls who had not had breast cancer.
Sources: Velentgas P, et al. Cancer 1999;85: 2424-2432; Averette HE, et al. Cancer 1999;85: 2301-2304.
We have previously discussed the apparent safety of pregnancy among women with a prior diagnosis of breast cancer. However, much of the existing data had certain flaws. A recent retrospective review has generated additional reassurance. With the success of primary breast cancer treatment, there has been, and will continue to be, increasing numbers of premenopausal women alive and well years after treatment. This, coupled with the trend to have children at later ages, has heightened the concern for the safety of women with regard to reactivation of breast cancer. Although this question has been studied previously, outcomes with regard to the influence of pregnancy on breast cancer survival have been difficult to interpret because of methodological difficulties.
In a recent report from the University of Washington, this question was carefully examined. Women diagnosed with invasive breast cancer between 1983 and 1992 who previously had participated in a population-based case-control study or, if deceased, proxy respondents were queried about subsequent pregnancies using self-administered questionnaire or telephone interview. Information regarding breast cancer recurrence was obtained by questionnaire and from cancer registry abstracts. Women who became pregnant after a diagnosis of breast cancer were matched with women without subsequent pregnancies based on stage of disease at diagnosis and recurrence-free survival time.
Almost 70% of women who became pregnant after being diagnosed with breast cancer delivered one or more live-born infants. However, miscarriages occurred in 24% of the patients who became pregnant compared to 18% of age-matched controls who had no history of breast cancer. Of the 53 women who became pregnant after breast cancer, five died of recurrent breast cancer. The age-adjusted relative risk of death associated with any subsequent pregnancy was 0.8 (95% confidence interval, 0.3-2.3). Thus, the findings of this survey do not suggest that pregnancy after a diagnosis of breast cancer has an adverse effect on survival.
COMMENTARY
In a recent review of previous epidemiologic studies, the conclusion was made that pregnancy did not increase the risk of recurrent breast cancer.1 However, Collichio and colleagues point out a significant form of bias that could explain the lack of effect. After all, the development and progression of breast cancer is known to be highly influenced by hormones. Thus, it is difficult to believe that the fluctuations of hormonal milieu created by pregnancy would not alter latent or residual microscopic breast cancer likely to exist in a certain fraction of those treated. The major potential bias in the prior epidemiologic studies may relate to what Sankila and colleagues2 have termed "the healthy mother effect." Women who become pregnant after breast cancer may be more likely to be free of disease at the time of pregnancy than similar breast cancer patients who do not have a subsequent pregnancy, even if selected prognostic factors measured at diagnosis are equivalent and the comparison group survives at least as long as the time from diagnosis to pregnancy. Without consideration of disease status at the time of pregnancy, this bias could obscure a countering harmful effect of pregnancy upon survival.
In this report, Velentgas and colleagues carefully gathered data to describe pregnancies occurring in a population-based sample of women diagnosed with breast cancer by age 40. They attempted to determine whether pregnancy after breast cancer was associated with disease recurrence or shortened survival. By taking into account recurrence after initial diagnosis, the effect of differences in health at the time of pregnancy for those who became pregnant vs. those that did not, "healthy mother effect" bias was minimized. Indeed the provision of carefully selected controls and rigorous statistical detail set forth by Velentgas et al allows confidence in the data analysis and interpretations provided.
However, it remains difficult to generalize these observations, especially because there was a relatively small number of individuals surveyed in this study who became pregnant, and there were only five total deaths in women who became pregnant after breast cancer.
One problem with a retrospective study such as this and others that have been published 3-5, is that it often depends on remote memory for those providing the care for the patients who had died. Pregnancies, particularly those that did not result in live births, may not have been accurately recorded and those patients might not have been included in the study group. The data from this study would suggest a higher rate of spontaneous abortions in patients with a prior history of breast cancer. This certainly is similar to the spontaneous abortion rate increase published for other human malignancies, and may reflect the effects of prior treatment.
In the editorial accompanying this report, Averette and colleagues have consolidated the findings from this report with those previously published. They provide six key conclusions. First, pregnancy does not appear to affect adversely the prognosis of patients with stage I or II breast cancer. Second, the decision to conceive should be influenced by the prognosis of the particular patient but should discount the effects of pregnancy on survival (as repeated studies have failed to demonstrate an effect of pregnancy on survival in this situation). Third, women with advanced stage breast cancer should be advised to avoid pregnancy for several years after treatment. Fourth, chemotherapy-induced ovarian failure may lead to infertility. Fifth, chemotherapy may also result in a higher rate of spontaneous abortion. And sixth, the decision to conceive is far more complicated than just these medical and physical factors but relates as well to psychological and social issues. Thus, counseling by physicians, other health providers, family and friends may be of critical importance. The data and discussion in this report (and accompanying editorial) should prove valuable in this regard.
References
1. Collichio FA, et al. Oncology 1998;12:759-765.
2. Sankila R, et al. Am J Obstet Gynecol 1994;170: 818-823.
3. Moseley RV, et al. Ann Surg 1970;171:329-333.
4. von Schoultz E, et al. J Clin Oncol 1995;13:430-434.
5. Kroman N, et al. Lancet 1997;350:319-322.
Which one of the following statements about pregnancy that occurs after treatment of breast cancer is true?
a. Fertility has been shown not to be adversely affected by prior history of breast cancer.
b. Pregnancy has been shown to increase the rate of recurrence of breast cancer for those with Stage II disease at diagnosis.
c. An unusually high rate of birth defects has been observed in offspring of women with breast cancer.
d. Unsuccessful pregnancies (spontaneous abortions) are not more frequent in women with a prior history of breast cancer.
e. Pregnancy does not appear to influence survival in women with a prior history of breast cancer.
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