In this study, we addressed for the first time the prognostic impact of subsequent pregnancy in women with a history of an endocrine-sensitive BC. The main analysis indicated that pregnancy did not seem to be protective against BC recurrence in patients with an endocrine-sensitive disease. Although we included a higher number than planned of pregnant patients with ER-positive disease (194 v161), the event rate was lower than expected (29% instead of 35%), which slightly reduced the power of the study (75% instead of 80%). However, the DFS analysis in the ER-positive population indicated that subsequent pregnancy is not detrimental. In addition, the pregnant group had a better OS independent of ER status. These findings point out that pregnancy after BC diagnosis could be considered safe in women with history of an ER-positive disease.
Apart from the safety of subsequent pregnancy, previous studies failed to show convincing evidence regarding other relevant questions such as the therapeutic role of induced abortion and the optimal time to become subsequently pregnant. Consistent with earlier studies,12–14
we found that approximately 30% of patients who became pregnant after BC diagnosis had an induced abortion. However, we did not find that abortion had an effect on BC outcome, irrespective of ER status. Hence, based on these findings, abortion should not be promoted for therapeutic reasons. On the other hand, we found no difference in DFS between patients who became pregnant within 2 years of BC diagnosis and those who became pregnant afterward. Of note, the study was not powered to provide a definitive answer for these end points, which should be taken into account. However, to the best of our knowledge, this is the largest matched study that addresses these questions.
Limited information was available about breastfeeding in our study. Previous reports have shown that breastfeeding after BC seems to be associated with relatively low rate of BC-related events.15,16
However, neither included a comparator group to allow proper evaluation of the safety of breastfeeding. Hence further studies are needed to elucidate the impact of breastfeeding on BC outcome in these patients.
Our study nevertheless has some limitations. The study was designed to show a protective effect of pregnancy rather than equivalence or absence of harmful effect, which is probably more clinically relevant. However, the feasibility of conducting a noninferiority trial in this setting is low. In addition, we wanted to confirm whether a true protective effect exists. Although our results failed to demonstrate any definite protective effect from pregnancy subsequent to the diagnosis of BC, there was no evidence of a deleterious effect either. Another limitation was the large number of patients who had missing information on HER2 status (80%). This is secondary to inclusion of patients who were diagnosed before routine testing of HER2.
The retrospective nature of the study hindered us from accurately registering the number of required events and from completely ruling out the impact of selection bias. However, it is important to note that addressing the impact of subsequent pregnancy on BC prognosis in a prospective randomized trial is impossible, and thus we will have to rely on data from large, well-conducted retrospective studies.
No information was available on the use of ART in patients who became subsequently pregnant in our study. However, this study included patients who were diagnosed with BC before 2008, the time when none of the participating sites were routinely offering ART for patients with BC. In addition, we lack strong evidence linking the use of ART to BC recurrence17
or the risk of developing BC in the general population.18,19
Hence it is unlikely that the absence of information on ART in this study would have significant implications on the interpretation of our findings.
Our study was not designed to address the feasibility and safety of early interruption of hormonal therapy in patients with endocrine-sensitive disease. Patients in both groups (ie, pregnant and nonpregnant) received a median duration of standard 60 months of hormonal therapy. However, not all patients with ER-positive disease received hormonal therapy, which was possibly due to the inclusion of patients diagnosed before routine implementation of adjuvant hormonal therapy in young women. Hence until further data are available, women should be advised to complete adequate hormonal therapy before considering becoming pregnant. This remains rather challenging for some patients, as chances of pregnancy could be low after 5 years of tamoxifen.20–23
Currently, the Breast International Group and the North American Breast Cancer Group are launching a study to provide guidance about adopting customized strategies for patients who wish to become pregnant before completion of classic endocrine therapy.23
In conclusion, this study indicated that pregnancy is not protective against BC recurrence in women with a history of an endocrine-sensitive BC at least during the first 5 years after pregnancy. However, the results are rather reassuring for a lack of detrimental effect irrespective of ER status. We believe that our study adequately addressed many of the limitations of previous studies and hence would be highly relevant to the counseling of young women wishing a pregnancy after BC diagnosis.