Breast cancer (BC) remains the most prevalent malignancy among women of reproductive age globally, with Asian regions demonstrating particularly high proportions of young-onset cases (1, 2). While improvements in early detection and treatment have increased survival rates, these advances have raised fertility considerations among young survivors (3). BC treatments, particularly endocrine therapy and chemotherapy, are known to potentially impair fertility, causing considerable distress among these young survivors (4). Approximately 63% of young women of childbearing age diagnosed with BC have concerns about their fertility post-treatment, and 39% report that these concerns influence their treatment decision-making (5–7). Notably, 2% of patients may decline recommended chemotherapy or endocrine therapy (ET) owing to fertility concerns, potentially compromising their oncologic outcomes (7). BC survivors exhibit significantly lower pregnancy rates (RR, 0.40; 95% confidence interval [CI], 0.32–0.49) compared to the general population, substantiating these fertility concerns (8). Prior studies have demonstrated the safety of pregnancy and fertility preservation in BC survivors (9, 10). A recent prospective study, the POSITIVE trial, demonstrated the safety of interrupting hormonal therapy to achieve pregnancy (11), as well as the safety of using assisted reproductive techniques in BC survivors (12). Nevertheless, concerns persist regarding potential treatment delays, increased recurrence rates, and decreased treatment adherence (4, 13). Moreover, while fertility preservation strategies exist, there remains uncertainty regarding their utilization and efficacy in patients with BC (14).

This study aimed to provide comprehensive real-world data on pregnancy following BC treatment, with the goal of informing clinical practice and patient counseling regarding this critical aspect of survivorship.

This large-scale retrospective study provides real-world data on pregnancy outcomes among young BC survivors. Patients with hormone receptor-positive BC had significantly lower pregnancy rates and longer pregnancy intervals after treatment. Outcomes for the 115 patients who conceived post-BC treatment showed varied intervals between surgery and conception, with the highest number of pregnancies occurring 3–4 years post-surgery. During the follow-up period, 82.7% of the conceptions resulted in one or more live births, and 85.2% were without evidence of disease, with no patient deaths reported. Among the patients who became pregnant, 46.1% had discontinued hormone therapy for pregnancy.

An interesting finding from this study is that even among patients who were >35 years old, unmarried at diagnosis, or had children, 7.8%, 17.8%, and 6.8%, respectively, became pregnant after BC treatment. These figures are noteworthy when compared to the overall cohort’s pregnancy rate of 14.2%. Therefore, adequate counseling and planning for having children should be conducted before starting treatment, even for BC patients who are older, unmarried, or have not previously given birth. In this analysis, a history of pregnancy before BC diagnosis significantly reduced the chances of conception after BC treatment. This might be attributed to the fact that women with one or more children are less motivated to have a baby after overcoming BC. Additionally, the vague fear among patients and physicians that pregnancy could negatively impact the prognosis of BC could contribute to low motivation. Survey studies conducted among BC specialists revealed that 20–30% of physicians incorrectly held the belief that pregnancy adversely affects BC prognosis (15, 16). However, a prior survey study on BC survivors revealed that 56% of young women who had one or more children before their diagnosis wished to have more children after their BC treatment (5). Our analysis revealed that subsequent pregnancies occurred even among patients who already had children. Among patients with one child, 11% (n=18/163) achieved an additional pregnancy, and notably, 1.9% (n=3/161) of patients with two or more children conceived after BC treatment ( Supplementary Table 1 ). These findings suggest that pre-existing parenthood status should not be a limiting factor when considering fertility preservation options for patients, and fertility preservation counseling should be offered to all patients regardless of their parental status.

Another significant factor influencing pregnancy outcomes after BC treatment was hormone receptor status. Our findings suggested that hormone receptor-positive patients were less likely to conceive post-treatment compared to their hormone receptor-negative counterparts. This could be attributed, first, to concerns shared by patients and physicians that increased estrogen levels during pregnancy may have negative effects on the prognosis of hormone receptor-positive BC (17). However, previous studies have shown that pregnancy and breastfeeding do not have a negative impact on the prognosis of hormone receptor-positive BC (18). Second, the fear of discontinuing treatment owing to pregnancy as a contraindication during hormone therapy could lead to the decision to forego pregnancy (19). Our analysis revealed that more than half of the patients received fertility preservation counseling prior to treatment, indicating their desire for future pregnancies. However, among patients receiving ET, only 7.6% discontinued treatment because of pregnancy. This suggests a tendency among younger patients to give up having a baby and opt for treatment continuation. In the POSITIVE trial, women with hormone receptor-positive early BC who temporarily stopped ET because of pregnancy had an 8.9% incidence of BC events (including distant recurrence) over 3 years, which did not show an increased risk compared to the external control group (11). Similarly, in the retrospective analysis of this study, the cumulative incidence of BC events over 10 years was 10.1%. These findings, from both the POSITIVE trial and our study, may provide reassuring evidence for patients who consider discontinuing ET to pursue pregnancy. Additionally, the results of this study revealed that the majority of pregnant patients discontinued their ET after 1–3 years ( Supplementary Table 2 ). Previously, there was no consensus on the duration of ET maintenance before attempting pregnancy. However, it is considered safe to interrupt ET after maintaining it for a minimum of one and a half years, based on the findings of the POSITIVE trial (11). Among participants in the POSITIVE trial who discontinued ET to pursue pregnancy, 74% achieved at least one successful conception, with the highest success rates documented in patients who underwent embryo/oocyte cryopreservation before initiating treatment (12). Therefore, comprehensive fertility and pregnancy counseling should be integrated into the initial BC management plan at the time of diagnosis.

In the results of this study, chemotherapy did not show a significant impact on pregnancy rates. This finding differs from the conventional belief that chemotherapy compromises ovarian function (20–22). GnRHa can be used concurrently with chemotherapy for ovarian protection (23). In our study, GnRHa was used for fertility preservation in 447 out of 679 patients (65.8%). The PROMISE-GIM6 study conducted by Lambertini et al. demonstrated a higher frequency of menstrual resumption in the GnRHa group (24), and the 2015 POEMS study by Moore et al. reported that GnRHa use, compared to chemotherapy alone, prevented ovarian failure, reduced premature ovarian failure, and showed higher pregnancy rates (25). However, as the primary outcome in most clinical trials using GnRHa was menstrual resumption rather than fertility, evidence verification is needed regarding its use for the purpose of fertility preservation.

Oocyte or embryo cryopreservation represents an established method of fertility preservation that can be implemented during chemotherapy treatment (26–28). In a recent international multicenter study (29) conducted on young patients with BC who are BRCA carriers, 659 out of 4,732 BRCA carriers had at least one pregnancy; among these, 8.2% became pregnant using previously cryopreserved oocytes or embryos after BC treatment. In contrast, our study found this rate to be slightly lower at 7%. The lower rate of fertility preservation procedures in this study, compared to that of international BRCA carriers who are at a higher risk for hereditary BC, may indicate that adequate counseling on the effectiveness and side effects of oocyte and embryo cryopreservation is not being provided. Moreover, a secondary analysis of the recently published POSITIVE trial demonstrated that embryo/oocyte cryopreservation followed by embryo transfer is a safe and effective method for achieving pregnancy after BC treatment (12). Furthermore, in contrast to the United States and European countries, South Korea imposes legal restrictions on pre-implantation or prenatal genetic testing (excluding BRCA mutations) (30–32), which may induce hesitancy in women diagnosed with cancer concerning their pregnancy and fertility preservation options. Therefore, the establishment of a comprehensive fertility preservation system that facilitates the dissemination of accurate information and supports informed decision-making is essential.

Fertility preservation counseling is also necessary to improve medication adherence for appropriate breast cancer treatment. Despite the beneficial impact on survival associated with tamoxifen use, a recent study revealed that 13.4% of women choose not to start taking tamoxifen, and an additional 15.5% discontinue its use before completing the recommended duration of 5 years (33). In this study, fertility emerged as a significant factor influencing early discontinuation of tamoxifen among young patients with BC. Alongside side effects, it is considered one of the most crucial causes for not initiating or discontinuing ET. According to another research finding, individuals who used tamoxifen did not exhibit a decrease in ovarian reserve compared to those who did not use tamoxifen (34). Therefore, providing education on these pieces of evidence to patients in the reproductive age group is necessary.

According to several survey studies conducted among healthcare providers treating breast cancer, there are significant barriers to implementing fertility preservation. These barriers include lack of knowledge (35) and insufficient system resources, such as time and human resources (36, 37). Consequently, there is a growing need for comprehensive multidisciplinary counseling programs that address both fertility preservation and BC treatment (38). Various research initiatives are currently underway to address these challenges. The PREFER study in Italy is collecting prospective data, including outcomes from patients who have successfully conceived, to improve oncofertility counseling (39). The MYBC trial in Korea is working to establish evidence for an effective multidisciplinary shared decision-making program for fertility preservation (40). The results from these trials, combined with real-world data, are expected to contribute to improving both treatment approaches and fertility preservation options for young patients with BC.

This study has some limitations. First, as a retrospective single-center study, it inherently carries the limitations associated with this study design, including potential selection bias and the inability to control for all confounding variables. Because randomized trials on pregnancy-related topics may raise ethical concerns, we are currently collecting prospective pregnancy data through an ongoing trial focusing on multidisciplinary decision-making in young breast cancer patients (40), and we plan to conduct future research based on these data. Second, decisions and outcomes related to pregnancy are significantly influenced by national policies, cultural factors, and societal norms, which may limit the generalizability of our findings to other populations and healthcare settings. Despite these limitations, our study has a notable strength. It represents one of the largest long-term follow-up studies conducted in a conservative Asian setting, providing valuable insights into pregnancy outcomes and fertility preservation in patients with BC within this cultural context. This unique perspective contributes significantly to the existing body of literature on fertility and pregnancy after BC treatment.

In conclusion, our study highlights that effective fertility preservation counseling is necessary for all patients with BC of reproductive age, regardless of age, marital status, or whether they had children before BC diagnosis. It provides real-world data that can be referenced to appropriately address and manage the impact of chemotherapy and ET on pregnancy after BC treatment. These findings can be valuable knowledge for clinical decision-making and counseling.