Study Reinforces Safety of Taxane-Based Chemotherapies for Pregnant Patients With Breast Cancer

In an interview at the 2023 San Antonio Breast Cancer Symposium, Ana Ferrigno Guajardo, MD, discussed research into the safety and efficacy of taxane-based chemotherapy use in pregnant patients with breast cancer.

Q: Can you elaborate on the results of the international cohort study of patients with breast cancer treated with taxane chemotherapy during pregnancy?

A: Sure. Breast cancer is one of the most common malignancies during pregnancy. Treatment of breast cancer during pregnancy is particularly challenging because we have limited options in the types of therapies that we can use, since targeted therapies are not really an option because of potential detrimental effects on the developing fetus. So, when we think about treating patients with breast cancer during pregnancy, we have to think about the potential antineoplastic benefits of the therapies that we're offering versus potential detrimental consequences on the developing fetus. Currently, anthracycline-based chemotherapy regimens are the backbone of chemotherapy that we can offer after the first trimester of pregnancy. We know that in select cases, the addition of taxanes may offer improved oncologic outcomes. But so far, there is a tendency to defer their use to the postpartum period because there are insufficient data regarding their safety in this context. That's why we decided to do an international cohort that evaluated the prevalence of maternal and neonatal adverse events after the use of taxanes during gestation.

We were able to recruit information from 103 patients treated with taxanes during pregnancy, and we found a small incidence of severe adverse events in this population, that is in general similar to what we observe in patients treated with non-taxane-containing chemotherapy agents. The most common obstetric complications were intrauterine growth restriction [and] preterm premature rupture of membranes, and both of these complications we found to be at a similar rate to what we would expect in the general population. We did find a higher incidence of preterm birth compared to what we would expect in the healthy population, but this is similar to what has been observed in previous breast cancer cohorts of patients treated during pregnancy.

In terms of neonatal outcomes, the most common reported adverse event was being small for gestational age, with 23% of the births being classified as small for gestational age. But this is, again, similar to what has been described in cohorts of breast cancer patients during pregnancy, even in patients that do not receive chemotherapy during pregnancy. Overall, we find our results to be reassuring in the sense that the addition of taxanes during pregnancy does not seem to increase the rate of adverse events. And we think that our findings can be rather reassuring to clinicians, and they can use these types of therapies [that are] clinically indicated.

Q: What were the inclusion criteria for selecting participants in this study, and how did you ensure a diverse representation from the participating centers?

A: We had very lax inclusion criteria because our goal was to include the most patients possible and ensure that our sample was representative of the general population that were treated with breast cancer during pregnancy. We were able to recruit patients from 10 referral cancer centers, from 6 different countries. And in that way, we ensured that we have ethnic variation in our sample. We still believe that there might be some mild selection bias in our cohort because we know that taxanes are usually given in a sequential manner to anthracycline and cyclophosphamide. So potentially, we could have included a population that has been diagnosed with breast cancer early in the pregnancy rather than later. And there are continents that were not included in other samples, such as Africa and Asia. But overall, we were able to recruit patients from the US, from Latin America, and from European referral centers, and we think that that reflects the population that were treated with breast cancer during pregnancy.

Q: Were there any factors identified that influenced live birth outcomes in patients exposed to taxane-containing regimens during pregnancy?

A: When we designed the study, we decided to evaluate complications that were found to have a prevalence of over 15% of our cohort and run logistic regression analysis to try to identify variables associated with them. There were only 2 complications that met this prespecified threshold. One of them was being small for gestational age—which as I said, we found in 23% of our of our cohort—and the other was neonatal ICU admissions that we found to be 16%. The variables that we studied to see if they were associated included maternal age at breast cancer diagnosis, weeks of gestation at chemotherapy initiation, country of treatment, year of treatment, and gestational age at delivery, as well as the cumulative dose of taxane received. We found that none of these variables were associated with small for gestational age neonates, which is rather reassuring that higher taxane chemotherapy did not yield a higher rate of small for gestational neonates, which suggests that taxane might not be the main etiology involved. And in terms of neonatal ICU admissions, the only variable that we found to be significantly associated was being treated in the USA. And we think that most of these submissions, based on what we've seen in previous studies that have actually documented the reason for neonatal ICU admission, were prophylactic admissions because of them being preterm and being exposed to toxic therapies during pregnancy. Overall, over 97% of our neonates had an Apgar score over 7 and no neonatal deaths were reported, so we don't think that there was a higher incidence of life-threatening events in this period.

Q: In the context of the reported outcomes, are there any specific recommendations or considerations for health care providers when managing breast cancer in pregnant patients?

A: So, we have new guidelines that just came out this year from the ECMO group and we have robust information saying what therapies pregnant patients are eligible to receive during pregnancy versus those that probably should be deferred to the postpartum period. So, for example, targeted therapies are not an option during pregnancy. We know that chemotherapy use in the first trimester leads to a higher rate of adverse events and should be reserved only for the second and third trimesters. I think that what our study adds to the current literature that we have is that taxanes are safe and effective therapy to use to improve the outcomes of these patients.

Another trend that we observed in our study is that even though our rate of preterm deliveries is still high at 43%, we saw a clear trend towards decreasing number of preterm births as time advances. So, before 2010, 69% of births were preterm, compared to only 23% after 2020 in our cohort. So, this is rather reassuring that clinicians are reading the guidelines and are incorporating them into their clinical practice. We know that preterm birth is one of the most important causes of mortality and morbidity in children below 5 years of age, and we see that that new focus of the guidelines on avoiding preterm births when possible has drastically changed clinical practice, and we have now a lower rate of preterm births. We think that by incorporating new information and clarifying which therapies are used, [which] are safe to use during pregnancy, can change clinical practice in the future and we hope that clinicians can now use taxanes during pregnancy with increased confidence.