Exclusion of pregnant and lactating persons from breast cancer clinical trials: a review of active trials registered on ClinicalTrials.gov

Abstract

IntroductionTreatment of pregnancy‐associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons.Material and methodsWe conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people.ResultsThe search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%).ConclusionsThe exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research‐related risks.

The challenges of cancer during pregnancy

“…Therefore systematic reviews and meta-analysis are also needed, which is well illustrated in the studies by Marasciulo et al, 9 and Zhang et al, 10 in this special issue. Importantly, as noted in the study reported by Metcalfe et al, 11 the systematic exclusion of pregnant and lactating patients from clinical trials has largely contributed to maintainance of evidence gaps on how best to treat these patients. The reason for excluding pregnant and lactating patients from studies appears to be the fear of research-related risks, which is currently a significant barrier to finding the best treatment approach to protect these patients from further complications.…”

Breast cancer during pregnancy—The oncologist's point of view

“…Interestingly, almost one‐fourth of behavioral studies excluded patients with PrBC. 9 This systematic exclusion creates an unfortunate knowledge gap on the treatment approach to PrBC and pertinent issues such as timing of chemotherapy, effect of pregnancy on pharmacokinetics, harmful effects of radiation therapy delivered with modern methods, and use of certain cytotoxic drugs and novel targeted agents are still largely unclear. Therefore, instead of evidence‐based guidelines, management of PrBC is guided by expert consensus statements such as one recently published by the European Society for Medical Oncology.…”

Risk of Death Due to Pregnancy-Associated Cancers—More Questions Than Answers—Reply

“…The increased risk of mortality for cancers diagnosed during pregnancy and postpartum observed in our study and others is an area of concern that could relate to underlying differences in biology, delays in diagnosis, and delays in treatment. As pregnant and lactating people with cancer are rarely included in randomized clinical trials, optimal treatment strategies for this complex group of patients are unclear.…”