Baby steps: Pregnancy outcomes after human epidermal growth factor receptor 2–targeted therapy

INTRODUCTION In the United States, approximately one-fifth of breast cancers are diagnosed among women aged ≤50 years, totaling nearly 50,000 new cases of invasive breast cancer per year. The percentage of incident cases among young women in Latin America, India, or sub-Saharan Africa is even greater, although whether this is due to differences in screening behavior, genetics, or lifestyle factors remains unclear. Breast cancer outcomes have been enhanced during the past decade due to improvements in early detection and treatment, with the largest decrease in breast cancer death rates noted among women aged 20 to 49 years. However, this improved survival presents us with unique considerations. One such consideration is the impact of breast cancer therapy on ovarian function. For young patients with breast cancer, ovarian failure is a major long-term side effect of adjuvant treatment. Premature menopause as a result of ovarian failure, removal, or suppression is associated with attendant symptoms (eg, hot flashes, sweats, vaginal dryness, decreased libido, etc) that negatively impact health-related quality of life. Premature menopause also increases long-term health risks (eg, bone health). In fact, in young women without breast cancer, premature ovarian failure/removal is reported to increase mortality, although any such impact in patients with breast cancer would be difficult to discern given both the competing effects of cancer on mortality as well as the impact of ovarian suppression on reducing the rate of recurrence of hormone receptor–positive (HR+) breast cancer and decreasing new breast cancer events. Younger patients also may desire to preserve fertility for childbearing. Because patients may be focused on prognosis at the time of the cancer diagnosis, clinicians must remain alert to the long-term consequences of treatment as breast cancer outcomes continue to improve. This is especially true when considering fertility, which must be acted on early to mitigate such consequences, and pregnancy, which necessitates careful individualized counseling. However, this counselling is limited by what to our knowledge is a relative lack of data regarding both outcomes either during or after breast cancer treatment. Discussions with patients may be particularly hampered for “newer” agents such as trastuzumab and pertuzumab as well as for older agents such as platinums and capecitabine, which currently are receiving increased use in the (neo) adjuvant setting and for which less information regarding the impact on fertility or pregnancy may be available. This issue of Cancer presents a report by Lambertini et al regarding prospectively collected pregnancy information among patients with human epidermal growth factor receptor 2 (HER2)–positive early breast cancer who were enrolled on the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization (NeoALTTO) and Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) randomized phase 3 trials. The authors compared pregnancy outcomes between patients who were unintentionally exposed to trastuzumab and/or lapatinib during gestation (exposed group) and those who became pregnant after the completion of trastuzumab and/or lapatinib treatment (unexposed group), as well as outcomes between those who became pregnant (pregnant cohort) and those who did not (not pregnant cohort) among women aged ≤40 years.