Abstract
BackgroundBreast cancer is the most common cancer in young women. Fortunately current survival rates of BC are significant which makes future fertility very important for quality of life of BC survivors. Chemotherapy carries a significant risk of infertility in BC patients so it is important to support fertility preservation decisions in premenopausal women. Amenorrhea has long been used as a surrogate marker of infertility in cancer patients but more reliable ovarian reserve (OR) markers are available. This study aimed to prospectively measure levels of OR in a cohort of young women with breast cancer exposed to chemotherapy, to identify adverse reproductive health outcomes in this population and to assess the influence of patient and treatment-related factors in those outcomes.MethodsThis prospective observational study included premenopausal women with breast cancer aged 18–40 years at diagnosis and proposed for (neo) adjuvant chemotherapy. Patients were evaluated before, during and a minimum of 9 months after the end of chemotherapy. Reproductive health outcomes: menses, hormonal and ultrasound OR markers, recovery of ovarian function and Premature Ovarian Insufficiency (POI).ResultsA total of 38 patients were included (mean age 32.9 ± 3.5 years). Levels of OR significantly decreased during the study. At the last follow up, 35 patients had AMH below the expected values for age; eight presented postmenopausal FSH; ten had not recovered their ovarian function and five met the defined criteria for POI. Age and baseline AMH were positively correlated with AMH at the last follow-up. AMH levels were higher in the group of patients treated with trastuzumab and lower in those under hormonal therapy, at the last follow-up.ConclusionsSignificant effects of systemic treatments on several reproductive outcomes and a strong relation of those outcomes with patient’s age and baseline level of AMH were observed. Our results point to a possible lower gonadotoxicity when treatment includes targeted therapy with trastuzumab. Also, this investigation highlights the lack of reliable OR markers in women under hormonal therapy.
Highlights
Breast cancer is the most common cancer in young women
AntiMullerian Hormone (AMH) was significantly higher in the group treated with CT + targeted therapy (TT) (n = 3) as compared to the groups exposed to CT only (n = 7) (U = 2; p = 0.046) and to CT + hormonal therapy (HT) (n = 16) (U = 0; p = 0.002). In accordance with these results, we found that AMH levels at the last follow-up were higher in all patients treated with trastuzumab (n = 12) as compared to those not exposed (U = 84.5; p = 0.036)
A considerable number of patients in our study were not evaluated for recovery or Premature Ovarian Insufficiency (POI) due to exposure to HT, so it is likely that the incidence of these adverse outcomes would increase with a longer follow-up
Summary
Breast cancer is the most common cancer in young women. Current survival rates of BC are significant which makes future fertility very important for quality of life of BC survivors. Chemotherapy carries a significant risk of infertility in BC patients so it is important to support fertility preservation decisions in premenopausal women. This study aimed to prospectively measure levels of OR in a cohort of young women with breast cancer exposed to chemotherapy, to identify adverse reproductive health outcomes in this population and to assess the influence of patient and treatment-related factors in those outcomes. Breast cancer (BC) is the most frequent cancer among women, with an estimated 1.67 million new diagnoses in 2012 [1]. Young BC women are often treated with chemotherapy (CT) regimens that include cyclophosphamide, anthracyclines and a taxane. As for TT agents, data is limited some clinical studies do not indicate ovarian toxicity [7, 8] and HT extends treatments for up to 10 years, further narrowing the reproductive window of BC patients
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