Chemotherapy-induced premature ovarian failure and its prevention in premenopausal breast cancer patients

Abstract

Breast cancer accounts for more than one quarter of all malignant tumors diagnosed in women of reproductive age: every year, more than 25,000 new cases of invasive breast carcinoma are diagnosed in patients under the age of 45 years in the United States [1]. This is a relatively small proportion (approximately 11%) of all new cases of breast tumors; however, breast cancer in young women represents a public health problem due to both medical and psychosocial challenges unique to or accentuated by their age [2]. Due to the fact that young women with breast cancer have an increased risk of presenting with biologically aggressive types of tumors, the majority are candidates to receive antineoplastic treatments that include the use of chemotherapy [3]. A possible side effect of chemotherapy in premenopausal patients is the occurrence of premature ovarian failure (POF), resulting in temporary or permanent amenorrhea. Even in the presence or resumed regular menses after chemotherapy, patients are still at risk of developing early menopause due to the damage of cytotoxic therapy to their ovarian reserve [4]. The effects of chemotherapy on ovarian function are variable and are strongly affected by patients’ age at the time of treatment, type, and dose of chemotherapy [4]. The most common chemotherapy regimens used in the adjuvant or neoadjuvant treatment of breast cancer are associated with an intermediate risk of developing POF (40–60%) in patients aged 30–39 years; however, the same regimens are associated with a high risk of developing POF (more than 80%) in women older than 40 and a low risk (less than 20%) in those under the age of 30 [4]. The development of chemotherapy-induced POF is associated with improved survival outcomes in premenopausal breast cancer patients [5]. However, the loss of ovarian function negatively impacts on global health of young breast cancer survivors being associated with several side effects, such as hot flashes, sweats, breast pain or sensitivity, vaginal dryness, vaginal discharge, lack of sexual desire, and weight gain [6]. Moreover, strongly associated with the loss of ovarian function is the risk of infertility: fertility issues represent a major concern for young breast cancer patients and can also influence their treatment decisions [7]. Recent data from the Suppression of Ovarian Function Trial (SOFT) study demonstrated excellent survival outcomes in premenopausal breast cancer patients who resumed their ovarian function after chemotherapy and were treated with ovarian suppression for 5 years as part of adjuvant endocrine therapy [8]. Moreover, it has been recently shown that having a pregnancy after prior breast cancer diagnosis and treatment should be considered safe, also in patients with endocrine sensitive disease [9]. These findings highlight the importance of maintaining ovarian function and fertility of young breast cancer patients who are candidates to receive chemotherapy during their reproductive age. Embryo and oocyte cryopreservation are considered standard procedure for fertility preservation, but no proven methods for preservation of ovarian function are yet available [10,11]. According to the American Society of Clinical Oncology and European Society for Medical Oncology guidelines, the two available strategies with the potential to preserve gonadal function of breast cancer patients undergoing chemotherapy, i.e. ovarian tissue cryopreservation and pharmacological protection of the ovaries with the use of gonadotropin releasing hormone analogues (GnRHa) during cytotoxic therapy, are still considered experimental techniques [10,11]. Unlike cryopreservation of embryos or oocytes, ovarian tissue cryopreservation can save not only fertility but also hormonal gonadal function. Moreover, ovarian tissue cryopreservation has other potential advantages: it can be performed at any time during the menstrual cycle and no hormonal stimulation is required, thus no delay EXPERT REVIEW OF QUALITY OF LIFE IN CANCER CARE, 2016 VOL. 1, NO. 1, 5–7 http://dx.doi.org/10.1080/23809000.2016.1139458