Is Fertility Preservation Feasible and Safe With Neoadjuvant Therapy for Breast Cancer?

Abstract

Many women of reproductive age who are newly diagnosed with cancer have not yet started their families, whereas others have not completed their families.1 Previously, the majority of these women would remain childless.2 Although spontaneous pregnancy is sometimes possible after treatment, fertility potential in the majority of these women will decline as a result of the gonadotoxic nature of some of the most effective chemotherapeutic agents, first and foremost alkylating agents.3 The immediate, long-term effect is, almost uniformly, diminished ovarian reserve, and in many cases, premature ovarian insufficiency (characterized by amenorrhea or oligomenorrhea in combination with low estradiol levels and high gonadotropin levels).3-7 With recent advances in assisted reproductive technology (ART), women newly diagnosed with cancer increasingly are pursuing fertility preservation (FP) before chemotherapy or radiation. These patients pursue controlled ovarian stimulation with gonadotropins to produce mature oocytes, which are surgically removed. Subsequently, oocytes can be frozen (through vitrification) if the patient does not have a partner. Alternatively, oocytes may be fertilized with a partner’s sperm and the resulting embryos (usually day 5 or day 6 blastocysts) vitrified. These frozen oocytes or embryos can be thawed and used to affect a pregnancy in cancer survivors after clearance by their oncologists to conceive. Breast cancer is the most common diagnosis among women referred to oncofertility programs8,9 for two reasons. First, breast cancer is the most common cancer in reproductive-age women,10 and second, the gold standard treatment has been surgery followed by chemotherapy, which provides oncofertility specialists a window of opportunity (approximately 6 weeks) between surgery and adjuvant therapy. This interval allows ample time for preparation of the patient, including the scheduling of ovarian stimulation according to the patient’s cycle and, in some instances, even in managing to complete two FP cycles.11,12 Neoadjuvant therapy (NAT) flips the order of treatment, where the oncologist recommends chemotherapy before surgery. Breast cancer treatment is one example of a growing shift from surgery first to NAT.13,14 The National Comprehensive Cancer Network has outlined clinical scenarios in which NAT is the preferred approach.15 Previous studies indicated that NAT candidates referred for FP are more reluctant to undergo FP, and many of them will have a consultation with a fertility specialist but never return.9 Among reasons that have influenced patients’ decisions not to pursue FP are concerns with the cost of the procedure (medications usually are donated) and the fear that FP will delay their cancer treatment. For women diagnosed with breast cancer where NAT is preferred, under what circumstances is a referral for FP appropriate and indicated? Does NAT obligate a shift in priorities? How can we manage to allow as many women as possible to undergo FP without compromising cancer care? We address the medical as well as the emotional aspects of these dilemmas. Although these issues are considered in the context of breast cancer, the most common type of cancer presenting to oncofertility centers, NAT treatment increasingly is used across a wide spectrum of cancer types. As a result, the discussion is relevant to any reproductive-age female diagnosed with cancer when the treatment plan includes NAT.