An increasing focus in oncology care is on survivorship and quality-of-life issues that arise once patients are living beyond treatment. For female breast cancer patients, important survivorship issues include sexual and reproductive health.

Breast cancer is the most common cancer in women, with 232,676 new cases expected in 2014; approximately 7% of these cases are diagnosed in women of reproductive age (<40 years).

 Despite the growing incidence of breast cancer, mortality has declined due to increased awareness, improved screening, and better treatment. However, the increase in the number of women who delay childbirth beyond age 35, as well as the increased use of cytotoxic adjuvant chemotherapy, have resulted in significant rates of infertility.

Fertility can be impaired in breast cancer patients for the following reasons: age at diagnosis, gonadotoxic chemotherapy, duration of endocrine treatment, or a combination of factors. As a woman ages, the number of oocytes diminishes over time. By the age of 37 years, only 10,000 out of 300,000 oocytes remain and by 40 years, fertility is halved and the chance of a spontaneous abortion is tripled.

 Therefore, age >35 at diagnosis is an obstacle to optimal fertility and should be discussed as a first step of counseling.

Beyond surgical management, axillary dissection, and radiotherapy, level I evidence has demonstrated that adjuvant use of chemotherapy and endocrine therapy has been shown to increase relapse-free and overall survival in young early-stage breast cancer patients.

 Many of these adjuvant therapies are both cytotoxic and gonadotoxic, significantly affecting fertility. The most common adjuvant chemotherapy regimens use an anthracycline-based combination therapy with an alkylating agent (ie, cyclophosphamide, cisplatin, and carboplatin). Gonadal toxicity occurs by two mechanisms: the direct induction of follicle and oocyte apoptosis and the vascular damage to the ovary. Both mechanisms are more pronounced in patients receiving alkylating agents.

The fertility effects of endocrine therapy are less clear. The use of tamoxifen sequentially with adjuvant chemotherapy has been shown to increase the risk for infertility. When used alone, it is associated with a low risk of premature menopause.

 The effects of tamoxifen is dependent on the length of treatment; the longer the treatment duration, the more reduced reproductive chances for a woman diagnosed after 35 years of age.

There is sufficient evidence to show that any breast cancer treatment option will have an inevitable effect on a woman’s fertility. Given the number of young women newly diagnosed with breast cancer and the rapid decline in fertility with age, provider discussions should be initiated as early as possible at diagnosis. Multiple studies have shown that early fertility counseling was associated with decreased psychosocial distress, less regret, and greater quality of life for survivors.

 Research on treatment-related infertility as well as qualitative studies on patient concerns and preferences, demonstrate a need for practice standards regarding fertility care of breast cancer patients.

In 2006, the American Society of Clinical Oncology (ASCO) issued recommendations on fertility preservation in cancer patients. The main purpose of the 2006 recommendations was to establish a standard of practice regarding counseling and fertility preservation methods.

 The following questions were addressed: What is the quality of evidence supporting current and forthcoming options for preservation of fertility in females? Are cancer patients interested in interventions to preserve fertility? What is the role of the oncologist in advising patients about fertility preservation options? In its 2013 guideline update, ASCO replaced “oncologist” with “healthcare provider,” emphasizing the interdisciplinary nature of fertility care and expanding its scope.

Current fertility preservation options for female breast cancer patients include embryo and oocyte cryopreservation.8 Other treatments, such as ovarian suppression with gonadotropin-releasing hormone (GnRH) agonists, are in development, but have insufficient evidence regarding effectiveness and safety. Options depend on age, diagnosis, treatment type, presence or participation of a male partner and/or patient preferences regarding use of banked donor sperm, time available, and likelihood that the cancer has metastasized to her ovaries.

It is unsurprising that the literature review revealed that fertility is of great importance to patients. Patients may fail to mention their concerns due to feeling overwhelmed, being more focused on the cancer diagnosis itself, being unaware of treatment effects on fertility, or fearing that pursuing fertility care would delay the actual cancer treatment. Key recommendations include discussing fertility preservation with all patients of reproductive age if infertility is a potential risk of therapy. Furthermore, all healthcare providers are responsible for fully informing patients about the risks that their cancer treatment may impair their fertility.

Oncology advanced practice providers (APPs) are in a key position to communicate with and educate young breast cancer patients regarding fertility issues at diagnosis. Discussions should start as early as possible in order to preserve the full range of options, reduce distress, and improve quality of life. With the growing incidence of both breast cancer and survivorship of breast cancer, fertility remains important for young women and should be an essential focus of their healthcare.

		American Cancer Society. What are the key statistics about breast cancer? http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics. Accessed November 13, 2014.

		Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy. Oncologist. 2006;11(5):422-434.

		Peccatori FA, Pup LD, Salvagno F, et al. Fertility preservation methods in breast cancer. Breast Care. 2012;7(3):197-202.

		Hickey M, Peate M, Saunders CM, Friedlander M. Breast cancer in young women and its impact on reproductive function. Hum Reprod Update. 2009;15(3), 323-339.

		Lambertini M, Anserini P, Levaggi A, et al. Fertility counseling of young breast cancer patients. J Thorac Dis. 2013;5(suppl 1:S68-S80).

		Klemp JR, Kim SS. Fertility preservation in young women with breast cancer. J Assist Reprod Genet. 2012;29(6):469-472.

		Lee SJ, Schover LR, Partridge AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917-2931.

		Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. http://www.asco.org/quality-guidelines/fertility-preservation-patients-cancer-american-society-clinical-oncology. Accessed November 13, 2014.

Victoria Sherry, MSN, CRNP-BC, AOCNP

Articles

Fertility Preservation in Breast Cancer Survivors