Addressing Fertility Issues in Younger Women with Breast Cancer

Infertility and early menopause associated with cancer therapy can present medical and emotional challenges for patients and clinicians, according to Ann H. Partridge, MD, MPH, Medical Oncologist, Dana-Farber Cancer Institute, Boston. Dr Partridge presented results of a survey at the 2015 Breast Cancer Symposium, suggesting that cancer survivors who become infertile as a result of cancer treatment are at risk for emotional distress, often associated with unresolved grief and depression.

“Like in many aspects of breast cancer care, patient preference is critical,” said Dr Partridge. “For us as clinicians, managing expectations is often necessary. We need to address fertility issues upfront and include fertility concerns in the risk-benefit analysis. We need to address side effects, both physical and emotional, of premature menopause in both long- and short-term follow-up, and ultimately, we need to continue to support our patients and support research in this area.”

Dr Partridge and colleagues conducted an online survey of 657 women who were, on average, 2 years from a breast cancer diagnosis (median age at diagnosis, 33 years). Overall, 57% of the women recalled substantial concerns about fertility after treatment, and 29% reported that fertility concerns had influenced their treatment decisions.

“This was a wake-up call for a lot of clinicians,” said Dr Partridge. “Patients may not be taking their tamoxifen, or may be passing on adjuvant therapy due to fertility concerns.”

These concerns are increasing because of the rising average age of first births around the world. In 1970 in the United States, the average age of first birth was 21 years; today it is 25 years, and in some countries, it is more than 29 years.

“More women are waiting to have children,” said Dr Partridge, “and breast cancer incidence increases, even in this young cohort. We treat our patients with good intentions, but this can threaten their future fertility.”

As Dr Partridge explained, the risk for amenorrhea, which is the best surrogate clinicians have in oncology practice for infertility, is directly related to age and treatment. However, studies assessing how long women remain amenorrheic after chemotherapy are limited.

Even in women who continue to have menses after chemotherapy, fertility may still be impaired, said Dr Partridge. In an earlier study of women who did not become menopausal after chemotherapy, survivors had worse ovarian reserve compared with a control group of women.

The American Society of Clinical Oncology’s recommendations for preservation of fertility include:

  • Oocyte/embryo cryopreservation
  • Cryopreservation of ovarian tissue
  • Ovarian suppression with luteinizing hormone-releasing hormone agonist through treatment
  • Oocyte donation or gestational surrogacy.
“The most important thing is to communicate with our patients about this,” Dr Partridge emphasized. “It’s important to allow the woman be a part of these decisions, and ultimately make the choice.” She suggested that these treatment decisions represent a complex balance of risk and benefit that must be individualized for every patient.

A recent study showed that for young women with breast cancer, ovarian suppression is correlated with disease-free survival.

“There may be risks to remaining premenopausal,” said Dr Partridge. “We really need to individualize treatment to the patient who actually wants a baby.”

Finally, it is also necessary to consider the risk associated with pregnancy itself. The conventional wisdom, Dr Partridge noted, has been to wait until the highest risk for disease recurrence is over (the first 2-3 years after diagnosis), but in patients with estrogen receptor–positive disease, that risk can last for nearly 1 decade.

The phase 2 clinical trial, the POSITIVE trials, is currently recruiting patients to evaluate the safety and pregnancy outcomes of interrupting endocrine therapy in young women with estrogen receptor–positive breast cancer who desire to get pregnant. “We’re going to answer this question, at least in a phase 2 way,” Dr Partridge concluded.

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