Hearing the words “You have cancer” for the first time can feel like your future has been upgraded into a hurricane-induced dust storm. Having breast cancer, in particular, comes with additional chaos and uncertainty, because it threatens so many things concerning your womanhood. You not only face losing your breasts, your hair, your lashes and brows, but also your ability to have children. Medical treatments for breast cancer can also send you into medically induced early menopause.
Breasts can be reconstructed and hair grows back, but the lasting effects on the female hormonal system can be particularly devastating − especially if you’re of childbearing age. Fortunately, it’s not all doom and gloom and many women go on to start or expand their families.
So far, scientific data and medical opinion point to the safety of pregnancy after breast cancer, but will interrupting a woman’s endocrine therapy (treatment that adds, blocks or removes hormones) to prepare for pregnancy increase her recurrence risk?
An International Breast Cancer Study Group (IBCSG) trial, known as the POSITIVE trial, is setting out to find the answers. The study, which is already in full swing, intends to evaluate the pregnancy outcomes and safety of interrupting endocrine therapy for hormone receptor-positive early stage breast cancer among 500 women.
Why would you choose to interrupt endocrine therapy instead of waiting until treatment is finished? For early stage hormone receptor-positive breast cancer, endocrine therapies are traditionally prescribed for five years (with 10 years recommended in some cases). If you’re diagnosed in your 20s, for example, you have more time, but if you’re diagnosed in your late 30s or early 40s, you might be advised to pause treatment in order to become pregnant before your age causes fertility issues. The longer a woman undergoes hormone therapies, the greater the risk of additional fertility damage.
According to Dr Carol Benn from the Breast Care Centre at Milpark hospital in Johannesburg, “There is no evidence for an increased risk of disease recurrence associated with most fertility preservation methods and pregnancy,” but data is still relatively sparse. “Conventional wisdom says to wait until the patient gets through the period of highest risk recurrence.” For most patients, this is considered the first two years after starting endocrine therapy.
According to Dr Benn, all the main breast cancer therapies, especially chemotherapy, do affect fertility. Side effects include damage or destruction of your eggs, going into early menopause and a compromised ability to carry your baby to term.
She explains that with chemotherapy, the ovaries become sensitised to the drugs. In normal premenopausal ovaries, there is a low recruitment of primordial egg-containing follicles, but when they are exposed to chemotherapy, there is a decrease in ovarian hormones (estradiol and FSH) resulting in an increase in follicular recruitment and more eggs being at risk of damage. In other words, your ovarian reserves will be significantly depleted by the time chemotherapy is completed, leaving you with fewer viable eggs.
For this reason, chemotherapy often results in early menopause, which can mean infertility. But not all women experience menopause after chemotherapy. In one study of 286 pre-menopausal Chinese women who underwent chemotherapy for breast cancer, published in 2016 in PLOS One, most women lost their periods after chemotherapy, but only 50% developed chemotherapy-related menopause.
According to Dr Benn, additional therapies for breast cancer, which involve follow-up treatments of tamoxifen or ovarian suppression to enhance the effect of chemotherapy or radiation, do not appear to cause permanent amenorrhea (loss of period) or infertility. However, endocrine therapy usually entails years of treatment with pregnancy contraindicated. Ageing over the period of treatment will compromise the woman’s fertility even if the treatment does not.
Depending on the nature of the diagnosis, some women are sent straight to the chemotherapy room without much time to consider fertility options. Others, like those who are not prescribed chemotherapy or are having surgery (such as a lumpectomy or mastectomy) before starting other treatments, have a grace period in which to consider their options. Fertility preservation options are generally discussed by the oncologist and a fertility specialist and weighed in terms of the risks, which include fuelling cancer growth by stimulating the ovaries for egg harvesting.
According to a review of fertility preservation options in breast cancer patients, published in Gynecological Endocrinology in 2015, current fertility preservation options range from well-established techniques to more experimental interventions. Most commonly, ovarian stimulation before chemotherapy is initiated, taking into account the hormone status of the particular cancer. Cryopreservation of either oocytes (eggs) or embryos are the most successful fertility preservation methods. You can choose to freeze just your eggs, which is often the case if you’re single, or to fuse the egg with sperm to form an embryo. However, not all oncologists will allow ovarian stimulation before chemotherapy − especially in fast-growing cancers. In these cases, fertility options will be considered depending on the nature of the tumour.
According to the study, another more experimental method is administering a GnRH (human gonadotropin-releasing hormone) agonist during chemotherapy, which helps minimise damage to the eggs by suppressing the ovaries. A 2018 analysis of multiple studies and looking at 873 patients, published in the Journal of Clinical Oncology, looked at the use of ovarian suppression during chemotherapy and found GnRH was both safe and efficient in preventing ovarian damage during chemotherapy and may potentially improve future fertility in pre-menopausal patients with early breast cancer.
Another experimental method, developed in Israel, takes slices of the pre-menopausal ovary and preserves them for later use. The ovarian tissue is then reconnected to the ovary when the woman is ready to try and conceive. The process, known as ovarian cryopreservation, is relatively new and further studies are needed to produce reliable data.
A 2018 review study in the Journal of Gynecology, Obstetric and Human Reproduction looked at cases from 2000 to 2017 and found that in 16 published cases of ovarian transplants among patients treated for breast cancer, there were 14 pregnancies, 11 births and three failures.
Some oncologists will not allow egg stimulation before chemotherapy. According to Dr Chris Venter, a fertility specialist at VitaLab fertility clinic in Johannesburg, stimulation of ovaries to retrieve eggs will postpone the chemotherapy for a maximum of 10 to 12 days. This should, in the majority of cases, not change the prognosis of the patient. He explains that due to the high levels of oestrogen during stimulation, women with oestrogen receptor-positive breast cancer could face a risk of disease progression. However, evidence has shown that adding the drug Letrozole (an aromatase inhibitor that reduces the amount of oestrogen available to tumours) reduces the risk of disease progression. GnRH agonists have some theoretical risks and are associated with side effects, including bone loss and menopausal symptoms. However, according to current research, the method is safe for use in breast cancer patients and there is no risk of disease progression with ovarian cryopreservation.
In the POSITIVE trial, once a woman has completed the minimum requirements of her endocrine therapy, she can stop and wait three months before attempting to fall pregnant. While it is possible to fall pregnant during this period, there isn’t a huge amount of time to keep trying. For safety, the POSITIVE trial offers up to two years interruption of endocrine therapy to allow pregnancy, delivery, breastfeeding, or failure to conceive.
For women who can’t fall pregnant naturally, in vitro fertilisation (IVF) or an alternative fertility method might be indicated. If you already have eggs or embryos frozen, you can use these. If you did not do any fertility preservation prior to treatment, ovarian stimulation will be required.
According to both Dr Benn and Dr Venter, these treatments do not increase breast cancer incidence. Results from a new long-term study in JAMA indicated that undergoing fertility treatment with IVF did not increase the risk for breast cancer, compared with other fertility treatments or with women in the general population.
Dr Venter explains that after cancer treatment, the patient needs to see a reproductive specialist to determine her natural fertility. The chances will be dictated mainly by a patient’s age, her egg reserve and other factors like the quality of her partner’s sperm. It is better to have a plan and set some timelines. If the prognosis is good, trying to conceive naturally would be the preferred route and to move on to assisted reproductive techniques.
Ultimately, the decision to undergo fertility preservation, or to stop treatment and to try for children, is a personal one that should be made in conjunction with a variety of specialists. Although many women will become infertile after breast cancer, modern medical advances continue to give hope to millions.