Episode 42 Shownotes - Pregnancy after Cancer

Welcome back friends, and welcome to all the new folks! If you are new to the podcast, I’m glad you’re here! This is one of those weeks where I didn’t know ahead of time what I was going to write about, and then I happened to have a minisession with a lovely young woman struggling with fertility decisions after treatment for breast cancer. This topic has been on my list, but not made it to the top, but after speaking with her, I realized the universe was telling me “It’s time”. The discussion with the young woman was so helpful, for me and for her as well. I love to know what people are struggling with so I can tailor what I am doing, and she said the free session helped her and her husband to reframe their discussions, and her to realize that her fear of missing out on the opportunity to grow her family was actually more pressing than her fear of recurrence.

So today, I am talking about pregnancy after cancer in general, and breast cancer treatment specifically, along with the currently available data that I was able to find. I am going to start at the beginning of the cancer journey and move through, discussing things that come up at each step. This is a matter of increasing importance, as 25% of breast cancer patients are diagnosed <50 years old, and 6% under 40 years old. There is a trend towards earlier cancers in Caucasian women in recent decades. Add that to women more and more frequently delaying pregnancy, and it is clear this issue will only become more prevalent as time passes. In the US, the number of women whose first pregnancy was >30 yo increased from 4.1% to 21.2% since the early 1990s. In talking about this, I want to discuss fertility options pre-treatment, which is clearly more standardized, and then the controversies about pregnancy following treatment.

When a woman of childbearing age is diagnosed with a cancer, we need to first address if they wish to have children. If their childbearing is complete, then normal treatment guidelines can be followed. The American Society of Clinical Oncology has published guidelines for fertility preservation in patients with cancer. They strongly recommend that ‘‘oncologists discuss at the earliest opportunity the possibility of infertility as a risk of cancer treatment, recognizing that in many cases, adequate data are not available to provide accurate predictions for any one individual. If patients are at risk for infertility and interested in considering options for fertility preservation, referral to appropriate specialists as early as possible is recommended’’. In discussions of this, I think it is helpful to understand that some types of cancer make conceiving and carrying a pregnancy after treatment almost impossible. The two that come to mind immediately are more advanced cervical cancers and rectal or anal cancers. Any cancer that requires pelvic radiation treatments will make carrying a fetus a major issue. The reason for this is that the ovaries usually get radiation and stop functioning, AND the uterus is scarred by the radiation and will not stretch and expand normally. BUT these patients can still have eggs harvested PRIOR to treatment, and through a surrogate, have a biological child. For most cancers treated with surgery alone, like thyroid cancer or melanoma, fertility may not be affected at all. For other patients, a team approach is needed. Many chemotherapies affect fertility and can induce menopause, so if a patient is desiring fertility, this should be discussed prior to initiating treatment. Several options are currently available to preserve fertility: the most effective and established is embryo cryopreservation (this is freezing fertilized eggs, which means a man’s sperm is required). This may require delaying adjuvant systemic therapy for up to 6 weeks for a patient to undergo ovarian stimulation. Early referral to reproductive specialists before breast surgery seems to increase the likelihood of obtaining a sufficient quantity of oocytes without a delay in breast cancer treatment. Cryopreservation of mature oocytes (unfertilized eggs) is possible but less successful than embryo freezing, although the paper I read quoted more than 500 live births have been reported with this method. For women with hormone sensitive tumors, alternative hormonal stimulation strategies such as letrozole or tamoxifen have been developed to reduce the potential risk of estrogen exposure. New methods, such as maturing follicles outside of the body in the lab and ovarian tissue cryopreservation and transplantation, are under active investigation. If none of these are an option, then suppressing the ovarian function to help the ovaries survive may be possible. In premenopausal women, medications like Lupron or Zoladex temporarily and reversibly shut off estrogen by decreasing hormones from the pituitary. Most human studies of this to date have been small, uncontrolled, and retrospective. However, a report in 2016 in JAMA by Munhoz reviewed 7 studies and found that the use of medication to suppress the ovaries was associated with a higher rate of recovery of regular menses after 6 months and a higher number of pregnancies. A 2015 trial in the NEJM looked at this in premenopausal hormone negative women, and found that there were lower rates of ovarian failure and higher pregnancy rates in women among the goserelin group, with pregnancy in 21% of the goserelin group and 11% of the chemo- alone group. The survival graphs appeared to have no worsening of survival, although this was not a trial endpoint. So, clearly there are options. Let’s get into some specifics that I was able to sort out from the literature.

Thyroid cancer is one of the more common cancers with women considering pregnancy after, due to the young age of many thyroid cancer patients. An overview by Speigal, et al, in 2019, found a higher incidence of blood clots and need for transfusions in women with a history of thyroid cancer, but no difference in newborn outcomes. Assuming that the woman is not currently receiving chemotherapy or radiation for the thyroid cancer, it appears that pregnancy is safe for both mother and baby, though clearly this should be discussed first with the treating endocrinologist. A Portuguese article by Guedes quotes that breast cancer is the most common malignancy in women of reproductive age, and a 2017 paper by DeSimone discusses what they call the “prejudice against pregnancy after breast cancer”, meaning that many doctors don’t really know what to recommend, and that women are often left to make these decisions alone. They stated in the article that all available retrospective data confirms that pregnancy after breast cancer is safe for both the mother and offspring, including in women with hormonally positive cancers. Timing of pregnancy is a clear matter of debate, especially in women receiving hormonal therapy. At the time of print, a worldwide trial was accruing to assess the safety of interrupting hormonal therapy to allow conception. It also noted that breastfeeding after surgery and radiation could be challenging, but should not be discouraged.

An article by Partridge in 2018 notes that the earlier a pregnancy occurs in a woman with a cancer diagnosis, the higher the risk of neonatal complications. The study looked at women 20-45 years old compared with matched women with no cancer history. Early pregnancy after treatment had a 2-3 times greater risk of preterm birth along with lower birth weight. Both of these risks decreased farther out from treatment, but clear guidelines on what was “early” vs. “later” was not clearly defined in this article. An article by Pagani in 2011 comprehensively reviewed the literature available at that time. The article states the best available modern evidence suggests that pregnancy after breast cancer does not increase a woman’s risk of recurrence, and in fact may even confer a protective effect. In several population-based retrospective studies, where patients are matched for age, disease stage, and year of diagnosis, relative risk of death was lower for women who conceived after breast cancer than for those who did not. In two of these studies, overall survival results were statistically significantly in favor of the cohort that became pregnant . A recent meta-analysis of 14 such studies, involving 1,244 cases and 18,145 controls, showed a 41% reduced risk of death in women who became pregnant following breast cancer compared to women who did not. One potential explanation for such a survival benefit is a selection bias called the ‘‘healthy mother’’ effect, which means that women with breast cancer who subsequently conceive are a self-selecting healthier group with better prognosis. Some studies in the lab suggest that cancer cell death is induced in endocrine-responsive breast tumor cells by high estrogen, progesterone, and human chorionic gonadotrophin levels similar to those observed during pregnancy. In addition, the fetal antigen hypothesis suggests that the mother’s immunity is boosted against breast cancer cells during pregnancy.

Recent data are also reassuring concerning the safety of pregnancies for BRCA1 and BRCA2 carriers: pregnancy should therefore not be discouraged in this population after comprehensive genetic counseling and adequate psychological support. One of the options for these patients is egg harvesting with embryo selection for those that do not have the mutated BRCA gene. This is possible because we all have 2 copies of our genes. One copy is from our mothers and one from our fathers. Women’s eggs have one copy of each gene, so we can select the ones to freeze that do not carry the mutation.

Despite this growing and encouraging body of evidence, the number of women who become pregnant and give birth to a live infant after breast cancer is low (3–15%, depending on the age of women considered). Several different factors may contribute to this low rate (i.e., treatment-induced infertility, competing risks, fear of recurrence, insufficient counseling, and patient’s preference.

What data is available on the effect of chemotherapy on ovaries? The most commonly used chemotherapies in breast cancer have a well-recognized negative impact on fertility; rates of permanent amenorrhea depend on specific drugs as well as the woman’s age at the time of treatment. Alkylating agents (carboplatin, cisplatin, cyclophosphamide or Cytoxan) in particular are quite toxic to the follicles in the ovaries. Literature regarding incidence of chemotherapy-induced amennorhea, or stopping of menstrual periods, is very inconsistent: the definition of amenorrhea is not uniform across studies, the time point at which it was assessed ranges widely, and the cut points to define age groups are not consistent. Transient menstrual irregularity or amenorrhea is common during chemotherapy, but a proportion of patients will resume menstruation within 6–12 months of treatment completion, which is the time required for damaged developing follicles to be replaced by new follicles from the remaining follicle pool. But clearly, the risk of permanent loss of periods, or start of menopause goes up dramatically as women get older. Overall, amenorrhea rates become pronounced in patients over 40 years of age. The very limited data on women under 35 show extremely low rates of permanent cessation of menses (0–10% in most studies). Overall, the risk of ovarian failure after chemotherapy is thought to be underestimated, as studies have only looked at lack of menses as a surrogate for fertility (meaning just because periods come back does not mean fertility is guaranteed). We also need to take into account the natural decline in the quality and quantity of ovarian follicles, also known as ovarian aging, is known to accelerate around age 35 naturally, when the number of oocytes drops to approximately 25,000 (having been approximately 300,000 at puberty) . The impact of tamoxifen on ovarian function is less well understood, since the number of young patients who have not also received adjuvant chemotherapy is very small. The relative contribution of tamoxifen to treatment-induced amenorrhea is debated: some studies demonstrate an increased incidence with the addition of tamoxifen, others report no impact, with tamoxifen having apparently less effect on amenorrhea in younger women. Standard radiation therapy for breast cancer is not associated with significant ovarian toxicity.

The next question is whether adjuvant therapies damage the fetus? One of patients’ major concerns is the potential teratogenic impact of breast cancer treatments on a future pregnancy. Two recent large population-based cohort studies are reassuring regarding the risks of adverse birth outcome for breast cancer survivors. However, in a Swedish study, an increased risk of delivery complications, cesarean section, very preterm birth (under 32 weeks) and low birth weight were reported in women with a history of breast cancer compared to healthy controls.

How long should a woman wait to think about pregnancy after breast cancer diagnosis and/ or treatment? The available data suggest that early pregnancy (even within 2 years from diagnosis or treatment) is unlikely to affect prognosis for women at low risk of recurrence, with no specific information according to hormone receptor status. Nevertheless, in common clinical practice, it is generally suggested to wait at least 2 years from diagnosis before attempting conception, mainly to allow early recurrences to manifest. Other factors such as risk at diagnosis, adjuvant treatment length, residual fertility, and age should be taken into consideration when counseling young patients about interval time between diagnosis and pregnancy. Taking into account the time of oocyte maturation, it is reasonable to advise waiting at least 6 months from the end of chemotherapy. For endocrine treatments, data are less conclusive: both tamoxifen and aromatase inhibitors (AIs) have been used during assisted reproduction to improve oocyte yield. Practical advice is to wait at least 2 months and up to 3–6 months after withdrawal from endocrine therapy before attempting conception.

Finally, while not exactly pregnancy related, the question is often asked “Is breast-feeding possible and safe after breast cancer?” No data specifically comparing women who nursed and women who bottle fed their babies after breast cancer, have been reported. The limited evidence available reports successful lactation in approximately 30% of women and no detrimental effect on survival. Apart from safety concerns, feasibility of nursing remains an important issue in women with unilateral mastectomy or reduced milk production from the operated and irradiated breast. The reported series after breast conservation and radiotherapy show an acceptable self-reported breastfeeding success, consistent with the historical data in young women treated with chest radiation for Hodgkin lymphoma. It is clear that one breast is able to nurse an infant, so even if the treated breast is less functional or there has been a mastectomy, nursing is possible. I will share that, personally, I nursed my twins for their first 4 months. Each got one side each feeding, and they swapped sides each feeding. Our bodies make the amount of milk our children are using, so increased demand on one side usually will lead to increased production. Studies in limited numbers of breast cancer survivors reported satisfactory outcomes in breastfeeding, despite the difficulties of lactating mostly or entirely with one breast. The conclusion is that women should not be discouraged by their physicians from breastfeeding after breast cancer but need adequate counseling and practical information and should not receive any additional therapy given the risk of drug transmission through the breast milk. I think that if a woman went off of hormonal therapy for pregnancy, the majority of doctors would advise NOT breastfeeding and resuming the hormonal therapy SOONER rather than LATER.

Now comes the time for a bit of coaching with this. With the client that I spoke about pregnancy, I offered two thoughts. We often delay making decisions waiting to know the “Right” answer. There are many places in life, though, where there is no “right” answers. There are just the decision you make with the best information that you have in the moment. Waiting for the right answer leads to confusion, waffling and indecision. It leads to people continuing to search for the “right” answer, getting opinions, asking everyone who will listen, spinning endlessly on the decision. It leads to doubting whatever decision you do ultimately make. I encourage clients to understand that, unless a doctor has told you there is a definite right answer, meaning you have been advised NOT to get pregnant, then you need to weigh your options and then make the best choice you can in the moment. I believe we often know in our hearts what the right answer is for us. I love the thought “I know in my heart what the right decision is for me and my family” and then LISTEN FOR THE ANSWER. What comes up may be that you don’t want to add any risk at all, in which case you should respect that, and move forward loving the family that you have. Or it might be “another child is worth the risk” understanding that you can’t guarantee that you will be here for that child’s whole life. But you know what? NONE of us can guarantee that we will be there for our kids. Every time we get in a car. Every time we leave the house in a pandemic. Every time we eat a bite of chewy steak. None of us have a guarantee. So, if your brain thinks you need a guarantee you will be there, well, none of us should have kids then.

My friends, such a challenging place to be. My thoughts are with you if you are struggling with this, especially as a mom who went through 5 years of fertility treatments personally. If you want help, consider a minisession to help you sort through this difficult decision. I’ll speak with you soon.