It is critical that we talk about these issues and break through potential preconceptions and move beyond them, so we make sure that they don’t hinder patients from moving forward with their cancer therapy and their survivorship goals.— Jacqueline Jeruss, MD, PhD
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“One of the most challenging oncologic situations that I face as a clinician is the diagnosis of breast cancer in a young pregnant patient,” Jacqueline Jeruss, MD, PhD, Director of the Breast Care Center at the University of Michigan Comprehensive Cancer Center, Ann Arbor, told the more than 250 oncologists, psychologists, genetic counselors, and others attending the 2016 Oncofertility Conference in Chicago.1 This topic had also recently been addressed in a dedicated course at the American College of Surgeons Meeting by Dr. Jeruss and Elisa Port, MD, Director of the Dubin Breast Center at Mount Sinai Hospital in New York.
“There is a breast cancer diagnosis in about 1 in every 3,000 pregnancies,” Dr. Jeruss reported, and the numbers may increase as childbearing is delayed. These patients can’t be managed like other new patients with breast cancer but rather “need additional time to process their treatment decisions, and may require more time for consultation from the whole treatment team,” she said.
Breast cancers detected during pregnancy tend to be more advanced cancers, Dr. Jeruss noted, because these are young women who are not typically being screened for breast cancer. For these women, the most common mode of detection in this setting is by the patient with a palpable finding.
“Management options and recommendations are fluid,” Dr. Jeruss noted, because of advances in neonatal care and changes in our understanding of who needs treatment. Treatment decisions must balance the need for treatment (the health of the mother) along with the impact of treatment (the health of the fetus). Surgery, chemotherapy, radiation, and endocrine therapy—“all have a potential impact on the developing fetus,” Dr. Jeruss stated.
Make No Assumptions
Initial discussions about pregnancy and future fertility have to be introduced into already very complicated issues associated with a new diagnosis of breast cancer. Physicians need to explain the recommended treatment guidelines and also listen carefully to understand the patient’s goals are concerning her own health, ongoing pregnancy, and future childbearing.
“It is important that we do not assume that fertility preservation is not desired” based on a patient’s age, marital or partner status, or because she already has one or more children, Dr. Jeruss said. Failure to listen to or address concerns about fertility preservation “could be a stopping point” for a patient, who might then decide not to proceed with treatment. “It is critical that we talk about these issues and break through potential preconceptions and move beyond them,” she emphasized, “so we make sure that they don’t hinder patients from moving forward with their cancer therapy, and their survivorship goals.”
Having contraception discussions is so important [for women with cancer]…. If we don’t have that conversation, then we need to have the really difficult conversation about cancer and pregnancy.— Teresa K. Woodruff, PhD
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In an interview with The ASCO Post, Dr. Jeruss and Teresa K. Woodruff, PhD, talked about the importance of discussing all reproductive health issues with women diagnosed with breast cancer and who are pregnant or could become pregnant. Dr. Woodruff is Director of the Oncofertility Consortium, Northwestern University, and one of the 2016 Oncofertility Conference Chairs.
These reproductive health issues include contraception. “Having discussions about contraception—both hormonal and barrier methods—is important,” Dr. Woodruff said. “So even in hormonally responsive cases, there are options for contraception. But if we don’t have that conversation, then we need to have the really difficult conversation about cancer and pregnancy.”
“We need to be mindful that patients have many different life goals,” Dr. Jeruss said. Patients need to know that physicians recognize and respect the patients’ autonomy. “If we do that, we are upholding our responsibilities as caregivers.”
Early Discussion Important
“Oncologists should engage their patients in discussion about fertility concerns as they relate to treatment at the earliest possible time point,” Dr. Jeruss stressed. “Breast cancer treatment contributes to or may cause infertility,” Dr. Jeruss noted, and “surgical procedures and radiation therapy can also have ramifications on future pregnancies in terms of breastfeeding and reconstruction options.” For example, for women undergoing breast-conserving surgery, radiation therapy is also often recommended and these patients may not be able to nurse from the affected breast.
Dr. Jeruss would like to see a day when referrals for oncofertility services are regarded as similar to referrals for reconstruction or genetic testing and counseling, addressing a range of patients’ needs as they go through treatment for breast cancer. “We need to have a multidisciplinary approach that includes surgical oncologists and medical oncologists, along with fertility specialists, to ensure that the continuum of care is as seamless as possible.”
Fertility Preservation Options
Embryo and oocyte cryopreservation are both now considered standard fertility preservation procedures. Embryo cryopreservation “is associated with the most robust and long-term outcomes data,” Dr. Jeruss noted. Ovarian tissue cryopreservation is still considered experimental and is only being performed in institutions with research study protocols, she added.
“Timing is critical,” Dr. Jeruss stressed. Oocyte harvesting can be performed before or after surgery. “We need to be very time sensitive about fertility discussions particularly for patients who are recommended to have neoadjuvant chemotherapy, before surgery,” she added.
In these situations she said, “We need to be sure that we have partnerships with fertility preservation specialists available to us, so that patients can come in at the earliest possible time, undergo fertility preservation, and then initiate chemotherapy.”
Breast cancer treatment including surgery, chemotherapy, radiation, and then tamoxifen, “could last up to 10 years from the time of diagnosis,” Dr. Jeruss pointed out. She also reported that several studies using retrospective data show that a subsequent pregnancy is not associated with an increased risk of recurrence or poorer survival among patients with breast cancer.
Discussions During Pregnancy
Discussing treatment options with a woman who is pregnant at the time of breast cancer diagnosis, “I’ve had to take a step back and be sure that I am broad-minded about what the patient may wish for along with my recommendations for the patient’s care,” Dr. Jeruss said. Factors to consider include the diagnosis, stage of disease when diagnosed, hormone receptor status, and trimester.
First trimester: “Surgery with mastectomy is the primary option for women diagnosed with breast cancer while in their first trimester of pregnancy,” Dr. Jeruss said. “Chemotherapy initiation does not typically occur until the second trimester.”
Teresa K. Woodruff, PhD, Director of the Oncofertility Consortium, Northwestern University, Chicago, expressed appreciation to Morton Schapiro, PhD, President of Northwestern University and an advocate and supporter of the consortium since its inception. The occasion was the 10th Oncofertility Conference, attended by more than 250 oncologists, nurses, embryologists, psychologists, genetic counselors, and other health-care professionals, as well as research scientists studying ways to mitigate fertility threats to patients with cancer.
“In the first trimester, fetal monitoring during surgery is typically not implemented, because the fetus would be considered below the threshold of viability,” Dr. Jeruss said, but the fetal heartbeat is typically checked before and after surgery.
The use of lymphatic mapping with dye throughout pregnancy remains controversial. Dr. Jeruss said that the use of radioactive tracer has not been found to impact the fetus, but analyses have been limited by small sample sizes.
“Some patients want reconstruction, but we tend to tell patients that the first trimester is not the optimal time when trying to limit anesthetic exposure for the patient and fetus as much as possible,” Dr. Jeruss noted. Breast-conserving surgery is not typically recommended because radiation therapy would be delayed for several months.
“So there are limits to what we can offer these patients in the first trimester,” Dr. Jeruss remarked. “Surgery can be implemented with a very clear consent process. There is typically no role for chemotherapy, radiation, or tamoxifen.” If adjuvant treatment is to follow, chemotherapy and radiation will be delayed for several months, and tamoxifen would be delayed until pregnancy is completed.
“Although it is a difficult conversation to have, termination of pregnancy can also be mentioned for these patients, and this can have significant ramifications—both religious and psychological—requiring great sensitivity.”
Second trimester: Mastectomy remains the primary surgical option for breast cancer patients in their second trimester, Dr. Jeruss said. “Organogenesis has largely occurred,” she noted, “and now we can start to talk about the use of chemotherapy. But radiation and tamoxifen are still not recommended.”
When performing surgery for women in their second trimester, the surgical oncologist should “work in collaboration with a neonatal group that is going to implement fetal monitoring and have that team available, in case the patient has preterm labor,” Dr. Jeruss advised. Reconstruction is generally not recommended.
Chemotherapy, surgery, and then delivery is “an accepted treatment plan for patients diagnosed in the second trimester,” she noted. Other sequential options are surgery, chemotherapy, and then delivery, or surgery, delivery, chemotherapy. All sequences may involve some delay in treatment.
“If a patient is BRCA-positive, the timing for a contralateral mastectomy becomes another issue and this procedure tends to be deferred until after delivery,” Dr. Jeruss said.
Third trimester: For patients diagnosed in the third trimester, Dr. Jeruss said, “the plan is often to deliver the baby as soon as it is safe to do so, and the recommended breast cancer treatment plan should not be significantly altered.”
A critical developmental time period during the third trimester is between 27 and 35 weeks. “By 34 to 35 weeks, the lungs are often mature, and delivery can be considered,” Dr. Jeruss said.
Patients interested in breast conservation can be offered lumpectomy with the intent to initiate radiation, particularly for patients who have reached mid third trimester. “During surgery, a neonatal/high-risk obstetric team should be standing by with fetal monitoring throughout the operative case,” Dr. Jeruss advised.
Women with BRCA1 or BRCA2 mutations have a significantly elevated risk for developing breast cancer, Dr. Jeruss noted. Although the timing of breast cancer is unpredictable, the mean age at diagnosis for BRCA carriers is in their early 40s, compared to around age 60 for noncarriers.
“Primary treating oncologists have a responsibility to take the initiative in discussing fertility preservation options with these patients,” Dr. Jeruss stated. “Early referral for fertility preservation consultation gives patients the greatest potential autonomy regarding this critical issue.”
For BRCA carriers, risk-reduction surgery should be done “at the earliest possible time that the patient feels ready to proceed,” Dr. Jeruss said. “These patients can feel a tremendous amount of internal and external pressure to make critical decisions that will be irreversible in terms of childbearing. So it is important to be sensitive to those issues when they arise.”
Bilateral salpingo-oophorectomy is generally recommended after childbearing has been completed, but “some patients may opt for oocyte harvest, bilateral salpingo-oophorectomy, and subsequent pregnancy with in vitro fertilization, potentially using a surrogate, based on family history.” Alternative plans, such as use of a donor egg and adoption, should also be discussed.
Mastectomy can be planned before or after pregnancy, “depending on how the patient feels most comfortable moving forward,” Dr. Jeruss said. Advantages of mastectomy before pregnancy include decreased screening once the woman is pregnant and decreased likelihood of diagnostic imaging and biopsy along with a decreased risk for a new cancer diagnosis. A consequence of mastectomy before pregnancy, Dr. Jeruss said, is that “breastfeeding will not be possible, and this must be clearly explained prior to surgery.”
“Tamoxifen is an incredibly important treatment for patients over the long-term survivorship period,” Dr. Jeruss noted, but it is a teratogen, and “pregnancy should be avoided during the 5 to 10 years of recommended tamoxifen use.” The considerable length of recommended treatment may be a deterrent to breast cancer survivors hoping to become pregnant.
To look at factors that could influence taking tamoxifen use in younger patients, researchers at the University of Michigan and Northwestern Medicine reviewed charts of 987 patients aged 45 and younger when diagnosed with estrogen receptor–positive breast cancer. Among patients who chose not to initiate tamoxifen, “we found that having a diagnosis of ductal carcinoma in situ, being noncompliant with other cancer therapies, as well as having a desire for future fertility correlated with those patients who were not going to initiate tamoxifen,” Dr. Jeruss reported.
The reasons cited by patients who did not follow recommendations to take tamoxifen were concerns about side effects and, nearly as frequently, fertility concerns, Dr. Jeruss reported. Concerns about fertility were also cited by patients who started the drug and then stopped it. Follow-up interviews confirmed that “side effects were the only thing that trumped concerns about fertility for our youngest patients who did not initiate or adhere to the drug,” Dr. Jeruss stated.
Patients who delay initiating tamoxifen and or discontinue tamoxifen therapy can still receive benefits of reduced risk of recurrence and mortality.2,3 “Some data support the potential for a tailored delay in tamoxifen therapy, allowing time for pregnancy, with expectation to ultimately complete 5 to 10 years of therapy, though this is an area of active study,” Dr. Jeruss said.
To this end, an ongoing study is looking at whether interrupted tamoxifen use is safe and effective and whether patients have outcomes equivalent to those who don’t take a tamoxifen break. Patients will stay on tamoxifen for about 2 years, take a 3-month drug hiatus, and then attempt a pregnancy, with a 2-year hiatus to allow for pregnancy and breastfeeding, and then go back on tamoxifen to complete a 10-year course of treatment, Dr. Jeruss explained.
The study, IBCSG 48-14 trial (ClinicalTrials.gov identifier, NCT02308085), started in July 2014 and has a target accrual goal of 500 patients. More information is available by phone at 716-834-0900 or by e-mail at ibcsg42_POSITIVE@fstrf.org. ■
Disclosure: Drs. Jeruss and Woodruff reported no potential conflicts of interest.