Cancer has a way of disrupting life’s plans. One stark example of this has always been for women diagnosed early in life, who are sometimes diagnosed with breast cancer before they have had children or decided to not have any more children. Having a breast cancer diagnosis change your family plan in unalterable ways is another example of the collateral damage of cancer care that Dr. Love always discusses.
Fertility preservation, whether freezing eggs or embryos, sperm-banking, or using ovarian suppressing medications during chemotherapy to minimize risk to the ovaries has been the standard of care in the United States for patients diagnosed with any cancer for years. However, many of these options have significant barriers to universal implementation—physicians do not always offer the services to patients, fertility preservation care is unaffordable, or sometimes logistical considerations with timing and collecting eggs, sperm, or embryos are at odds with timely initiation of cancer treatment.
Recently, we have learned great news on the outcomes for patients who face one of these barriers: Understanding how endocrine therapy (hormone-blocking medications) for estrogen-receptor (ER) and/or progesterone receptor (PR) positive breast cancer treatments can be modified to accommodate pregnancy. Endocrine therapy here means hormone-blocking medications, including tamoxifen, anastrozole, letrozole, or exemestane. Previously there has been concern that if endocrine therapy is held to allow pregnancy and delivery to occur, a patient’s risk of breast cancer recurrence would increase. There has also been concern about the hormonal changes of pregnancy increasing the risk of breast cancer recurrence.
Now we have the results of an important clinical trial, POSITIVE1, which looked at 497 women who were followed for pregnancy, cancer recurrence, and pregnancy outcomes with an average of 3.5 years of follow-up. The patient volunteers in the POSITIVE trial had mostly stage I or stage II breast cancer (93%) and about 60% had received chemotherapy. Patients all had taken endocrine therapy for at least 18 months, at which time they were allowed to temporarily interrupt endocrine therapy for up to two years to conceive, deliver, and breastfeed (if desired and/or feasible). Patients were allowed to use reproductive technology and encouraged to undergo fertility evaluation if they did not conceive in the first year, and after the 2 years, they were re-started on endocrine therapy to complete a full 5 to 10 years of medications.
Among 497 patients, 368 (74%) reported becoming pregnant. Age was a key variable in the success of achieving pregnancy, and 43% used reproductive technology. As compared to historical controls—similar patients in older studies with the same breast cancer features—patients who interrupted treatment for 2 years had no higher risk of breast cancer recurrence. Additionally, among those who became pregnant, there was no increased risk of recurrence. Long-term follow-up for late risk will be important.
Among the pregnancies that occurred, 69% resulted in a live birth. Rates of pregnancy complications (pre-eclampsia, low birth weight, diabetes) were similar to the general population (11%) as were birth defects (2.2%).
POSITIVE tells us that it is both feasible and safe for patients with early-stage, hormone receptor-positive breast cancer to interrupt therapy for 2 years to achieve pregnancy. Furthermore, after breast cancer and 18 months of endocrine therapy, patients that interrupt therapy for pregnancy have similar pregnancy outcomes and similar rates of pregnancy complications and adverse birth outcomes. I am excited to be able to use these results to counsel patients on timing, risk and outcomes with endocrine therapy interruption for pregnancy. Bring on the babies! The next generation of the Dr. Susan Love Research Army is born!
