1. Goodwin, Peter M.

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BERLIN-Evidence from population-based data and clinical trials collectively confirmed that pregnancy was safe and compatible with breast cancer treatment for young patients who wanted to become mothers, according to an onco-fertility specialist speaking at the European Society for Medical Oncology (ESMO) Breast Cancer 2019 annual congress.

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"We don't have outcome data that really tell us that women cannot have pregnancy after breast cancer. Having babies after breast cancer is safe. And the same is valid for breastfeeding," Fedro Peccatori, MD, PhD, Scientific Director of the European School of Oncology in Milan, told Oncology Times.


"Many young women with breast cancer are really keen on having a baby after the diagnosis and treatment. But, unfortunately, just a small minority succeed. And so we started looking [at] the toxicity of chemotherapy on ovarian reserve and the safety of pregnancy after breast cancer," he said.

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The researchers had been concerned that chemotherapy and endocrine treatment could have affected ovarian function. They had also been worried about any potential hazard it posed to the fetus.


"We are happy to say that there are no issues for the babies," noted Peccatori. But the group did find that chemotherapy and prolonged endocrine treatment could be detrimental to ovarian function. "And that's why it's so important to have fertility preservation before starting treatment."


Fertility Choices

There are three options for preserving fertility, he said. Patients could be offered treatment with a luteinizing hormone-releasing hormone (LHRH) analog during chemotherapy. Or they could choose to have ovarian stimulation and oocyte harvesting before the start of any chemo-endocrine treatment. The third possibility was to use ovarian tissue cryopreservation.


When Pecccatori was asked about the safety of these approaches and of pregnancy itself, he said that recent data from meta-analyses of "real-life" experience and reports from individual patients confirmed that pregnancy was safe-even though randomized trial data had been scarce.


"The relative risk of relapse is not increased by the pregnancy per se. The risk of relapse depends on the biologic characteristics of the tumor at the onset and the treatment, but not on the pregnancy," he explained.


But age was important for a successful pregnancy. "If you have a 45-year-old woman who comes for fertility preservation, unfortunately, it is too late because fertility is already reduced physiologically. But women below 40 years of age still have good chances-even if the best chances are when the woman is younger than 35," he said.


Pecccatori recommended that clinicians explain the risks from chemotherapy and prolonged endocrine treatment and then make a plan together with each patient according to her age and her wishes for preserving fertility. He favored two of the three options: To choose oocyte harvesting after ovarian stimulation or give LHRH analogs. "These two means are well-known and usable and approved in many countries."


He said some of the uncertainties still outstanding should soon be resolved by the ongoing, multinational POSITIVE trial in patients with endocrine-responsive breast cancer that investigates whether temporary interruption of endocrine treatment and subsequent pregnancy could be associated with a good outcome (NCT02308085).


Peccatori regarded oocyte harvesting after ovarian stimulation as the "front-runner" among fertility preservation methods.


"That is the real way of preserving gametes. The others just reduce the impact of chemotherapy on ovarian function and ovarian reserve. So, for older women who are really interested in preserving their fertility, we offer ovarian stimulation with letrozole (to reduce the amount of estrogen and the estrogenic peak) and oocyte harvesting. In some countries, you can also fertilize the oocytes [and] freeze the embryos directly."


Fertility preservation for young women with cancer needs a multidisciplinary team. "The cancer doctor has to do the counseling, but then has to refer the patient to the reproductive endocrinologist who is the doctor in charge of doing the ovarian stimulation and then harvesting, freezing, and storing eggs for the time needed. So there should be a network between the oncologist and the reproductive endocrinologist," Peccatori said. This was already happening in many countries but not in all. "And that's something we have to work on."


Examining Outcomes

Peccatori was insistent that the data set was already robust enough to give clear advice to patients. "Don't tell women that we don't have enough data. We do have enough data. But be very clear: Having babies or breastfeeding after breast cancer is an individual patient choice and the prognosis very much depends on the tumor characteristics and the treatment at the diagnosis," he said. Since oncologists were in the frontline, he regarded "oncologist-led onco-fertility counseling" as mandatory.


When asked whether pregnancy could even be protective, Peccatori said that real-life data from his group's study were reassuring. "Those women decided to stop treatment-or not to stop-and have the pregnancy. And the time to pregnancy was 2.6 years from diagnosis. So I think there is an effect of pregnancy. I don't know if it is protective, but I can say that it does not influence the long-term outcome."


To predict long-term outcomes the evidence was that classical prognostic features such as tumor stage and type and nodal status were likely to remain the key factors, but that current evidence should not discourage pregnancy.


"Women should be free to [make] their choices. Cancer is already a big burden for women and the choice of giving birth is a very important [one] for women, and we don't have sufficient data to just say no. No is not correct," Peccatori stated.



Is breastfeeding safe after cancer therapy? Peccatori referred to his group's data from 332 patients among whom this had been analyzed that showed no influence at all of breastfeeding on relapse-free survival. But he acknowledged that breastfeeding was challenging for women who have had breast cancer.


Quite apart from physical issues, his group also investigated the influence of breastfeeding on the relationship between mother and baby. "Breastfeeding helps restore a normal relationship with your baby," he said. In the absence of data showing any detriment from breastfeeding, his group recommended it for women who wanted to do it.


Peter M. Goodwin is a contributing writer.