Pregnancy does not appear to affect efficacy of chemotherapy for breast cancer
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The prognosis of women who received chemotherapy for breast cancer did not appear to differ between those who were and were not pregnant, according to study results presented during the virtual ASCO Annual Meeting.
These findings suggest pregnancy’s impact on chemotherapy concentration does not influence outcomes, supporting the use of chemotherapy among pregnant women when indicated for their breast cancer.
“When treating cancer during pregnancy, both maternal and fetal safety are a concern,” Frédéric Amant, MD, PhD, professor at Katholieke Universiteit Leuven in Belgium and at University of Amsterdam in the Netherlands, and head of the department of gynecological oncology at Netherlands Cancer Institute and Amsterdam University Medical Center, told Healio. “We [previously] showed that the offspring does very well after in utero exposure to chemotherapy. The maternal safety is also very important, and this study resolves this concern to an important level. Fear for a worse maternal outcome is no longer a reason to either delay maternal pregnancy or to terminate the pregnancy.”
Because pregnancy causes pharmacokinetic changes in the distribution, metabolism and excretion of drugs, it had been unknown whether this may lead to reduced chemotherapy concentration and poorer maternal outcomes.
“We wondered in this study whether the dilution of chemotherapy during pregnancy could affect the maternal prognosis,” Amant said. “In a pharmacokinetic study, we showed lower [maximum concentration] and area under the curve levels for doxorubicin, epirubicin, docetaxel and paclitaxel, all of which are used for [patients with breast cancer.]”
Thus, Amant and colleagues sought to compare the prognosis of 2,743 women with breast cancer treated with chemotherapy who were (n = 662; median age at diagnosis, 34 years; range, 22-47) and were not (n = 2,081; median age at diagnosis, 38 years; range, 19-45) pregnant. Researchers used Cox proportional hazards regression to compare DFS and OS between the two groups after adjusting for age, stage, grade and other tumor characteristics.
A greater proportion of pregnant women had stage II breast cancer (60.1% vs. 56.1%; P = .035), grade 3 tumors (74% vs. 62.2%; P < .001), hormone receptor-negative tumors (48.4% vs. 34%; P < .001) and triple-negative disease (38.9% vs. 26.9%; P < .001) compared with women who were not pregnant.
Median follow-up was 66 months.
Researchers observed no difference in outcomes between pregnant and nonpregnant women in terms of DFS (HR = 1.02; 95% CI, 0.82-1.27) and OS (HR = 1.08; 95% CI, 0.81-1.45).
There also was no difference in DFS (HR = 0.81; 95% CI, 0.62-1.06) and OS (HR = 0.85; 95% CI, 0.58-1.23) in a subgroup of 339 women who received more than 60% of chemotherapy during pregnancy.
“[Importantly, it may be that] these findings can be extrapolated to other less common cancer types where this chemodilution issue also exists,” Amant said.
“Chemodilution varies along the chemical properties and is most important for paclitaxel,” he added. “A study on the safe use of paclitaxel during pregnancy may be a future avenue of research.”
Perspective
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Fatima Cardoso, MD
Thanks to the important work of Amant and the [International Network on Cancer, Infertility and Pregnancy], as well as others around the world, we now have sufficient data to know it is safe to treat breast cancer during pregnancy and that the prognosis of breast cancer during pregnancy is comparable to that of nonpregnant controls if we adjust for certain characteristics such as age. However, we also know that there is a change in pharmacokinetics of chemotherapy during pregnancy, with a reduction of chemotherapy concentration in pregnant patients. This study aimed to see if these pharmacokinetic changes would impair long-term outcome for pregnant patients who were treated for breast cancer.
Of course, this was a nonrandomized trial, so a lot of adjustments were done for the statistical analysis to avoid any bias as much as possible. Still, there was already some bias because pregnant patients were more likely to have stage III, grade 3, ER-negative and triple-negative tumors. However, after considering all the caveats of a nonrandomized study, DFS and OS were comparable for pregnant and nonpregnant patients.
With this and other studies, we can conclude that pregnancy-induced alterations in chemotherapy concentration due to altered pharmacokinetics do not seem to affect maternal prognosis and, therefore, we should initiate treatment of breast cancer during pregnancy wherever it is indicated for oncologic reasons, knowing that you can only use chemotherapy during the second or third trimester.
Managing breast cancer during pregnancy is a rare situation that requires specialized care. Clinicians who aren’t familiar with these cases should refer patients to a specialized center with an experienced multidisciplinary team. Interrupting pregnancy does not improve the prognosis of the mother, so we have to spread the word to all health professionals who come across these women to stop advising them to immediately terminate the pregnancy. Also, we should treat these women as much as possible as we would nonpregnant women, with some exceptions, such as avoiding endocrine and anti-HER2 therapy until after delivery. We also have sufficient data showing that chemotherapy during pregnancy is safe for the children.
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Amant F, et al. Abstract 515. Presented at: ASCO Annual Meeting (virtual meeting); June 4-8, 2021.
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