Treating breast cancer in pregnancy: Good news for mother and child
by Dr. Lorne Brandes October 22, 2010
For decades, it was every oncologist’s nightmare: a pregnant woman diagnosed with rapidly growing breast cancer. What to do? Terminate the pregnancy? Wait until delivery before starting chemotherapy? Treat immediately but reduce the dose of chemotherapy in an attempt to protect the fetus? Until recently, nobody knew the answers to these very difficult questions.
Now, thanks to pioneering studies carried out at Houston’s prestigious University of Texas MD Anderson Cancer Center, we do. Not only has a clear roadmap emerged to help us safely navigate this minefield, but we can also confidently offer a much more encouraging prognosis to the pregnant patient and her unborn baby. Here is the story.
Starting in 1992, MD Anderson oncologists began treating pregnant women with standard (full) doses of three widely-used breast cancer drugs in a regimen called "FAC" (5-fluorouracil, doxorubicin [Adriamycin] and cyclophosphamide). To minimize harm to the fetus, they waited until after the first trimester to begin the chemotherapy. After delivery, radiation treatment, and additional drugs, such as tamoxifen and Herceptin, were administered when indicated.
Close follow-up was provided over the ensuing years to monitor the mothers for any signs of recurrence and to assess the health and development of the children.
The first encouraging news emerged in a 2006 paper that described the MD Anderson team’s results in the first 57 women and their offspring. Not only was the short-term outcome better than expected, with 44 of 57 (77%) women alive and cancer-free after 3 years of follow-up, 97% of the children were reported to have "normal development compared to siblings or other children." Only three had congenital birth defects: one with Down syndrome, one with a club foot, and one with a relatively common and treatable abnormality (called "reflux") of the ureters that drain urine from the kidneys into the bladder.
That wasn’t all we learned from the study. Prior to that time, it had been generally believed that breast cancer in pregnant women grows and spreads rapidly because of high levels of maternal estrogen; this hormone drives tumour growth in two-thirds of non-pregnant women with the disease. However, meticulous analysis of the pregnant women’s tumours revealed that they were estrogen-driven in only 30% of cases, while 70% were "triple-negative" high grade cancers that typically grow independent of estrogen and carry a poorer than average prognosis. Suddenly, we had an alternative explanation for the aggressive behaviour of breast cancer in pregnant women!
But the surprises didn’t end there. At the recent 2010 Breast Cancer Symposium, the MD Anderson’s Dr. Jennifer Litton reported that 75 pregnant women have now been treated and followed for an average of five years. Given the aggressive nature of breast cancer in pregnancy, their disease-free survival rate remains remarkably high at 74%.
However, what really caught everyone’s attention was how that result compared to the outcome her group obtained using the same "FAC" chemotherapy treatment in 150 non-pregnant women with breast cancer who were closely matched for age, year of diagnosis, and stage of disease. As opposed to pregnant women, non-pregnant women had a significantly lower five-year disease-free survival rate of 56%!
How to explain the difference? According to Dr. Litton, "We are not sure why our pregnant breast cancer patients had better outcomes than those who were not…is there something biological in the milieu of pregnancy that changes the response to chemotherapy?" Finding that answer will be her group’s "research priority", she said.
As an oncologist who treats this disease on a daily basis, I wish her and her colleagues every continuing success. While much longer follow-up will be required to determine the ultimate cancer-free survival of the mothers, as well as any long-term effects of in utero exposure to chemotherapy in their children, thanks to the MD Anderson researchers we are already light years ahead in our ability to advise, reassure, and treat pregnant women with breast cancer.