Mother-To-Be and Cancer Patient-New Treatment Guidelines

February 14, 2012

Four publications on cancer treatment during pregnancy were published last week in the journal Lancet, serving as new treatment guidelines for chemotherapy and surgery in pregnant patients with solid tumors and hematologic malignancies.

Four publications on cancer treatment during pregnancy were published last week in the journal Lancet, serving as new treatment guidelines for chemotherapy and surgery in pregnant patients with solid tumors and hematologic malignancies.

The first study shows that the children of women treated with chemotherapy during pregnancy developed no different than their nonexposed cohorts. This is the first comprehensive study of the longer-term effects of chemotherapy on children exposed during prenatal development and was first presented at the 2011 European Multidisciplinary Cancer Congress by lead study author, Dr. Frdric Amant of the Multidisciplinary Breast Cancer Center at Katholieke Universiteit in Leuven, Belgium.

The second paper describes the current European practice among gynecological oncologists in treating pregnant women with a gynecological cancer, including attempting to preserve the pregnancy of their patients when possible. Professor Philippe Morice of the Institut Gustave Roussy in France and colleagues highlight that chemotherapy should not be used in the first 8 weeks of pregnancy, but believe that chemotherapy use during the second and third trimesters greatly increase the chances of carrying the fetus to term. A conclusion which supports the results of the first paper.

The third publication suggests that pregnant women with breast cancer can undergo surgery or chemotherapy as treatment of their breast cancer with the goal of preventing the termination of pregnancy.

The last paper discusses risks and treatment options for women with blood cancers who are also carrying. The authors point out that because most blood cancers are quite rare, trials such as the solid tumor trial conducted by Dr. Amant and his colleagues are not achievable and all evidence is based on compiled case reports. At the American Society of Hematology (ASH) 2011 meeting, Andrew Evens, MD presented a study on the fetal outcomes of pregnant patients with lymphoma. Collaboration efforts are particularly important to facilitate knowledge and experience for the treatment of rare blood cancers in pregnant patients.

Pregnancy-associated cancer is still relatively rare, about 1 in 1,000 pregnancies, but the incidence is on the rise. The reason is that women are waiting longer to have children and cancer is predominantly a disease of aging. Breast cancer is still the most commonly diagnosed cancer during pregnancy, about 1 in 3,000 pregnancies, and the chances of developing breast cancer increases if a woman’s first pregnancy is in her 30s or 40s.

While there has been much progress in cancer treatments and a substantial amount of research shows that pregnancy termination does not improve cancer prognosis, many oncologists are not experienced with dealing with a cancer patient who is also with child or are concerned about being liable for harming the fetus. Pregnant women may also be afraid to undergo treatment while pregnant. "Some pregnant women choose to delay treatment in order to preserve the pregnancy, others do not," says Dr. Lloyd H. Smith, a US-based oncologist at the UC Davis School of Medicine.

Comprehensive Study Shows Children Whose Mothers Had Chemotherapy During Pregnancy Develop Normally

The first study evaluated 68 pregnancies that produced 70 children, following the children up to 18 months of development. On average, each woman received 3 or 4 cycles of chemotherapy during her pregnancy, and the children were born at a median of 36 weeks into the pregnancy. Premature births were more common, with more than two-thirds of the women giving birth prior to 37 weeks.

Chemotherapy treatment was strictly delivered after the first trimester in all women. The researchers measured the children's health, behavior, hearing, and growth and found that all aspects correlated well with children of the same age whose mothers were not exposed to chemotherapy during their gestation. There were subtle changes in cardiac and neurocognitive measurements that may require longer-term follow-up. However, the authors believe that this result is not unique to children exposed to chemotherapy during development and the difference is found in all children born prematurely.

European Oncologists Emphasize Pregnancy Does Not Have a Deleterious Effect on the Prognosis of Cervical or Ovarian Cancers

The second publication outlines the best course of action for the assessment and treatment of pregnant women with a gynecological cancer. Dr. Morice and colleagues believe that for early-stage cervical cancer during the first and second trimester, women without nodal spread and small tumor size can postpone treatment until either the third trimester or delivery as long as the patient is carefully monitored. Locally advanced cervical disease is noted as controversial, however, with neoadjuvant chemotherapy as an option that should be assessed on an individual patient basis.

"I agree with Dr. Morice," said Dr. Nicoletta Colombo, associate professor in obstetrics and gynecology, at the European Institute of Milan, Italy. "There is room to preserve pregnancy particularly when the tumor is small and confined to the cervix. In our experience even bigger tumors could be managed conservatively by administering chemotherapy, but this should be carefully discussed with the patient since the topic is more controversial. For ovary (early stage), the same consideration are valid," she added.

Dr. Smith believes that while there is hope for women, and that the technologies and therapies are getting better, it is still a personal choice for the patient and depends on the comfort level of the clinician as well.

"My first obligation as a gynecologic oncologist is to advise my patients of treatment recommendations to optimize their own survival and function. For pregnant women, this may mean the loss of the pregnancy. For those who wish to preserve the pregnancy, there is increasing evidence that it is safe to do so if the length of the delay can be minimized (early obstetric delivery as soon as the fetus can survive normally), and the patient can be frequently clinically evaluated and sometimes partially treated during the delay," he said.

Dr. Smith cautions that delaying treatment can cause cancer progression that can affect treatment outcomes. "I have personally seen cases of cervical and ovarian cancer progress during pregnancy when longer delays have been chosen by patients whose first priority is the pregnancy. While we are getting better at delaying delivery for pregnant patients with cervical or ovarian cancer who choose this approach, many women will still elect to initiate treatment immediately to optimize their chances of cure."

Goal of Treatment of Pregnant Women With Breast Cancer Should Be Normal-Term Pregnancy

Dr. Amant and colleagues highlight that the majority of pregnant women can have surgery, chemotherapy, or both and aim to have a normal-length pregnancy. The authors emphasize that termination of the pregnancy does not improve the outcome for the mother.

While radiation therapy should be avoided, as it is difficult to protect the fetus from this treatment, chemotherapy can be given in the second or third trimester using the same guidelines as for nonpregnant women. The researchers emphasize that chemotherapy has not been shown to do harm to the fetus, citing the first paper by Dr. Amant as evidence. They do not recommend breast-feeding in the first few weeks after chemotherapy, however.

"The new insights we gained during our research facilitate cancer treatment and provide hope for mother and child in most cases. Most mothers feel stronger and are even more motivated to undergo the cancer treatment and its side effects, since she is fighting for her child as well," said Dr. Amant of the research.

Blood Cancer Complications Often Lead Oncologists to Advise Early Termination of Pregnancy

Because chemotherapy needs to be administered promptly for patients with Non-Hodgkin lymphoma, acute leukemia, and other blood cancers, waiting until the second or third trimester is not advisable. Dr. Benjamin Brenner of the department of hematology and bone marrow transplantation at the Rambam Health Care Campus in Haifa, Israel, and colleagues advise that early termination may be necessary in some cases. Blood cancers also increase the risk of blood clotting which are more frequent during pregnancy, posing a formidable risk for pregnant women. The authors state that at later pregnancy stages, the fetus can be preserved and the cancer treated.

Women who do undergo treatment during pregnancy need prophylaxis from potential venous thromboembolism. A subsequent pregnancy within 2 to 3 years after remission is also to be avoided, as there is greater recurrence during this time period.

Studies such as these are important to raise awareness and to educate clinicians on the options of cancer treatment during pregnancy. Patients can benefit from learning that other women have gone through the same ordeal. Support groups are available for these women and studies such as these can help them make an educated decision.

"The patient has autonomy of choice and there is some risk in [delaying treatment]. The risk in delaying treatment is cancer progression and reduced prognosis," said Dr. Smith, emphasizing the point of view of the oncologist-preserving the health and life of the patient, mother-to-be.