Minnie and Paul Narth found out in the second trimester of her pregnancy with their son, Kieron, that she had cancer.

Minnie and Paul Narth spent their first wedding anniversary in the hospital. It wasn’t terribly romantic — Minnie wore a hospital gown, and an IV fed medication into her arm as she toasted the day with a glass of grape juice — but the Narths were content. It was the evening of Aug. 8, 2009, and Minnie, 37 weeks pregnant, was having labor induced. In a few hours, the Narths would meet their eagerly awaited baby boy. And they had good news from Minnie’s obstetrician, who thought she could avoid a cesarean section, which would carry high risks in her fragile medical state.

Minnie Narth’s immune system was running a marathon. She had spent the last three months fighting an extremely aggressive form of lymphoma.

Twenty years ago, the happy scene in Minnie and Paul’s delivery room at Lucile Packard Children’s Hospital could probably not have happened. For decades, pregnant women with cancer were almost universally advised to terminate their pregnancies. Oncologists saw pregnancy as a liability — not only could cancer treatments harm the fetus, doctors thought, being pregnant might worsen the cancer prognosis.

The Narths were surprised to learn about Minnie’s treatment options.

“Our concern was — give chemo while she’s pregnant?” says Paul. The response he remembers from Stanford lymphoma specialist Ranjana Advani, MD, was, “Of course we can!”

The surprise is understandable, says Richard Theriault, MD, a breast oncologist at MD Anderson Cancer Center in Houston who has studied cancer and pregnancy for 20 years. Expectant mothers arrive for treatment having spent months avoiding pregnancy no-nos like poached eggs, sushi, aspirin.

“We basically tell them, don’t breathe, don’t do any of these things — but we’re going to give you chemo,” Theriault says. “It does sound really crazy, doesn’t it?”

When Paul and Minnie married on Aug. 8, 2008, his parents and her large, close-knit Filipino family were ecstatic. The news of her pregnancy a few months later added to everyone’s joy. She was 38 and hadn’t been sure she would ever have children — the pregnancy felt like “such a gift,” she says.

Then came the heavy bleeding and contractions, the rushed trip to her doctor, the ambulance ride to Packard Children’s.

“The doctors came back and said it was cancer,” says Paul, remembering the day in May 2009 that his six-months-pregnant wife was diagnosed with stage-4 diffuse large B cell lymphoma. “I went to pieces.”

Minnie’s first reaction was denial: “It’s impossible that I have cancer everywhere, all of a sudden.”

Her own doctor had thought the on-and-off bleeding Minnie experienced throughout the pregnancy was due to a benign dermatologic condition, lichen planus, inside her vagina. But Minnie also had a new lump in one breast, she told obstetrician Natali Aziz, MD, and the maternal-fetal medicine team at Packard Children’s, who took over her care after she arrived at the hospital via ambulance. Suspicious, Aziz — who specializes in high-risk pregnancies — admitted Minnie to the hospital and called for a full diagnostic workup.

Minnie’s parents happened to be arriving the next morning from the Philippines for a visit to Paul and Minnie’s Menlo Park home. Paul picked them up at the airport, telling them all he knew — that the doctors suspected Minnie had cancer.

 

At the hospital later that day, the diagnosis was confirmed. An MRI scan, chosen because it wouldn’t require radiation exposure, showed that Minnie had tumors in her vagina, breast and ovaries. “The one thing I can never forget is my dad’s face,” Minnie says. At the news of her diagnosis, her father, usually a tremendously talkative person, was speechless.

A delayed diagnosis like Minnie’s is unfortunately not unusual. Obstetricians see few cancers, so they sometimes mistake early cancer signs, especially with tumors of the breast or reproductive organs, for side effects of pregnancy. For instance, pregnant breast cancer patients are diagnosed two to six months later than non-pregnant women, researchers estimate. But as more women delay childbearing, cancer in pregnancy is becoming more common, with one in 3,000 to one in 10,000 pregnancies now affected by malignant disease.

In one sense, Minnie’s late diagnosis was lucky. If the cancer had been discovered in her first trimester, she would have been strongly encouraged to abort, because chemotherapy can’t be given while the fetal organs are forming. Fortunately, the scientific debate that raged during the 1980s and ’90s about continuing pregnancy after a second- or third-trimester diagnosis has been resolved, with researchers concluding that staying pregnant does not impede a woman’s ability to survive cancer.

Minnie was relieved to know that her disease could be treated without ending her pregnancy. The diagnosis became a motivation to fight for her family.

“It took me a while to find Paul, to even think that I was going to have a child,” she says. “There was no way I was going to give that up without a fight.”

“She’s my hero,” Paul says, listening to his wife. He began learning all he could about lymphoma, a mechanism for coping with his fear that he would lose his wife, the baby or both.

Minnie urgently needed chemotherapy. But first, Aziz had to check on the baby and review obstetric considerations with Minnie and Paul. In theory, she could have performed a cesarean right after diagnosis, but it was highly debatable whether this would have been better for the baby than continuing the pregnancy while Minnie received chemo.

“She was only about 26 weeks along,” Aziz says. “Delivering the fetus that early would pose significant prematurity risks, which are far greater than those posed by chemotherapy.”

So Aziz performed an ultrasound and a fetal non-stress test to provide a baseline for monitoring the baby’s growth. She gave steroids to mature his lungs as a hedge against early delivery. And she did a baseline echocardiogram of the baby’s heart because Advani planned to give Minnie a cancer drug that could have cardiac side effects. The fetal assessment was the beginning of a well-coordinated dance between the high-risk obstetrics team at Packard Children’s and the adult oncology team at Stanford Hospital & Clinics, as both groups kept watch over two intertwined lives.

The fetus evaluated, Minnie began receiving a standard mixture of lymphoma drugs: cyclophosphamide, doxorubicin, vincristine and prednisolone. A fifth drug, the monoclonal antibody rituximab, was omitted. Advani’s decision not to give the medication illustrates a classic dilemma of cancer treatment in pregnancy.

 

“Rituximab is the one biggest advances in lymphoma in the last decade,” Advani says. However, the literature contains scant reports of its use in pregnant patients, and although the rituximab molecule is theoretically too large to cross the placenta, there are limited data available regarding its safety in pregnancy. “What if it’s harmful to the baby?” Advani says.

There’s no good way to find out. Ethical and practical restrictions prevent the clinical trials and pharmacokinetic studies normally used to assess chemotherapy drugs.

“A lot of the science is missing,” says MD Anderson’s Theriault. “We don’t know what happens to these drugs in pregnant women — how they’re cleared, what the levels are.” Though there is more scientific literature on cancer and pregnancy than there was when he first treated a pregnant breast cancer patient in 1989, research is still sparse.

A few observations suggest that the body’s handling of chemo drugs in pregnancy may not be straightforward. For one thing, pregnant women experience few side effects from chemo — they have much less chemo-related nausea than other patients, for instance. Also, “most of our pregnant cancer patients are bald at delivery, but the babies have a full head of hair,” Theriault says. “So that’s odd.”

Physiologic changes in pregnancy, such as greater blood volume and altered blood filtering by the liver and kidney, could theoretically change drug metabolism. Plus there’s the unknown factor of the placenta. The molecules of some chemo drugs are too big to pass through the placenta’s mesh-like membranes and cross into the fetal circulation, but many are quite small. Possibly the placenta filters some of them anyway, though no one knows how.

To improve the educated guesswork involved in giving chemotherapy to a pregnant woman, oncologists draw upon a few sources of information. Some chemo medications have clear contraindications for pregnancy. Thalidomide, known for causing birth defects in the 1960s, is today used for chemo in non-pregnant patients; it’s unequivocally avoided in pregnant women.

“A lot of the science is missing. We don't know what happens to these drugs in pregnant women.”

Scientists are also tracking large groups of mother-child pairs who received chemo during pregnancy. Theriault is following more than 90 women who had breast cancer treatment at MD Anderson while pregnant; Advani is working with colleagues across the country to write up a series of outcomes for pregnant lymphoma patients.

And finally, oncologists rely on old-fashioned caution.

“I recheck with the pharmacy the safety of nausea drugs, antacids, things I normally prescribe and don’t think twice about,” Advani says, “When someone’s pregnant, there’s an extra responsibility.”

Obviously, no one would give a powerful drug to a pregnant woman without good cause. “You have to put it in the context of cancer — what the consequences would be of not treating,” Theriault says.

On this point, Advani is bluntly clear: “If you don’t do anything, the patient dies.”

As Minnie’s pregnancy progressed, Aziz continued to manage her obstetric course with the oncology team and monitor the baby, whom Paul and Minnie decided to name Kieron Anthony, a choice that combined their own middle names. (Paul’s given name is Paul Kieron Carl; Minnie’s middle name is Antonia.) Frequent ultrasounds and fetal non-stress tests showed the little guy was growing and doing well.

Minnie’s tumors were shrinking, too. The vaginal tumor had originally been so large it would have obstructed delivery, but by the time her pregnancy reached 37 weeks, it was undetectable. Aziz was relieved. “The truly remarkable aspect of Minnie’s delivery planning was that we were able to decide from a medical standpoint that she was safe to have a vaginal delivery, considering the obstructive vaginal mass we saw at diagnosis,” she says. Aziz felt that a cesarean would have carried extra risks for Minnie’s chemo-weakened body and could have slowed her recovery from the birth and return to cancer treatment.

A few hours after Paul and Minnie toasted their anniversary, there was again a celebratory mood in the delivery room as Kieron prepared to make his appearance. “My older sister was there, and she was,” Minnie pauses, laughing, “filming the damn thing.”

Then she grows more serious, describing how the nurses whisked newborn Kieron away so quickly for testing that she didn’t get to give him the first hug she’d imagined. “All I wanted was to hold him,” she says.

Nonetheless, Minnie and Paul were jubilant. Kieron was healthy and had — yes! — a full head of jet-black hair.

Advani soon came to Packard Children’s to meet the baby. “It’s a joy to see a newborn, especially when the mother has been through so much,” she says.

 

A week after delivery, Minnie began having unexplained new symptoms and received a whole-body CT scan. The news was unexpectedly bad: She had tumors in her kidneys and her brain. She was switched to a different, more intense chemotherapy regimen, including methotrexate, a drug avoided in pregnancy because it induces miscarriage. She spent several days in Stanford Hospital in an extremely fragile state.

This was one of the hardest periods for Paul. Today, Minnie says she never seriously considered the possibility that she might not be around to see Kieron grow up; Paul’s response is, “She’s much better than I was.”

“Initially it was, lose her; then, lose both of them; or then it was, we have to choose,” he says. “And then we were OK, and then I was going to lose her again.”

 

A few weeks later, when Minnie’s hold on life seemed especially tenuous, the Narths decided to have Kieron baptized at Stanford Hospital. Minnie is Catholic and Paul, Hindu. They plan to expose Kieron to both faiths. “I asked the social worker if she could schedule a baptism while I could still hold him,” Minnie says. Together with a Catholic priest, a nurse, a few friends and Minnie’s sister, the Narths celebrated their tiny son’s baptism in one of the hospital’s gardens.

The next several months were a blur: powerful systemic chemotherapy that got rid of the tumors in Minnie’s body, then, to target the brain tumor, surgery to implant a port that would deliver chemo directly to it. Soon after surgery, a terrifying 45-minute seizure. Then more chemo. Then, Minnie’s doctors determined that the chemo wasn’t eliminating the brain tumor, so she had 13 rounds of whole-brain radiation.

Throughout this time, Paul kept a very close watch on his wife. An engineering manager at Hewlett-Packard, he often worked from her hospital bedside — the connection to his job helped the medical odyssey feel more normal, he says. At home, he watched for signs that she might be going downhill. During one ER visit, Paul rattled off a string of Minnie’s recent lab results to the medical resident attending to them.

“Are you a doctor?” the resident said, startled. The Narths laugh about this now.

“My friend Anna Mae says, ‘Go, Paul!’” Minnie says. “He knew my history inside and out. I don’t think I would have survived anything without him.”

As Minnie lay with her head immobilized in a mesh mask to receive her whole-brain radiation, she calmed herself by visualizing Paul and Kieron as superheroes, a strategy inspired by her husband’s heroics and Kieron’s tiny Superman costume. “During each session I would imagine them blasting away the tumors,” she says, raising one arm in a streamlined superhero salute.

Minnie’s continued treatment left her with almost no energy for Kieron. “It was a little heartbreaking for me because I couldn’t take care of him,” she says. During periods in the fall of 2009 when Minnie was well enough to be home, the two nannies who took turns caring for the baby would put him to sleep and then bring him to Minnie so they could nap together. She was too exhausted for much else. “Kieron was very close to his nannies,” she says. “It’s hard that they saw his milestones, and I only got them secondhand. But there was no choice.”

“I don’t think you missed a huge amount,” Paul says gently to his wife. “It was better that he was so young.”

Today, 2-year-old Kieron obviously has a strong bond with both parents. He has the bright eyes and wide, baby-toothed grin of a happy little boy, and a sharp interest in gadgets, too. “Don’t type, Kieron!” both parents say when he gets dangerously close to an open laptop.

Paul and Minnie are keeping an eye out not just for mischief but also for possible aftereffects of the chemo. They had a scare when a friend suggested Kieron’s speech was delayed, but a formal assessment reassured them that his language development is on track. And they’re comforted by the news that, in general, babies who get chemotherapy in the womb seem to do well. The first baby in Theriault’s case series is now a healthy 22-year-old, and a group in Mexico City that has followed “chemo babies” even longer than Theriault has documented that these young people can have healthy children of their own.

 

Epilogue:

After Minnie’s radiation treatments put her brain tumor into remission, she received an autologous stem cell transplant February 2010 to lower the chance that her disease would relapse. In August of that year, the Narths threw a big party to celebrate Minnie’s good health, their second anniversary and Kieron’s first birthday. Aziz remembers feeling overwhelming joy as she watched Minnie interacting with her family: “I kept thinking of the wonders of the medical therapy that enabled her to get to that point,” Aziz says. “And also, here was this sweet little boy who, during his gestation, had undergone such an amazing experience with his mother … here he was beautiful, healthy and able to enjoy the love of his mother and father. It was the most wonderful celebration.”

Now in remission for more than a year, Minnie suffers some short-term memory problems but is otherwise healthy. She’s caring for Kieron and enjoying the ordinary fun that comes with being the mother of a toddler: playing together, listening to music and dancing, taking him to preschool. And she ran the San Francisco Nike Women’s Marathon in October.

 

E-mail Erin Digitale