Victoria is a San Francisco Chronicle staff writer.
Natalie DiMarco's only obvious risk factor for getting lung cancer was having lungs.
"I'm young, didn't have any history of smoking, and that's why a doctor didn't X-ray me from the beginning," said DiMarco, now 36, who lives in Penngrove with her husband, daughters, ages 5 and 6, and a teenage stepson.
An estimated 4,600 to 6,900 people under 40 in the U.S. are diagnosed every year with lung cancer that has no apparent cause.
The disease appears to be quite different from the lung cancer found in longtime smokers and, aside from initial research that indicates that young patients, like DiMarco, tend to share certain genetic changes, the source remains a mystery.
A new study just getting under way hopes to find out more about these patients, what they have in common and, potentially, why they get lung cancer. If researchers can find a common thread, or several, it could lead to more effective treatment or point the way to new targeted therapies.
The $300,000 Genomics of Young Lung Cancer Study is small - just 60 patients - but the lead researchers hope it will help find the answers they're looking for and even help others with lung cancer, particularly the 15 percent of the nearly 230,000 Americans diagnosed with lung cancer each year who have never smoked.
Addario Lung Cancer Medical Institute, a partner organization of the Bonnie J. Addario Lung Cancer Foundation in San Carlos, initiated and is paying for the study along with Genentech.
Not much is known.
Bonnie Addario, who was diagnosed with lung cancer in her mid-50s in 2003 and founded the organizations that bear her name, said much is unknown about this population of patients because it's never been systematically studied.
"We're hoping to find something that may be in another cancer or another disease that could be part of their therapy," she said.
Dr. Barbara Gitlitz, a lead researcher of the study and director of the lung, head and neck program at the University of Southern California's Norris Comprehensive Cancer Center, said the disease should be thought about as its own entity.
"We may discover that by looking at the genomics of these people, we may find driver mutations. We'll see patterns that might be specific to this population and we might see something new," she said.
Time is of the essence, considering how devastating a lung cancer diagnosis is.
"What we're hearing quite often is that they're athletes and they're very fit - the people you would least expect to have cancer, let alone lung cancer," Addario said.
She added that the disease appears to be more common in young, nonsmoking women than in their male counterparts.
Inspired by Cal athlete.
Researchers do know that young people and nonsmokers with non-small-cell lung cancer - the most common kind - typically have alterations in their genes that can affect how the disease is treated.
The genetic mutation found most often - EGRF, for epidermal growth factor receptor - occurs in about 10 to 15 percent of non-small-cell lung cancer patients.
But a host of other known mutations - ALK, ROS1, BRAF, HER2, MET, RET - have also been identified as contributing to lung cancer in young patients, said Dr. Geoffrey Oxnard, a lung cancer specialist at the Dana-Farber Cancer Institute in Boston, also a lead researcher of the study.
Drugs have been developed in recent years to "target" those mutations, or go after those specific cells to thwart their growth. The first EGRF therapies, AstraZeneca's Iressa, or gefitinib, was approved by federal regulators in 2003 followed by Roche's Tarceva, or erlotinib, in 2005.
But even these relatively new treatments don't cure the disease; at most they buy time - from several months to five years - before the cancer returns.
Oxnard said he hopes the study - which will test for more than 200 mutations - will not only show a pattern of these genetic alterations but also spotlight the necessity for young and nonsmoking people to get genetically tested after diagnosis, which is not routinely done in all centers.
"We know comprehensive genetic testing has the potential to make a difference in any cancer patient, but we think in these patients, it's really going to be transformative," Oxnard said.
DiMarco, who hopes to participate in the study, said she learned her genetic subtype by seeking out specialists around the country. Almost by chance her biopsy was tested by a Boston surgeon for the ROS1 alteration, which in 2010 was just newly identified.
The mutation makes DiMarco a candidate for a drug called crizotinib, sold under Pfizer's brand name Xalkori. DiMarco, who has undergone numerous rounds of chemotherapy and radiation, has not yet resorted to Xalkori because she and her doctors want to keep that in the arsenal to use only if and when it becomes necessary. So far her disease has been kept in check, and she's been off chemotherapy for 17 months while undergoing regular scanning.
Like DiMarco, Goldman has tested positive for the ROS1 mutation and has also chosen to hold off on Xalkori after receiving other therapies in combination with traditional chemotherapies.
"I have that in my back pocket to use next," she said, referring to the Pfizer drug.
Goldman, who may not be eligible for the study now that she's 41, said the stigma of lung cancer because of its connection to smoking causes her to hesitate about naming her disease and then assert she's never smoked. But she speaks out about having lung cancer because she says she has to.
"People need to know this happens. I'm not a fan of smoking, but nobody deserves to get cancer," she said. "Smoking is a contributor to breast cancer and heart disease and other disease, but people don't ask you if you caused this yourself."
Goldman's latest scan showed her tumors had shrunk or remained stable, with the exception of one tiny new spot. But she tries to retain a sense of normalcy, particularly for her kids, ages 8 and 11.
"How do you live with something like this hanging over your head?" she said. "You just can't live like every day is your last."
Living in the present.
DiMarco manages by incorporating Chinese medicine - acupuncture, massage, cupping therapy - into her life. As far as her young children know, their mom has some "bad cells in her body" that "made a spot in her lung" and that she has to take medications to get rid of it.
While DiMarco knows she's been dealt a difficult hand, she tries to live in the present but look to the future about the potential treatment options.
"It's all about what card you play that buys you the most time," DiMarco said. "If I understand what to do now ... I can sleep easier and not have to worry. But I need to have a plan. I need to know, what do we do next?"
About lung cancer:
- Every year, more than 228,000 people are diagnosed with lung cancer in the U.S. and about 160,000 will die of the disease.
- An estimated 7,000 to 9,000 people under age 40 are living with lung cancer. The average age at diagnosis is 70.
- Lung cancer takes more lives than any other cancer. It accounts for 27 percent of all cancer deaths - more than breast, prostate and colon cancers combined.
- Funding for lung cancer lags behind other cancers, especially considering the impact of the disease. The federal government spent $315 million on lung cancer research in 2012 compared with $603 million for breast cancer.
- Most people diagnosed with lung cancer are former smokers or people who've never smoked - about 15 percent have never smoked and more than 50 percent have smoked in the past but quit.