For nearly 10 years, Dana Reeve helped her husband, Christopher Reeve, fight a good fight. Now she’s fighting one of her own, for her own life. And she’s not alone.

This story made headlines across the world, not just because Dana Reeve is famous, but also because she now personifies lung cancer in much the same way that Rock Hudson’s death personalized the AIDS epidemic. And lung cancer is indeed billowing into an epidemic, as it is now the No. 1 cancer killer of both women and men.

Reeve’s diagnosis, preceded only two days before with news of the cancer-related death of longtime ABC news anchor Peter Jennings, presents an opportunity to highlight that lung cancer claims more lives than colon, prostate, lymph and breast cancer combined. It’s also important to note the differences between women and men in lung cancer, according to the Society for Women’s Health Research (SWHR).

Founded in 1990, SWHR is the nation’s only non-profit organization that’s mission is to improve the health of all women through research, education and advocacy. The society encourages the study of biological sex differences between women and men that affect the prevention, diagnosis and treatment of disease.

Jo Parrish, vice president for institutional advancement with the Washington D.C.-based SWHR, says experts are only beginning to scratch the surface of all the medical-related gender differences. Prior to 1990, she says, research was typically done on middle-aged Caucasian males. Parish adds, “I think a lot of it was well-intentioned, but misinformed.”

“It began with a protectionist attitude that if you include women, particularly in their reproductive years, in medical research studies, there would be a risk to the fetus if they were to become pregnant,” Parrish explains. “Therefore, it was widely accepted – and policy, in fact, at the National Institutes of Health – that women were excluded from medical research studies. It was assumed that whatever worked on the typical, middle-aged male would work for women, perhaps in smaller dosages, because women were essentially just smaller men.”

One major discovery quickly surfaced once women were included in medical research studies: Women aren’t just small men. Parrish says research within the past 15 years shows gender affects elements from drug metabolism to symptoms shown for various diseases.

“Because we metabolize drugs differently, the dosage and perhaps the delivery system need to be different for certain drugs,” Parrish says. “In other cases, we learned that some drugs just work in one sex better than the other.”

But don’t jump out of your seat too quickly to celebrate in the name of new women’s health discoveries. Parrish says there can be anywhere between 15 to 20 years before new research is used in the physician’s office.

Here’s the dilemma. If women don’t present with the symptoms that have been studied traditionally, they may not receive as aggressive of treatments for some conditions.

Parrish says consumer awareness about the gender gap of lung cancer risk factors and symptoms is key to proliferating awareness in the medical field. Regina Vidaver, PhD, executive director of the Women Against Lung Cancer advocacy group based in Madison, Wis., has similar sentiments. She says the best-informed patient often feels most empowered in their treatment regimens, and she encourages patients to stay updated on these sex differences as well.

Others, such as Jyoti Patel, MD, thoracic oncologist at the Northwestern Memorial Hospital in Chicago, encourages medical professionals to muster up the initiative now. Patel says, “The time is ripe for investigation and enrollment in clinical trials for screening techniques or treatment outcomes.”

While much more research needs to be done to learn more, studies do suggest that differences in susceptibility exist based on genetic and hormonal profiles. The distinct gender-based variations are grouped into the following three categories, according to Patel:

• Genetic differences: Women are more likely to express certain genes that make them more likely to have damage from carcinogens. Research shows, Patel says, women may have higher levels of these genes, which makes them more prone to damage. In addition, women are more likely to have mutations in the p53 and K-ras genes. In fact, p53 mutations are more common in women smokers compared to women who have never smoked; this effect was not seen in men
• Molecular differences: There are notable differences across genders in the expression of tumor suppressor and oncogenes. Tumor suppressor genes repair DNA and maintain a certain level of health. Oncogenes, when over-expressed, lead to malignant potential. The epidermal growth factor receptor is an example, and mutations in this gene are more common in women than men
• Hormonal differences: Estrogen receptors are found in men and women, but the difference is with ambient estrogen and how it results in biological differences. For example, lung cancer sufferers that never smoked are more likely to be women. Also, adnocarcinoma, a cancer involving the cells lining internal organs, is more likely in women.

Understanding Sex Differences

According to the US Department of Health and Human Services, smoking causes approximately 80 percent of the lung cancer deaths in women in the United States. Several studies indicate, when compared to men, women who smoke are more likely to develop lung cancer at a younger age and at lower levels of exposure to cigarette smoke. Although a recent study sponsored by the National Cancer Institute (NCI) fueled controversy over the existence of sex differences in lung cancer risk by reporting equal risk between the sexes, SWHR maintains that sex differences are present in the histological, molecular and physiological aspects of the disease.

Nevena Damjanov, MD, associate professor of medicine at Temple University in Philadelphia, says there is another difference between men and women, but it’s less classifiable because it’s more mental than physical. Damjanov says women tend to complain much less than men because they are usually the caregivers. Coupled with the fact that women are in the physician’s office more often because they subscribe to the family caretaker role, women are taken less seriously.

“This is a problem for many diseases like lung cancer and heart disease,” Damjanov says. “If a woman comes in with a dry cough, she’s likely to just get a recommendation for Robitussin®. If a man comes in, it’s considered a major complaint because men don’t come in as often and aren’t thought to come into a doctor’s office over a minor complaint. With men, doctors tend to think of more serious illnesses with the same set of complaints between men and women.”

Vidaver says it’s imperative for physicians and researchers to put all things aside and be vigilant of these differences and new research findings so treatments can be best tailored to each individual.

In terms of ongoing research, much progress is being made. Vidaver says her organization is working with Christoph Plass, PhD, at the Ohio State University, Columbus, to institute research to understand sex differences in lung cancer to help propel the research forward.

One of the biggest recent discoveries made, Damjanov says, are less toxic agents like tyrosinase kinase inhibitors (TKIs). They act on the cellular level of the cancer cell and reduce mortality rates. She adds: “While we see that TKIs can be effective against lung cancer in both sexes, they seem to be much more reliably effective in women, especially non-smoking women of Asian decent. Ongoing research is trying to discover a way to predict which cancer cells are more likely to respond to certain agents. Because, as we all know, chemotherapy is like killing a mosquito with a bazooka.”

Looking for Lung Cancer

Studies have shown traditional chest X-rays do not catch lung cancer early enough to reduce the death rate, and that’s why some researchers are so enthusiastic about the new, more sensitive CT scans.

CT scans have been shown to detect lung cancers much earlier in smokers compared to an annual chest X-ray, Damjanov says. “The CT scan is a good tool for screening, the only problem is that it isn’t cost-effective,” she adds.

Claudia Henschke, PhD, MD started the Early Lung Cancer Action Program at New York Presbyterian Hospital, New York City, a decade ago and since then, more than 30,000 people received scans in the program.

The scan takes only a few minutes and delivers approximately 260 images of the lungs. In one patient, two tumors about 4 cm in size that were clearly visible on the CT scan did not show up at all on the X-ray. That’s why many people at high risk for lung cancer have chosen to undergo CT scans, even though they are not covered by insurance.

Money is proving to be an issue for many facets of lung cancer detection and treatment. The NCI estimates expenditures of approximately half as much on lung cancer research this year as it does on breast cancer research, even though lung cancer is expected to kill four times as many people.

Why is lung cancer neglected in comparison to other cancers? One reason is stigmatization. Lung cancer patients are frequently blamed for having smoked. “For lung cancer, there isn’t a big advocacy group behind it yet because it’s still perceived as a self-inflicted disease,” Damjanov says. “That stigma is really holding back awareness and treatments.”

But regardless of the stigmatization, SWHR and other organizations are chugging full steam ahead to make new discoveries and raise awareness about their findings. In 2006, SWHR plans to work with the Komen Foundation on a new network to analyze the biological gender differences in various cancers.

“It’s a slow process for the research and new findings to become accepted, and for consumers to be aware,” says Parrish. “But we are seeing noticeable improvements and that’s very encouraging.”


Amy Storer is the editor of TherapyTimes.com. Questions or comments can be directed to editorial@TherapyTimes.com.