Lung Cancer Risk Higher in Women Smokers but Survival Better

NEW YORK, July 11 -- Women who smoke appear more susceptible to tobacco carcinogens than men, but women's lung-cancer death rate is lower, according to researchers here on the basis of a screening study.

For women smokers, the risk of lung cancer was almost twice that of men's risk, although their lung-cancer death rate was lower by about half, reported Claudia Henschke, Ph.D., M.D., of Weill Cornell Medical College here, and colleagues, in the July 12 issue of the Journal of the American Medical Association.

Lung cancer now accounts for more deaths in women than any other cancer, more even than the second and third cancer killers (breast and colon cancer) combined, Dr. Henschke wrote.

In a study of 7,498 women and 9,427 men, at least 40 years old, with a history of cigarette smoking, lung cancer was diagnosed in 156 women and 113 men (rates of 2.1% and 1.2%, respectively). Controlling for age and pack-years of smoking, the prevalence odds ratio (OR) comparing women with men was 1.9 (95% CI, 1.5-2.5), Dr. Henschke's team reported.

However, the hazard ratio of fatal outcome of lung cancer comparing women with men was 0.48 (95% CI 0.25-0.89), when controlling for pack-years of smoking, disease stage, tumor cell type, and resection, the investigators reported.

The non-experimental, etiologic study from the International Early Lung Cancer Action Program, involved the prospective collection of baseline lung-cancer CT screening data and follow-up of diagnosed lung cancer cases in North America in a combination of two series from 1993 to 1999 and 1999 to 2005.

In commenting on possible confounding factors, the researchers wrote:

• It was unlikely that the pursuit of a malignancy diagnosis was more vigorous among women screenees, because the diagnostic protocol was the same for both sexes and its recommendations were followed equally, and the proportions of small tumors under 10 mm were similar for both sexes.
• It did not seem that women were more likely to present themselves for screening because of possible risk or cancer-suggestive symptoms. If this were the case, the tumors would more likely have been larger and symptomatic. Actually the proportion of tumors more than 20 mm was lower in the women.
• The degree of aggressiveness of the women's tumors tended to be slightly lower than that of the men's. But if in 10% of the women's cases the growth rate was, for example, half of that in the men's cases, this would have made the prevalence OR no higher than 1.1%.

The hypothesis that women may be biologically more susceptible to tobacco carcinogens is entirely plausible, Dr. Henschke said. Studies have been mixed, she said, but if additional studies add supporting evidence to the notion of women's susceptibility, serious consideration is warranted.

If the risk for women is higher, as these findings suggest, then "antismoking efforts directed toward girls and women need to be even more serious than those directed toward boys and men," the investigators wrote. It would also call for screening at lower levels of smoking history than the corresponding indication threshold in men, they added.

As for the difference in cancer survival, stage at diagnosis, cell type, or treatment do not appear to entirely explain the difference, the investigators said. "It is not clear whether this survival difference is because lung cancer in women tends to be more commonly curable or less malignant," they wrote.

They concluded that if lung cancer is more curable in women "then the need to screen women at a lower threshold than men is warranted." But if lung cancer is less malignant in women, "then there may be less need to screen women at a lower threshold."

In an accompanying editorial, Alfred Neugut. M.D., Ph.D., and Judith Jacobson, Dr. P.H., M.B.A., of Columbia y in New York wrote that the findings of this "important study" with regard to female susceptibility are "provocative." But, they added, the analysis in the context of a screening study "raises concerns about the possibility of overdiagnosis bias, in which a significant excess of lung cancers may be diagnosed in which unknown gender differences may play a role."

As for women's survival advantage, they said the reasons are unclear. Do women fare better, they asked, because of their body size, better health behaviors, hormonal and reproductive factors, different smoking patterns, or other factors?

Women's advantage in survival, they said, appears to be a host effect and applies to all major histological types of lung cancer. Tumor biology appears to play a key role, they wrote, adding that an effort to understand the tumor and host factors could potentially yield major benefits for both sexes.

The once prevalent adage, "You've come a long way, Baby," now unfortunately applies to lung cancer risk among women, they wrote. "To prevent gender equality in lung cancer from becoming a reality, it's now time to turn back."