More Evidence That Estrogen Modifies Lung Cancer Outcome

Zosia Chustecka

January 25, 2011

January 25, 2011— More evidence that estrogen modifies the outcome of lung cancer comes from a huge study of women with breast cancer, about half of whom were taking antiestrogens such as tamoxifen.

Among the women who subsequently developed lung cancer, the use of antiestrogens was associated with a significantly reduced risk for death from lung cancer, compared with the general population.

The finding comes from a study published online January 24 in Cancer.

"Our results support the hypothesis that there is a hormonal influence on lung cancer, which has been suggested by findings such as the presence of estrogen and progesterone receptors in a substantial proportion of lung cancers," senior author Elisabetta Rapiti, MD, from the Geneva Cancer Registry, said in a statement.

"If prospective studies confirm our results and find that antiestrogen agents improve lung cancer outcomes, this could have substantial implications for clinical practice," she added.

Approached by Medscape Medical News for independent comment, Howard West, MD, from the Swedish Cancer Institute in Seattle, Washington, said: "These results are very provocative, especially since they are compatible with the findings from the Women's Health Initiative [WHI], which demonstrated a higher mortality rate from lung cancer in women who received estrogen and progestins, compared with the placebo arm."

"I completely agree that these results warrant prospective testing of antiestrogens," Dr. West continued. "Until we have results from such trials, I would be inclined to discuss these results with women who are taking hormone replacement therapy, as I already do, which may lead to their stopping hormone replacement therapy after considering the balance of benefit vs risk. I wouldn't, however, go so far as to say that these results justify giving antiestrogen therapy as a treatment for lung cancer."

Study Prompted by WHI Findings

The current study was, in fact, prompted by those findings on lung cancer from the WHI study, the authors explain.

When that finding was published, the WHI researchers noted that "treatment with estrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, [but] it increased the number of deaths from lung cancer, in particular deaths from nonsmall-cell lung cancer."

Dr. Rapiti and colleagues, including first author Christine Bouchardy, MD, hypothesized that if it is true that hormone therapy increases the risk for lung cancer death, then the use of antiestrogens should be associated with a decreased risk for lung cancer death.

This was, indeed, what they found.

The team analyzed data from 6655 women with breast cancer from the Geneva Cancer Registry, nearly half of whom (46%) had taken antiestrogens.

Over a median follow-up of 7.3 years, the researchers found that 40 of these women developed lung cancer. The incidence of lung cancer was similar in the group taking and the group not taking antiestrogens (P = .39).

The team then compared outcomes for this small group of women with population results from standardized mortality ratios.

They found that the incidence of lung cancer was similar among women who had and had not taken antiestrogens and the general population.

However, the risk for death from lung cancer was significantly lower in women who had taken the drugs than in those who had not, and than in the general population. Specifically, there were 87% fewer cases of death from lung cancer in the antiestrogen group than in the general population.

Lung cancer mortality rates were 9.2 per 100,000 for women taking antiestrogens and 45.0 per 100,000 for women not taking these drugs (P = .026).

The finding is unlikely to be due to differences in smoking, the authors note, because patterns of tobacco exposure were similar in the 2 groups. However, they also note that they obtained this information for only about half of the entire cohort.

New Evidence for the Role of Estrogen

The team concludes: "In analyses comparing tumor registry to population results from standardized mortality ratios, we found that antiestrogen treatment for breast cancer was associated with a reduced risk of death from lung cancer, providing new evidence on the role of estrogen in lung cancer progression."

"From a biological perspective, the observation that estrogen intake is associated with increased lung cancer mortality, and that antiestrogen treatment is associated with a decreased lung cancer mortality, as demonstrated in this study, strongly suggests that estrogens are involved in lung cancer progression," they add.

When approached for independent comment by Medscape Medical News, Dr. West noted that the finding showed a significant reduction in the rate of lung cancer mortality among women who were taking antiestrogens, compared with age-adjusted mortality rates in the general population.

"In fact, the rate was only 13% of the calculated result that would be expected, a statistically significant difference," he said.

"However, these results are predicated on a very small number of patients, compared with a prediction based on a model," Dr. West pointed out.

The study authors and Dr. West have disclosed no relevant financial relationships.

Cancer. Published online January 24, 2011.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.