This finding, presented here at the 32nd Annual San Antonio Breast Cancer Symposium, supports the hypothesis that estrogens play a role in lung cancer, said lead researcher Elisabetta Rapiti, MD, MPH, from the Geneva Cancer Registry at the University of Geneva in Switzerland.
Dr. Rapiti explained that the idea for the study was sparked by the report earlier this year of a link between lung cancer and hormone replacement therapy, based on an analysis of data from the Women's Health Initiative. These data suggested that hormone replacement therapy increases the risk of dying from lung cancer, especially nonsmall-cell lung cancer, although there was no increase in the incidence of lung cancer. This finding was reported in May 2008 by Rowan Chlebowski, MD, PhD, from the Harbor-UCLA Medical Center in Los Angeles, California, at the annual meeting of the American Society of Clinical Oncology, and subsequently published in The Lancet (2009;374:1243-1251).
"If hormones are associated with an increase in mortality from lung cancer, then maybe antiestrogens would be associated with a lower risk," Dr. Rapiti said.
To investigate this possibility, her team analyzed data from the Geneva Cancer Registry and identified 6715 patients with breast cancer between 1980 and 2003. Nearly half of these women (46%, n = 3066) received antiestrogen therapy, mostly tamoxifen.
In this patient cohort, there were 40 cases of lung cancer (diagnosed at least 6 months after the breast cancer). Of these, 12 cases (and 2 deaths) were found in women taking antiestrogens and 28 cases (and 16 deaths) were found in the remaining women.
Next, the team calculated standardized incidence ratios and standardized mortality ratios to compare the study population with the general female population in Geneva.
The incidence of lung cancer in both groups of women with breast cancer was similar to that of the general population, Dr. Rapiti said. Compared with the general population, the risk of developing lung cancer was 0.63 among women taking antiestrogens and 1.12 among those not taking these drugs.
Commenting on this finding, chair of the session, Patricia Ganz, MD, from the University of California in Los Angeles School of Medicine, told Medscape Oncology that the difference was not statistically significant, but that the rate was lower among women taking antiestrogens, and the "trend was clear." However, she added that there was likely to be an ascertainment bias here, in that these women with breast cancer would be followed and monitored more closely than women in the general population, and thus would be more likely to have lung cancer diagnosed if it did occur.
In addition, Dr. Rapiti made the point during the question period that women with breast cancer were likely to have received radiotherapy to the chest area, which increases the risk for lung cancer.
Significant Reduction in Risk for Death
When the researchers calculated mortality rates from lung cancer, they found a significant decrease in the risk for death from lung cancer in women taking antiestrogens. The rate in the general population was 31.44 per 100,1000; for women taking antiestrogens, it was 9.23 per 100,000, and for women not taking antiestrogens, it was 44.97 per 100,000. The standardized mortality ratio for lung cancer was significantly lower in women taking antiestrogens than in women not taking these drugs (0.13 vs 0.76; P < .001).
Women taking antiestrogens for the prevention of breast cancer had a significantly reduced risk of dying from lung cancer, Dr. Rapiti concluded. "This result further supports the role of estrogens in lung cancer prognosis and suggests that exposure to antiestrogens may offer some protection against tumor mortality."
She noted that there are phase 2 clinical trials currently underway that are evaluating the use of antihormone therapy as an adjunct to traditional chemotherapy for lung cancer. "If prospective studies confirm our results and find that antiestrogen agents improve lung cancer outcomes, this could have substantial implications for clinical practice," she said.
However, Dr. Rapiti emphasized, this is an observational study, and so "we cannot exclude residual confounding factors."
Approached for comment, Dr. Ganz said this finding is hypothesis-generating, and supports a role for estrogens and hormones in the control of lung cancer in women. She said this is an area of great interest at the moment, because other results are also pointing in this direction.
32nd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract 35. Presented December 11, 2009.
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