ASCO 2009: HRT Increases Risk for Death from Non-Small-Cell Lung Cancer

Zosia Chustecka

May 31, 2009

May 31, 2009 (Orlando, Florida) — Another adverse effect from hormone replacement therapy (HRT) in postmenopausal women has emerged — the use of combined progestin and estrogen hormone therapy increases the risk for death from non-small-cell lung cancer (NSCLC).

Dr. Rowan Chlebowski (Photo courtesy of ASCO)

The finding comes from a secondary analysis of the Women's Health Initiative (WHI) study, which found that among current smokers who were using hormones, 1 in 100 experienced an avoidable death during the 8 years of the study.

"One in 100 is a colossal mortality for a treatment that is used for symptom management," said lead author Rowan Chlebowski, MD, PhD, medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.

The clear message is don't smoke and take hormones.

"The clear message is don't smoke and take hormones," Dr. Chlebowski told Medscape Oncology .The other message is that women who are taking hormones and who are diagnosed with NSCLC should stop taking the hormones, he added.

Dr. Chlebowski was speaking at a press conference here at the American Society of Clinical Oncology 45th Annual Meeting, where he presented the findings.

The moderator of the press briefing, Bruce Johnson, MD, director of the Dana-Farber Harvard Medical Center Lung Cancer Program, in Boston, Massachusetts, explained that these findings are robust because they come from a randomized clinical trial, where the effect of hormones was isolated. Many of the previous data about hormones and lung cancer have come from case–control studies. There are also preclinical data suggesting that estrogen can increase the growth of lung cancer, and so the finding "makes a lot of sense from a pathophysiological standpoint."

The new data showing an increase in mortality from NSCLC are "yet another reason not to take hormones," Dr. Johnson noted.

"We already know that combined hormone therapy has more risks than benefits, including a higher risk of stroke and breast cancer," said Dr. Chlebowski. These new data showing a link with death from NSCLC "should influence discussions between physicians and women considering hormone therapy use, especially those with a smoking history," he added.

About 15% of postmenopausal women in the United States currently use HRT, he said, which is about half the number doing so before 2002, when the WHI study was stopped prematurely because of the adverse effects of HRT. About 15% of postmenopausal women in the United States smoke, he added .

Effect on NSCLC, but Not on SCLC

The WHI was conducted in 16,608 mostly healthy postmenopausal women, aged 50 to 79 years, who were randomized to receive either placebo or combined hormone therapy with conjugated equine estrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg). The 2 groups were well balanced for all factors, including smoking.

The analysis for lung cancer was carried out after 5.6 years on the trial intervention and 2.4 years of additional follow-up. The incidence of small-cell lung cancer (SCLC) and deaths from SCLC were similar in the 2 groups. The incidence of NSCLC showed a nonsignificant trend toward an increase in the hormone group, whereas mortality after NSCLC diagnosis was significantly higher in the hormone group than in the placebo group (46.3% vs 27%, respectively; hazard ratio [HR], 1.59; P = .04).

As a result, women taking hormones were more likely to die from NSCLC than those taking placebo (p=.02), Dr. Chlebowski reported.

Dr. Chlebowski also presented absolute numbers:

  • For all participants, there were 67 deaths in the 8052 patients in the hormone group and 39 deaths in the 7678 patients in the placebo group (HR, 1.61).

  • For women who had never smoked, there were 9 deaths in the 4178 patients in the hormone group and 5 deaths in the 3999 patients in the placebo group (HR, 1.67).

  • For women who had smoked in the past, there were 29 deaths in the 3362 patients in the hormone group and 15 deaths in the 3157 patients in the placebo group (HR, 1.83).

  • For current smokers, there were 27 deaths in the 800 patients in the hormone group and 19 deaths in the 838 patients in the placebo group.


It was from the figures for current smokers that Dr. Chlebowski estimated the difference of 8 deaths in approximately 800 women, giving an excess risk for mortality of 1 in 100.

Asked to comment by Medscape Oncology, Julie Brahmer, MD, assistant professor at Johns Hopkins University in Baltimore, Maryland, who was not involved in the study, said the finding is "intriguing." Previous studies have hinted at an increase in the incidence of lung cancer in women taking hormonal therapy, but this study shows an increase in the risk of dying from NSCLC, she said.

"It adds credence to our discussions with patients," Dr. Brahmer added, "for when we sit down to discuss the pros and cons of hormone therapy, and ask: Is it worth it?"

For women who have been diagnosed with lung cancer, Dr. Brahmer said her advice is not to take hormones, or to stop taking them, although she added that each case has to be considered individually, to take into account how many postmenopausal symptoms are disrupting quality of life.

Dr. Chlebowski also emphasized this point, and noted that in the WHI study, about 30% of women who were diagnosed with NSCLC continued to take hormones. "The message now is that these patients should stop taking them," he said.

Dr. Chlebowski has acted as a consultant or in an advisory role and has received honoraria from for Amgen, Eli Lilly, Wyeth, AstraZeneca, and Novartis. Dr. Johnson has acted in a consultancy or advisory role with Genzyme; has stock ownership in Boston Scientific, Celgene, and Johnson & Johnson; and receives royalty payments from a license to Genzyme for doing EGFR mutation testing. Dr. Brahmer has acted as an adviser to AstraZeneca, Eli Lilly, and ImClone.

American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract CRA1500. Presented May 30, 2009. Abstract


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