Hormone Replacement Therapy Linked to Risk for Death From Lung Cancer

Yet another reason to avoid Hormone Replacement Therapy.  Remember when pharmaceutical companies were advertising how great were the health benefits for all women to take HRT?  Wasn’t that long ago, was it.  Wonder how many women have died or been permanently injured?  Wonder why the same pharmaceutical companies are not required to advertise the below findings? 

**A. Jordan, RN – Legal Nurse Consultant

From Medscape Medical News CME

Hormone Replacement Therapy Linked to Risk for Death From Lung Cancer CME/CE

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

CME/CE Released: 09/29/2009; Valid for credit through 09/29/2010

September 29, 2009 — Hormone replacement therapy (HRT) using estrogen and progestin is associated with an increased risk for death from lung cancer, according to the results of an analysis of data from the Women's Health Initiative (WHI) trial reported in the September 20 Online First issue of The Lancet. These results were initially presented at the American Society of Clinical Oncology 45th Annual Meeting as reported by Medscape Oncology.

"In the post-intervention period of the...WHI trial, women assigned to treatment with oestrogen plus progestin had a higher risk of cancer than did those assigned to placebo," write Rowan T. Chlebowski, from Los Angeles Biomedical Research Institute at Harbour-University of California, Los Angeles, Medical Center, Torrance, California, and colleagues from the WHI Investigators. "Results also suggested that the combined hormone therapy might increase mortality from lung cancer. To assess whether such an association exists, we undertook a post-hoc analysis of lung cancers diagnosed in the trial over the entire follow-up period."

The WHI study, which was a randomized, double-blind, placebo-controlled trial performed at 40 US centers, was stopped early when health risks of HRT were found to exceed benefits. With use of a computerized, stratified, permuted block algorithm, 16,608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive a once-daily tablet of 0.625-mg conjugated equine estrogen plus 2.5-mg medroxyprogesterone acetate (n = 8506) or matching placebo (n = 8102). Data from treatment and postintervention follow-up periods allowed determination of incidence and mortality rates for all lung cancer, small-cell lung cancer, and non–small-cell lung cancer, with analysis by intent-to-treat. Mean treatment duration was 5.6 ± 1.3 years, and mean additional follow-up duration was 2.4 ± 0·4 years.

Lung cancer was diagnosed in 109 women in the combined hormone therapy group vs 85 in the placebo group (incidence per year, 0.16% vs 0.13%; hazard ratio [HR], 1.23; 95% CI, 0.92 - 1.63; P = .16). Non–small-cell lung cancer was diagnosed in 96 women in the HRT group vs 72 in the placebo group (0.14% vs 0.11%; HR, 1.28; 95% CI, 0.94 - 1.73; P = .12).

Mortality rate from lung cancer was greater in the combined hormone therapy group vs the placebo group (73 vs 40 deaths; 0.11% vs 0.06%; HR, 1.71; 95% CI, 1.16 - 2.52; P = .01). This excess mortality rate in the HRT group was primarily attributed to more deaths from non–small-cell lung cancer (62 vs 31 deaths; 0.09% vs 0.05%; HR, 1.87; 95% CI, 1.22 - 2.88; P = .004). Both groups had similar incidence and mortality rates of small-cell lung cancer.

"Although treatment with oestrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, it increased the number of deaths from lung cancer, in particular deaths from non-small-cell lung cancer," the study authors write. "These findings should be incorporated into risk–benefit discussions with women considering combined hormone therapy, especially those with a high risk of lung cancer."

Limitations of this study include post hoc analysis, small number of lung cancers and small-cell lung cancers, and absence of information on treatment after diagnosis. In addition, the results cannot be extrapolated to other oral or topical hormone treatments or other treatment durations.

"There were significantly more poorly differentiated cancers and cancers with metastatic spread in the combined hormone therapy group than in the placebo group," the study authors conclude. "These findings, together with the substantial increase in mortality after a diagnosis of non-small-cell lung cancer, suggest that the main effect of combined hormone therapy might be on stimulating growth of already established non-small-cell lung cancers."

In an accompanying comment, Apar Kishor Ganti, MD, from the University of Nebraska Medical Center in Omaha, discusses the clinical implications of these findings for women considering use of HRT for perimenopausal symptoms.

"Because the optimum safe duration of hormone-replacement therapy in terms of lung-cancer survival is unclear, such therapy should probably be avoided in women at a high risk of developing lung cancer, especially those with a history of smoking," Dr. Ganti writes. "These results, along with the findings showing no protection against coronary heart disease, seriously question whether hormone-replacement therapy has any role in medicine today. It is difficult to presume that the benefits of routine use of such therapy for menopausal symptoms outweigh the increased risks of mortality, especially in the absence of improvement in the quality of life."

The National Heart, Lung and Blood Institute, National Institutes of Health, funded this study. Some of the study authors have disclosed various financial relationships with AstraZeneca, Novartis, Lilly, Amgen, Pfizer, the National Institutes of Health, the National Cancer Institute of Canada, and/or Wyeth. Dr. Ganti has disclosed no relevant financial relationships.

Lancet. Published online September 20, 2009. Abstract

Additional Resource

More infomation about the Women's Health Initiative is available on the National Heart, Lung, and Blood Institute's Web site.

Clinical Context

The WHI study was stopped early because the risks for HRT exceeded the benefits in regards to cardiovascular disease, stroke, venous thromboembolism, and breast cancer. However, all-cause mortality rate was similar between HRT and control groups, but an additional follow-up of 2.4 years showed an excess risk for cancer in the HRT group. Estrogen has been shown to affect lung cancer, and it is uncertain if HRT affects the incidence and mortality rates from lung cancer.

This is an analysis of women in the WHI diagnosed with lung cancer to compare the incidence, type, and mortality from lung cancer of those assigned to HRT vs those assigned to placebo.

Study Highlights

• The WHI included postmenopausal women aged 50 to 79 years with an intact uterus from 40 US clinical centers, recruited from 1993 to 1998.


• Excluded were women with previous breast cancer, survival duration of less than 3 years, or other cancers within 10 years.


• Women taking HRT at baseline were included, with a 3-month washout period before randomization.


• 8506 women were randomly assigned to combined HRT consisting of equine estrogen 0.625 mg and medroxyprogesterone 2.5 mg daily, and 8102 were assigned to placebo.


• Drugs were discontinued if women went on to have breast cancer, endometrial pathologic disease, venous thromboembolic events, or malignant melanoma, or if they had used tamoxifen or androgens.


• Participants were contacted by telephone for clinical outcomes at 6-month intervals and were seen annually in clinic.


• Main outcomes were coronary heart disease, invasive breast cancer, stroke, embolism, colorectal and endometrial cancer, hip fracture, and death.


• Self-reports of lung cancer were confirmed by physician adjudicators at the local clinic.


• The intervention was stopped after 5.6 years when risks exceeded benefits, and WHI participants stopped taking study drugs.


• In post hoc analysis, incidence of all lung cancers, small-cell and non–small-cell lung cancers, and mortality from lung cancer was assessed.


• Chest radiology was not specified.


• 78% of women were aged 50 to 69 years, 84% were white, 74% had never used HRT, 11% were current smokers, and 43% had previously use oral contraceptives.


• At a mean follow-up of 7.9 years, 109 women in the combined HRT group had been diagnosed with lung cancer vs 85 in the placebo group (incidence per year, 0.16% vs 0.13%; difference not significant).


• The incidence of non–small-cell cancer did not differ significantly between groups overall (96 vs 72 cases; 0.14% vs 0.11%; difference not significant).


• However, after 5 years the incidence of non–small-cell lung cancer was higher in the HRT group.


• Cases of non–small-cell lung cancer with metastases or that were poorly differentiated were also higher in the HRT group.


• The incidence of small-cell cancer was similar in the 2 groups (13 in each).


• Mortality rates were 0.12% in the HRT group and 0.08% in the placebo group (HR, 1.5; P = .03).


• 94% of deaths in the HRT group and 82% in the placebo group were attributed to lung cancer (HR, 1.71; P = .01).


• Deaths attributable to non–small-cell lung cancer were higher in the HRT group (62 vs 31 deaths; 0.09% vs 0.05%; HR, 1.87; P = .004).


• Median survival time for those in the HRT group with non–small-cell lung cancer was 9.4 months vs 16.1 months in the placebo group.


• After 4 years from diagnosis, mortality rate was 70% in the combined HRT group vs 54% in the placebo group (HR, 1.59; P = .04).


• The effect of HRT on lung cancer mortality rate was not modified by age at screening, years since menopause, previous hormone use, or smoking status.


• The absolute increase in the risk for death from lung cancer in women in the combined HRT group vs women in the control group was higher in those who were current smokers vs never-smokers at baseline.


• Deaths from lung cancer accounted for 43% of excess total deaths in the postintervention period of the WHI.


• The authors concluded that women taking HRT who were at risk for lung cancer did not have a higher incidence of lung cancer but were more likely to have aggressive forms of lung cancer and to have poorer survival duration.

Clinical Implications

• Use of HRT in postmenopausal women is not associated with an increased incidence of lung cancer overall, but the incidence of non–small-cell lung cancer is higher.