How Does Hormone Replacement Therapy Affect Lung Cancer?

A new study in The Lancet looks at hormone replacement therapy, and concludes that while the combination of estrogen and progestin doesn’t increase women’s risk of lung cancer, it increases their risk of dying from the disease. This finding has generated a fair bit of media coverage, but – although the issue of HRT and lung cancer is an important one – the study itself is perhaps not as definitive as that coverage might suggest.

The authors analyzed data from the Women’s Health Initiative study, a trial of estrogen plus progestin hormone therapy in postmenopausal women that was stopped early when the associated health risks (including cardiovascular disease and breast cancer) were found to exceed the benefits. For this analysis, they looked at data on the incidence and mortality rates of all lung cancer, small-cell lung cancer, and non-small-cell lung cancer.

They found:

78 women in the combined hormone therapy group who had received a diagnosis of lung cancer died during follow-up, compared with 49 in the placebo group (0·12% vs 0·08%; HR 1·50, 1·05—2·14, p=0·03). Of these deaths, 73 (94%) in the combined hormone therapy group and 40 (82%) in the placebo group were directly attributed to lung cancer by chart review (HR 1·71, 1·16—2·52, p=0·01).

The impact of the study is limited, as the authors acknowledge, because of the unplanned post-hoc analysis (a statistically weak method), and because of the small number of lung cancers in the population (fewer thank 130 out of more than 16,000 women studied) and the absence of information on treatment after diagnosis. An accompanying commentary in the journal explains that “data on the effect of oestrogens on both the incidence of lung cancer and outcomes from lung cancer are controversial,” with conflicting findings and limited study designs.

Due to its limitations, the new Lancet paper does not provide strong evidence on whether hormone replacement therapy significantly raises the risk of death from lung cancer, but it may encourage future research and suggest something that should, as the authors conclude, “be considered before the initiation or continuation of combined hormone therapy in postmenopausal women, especially those with a high risk of lung cancer, such as current smokers or long-term past smokers.”

Related: The National Cancer Institute provides information on hormone replacement therapy and risks for breast, ovarian, colorectal, and endometrial cancer and related issues here.