Systematic reviews have shown that lutenizing hormone-releasing hormone agonists, including goserelin, reduce the risk of disease recurrence and death due to breast cancer in premenopausal women. However the long-term impact of goserelin was not known, particularly in comparison to women who did or did not take tamoxifen.

Women with breast cancer were randomly assigned to take goserelin (Zoladex), tamoxifen, both agents, or neither drug for two years in the Zoladex in Premenopausal Patients study. In this analysis, which included 2,706 women, Allan Hackshaw, of the Cancer Research UK Trials Centre at University College London, and colleagues examined the long-term impact of the agents on various outcomes, including the risk of the cancer returning and the risk of dying from breast cancer or any cause.

The effect of two years of goserelin treatment was comparable to that conferred by two years of tamoxifen. Among patients who took goserelin alone, there were 13.9 fewer events per 100 women 15 years after starting treatment, compared with those who did not take either drug. Among women who took both drugs, the benefit of adding goserelin to tamoxifen was smaller (2.8 fewer events per 100 patients) and did not reach statistical significance.

The number of breast cancer deaths was lower by 8.5 per 100 women in those who took goserelin alone, compared to those who took neither drug. The difference was statistically significant. Among those who added goserelin to tamoxifen, there was an additional reduction of 2.6 deaths per 100 women. But again, the additional reduction was not statistically significant.

"In summary, long-term follow-up of our large trial showed that goserelin had a demonstrable effect on survival and recurrence 15 years after starting treatment and is as effective as tamoxifen when each are given for 2 years," the authors write. "It may be that women who are unlikely to complete 5 years of tamoxifen tablets may prefer 2 years of goserelin injections."

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Each additional alcoholic drink regularly consumed per day was associated with 11 additional breast cancers per 1000 women up to age 75; one additional cancer of the oral cavity and pharynx; one additional cancer of the rectum; and an increase of 0.7 each for esophageal, laryngeal, and liver cancers. For these cancers combined, there was an excess of about 15 cancers per 1000 women per drink per day. (The background incidence for these cancers was estimated to be 118 per 1000 women in developed countries.)

"Although the magnitude of the excess abso?¬lute risk associated with one additional drink per day may appear small for some cancer sites, the high prevalence of moderate alco?¬hol drinking among women in many populations means that the proportion of cancers attributable to alcohol is an important public health issue," the authors write.

In an accompanying editorial, Michael Lauer M.D., and Paul Sorlie, Ph.D., of the National Heart, Lung, and Blood Institute, in Bethesda, M.D., emphasize that these new results derived from such a large study population should give readers pause. Although previous epidemiological studies have suggested that there is a cardiovascular benefit associated with moderate alcohol consumption, the excess cancer risk identified in the current study may outweigh that benefit. "From a standpoint of cancer risk, the message of this report could not be clearer. There is no level of alcohol consumption that can be considered safe," the editorialists write.

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