1. Samson, Kurt

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Taking the nonsteroidal aromatase inhibitor anastrozole appears to protect high-risk postmenopausal women from breast cancer for years after discontinuing therapy, according to a 10-year analysis of data from researchers with the IBIS-II clinical trial, a double-blinded, randomized study in nearly 4,000 high-risk women.


The protective benefits continued for at almost 6 years after the women in the study had completed treatment, said Jack Cuzick, PhD, Co-Chairman of the International Breast Cancer Intervention Studies (IBIS).


"In 2013, we reported that in the first 7 years of follow-up, anastrozole significantly reduced breast cancer incidence compared with placebo and that it did so with very few side effects," he told a press conference during the 2019 San Antonio Breast Cancer Symposium. "Our new data show that, after a median of 10.9 years of follow-up, there continues to be a significant reduction in breast cancer incidence," said Cuzick, who also directs the Centre for Cancer Prevention at Queen Mary University, London.

Jack Cuzick, PhD. Ja... - Click to enlarge in new windowJack Cuzick, PhD. Jack Cuzick, PhD

"It is exciting to see that anastrozole has a continued impact on breast cancer incidence even after stopping treatment, as this strengthens the case for its use as a breast cancer prevention therapy," he said.


The IBIS-II clinical trial, conducted between 2003 and 2012, involved 3,864 postmenopausal women categorized as being at significantly increased risk of developing breast cancer. The women had two or more blood relatives with breast cancer, a mother or sister who developed breast cancer before the age of 50, or a mother or sister who had cancer in both breasts. A total of 1,920 subjects were randomly assigned to receive anastrozole therapy for 5 years, while the remaining 1,944 women were given a placebo. Five-year adherence to anastrozole treatment was 74.6 percent and 77.0 percent for women who were given the placebo.


After a median follow-up of 10.9 years, women in the anastrozole arm were 50 percent less likely than their counterparts who had been administered the placebo to have developed breast cancer. Moreover, no new adverse side effects emerged to add to those reported in 2013-mostly small increases in muscle aches and pains, as well as hot flashes-nor were there any excess fractures, Cuzick reported.


"The 50 percent reduction in likelihood of breast cancer incidence was slightly less than the 53 percent reduction we reported after the first 7 years of follow-up, but it is still a significant effect and larger than that seen for tamoxifen," Cuzick told reporters.


Another way to consider the data, he said, is that it translates into an estimated 29 women needing to be treated with anastrozole for 5 years to prevent one case of breast cancer during treatment.


"This is far fewer women than the estimated 49 women that need to be treated with tamoxifen for 5 years to prevent one breast cancer in the same time period," Cuzick noted. "Our new results strongly suggest that anastrozole should be the preferred therapy for breast cancer prevention in postmenopausal women at increased risk, with tamoxifen used for women who experience severe side effects from anastrozole."


He cautioned, however, that the preventive benefits of anastrozole were for women with estrogen receptor-positive breast cancer and ductal carcinoma in situ, but not in those with estrogen receptor-negative cancer.


At the time of the follow-up analysis, there had been 129 deaths, but no significant difference in all-cause mortality between the two groups. In terms of deaths from breast cancer, five women had died-two in the anastrozole arm and three among women who were administered the placebo.


"This is too few breast cancer deaths to determine if anastrozole reduces breast cancer mortality, so we are planning to follow the participants for longer to investigate this," Cuzick said.



There have been two large clinical trials that have demonstrated the benefit of aromatase inhibitors in healthy women at risk of developing breast cancer: IBIS-II and MAP.3, a randomized, placebo-controlled, double-blind trial of another inhibitor called exemestane.


In 2011, MAP.3 investigators reported that exemestane significantly reduced invasive breast cancers in a clinical trial involving 4,560 postmenopausal women at moderately increased risk of developing breast cancer who were treated either with placebo or the aromatase inhibitor. During a median follow-up period of 3 years, no serious toxic effects and only minimal changes in health-related quality of life were reported among women treated in the MAP.3 study.


The IBIS-II investigators designed the new trial to detect a 65 percent relative reduction in invasive breast cancer among postmenopausal women 35 years of age or older who had at least one of these risk factors: 60 years of age or older; Gail 5-year risk score above 1.66 percent-which indicates a 100 percent risk of developing invasive breast cancer within 5 years-prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ, or ductal carcinoma in situ with mastectomy.


The women received either anastrozole or a matching placebo for 5 years. The primary endpoint was prevention of breast cancer, while the secondary endpoints included prevention of estrogen receptor-positive breast cancer, breast cancer mortality, non-breast cancer deaths, other cancers, cardiovascular disease, fractures, and musculoskeletal events. After a median follow-up of 10.9 years, the researchers reported a total of 241 breast cancers.


Kurt Samson is a contributing writer.




* Cuzick Jm Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol 2015; 16: 67-75.


* Cuzick J, Sestak I, Baum M, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 2010; 11: 1135-1141.


* Goss PE, Ingle JN, Ales-Martinez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Eng J Med 2011;364:2381-2391.