Anastrozole was found to be at least as safe and effective as tamoxifen in preventing breast cancer recurrence in women with ductal carcinoma in situ, in the large NSABP B-35/SWOG-35 study.¹ Among all women in the trial, however, the 10-year breast cancer–free interval rates were higher in women taking anastrozole than tamoxifen (93.5% vs 89.2%).

This is the first study to compare an aromatase inhibitor vs tamoxifen in ductal carcinoma in situ, the earliest form of breast cancer sometimes considered precancer. Breast cancer–related death is uncommon in women treated with lumpectomy and radiation for ductal carcinoma in situ, like the women in this study. Other studies have compared the two drugs in more invasive forms of cancer.

“The good news is tamoxifen and anastrozole are both very effective, but it seems that women have better chances of staying well with anastrozole. Women will need to discuss the risks and benefits of both drugs with their doctors, because the side-effect profiles differ,” said lead author Richard G. Margolese, MD, Professor of Surgical Oncology, Jewish General Hospital, McGill University, Montreal, Canada.

He emphasized that adverse events are uncommon with these drugs—from 1% to 3% of all women treated. “Depending on the drug, the side effects are different. It is a personal choice that a woman should make with her physician about the relative benefits of a reduced chance of recurrence, with respect to the differing safety profiles,” Dr. Margolese commented at a press conference.

Other experts at the 2015 ASCO Annual Meeting, where these data were presented, were quick to note that this study expands the options for treatment of ductal carcinoma in situ and does not represent one standard of care.

Study Details

The study randomized 3,104 postmenopausal women with hormone receptor–positive ductal carcinoma in situ to treatment with 5 years of daily tamoxifen or anastrozole. Prior to randomization, all women had been treated with lumpectomy and radiation and were stratified by age: < 60 years vs ≥ 60 years.

At an average follow-up of 8.6 years, 114 cancers were identified in the tamoxifen group vs 84 in the anastrozole group. The 10-year breast cancer–free rates by age were similar in older women: 92.2% for anastrozole vs 88.2% for tamoxifen. There was a larger difference among younger women: 94.9% with anastrozole vs 88.2% with tamoxifen, but this difference was not explainable by body mass index, death due to other causes, or compliance. “We are still looking for other reasons [for this difference],” Dr. Margolese said. “It is a stimulus for further research.”

Overall, there was a 45% relative risk reduction for invasive recurrences with anastrozole, he continued. The number of recurrences was 60 in the tamoxifen group vs 30 in the anastrozole group. The numbers of recurrent ipsilateral or contralateral ductal carcinoma in situ cases were relatively small and not statistically significant between the two treatment arms, but the number of contralateral invasive cancers was significantly reduced in the anastrozole arm.

There were eight deaths due to breast cancer in the tamoxifen group and five deaths in the anastrozole group.

As for expected side effects, there was a slight increase in the cases of uterine cancers with tamoxifen vs anastrozole: 17 cases vs 8 cases. The average annual rate of the number of new osteoporotic fractures per 1,000 women was increased in women receiving anastrozole (69 vs 50 events), but this difference was not statistically significant.

“Severe adverse events were uncommon in general and less common with anastrozole. Events of concern with tamoxifen are thromboembolism and uterine cancer,” he said.

Dr. Margolese did not report in detail on quality of life and other side effects in the trial, including arthralgias and myalgias, which are commonly experienced by women taking aromatase inhibitors. He said a separate analysis of these events would be reported in the future.

Additional Comments

“In my view, this does not set a single standard of care for all women with ductal carcinoma in situ,” said ASCO expert Don S. Dizon, MD, Clinical Co-Director of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Boston. “The main take-away point is that we now have a new breast cancer prevention option for women treated with ductal carcinoma in situ.”

“Until now, the only option for adjuvant medical treatment of ductal carcinoma in situ was tamoxifen. The availability of both drugs means there are choices, and we can individualize therapy,” Dr. Dizon stated at a press conference.

“Patients will make this choice depending on what motivates them. For some women with ductal carcinoma in situ, the main fear is recurrence. For others, the fear of toxicity is more important,” Dr. Dizon noted.

The formal discussant of this trial, ­Joseph Sparano, MD, of Montefiore Medical Center and Albert Einstein College of Medicine, New York, said: “Anastrozole and probably other aromatase inhibitors are a good option for preventing ipsilateral recurrence and contralateral breast cancers in women with ductal carcinoma in situ. Anastrozole is probably more suitable for younger patients who are postmenopausal and have a history of thromboembolism.” ■

Disclosure: The study was funded by the National Institutes of Health. Drs. Margolese and Sparano reported no potential conflicts of interest.

Reference

1. Margolese RG, Cecchini RS, Julian TB, et al: Primary results, NRG Oncology/NSABP B-35. 2015 ASCO Annual Meeting. Abstract LBA500. Presented May 30, 2015.