CHICAGO (FRONTLINE MEDICAL NEWS)The aromatase inhibitor anastrozole reduces the risk of disease recurrence better than tamoxifen for postmenopausal ductal carcinoma in situ (DCIS), particularly in younger women, preliminary results of a phase III study show.

At 10 years, 93.5% of women treated with anastrozole ( Arimidex ) were breast cancer free, compared with 89.2% of women treated with tamoxifen ( Nolvadex ) (hazard ratio, 0.73; P value = .03).

This benefit was driven by a significant effect for anastrozole in younger women aged less than 60 years (HR, 0.52; P = .003), but not in those aged 60 years and older (HR, 0.95; P = 0.77). The interaction between treatment and age was statistically significant (P = .04), Dr. Richard Margolese reported in a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology.

“We now have another option for adjuvant therapy with DCIS. Women can take tamoxifen or anastrozole and, if they’re in the right group, it might be preferable to take anastrozole,” Dr. Margolese , professor of surgical oncology at Jewish General Hospital, McGill University, Montreal, said.

Aromatase inhibitors have been shown in invasive cancer to be superior to tamoxifen with regard to improved disease-free survival (DFS) and reduced contralateral breast cancer.

To determine whether they could offer better suppression with fewer side effects in DCIS, investigators for the NRG Oncology/NSABP B-35 study randomly assigned 3,104 postmenopausal women with DCIS treated by lumpectomy to tamoxifen 20 mg/day or anastrozole 1 mg/day, each for 5 years plus breast radiation. Patients could have estrogen receptor– or progesterone receptor–positive disease. Most were white (87.4%), and 53% were at least 60 years old. Median follow-up was 9 years.

At 10 years, DFS rates were similar between the anastrozole and tamoxifen groups (82.7% vs. 77.9%; P = .21).

When broken down by age, however, once again the benefit with anastrozole was significant in younger women (HR, 0.69, P = .02), but not in older women (HR, 1.03; P = .79), Dr. Margolese said.

Overall survival rates at 10 years were similar at 92.1% in the tamoxifen group and 92.5% in the anastrozole group (P =.48).

The number of uterine cancers, one of the more worrisome side effects of tamoxifen, was reduced from 17 with tamoxifen to 8 with anastrozole, but the confidence intervals were too wide to be meaningful (relative risk, 0.47; 95% CI, 0.18-1.15), he said.

As expected, osteoporotic fractures were higher with anastrozole at 69 vs. 50 with tamoxifen, but the difference also was not significant (RR, 1.38; 95% CI, 0.95-2.03).

With respect to thromboembolic events, grade 2 deep vein thrombosis was reported in 4 patients treated with tamoxifen and 1 treated with anastrozole. In the tamoxifen group, 20 patients had grade 3 pulmonary embolism, and 17 had grade 4 life-threatening PE, compared with 8 and 3 patients, respectively, in the anastrozole group. There was one thromboembolic death, with anastrozole, Dr. Margolese said.

Grade 0-1 hot flashes were more common with anastrozole than tamoxifen (965 events vs. 881 events), while the reverse was true for grade 2 hot flashes (570 events vs. 654 events). No grade 3 or 4 events occurred.

Joint and muscle pains are widely known to be a problem peculiar to aromatase inhibitors, but a self-report system showed roughly equal rates of these events in the two groups, Dr. Margolese said. Most tamoxifen and anastrozole patients reported low-grade 0-1 arthralgia events (1,177 vs. 1,031), with fewer grade 2 (302 vs. 427) or grade 3 (55 vs. 77) events, and only 1 grade 4 event with tamoxifen. Myalgia followed a similar pattern: grade 0-1 events (1,367 vs. 1,317), grade 2 (150 vs. 187), grade 3 (18 vs. 30), with 1 grade 4 event with anastrozole.

“Anastrozole is quite a suitable drug for treatment of DCIS,” Dr. Margolese said. “The safety factors and contraindications show it to be less of a problem than tamoxifen, especially in the possibly life-threatening side of the contraindications, and it is at least as effective, and in some groups more effective than tamoxifen.”

Finally, anastrozole reduced the number of contralateral invasive breast cancers from 36 with tamoxifen to 20. This translated into a significant 55% risk reduction (HR, 0.55; P = .03), which compares favorably with a roughly 50% reduction for tamoxifen in prior breast cancer prevention studies and raises the question of anastrozole as a prevention therapy, he said.

During a press briefing on the study, concerns were raised about the side effects associated with aromatase inhibitors. Dr. Margolese responded that the choice of therapy is a personal judgment to be made with a woman’s physician. For some women, the trauma of a cancer diagnosis drives the decision to take adjuvant therapy, while for others potential side effects weigh more heavily.

ASCO expert Dr. Don Dizon agreed and said the results of B-35 answer a very important clinical question and will allow physicians who treat women with DCIS to counsel them on an individual level about their treatment options.

The study was funded by the National Institutes of Health. Dr. Margolese reported no relevant conflicts of interest. Dr. Dizon reported employment and a consultant or advisory board role with UpToDate and research funding to his institution from AstraZeneca and GlaxoSmithKline.

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