ASCO 2015: Anastrozole Offers Higher Breast Cancer–Free Interval Rates Than Tamoxifen Following Lumpectomy and Radiation for DCIS
A phase III trial comparing 5 years of tamoxifen vs 5 years of the aromatase inhibitor anastrozole for postmenopausal women treated for ductal carcinoma in situ (DCIS) found 10-year breast cancer–free interval rates were higher in the anastrozole group than in the tamoxifen group (93.5% vs 89.2%). The benefit was primarily seen in women < 60 years old. Results were presented at the 2015 ASCO Annual Meeting in Chicago (Abstract LBA500).
“The good news is that tamoxifen and anastrozole are both very effective, but it seems that women have better chances of staying well with anastrozole,” said lead study author Richard G. Margolese, MD, Professor of Surgical Oncology at Jewish General Hospital, McGill University, in Montreal. “This represents the first trial for anastrozole vs tamoxifen for DCIS,” Dr. Margolese noted at a press briefing, and it also represents an important step along a treatment path that has included breast-conservation therapy and tamoxifen as adjuvant therapy.
Difference Was Statistically Significant
While breast cancer–related death is uncommon following DCIS treated with radiation and lumpectomy, women with DCIS are at increased risk of developing invasive breast cancer. To compare breast cancer–free interval rates, the investigators randomly assigned 3,104 postmenopausal patients with hormone receptor–positive DCIS to 5 years of tamoxifen at 20 mg/d or anastrozole at 1 mg/d and placebo. Breast cancer–free interval, the primary endpoint of the study, was defined as time from randomization to any breast cancer event, including local, regional, or distant recurrence or contralateral disease, invasive disease, or DCIS.
Prior to starting hormone therapy, all study participants had undergone lumpectomy with clear resection margins and radiation therapy. All the women were postmenopausal and were stratified by age as < 60 or ≥ 60 years.
With a mean follow-up time of 8.6 years, 114 breast cancer–free interval events were detected in the tamoxifen group compared to 84 in the anastrozole group. The difference in 10-year breast cancer–free interval rates, 93.5% with anastrozole vs 89.2% with tamoxifen, was statistically significant (hazard ratio [HR] = 0.73, P = .03).
Conspicuous Difference in Younger Women
Increasing the breast cancer–free interval “was done conspicuously” in women younger than 60 years old, Dr. Margolese said. Breast cancer–free interval rates at 10 years were 88.2% in the tamoxifen group vs 94.9% in the anastrozole group (HR = 0.52, P = .003). “In women older than 60, they all do well; tamoxifen and anastrozole are of equivalent benefit, and there are no significant differences,” Dr. Margolese noted. Breast cancer–free interval rates at 10 years were 90.2% in the tamoxifen group vs 92.2% in the anastrozole group (HR = 0.95, P = .77).
“We do not have a good explanation for this,” Dr. Margolese said. “It requires more biologic probing, which is another object of clinical trials, to use the results as a biologic probe to see if we can learn something useful.”
Ipsilateral recurrences and contralateral breast cancer were both reduced with anastrozole compared to tamoxifen, and for invasive contralateral breast cancer, the incidence “was cut by almost half” (HR = 0.55, P = .03), Dr. Margolese noted. “All of the events in the anastrozole group are less than the events in the tamoxifen group, but they are not statistically significant and all of the numbers are relatively small.”
Concerns About Uterine Cancer and Fractures
“With tamoxifen, one of the more worrisome side effects was always the increased risk of uterine cancer,” Dr. Margolese pointed out. In the current study, there were 17 cases of uterine cancer among women receiving tamoxifen vs 8 for women receiving anastrozole, but the difference did not reach statistical significance. “So the evidence is that tamoxifen does carry a slight risk of uterine cancer,” Dr. Margolese stated.
“The number of osteoporotic fractures would be expected to be higher with anastrozole because it inhibits the production of estrogen,” Dr. Margoles said. The number of these fractures was higher with anastrozole, 69 vs 50 with tamoxifen. “But again the results are not significant in the statistical sense,” Dr. Margolese said.
“The severe adverse reactions are uncommon and they are a little bit less common with anastrozole. So it might turn out to be the preferable treatment for adjuvant treatment with DCIS, especially for women for whom there is concern about thromboembolism or uterine cancer because of various features in that person’s history,” said Dr. Margolese. “So all in all, we believe that this is a safer and more effective drug for the treatment of DCIS.”
Opportunity to Further Individualize Therapy
In response to a reporter’s question about whether the side effects of either treatment might outweigh the benefit, Dr. Margolese replied: “The adverse effects described here are uncommon, bordering on rare. They happen, but are in the 1% to 3% range. More women than that will have untoward side effects such as hot flashes,” he noted, and data on that will be published later.
“So it becomes a personal judgment as to whether a patient, in discussion with her physician, wants to use the adjuvant treatments in the hope of gaining some benefit in terms of decreased incidence of recurrence and especially of invasive cancer. It is not an overwhelming ‘knock-your-socks-off’ kind of decision. There is a benefit, and for some women, the benefit will be attractive. For others, it will be their decision to say, ‘I don’t think the risks are worth it, and the advantages don’t seem to balance, so I’ll stay off it.’”
ASCO spokesperson and press briefing moderator, Don S. Dizon, MD, said, “I would agree with that. It does provide us additional ways to individualize therapy. A lot of my own patients did not want the risk of uterine cancer, although I do agree with Dr. Margolese that the risk is actually quite small. But now I can say if that’s not what you want to deal with, let’s talk about the use of anastrozole.” Dr. Dizon is Clinical Co-Director of Gynecologic Oncology and Director of the Oncology Sexual Health Clinic at Massachusetts General Hospital, Boston.
The study received funding from the National Institutes of Health. For full disclosures of the study authors, view the study abstract at abstract.asco.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
