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Anastrozole prolongs breast cancer-free survival following DCIS diagnosis
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CHICAGO — Anastrozole prolonged the breast cancer-free interval compared with tamoxifen in postmenopausal women with ductal carcinoma in situ who underwent lumpectomy, according to results of a phase 3 study presented at the ASCO annual meeting.
Although aromatase inhibitors and tamoxifen have been used to prevent advanced breast cancer recurrence, this study marks the first time they were compared in women with ductal carcinoma in situ (DCIS), according to the researchers.
Both agents target the estrogen growth signal — which hormone receptor-positive breast cancer relies on to grow — but operate in different ways. Tamoxifen blocks ER, preventing estrogen from reaching the cancer cells, whereas anastrozole slows down or stops the manufacturing of estrogen, according to the researchers.
“The good news is tamoxifen and anastrozole are both very effective, but it seems women have better chances of staying well with anastrozole,” Richard G. Margolese, MD, the Herbert Black Chair in Surgical Oncology and past director of the department of oncology at McGill University’s Jewish General Hospital, said in a press release.
Margolese and colleagues compared the long-term efficacy of the two agents in a population of 3,104 postmenopausal women with ER-positive or PR-positive DCIS who underwent a lumpectomy between 2003 and 2006. Researchers stratified patients according to age (younger than 60 years vs. 60 years or older) and randomly assigned women 1:1 to receive
20 mg daily tamoxifen or 1 mg daily anastrozole for 5 years.
The primary endpoint was the breast cancer-free interval — defined as the time from randomization to any breast cancer event including local, regional or distant recurrence or contralateral disease, invasive disease or DCIS — and DFS and OS served as secondary endpoints.
Researchers evaluated available follow-up information from 3,083 patients for OS and 3,077 patients for all other disease-free endpoints.
After a mean follow-up of 8.6 years, 114 breast cancers occurred in the tamoxifen arm compared with 84 in the anastrozole arm (HR = 0.73; P = .03).
A significantly greater proportion of women in the anastrozole arm achieved 10-year breast cancer-free survival compared with women in the tamoxifen arm (93.5% vs. 89.2%). A time-by-treatment interaction indicated that this effect wasn’t evident until later in the study (P = .02). The researchers noted there was a significant interaction between treatment and age group (P = .04) and that only women aged younger than 60 years benefited from anastrozole.
Further, 260 DFS events occurred in the tamoxifen group compared with 235 in the anastrozole group (HR = 0.89). The estimated rates for 10-year DFS were 77.9% for tamoxifen and 82.7% for anastrozole.
Overall, 186 deaths occurred during the study, which included 88 in the tamoxifen arm and 98 in the anastrozole arm (HR = 1.11). Eight women died due to breast cancer in the tamoxifen arm and five women died due to breast cancer in the anastrozole arm.
The 10-year point estimates for OS were similar between the two arms (tamoxifen, 92.1%; anastrozole, 92.5%).
Sixty-three cases of invasive breast cancer occurred in the tamoxifen arm, whereas 39 occurred in the anastrozole arm (HR = 0.61; P = .02).
The researchers also noted there was a trend toward a reduction in second primary breast cancer incidence with anastrozole (HR = 0.68); however, the researchers did not consider this association statistically significant.
There was no major difference in toxicity between the two agents. More women who received anastrozole experienced bone fractures and more women assigned tamoxifen experienced uterine cancer; however, neither difference between the two drugs was considered statistically significant. More safety data are scheduled for presentation later in the conference.
“The adverse effects described here are uncommon and bordering on rare,” Margolese said during a press briefing. “They happen, but they are in the 1% to 3% range. More women than that will have some untoward side effects like hot flashes and so on, 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.
“It’s not an overwhelming, knock-your-socks-off type of decision,” Margolese said. “There is a benefit and for some reason, for some women the benefit will be attractive and for others they will be in a position to say, ‘I don’t think the risks are worth it and the advantages don’t seem to balance them, so I’ll stay out of it.’”
Although anastrozole only conferred a 4% higher survival rate and still had toxicity, Margolese said that the benefit may not be measurable in the data alone and that having an individualized treatment option can be beneficial for a patient.
“We tend to look at gains which are small or scant as if they are not worth the effort,” Margolese said. “But there is a whole array of emotions, psychology and physical problems that go with the recurrence of cancer. … A benign breast biopsy is not a benign experience. So, you have to let women make the decisions for themselves.” – by Anthony SanFilippo
Reference:
Margolese RG, et al. Abstract LBA500. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: Margolese reports no relevant financial disclosures. See the full study for a complete list of disclosures for the other researchers.
Perspective
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Don S. Dizon, MD
Women with DCIS already have several great treatment options and now they have one more. [This study] provides us additional ways to individualize therapy. Before these results, we had tamoxifen, and the discussions here concerned the benefits of reducing the risk for recurrence without an overall survival advantage and the potential risk that you could get endometrial cancer vs. not if you didn’t take the drug. Ultimately, people are going to make distinctions in their own minds for their own reasons. If the side effects are present will they really care about the recurrence risks if there is no survival advantage? Our patients who have to face that decision are very diverse on how they come down on that. For some women the risk of relapse — after what they’ve been through and the trauma of an initial diagnosis — is not an experience they want to go through and are more likely to take an adjuvant treatment. Others are very afraid of these toxicities and would prefer not to do anything. That’s part of the individualization of therapy. Patients and their doctors should still consider all of their options.
Perspective
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Robert Wesolowski, MD
The reason I found this study less important is because patients with DCIS have an excellent prognosis. When the survival at 5 years is nearly 100%, you want to ask yourself whether you want to add more toxicities and costs to a patient’s therapy, and what kind of benefit would justify that. If the difference is modest, you have to ask yourself if you prefer the toxicities of tamoxifen or the toxicities of anastrozole. It is certainly an important study for breast cancer, but I can see that many oncologists still will consider tamoxifen to be a very viable option — especially for women who are at risk for anastrozole-induced toxicity, such as osteoporosis, hip fractures, arthritis, etc. Further, there seems to be a benefit in younger women vs. older women; however, we know that breast cancer tends to be slightly slower in progression in older women, and it is more responsive to endocrine therapy. So, perhaps older women do not live long enough to develop recurrence, and the recurrence usually develops later than in younger women.Click Here to Manage Email Alerts