Treatment of postmenopausal women with ductal carcinoma in situ (DCIS) with the aromatase inhibitor anastrozole resulted in higher breast cancer–free survival rates compared with standard treatment with tamoxifen. These results (abstract LBA500) were presented today in a press conference at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2, 2015, in Chicago.
The 10-year breast cancer-free survival rates in the federally funded phase III trial were 93.5% in the anastrozole group compared with 89.2% in the tamoxifen group. The study was funded by the National Institutes of Health.
According to study presenter Richard G. Margolese, MD, professor of surgical oncology at the Jewish General Hospital, McGill University in Montreal, this is the first study to compare an aromatase inhibitor to tamoxifen in women with DCIS.
“I do not think this sets a single standard of care for all women with DCIS,” Don S. Dizon, MD, clinical co-director of gynecologic oncology at the Massachusetts General Hospital Cancer Center in Boston, told Cancer Network. Dr. Dizon was not involved in the trial. “The more important point is that we now have an additional option for breast cancer prevention for women treated for DCIS.”
“The availability of both drugs, anastrozole and tamoxifen, means choices, so we can now individualize therapy more,” added Dizon. “Until now, the only option for adjuvant medical treatment of DCIS was tamoxifen.”
This NSABP B-35/SWOG-35 study randomized 3,104 postmenopausal women with hormone receptor–positive DCIS to either daily 20 mg tamoxifen or 1 mg anastrozole for 5 years. All patients in the trial also had a lumpectomy and radiation therapy prior to starting their assigned 5-year regimen.
After a median follow-up of 8.6 years, 84 patients in the anastrozole arm and 114 patients in the tamoxifen arm were diagnosed with breast cancer—including both recurrences of DCIS or the development of invasive breast cancer in either the same or the other breast (hazard ratio [HR] = 0.73; P = .03). Anastrozole seemed to reduce the diagnosis of a second primary breast cancer in the other breast, but this trend was not statistically significant (HR = 0.68, P = .07).
“While anastrozole does reduce the risk of breast events compared to tamoxifen, notably, it may be of more use in younger postmenopausal women who are under 60 years,” said Dizon.
A subpopulation analysis showed that in women over 60 years, tamoxifen is more effective (P = .04). The breast cancer–free survival in women 60 years and over was similar in both the anastrozole and tamoxifen treatment arms (92.2% and 90.2%, respectively, P = .77). But a larger percentage of women younger than age 60 were breast cancer free when treated with anastrozole (94.9%) compared with tamoxifen (88.2%; P = .003).
Women diagnosed with DCIS have an increased risk of later being diagnosed with invasive breast cancer. However, women with DCIS who undergo a lumpectomy and radiation therapy rarely die of invasive breast cancer.
There were eight deaths from breast cancer in the tamoxifen study arm compared with five deaths in the aromatase inhibitor arm. The 10-year overall survival rates were comparable—92.5% and 92.1% in the anastrozole and tamoxifen groups, respectively.
Sixty-three women in the tamoxifen arm and 39 women in the anastrozole arm were diagnosed with invasive breast cancer (HR = 0.61, P = .02).
The toxicity profiles of both therapies were similar. Anastrozole resulted in faster development of osteoporosis and a higher rate of bone fractures compared with tamoxifen, although the difference was not statistically significant (50 and 69 fractures per 1,000 women annually in the tamoxifen and anastrozole arms, respectively).
Tamoxifen was linked with higher rates of uterine cancer, but this increase was not statistically significant. The annual rates of uterine cancers were 17 and 8 per 1,000 women in the tamoxifen and anastrozole arms, respectively.
“The side effects described here are uncommon and borderline rare,” said Margolese during the press briefing. “It becomes a personal decision [for the patient] to discuss with her clinician. For some women the benefit will be attractive.”
Patients and clinicians need to consider potential side effects of both treatments, especially because these therapies are not likely to impact overall survival. “Tamoxifen can increase the risk of blood clots and is associated with a risk for endometrial cancer, which presents with dysfunctional uterine bleeding,” said Dizon. “Aromatase inhibitors, including anastrozole, result in muscle and joint aches and pains, and in women with invasive breast cancer, is one of the reasons that treatment is discontinued. The aromatase inhibitors can also impact bone health and strength and can cause more issues in terms of vaginal health and sexual function,” added Dizon.