Ductal carcinoma in situ is a relatively benign form of breast cancer (stage 0), yet up to 10% of women with ductal carcinoma in situ will have a recurrence within 10 years. At present, there is no way to identify which women will recur, so standard treatment is lumpectomy plus radiation therapy. Hormonal therapy is offered to women with estrogen receptor–positive ductal carcinoma in situ to prevent recurrence.

Two studies presented at the 2015 San Antonio Breast Cancer Symposium shed some light on how women with ductal carcinoma in situ who choose to take a hormonal agent can make the decision, in consultation with their oncologists, between an aromatase inhibitor, anastrozole, and tamoxifen. The bottom line is that the choice depends on patient preferences, side-effect profiles, and other risk factors.

The first study presented final results of the large, placebo-controlled IBIS-II DCIS trial that compared tamoxifen vs anastrozole in 2,980 postmenopausal women with ductal carcinoma in situ.¹ The key finding was that there was no significant difference between these two hormonal therapies in preventing recurrence at a median of 7.2 years of follow-up.

A second study compared patient-reported outcomes in a subgroup of 1,193 postmenopausal women with ductal carcinoma in situ treated with tamoxifen vs anastrozole in the large, randomized NSABP B-35 trial.² Again, the evidence suggests that either hormonal agent is a good treatment option for preventing breast cancer recurrence, but different symptom profiles for these agents can inform treatment selection. Side effects differed by age, and the pattern of severity of some symptoms was greater in younger women. For older women, since the treatment benefits are similar, treatment can be based on symptoms and tolerability.

IBIS-II DCIS Study Details

Both anastrozole and tamoxifen had a similar effect on preventing recurrence in postmenopausal women with ductal carcinoma in situ randomized to treatment with either drug. The rate of recurrence for all breast cancers (including invasive cancers and ductal carcinoma in situ) was 7.4% for tamoxifen vs 6.6% for anastrozole at a median follow-up of 7.2 years, representing 11% fewer recurrences with anastrozole. There were 67 cancers reported in the anastrozole group vs 77 in the tamoxifen group. The difference was not statistically significant.

In an exploratory post hoc subgroup analysis of rate of invasive breast cancers only, it appeared that tamoxifen was superior for estrogen receptor–positive/HER2-positive ductal carcinoma in situ, whereas anastrozole seemed to have a better effect in HER2-negative patients and estrogen receptor–positive/HER2-negative patients.

“The differences in efficacy were small. There is no clear difference between these agents in efficacy, but there were significant differences in toxicity profiles,” said lead author Jack Cuzick, MD, of the Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University London, London, United Kingdom. “Anastrozole is another agent to be considered for estrogen receptor–positive ductal carcinoma in situ for women who can’t take tamoxifen because of a history of deep-vein thrombosis or other factors.”

“The differences in side-effect profiles were expected, with the exception of an unexpected slight increase in stroke with anastrozole. This was not seen in other large trials of this agent, and the significance is unclear,” Dr. Cuzick said. “It appears to be a chance finding, and we need to look into it.”

In general, increases in fracture and joint-related symptoms were seen with anastrozole, and more vasomotor and gynecologic symptoms (except vaginal dryness) were seen with tamoxifen.

As expected, there were more gynecologic cancers in the tamoxifen group than in the anastrozole group (17 vs 1). Also, there were 23 skin cancers in the tamoxifen group compared with 12 in the anastrozole group. The difference in skin cancer was driven by nonmelanoma cancers (8 in the anastrozole group vs 19 in the tamoxifen group). Other cancers reported at slightly higher rates in the anastrozole group included gastrointestinal, lung, lymphoma/leukemia, and “other,” but these differences were not significant.

Again as expected, the rate of fracture was higher in the anastrozole group, with 129 fractures vs 100 in the tamoxifen group. Major thromboembolic events were reported more frequently with tamoxifen than with anastrozole (24 vs 7). They included pulmonary embolism (5 with anastrozole and 8 with tamoxifen) and deep-vein thrombosis (without pulmonary embolism) in 2 and 16 patients, respectively.

A surprising finding was that cardiovascular events, specifically stroke and transient ischemic attack, occurred more frequently in the anastrozole group. There were 13 strokes, vs 4 in the tamoxifen group, and 13 transient ischemic attacks, compared with 5 in the tamoxifen group.

NSABP B-35 Study Details

NSABP B-35 was also conducted in postmenopausal women with ductal carcinoma in situ. Previously reported results showed that anastrozole was slightly better than tamoxifen in preventing recurrence. The 10-year breast cancer–free interval rate was 89.2% for tamoxifen and 93.5% for anastrozole (P = .03). An interaction with age was observed, with significantly better results for anastrozole vs tamoxifen in patients younger than age 60 (94.9% vs 88.2% for tamoxifen, P = .04), whereas the rate of breast cancer–free interval was not significantly different for those over age 60 (92.2% vs 90.2%, respectively).

A battery of 5 different validated quality-of-life instruments assessed patient-reported outcomes in a subgroup of 1,193 women to explore how women who take these drugs actually experience them; 601 were randomized to tamoxifen and 592, to anastrozole. Patients were treated for 5 years. About 53% were age 60 or older, and about 47% were under age 60. The quality-of-life results were reported this year at SABCS and published in The Lancet online December 10, 2015, along with the primary trial results.³

Anastrozole significantly improved breast cancer free interval in women under age 60 (P = .003), but there was no significant quality-of-life benefit for either drug in women aged 60 or older.

“Both drugs are well tolerated in patients with ductal carcinoma in situ, but younger women under age 60 experience greater severity of some symptoms. The symptom profiles of both drugs differ in expected directions,” said lead author Patricia A. Ganz, MD, Director of Cancer Prevention & Control at UCLA’s Jonsson Comprehensive Cancer Center, Los Angeles, California.

“Tamoxifen significantly increased the severity of vasomotor symptoms, bladder control, and gynecologic symptoms compared with anastrozole, while anastrozole-treated patients had significantly increased severity of musculoskeletal and vaginal symptoms compared to tamoxifen. Patients under age 60 had worse vasomotor and vaginal symptoms, whichever drug they were taking. With this kind of information on patient-reported outcomes in women with ductal carcinoma in situ, patients and their physicians can now make personalized decisions on which of these two effective agents to select,” she told listeners at a press conference.

Case Examples

Dr. Ganz offered two case examples of how to use these findings in treatment selection.

“In a lean, 65-year-old woman with osteoporosis and a hysterectomy, I would be concerned about osteoporosis progression on an aromatase inhibitor. Since this women is at low risk for cardiovascular events and not at risk for uterine cancer, tamoxifen would be a better choice.”

“By contrast, for a younger women with frequent hot flashes, I would stay away from tamoxifen; and if her bones are healthy, I wouldn’t worry about her taking an aromatase inhibitor. On the other hand, if she developed severe joint aches and pains and pain with sexual intercourse, then going on tamoxifen is a good choice, and we can use topical estrogen to help vaginal dryness if she is on tamoxifen but not if she is taking an aromatase inhibitor,” Dr. Ganz said. ■

Disclosure: Dr. Cuzick has received research grants from AstraZeneca. Dr. Ganz reported no potential conflicts of interest.

References

1. Cuzick J, Forbes JF, Sestak I, et al: Anastrozole versus tamoxifen for the prevention of loco-regional and contralateral recurrence in postmenopausal women with locally excised ductal carcinoma-in-situ (IBIS-II DCIS). 2015 San Antonio Breast Cancer Symposium. Abstract S6-03. Presented December 11, 2015.
2. Ganz PA, Cecchini RS, Julian TB, et al: Patient-reported outcome results, NRG Oncology/NSABP B-35. 2015 San Antonio Breast Cancer Symposium. Abstract S6-04. Presented December 11, 2015.
3. Ganz PA, Cecchini RS, Julian TB, et al: Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35). Lancet. December 10, 2015 (early release online).