Neil Osterweil

December 11, 2015

SAN ANTONIO ― Oncologists can now offer postmenopausal women with ductal carcinoma in situ (DCIS) two options for prevention of breast cancer recurrence: anastrozole (Arimidex, AstraZeneca Pharmaceuticals LP), which may suit some younger women, or tamoxifen (multiple brands), which may be the drug of choice for some older women.

Either drug would be a good selection for the majority of patients, suggest results from two randomized, placebo-controlled trials involving nearly 4200 patients.

Both the IBIS-II DCIS trial, conducted in Europe, Australia, and New Zealand, and the NRG/Oncology/NSABP B-35 trial show that anastrozole and tamoxifen are comparably efficacious for preventing recurrence of both DCIS and invasive breast cancers in postmenopausal women.

Each drug has a distinct adverse event profile, which may drive drug choice in individual patients.

"Overall, there's no clear differences in efficacy ― a slight favor, I think, in terms of anastrozole when you look at all of the data," said Jack Cuzick, PhD, director of the Wolfson Institute of Preventive Medicine and head of the Centre for Cancer Prevention at Queen Mary University of London, United Kingdom.

Dr Cuzick is the lead author of the report on the IBIS-II DCIS trial, for which 10-year results were presented here at San Antonio Breast Cancer Symposium (SABCS) 2015 and were published simultaneously in the Lancet.

Dr Jack Cuzick

"Both anastrozole and tamoxifen are well tolerated in patients with DCIS, with greater severity of some symptoms in women less than 60 years of age. The symptom profiles actually differ in the expected directions, and now, 12 of 13 years after we originally designed this trial, we know a lot more about these two drugs, and it's very consistent," said Patricia A. Ganz, MD, PhD, of the University of California, Los Angeles, Fielding School of Public Health.

Dr Ganz is the lead author of a study showing patient-reported outcome results from NASBP B-35. (Ten-year primary efficacy results were presented at the 2015 annual meeting of the American Society of Clinical Oncology, as reported by Medscape Medical News.

AI Edge in Invasive Cancers

Previous studies have shown that anastrozole and other third-generation aromatase inhibitors (AIs) are more effective than tamoxifen for preventing recurrence of invasive, hormone receptor– positive breast cancer in postmenopausal women. Whether the same would be true for women with DCIS was unclear, however, prompting the US national and international trials.

In each trial, women were randomly assigned to receive either oral anastrozole 1 mg or oral tamoxifen 20 mg every day for 5 years, plus a placebo that matched the compartor drug (ie, tamoxifen placebo for women receiving anastrozole, and vice versa).

In IBIS-II DCIS, the study analysis included 1449 women who had been assigned to anastrozole and 1489 who had been assigned to tamoxifen. At a median follow-up of 7.2 years, there was no significant difference in recurrence of DCIS or other breast cancers (67 in the anastrozole group and 77 in the tamoxifen group; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.64 - 1.23). Anastrozole was shown to be neither inferior nor superior to tamoxifen in efficacy.

There were 33 deaths in the anastrozole group and 36 in the tamoxifen group (ns); there were no differences in the specific causes of death.

Overall, 91% of women who received anastrozole and 93% of those who received tamoxifen reported any adverse events (see table).

Table: Adverse Events With Anastrozle vs Tamoxifen in IBIS-II DCIS

More Common With Anastrozole More Common With Tamoxifen
Fractures Muscle spasms
Musculoskeletal events Gynecologic cancers/symptoms
Hypercholesterolemia Vasomotor symptoms
Strokes Deep vein thrombosis


Patient-Reported Outcomes

Dr Ganz presented patient-reported outcomes in NSABP B-35, including the Short Form 12 (SF-12) physical and mental component scores, measures of vasomotors symptoms and musculoskeletal pain, sexual functioning (including vaginal dryness), and weight problems.

There were no significant differences between treatment groups in physical or mental health scores, energy and fatigue, or depressive symptoms.

Patients receiving anastrozole reported significantly more musculoskeletal pain (P = .0006) and vaginal symptoms (P = .035), whereas patients receiving tamoxifen reported significantly more vasomotor symptoms (P = .011), bladder control problems (P = .0002), and gynecologic symptoms (P < .0001).

A breast cancer specialist who was not involved in the study said that choosing the right drug in this population is "a complicated issue."

"Does the patient have osteoporosis already? Does the patient have a history of thromboembolism? If you put them on an aromatase inhibitor and they have intolerable joint pain, do you switch them?," asked Kent Osborne, MD, codirector of the San Antonio Breast Cancer Symposium and director of the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine, Houston, Texas, at a briefing in which details of both studies were presented.

He added, "Most patients prefer to be on tamoxifen. They just feel better on tamoxifen.... I think that probably tamoxifen is going to remain the major therapy for this indication."

I think that probably tamoxifen is going to remain the major therapy. Dr Kent Osborne

In an editorial accompanying the studies in the Lancet, Stephen R. D. Johnston, MD, from the Department of Medicine at the Royal Marsden NHS Foundation Trust in London, indicated that age should play an important role in drug choice.

"For premenopausal or perimenopausal women, tamoxifen should remain the endocrine therapy of choice. For postmenopausal women aged younger than 60 years, an aromatase inhibitor could offer more protection after excision of ER-positive ductal carcinoma in situ, but with different tolerability to tamoxifen," he writes.

The IBIS-II DCIS study was supported by Cancer Research UK, the National Health and Medical Research Council Australia, the Breast Cancer Research Fund, and AstraZeneca. Dr Cuzick received research grants from and is an ad hoc speaker for AstraZeneca. NSABP B-35 was supported by the National Cancer Institute and AstraZeneca. Dr Ganz has disclosed no relevant financial relationships.

San Antonio Breast Cancer Symposium (SABCS) 2015: Abstracts S6-03 (Cuzick et al) and S6-04 (Ganz et al). Presented December 11, 2015.

Lancet. Published online December 11, 2015. IBIS-II DCIS trial, full text; NSABP B-35 trial, abstract; Editorial


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