J. Michael Dixon, MD, OBE
The reduction of breast cancer risk with 5 years of tamoxifen does not outweigh the lack of a mortality benefit, according to J. Michael Dixon, MD, OBE, who shared his view in a session at the 32nd Annual Miami Breast Cancer Conference (MBCC).
In long-term follow-up data (16-22 years) from the IBIS-I trial presented at SABCS in December, 5 years of tamoxifen was shown to reduce the risk of breast cancer by 29% in otherwise healthy women at high risk of the disease; however, tamoxifen continued to have no impact on breast cancer mortality. At 20 years’ follow-up, there were 31 breast cancer–related deaths in the tamoxifen arm versus 26 with placebo.
In an interview with OncLive
, Dixon, who is professor of Surgery, consultant surgeon, and clinical director of the Breakthrough Breast Cancer Research Unit at the University of Edinburgh in Scotland, said he considers these results “sobering.”
“If you can prevent breast cancers but can’t prevent people from dying of breast cancer, it’s a point for discussion, because patients are taking 5 years of a drug that has significant side effects,” said Dixon. “If you don’t prevent people from dying, then how valuable is that? I’m not sure it’s that valuable.”IBIS-I Basics
The ongoing IBIS-I study, known formally as the International Breast Cancer Intervention Study-I, recruited 7154 women at breast care and genetics clinics in eight countries between 1992 and 2001 and randomized them evenly to receive 20 mg of daily tamoxifen for 5 years (n = 3579) or matching placebo (n = 3575).
The median age of participants across both cohorts was 50.8 years; slightly more than 50% were postmenopausal, and the mean body mass index was 27. Women with an increased risk of breast cancer, largely due to a family history of the disease, were eligible for the study regardless of whether they were using hormone-replacement therapy (HRT) before the trial, during it, or had not used HRT, or whether they had undergone a hysterectomy. These characteristics were also balanced across the two arms.
“Between 40% and 50% of patients in the two arms took HRT during the trial and nowadays you wouldn’t get many women on HRT. Nevertheless, 50% of patients in the two groups were never-users of HRT and about 35% of women on each arm had had a hysterectomy,” said Dixon.
At 10 years of follow-up, substantial differences between the two groups were observed confirming previously reported analyses. One-hundred sixty-three breast cancers were reported in the tamoxifen arm (4.6%), versus 226 (6.3%) with placebo (HR = 0.72; 95% CI, 0.59-0.88). For invasive estrogen receptor (ER)–positive disease specifically, 100 breast cancers were reported in the treatment arm versus 145 among the control group (HR = 0.68; 95% CI, 0.53-0.88). For all breast cancer, the number needed to treat (NNT) for 5 years to prevent one breast cancer was 59.
At 20 years’ follow-up, there was a 29% reduction in breast cancer risk with tamoxifen (HR = 0.71; 95% CI, 0.60-0.83; P
<.0001). A total of 601 breast cancers were reported. In the tamoxifen cohort, breast cancer was reported in 251 women versus 350 in the placebo arm. For invasive ER-positive breast cancer, risk was reduced by 35%; 160 cases were reported in the treatment arm versus 238 with placebo (HR = 0.66; 95% CI, 0.54-0.81; P
= .0001). Dixon did note, however, that “In the second 10 years, there is a suggestion—it’s not significant, though—that you get more invasive ER-negative cancers.”
Although the overall risk reduction remained comparable in the second 10 years, the NNT dropped to 22. Also, the difference between breast cancer incidence rates between the two arms grew: 7.8% in the tamoxifen arm versus 12.3% in the placebo arm. For invasive ER-positive breast cancer, NNT was 29 and incidence rates were 4.9% versus 8.3%.
The effects were larger for women who did not receive HRT during the trial, at 38% versus 12%, respectfully. “If you took HRT during the trial, you didn’t get much of a reduction in the incidence of breast cancer. You got a much bigger decrease in the incidence of breast cancer in the women who had never taken HRT,” said Dixon.
“So, after 20 years, it’s quite clear that you can prevent breast cancer, and if you look at the numbers needed to treat, you only need to treat 22 women to stop one breast cancer from developing, 29 to stop 1 ER-positive invasive cancer,and the effects are largest for the women not taking HRT,” said Dixon.
With non-breast cancers, there were 36 more incidents in the tamoxifen arm (n = 351; 9.8%) compared with the placebo arm (n = 315; 8.8%). The gap was due, respectively, to occurrences of non-melanoma skin cancers, at 116 versus 84, and endometrial cancers at 29 versus 20. With the combined incidence of all other cancers, there were slightly fewer in the tamoxifen arm.