Of 565 eligible patients whose physicians agreed they could participate, 524 enrolled and completed the questionnaire. At the time of diagnosis, the patients ranged in age from 29 to 72 years (). Of the 524 patients, 248 (47.3%) were pre-menopausal, 276 (52.7%) were postmenopausal, 446 (85.1%) received adjuvant chemotherapy, and 55 (10.5%) underwent postoperative radiotherapy. All 248 of the premenopausal patients and 190 of the postmenopausal patients received tamoxifen as adjuvant endocrine therapy, and 86 of the post-menopausal patients received anastrozole. All of the patients had cancer that was positive for estrogen receptor, positive for progesterone receptor or positive for both (). The median interval between surgery and the study interview was 120 days.
Demographic and clinical characteristics of 524 patients with breast cancer
In these patients, soymilk accounted for 26% of total intake of soy isoflavones, followed by tofu (21%) and soy flour (15%). The mean daily intake of isoflavones was 25.6 mg/day for all patients. Within the quartiles for isoflavone consumption, the mean intake was 6.5, 18.2, 35.8 and 49.6 mg/day. These amounts fall within the average range of intake of soy isoflavones in Asian countries (25–50 mg/day).14
All participants completed the supplementary survey about intake of soy foods. Most participants (452 [86.3%]) reported no change in intake of soy foods over the previous five years, 29 (5.5%) reported an increase and 43 (8.2%) reported a decrease.
Of the original 524 patients, we were able to contact 508 directly for follow-up in July 2008. Among the 16 patients who could not be contacted directly, the mortality registry revealed 10 deaths. For six patients there was no match in the registry, and we assumed that they were still living. The total number of deaths was 154, and 132 of these were due to breast cancer. The other causes of death were cardiovascular disease (12 patients), respiratory disease (5), other cancers (2) and other causes (3).
The five-year recurrence rate of premenopausal patients was higher than that of postmenopausal patients, but this difference was not statistically significant. There was a trend for an increase in rates of recurrence and death with worsening TNM stage (p < 0.01). The rates of recurrence and death did not vary significantly with estrogen and progesterone receptor status or with endocrine therapy.
There was no association between intake of soy isoflavones and recurrence or death among premenopausal patients, and this relationship did not vary by selected prognostic factors, including age at diagnosis, hormonal receptor status, TNM stage or cancer treatment (). Among the post-menopausal patients, an inverse association was observed between intake of soy isoflavones and recurrence. Compared with postmenopausal patients in the lowest quartile of soy isoflavone intake (< 15.2 mg/day), those in the highest quartile (> 42.3 mg/day) had a significantly lower risk of recurrence (HR 0.67, 95% CI 0.54–0.85, p for trend = 0.02). In contrast, there was no association between soy isoflavone intake and death in postmenopausal patients. The results of analyses for mortality specific to breast cancer were similar to those for all-cause mortality (HR 0.92, 95% CI 0.60–1.31, p for trend = 0.82 for risk of death). We also examined the association between intake of soy isoflavones and recurrence or death among patients with no change in intake over time, to determine whether a change in intake after diagnosis might alter these associations. The associations were similar for those patients (HR 0.68, 95% CI 0.59–0.87, p for trend = 0.02 for risk of recurrence among postmenopausal patients).
Adjusted association between soy isoflavones and recurrence of breast cancer or death in 248 premenopausal and 276 postmenopausal patients (total n = 524)
Hormonal receptor status and endocrine therapy
We stratified the analyses for risk of recurrence according to estrogen and progesterone receptor status and endocrine therapy for postmenopausal patients. Statistically significant inverse associations between intake of soy isoflavones and recurrence were observed for patients with estrogren- and progesterone-positive disease and for patients receiving anastrozole therapy (). Among postmenopausal patients with estrogren-and progesterone-positive breast cancer, those in the highest quartile of isoflavone intake had a significantly lower risk of recurrence than those in the lowest intake quartile (HR 0.66, 95% CI 0.49–0.86, p for trend = 0.01). The recurrence rate of estrogren-and progesterone-positive breast cancer was 12.9% lower among patients in the highest quartile of soy isoflavone intake than among those in the lowest quartile. Among postmenopausal patients receiving anastrozole therapy, those in the highest quartile of isoflavone intake had a significantly lower risk of recurrence than those in the lowest intake quartile (HR 0.65, 95% CI 0.47–0.85, p for trend = 0.005). The recurrence rate for post-menopausal patients receiving anastrozole therapy was 18.7% lower among patients in the highest quartile of soy isoflavone intake than those in the lowest quartile.
Figure 1 Forest plot of adjusted hazard ratios (HRs) for the effect of intake of soy isoflavones on recurrence among postmenopausal patients with breast cancer, stratified by estrogen and progesterone receptor status and endocrine therapy. CI = confidence interval, (more ...)