Results of this retrospective analysis suggest that toremifene and tamoxifen have similar efficacies in premenopausal breast cancer patients, and have comparable side effects. Although the standard therapy for premenopausal women with breast cancer is tamoxifen, some patients are offered treatment with ovarian suppression in conjunction with AI therapy, either because tamoxifen is contraindicated or they have an intolerance to tamoxifen, or because their physicians believe that the AIs are superior based on data from postmenopausal women. Although AIs are increasingly being used in breast cancer patients, the importance of classic drugs for premenopausal patients should not be ignored. Chemotherapy in young breast cancer patients frequently causes abrupt menopause, although many menstruate again following chemotherapy, especially very young patients. Further, some postmenopausal patients recommence menstruation after treatment with AIs. As is widely known, AIs are harmful for premenopausal patients. However, with respect to toremifene clinical trials have shown that toremifene does not increase the incidence of adverse events for moderate to severe mastalgia patients
. Other reports have shown that toremifene (60 mg daily) has no substantial negative effects on bone mineral density in pre- or postmenopausal women and may actually have a minor favorable influence
. In this situation, when considering safety tamoxifen or toremifene should be considered. However, few studies have investigated the therapeutic role of toremifene as adjuvant endocrine therapy for premenopausal breast cancer patients. Since there are more young breast cancer patients in Asian countries, than in other regions, researchers from Asia are increasingly becoming interested in this issue. In a Korean study, toremifene was suggested to young patients, but this study failed to compare the impact and side effect of tamoxifen and toremifene, and the treatment duration was not followed up
. Another study, from the Seoul National University College of Medicine, evaluated the use of toremifene as an adjuvant hormonal therapy for estrogen receptor positive early breast cancer patients in terms of its therapeutic efficacy and effect on the endometrium, as compared with tamoxifen, but the study did not consider how treatment affected these patients’ menstrual cycles. In our study, therapy duration was investigated, in addition to the effect of treatment on the menstrual cycle, by evaluating estradiol and follicle stimulating hormone levels.
Multivariate analysis showed that toremifene was associated with improved recurrence-free survival and that no factor was independently related to overall survival. Future studies may need to increase samples sizes in order to establish the optimal therapy. Moreover, our study was also limited by a lack of investigation as the expression of the estrogen and progesterone receptor and changes in HER-2 status.
All objective adverse events were obtained by searching the internal hospital database and medical records during the period when the patients were undergoing endocrine therapy. With respect to the gynecological side-effect such as ovarian cysts and uterine fibroids, these always occurred a few months after taking the drugs, and were mostly so mild and stable that we did not need to disrupt the endocrine therapy. As for other side effects, such as skin rash and nausea, the patients were frequently unable to recall when these events had occurred, the seriousness, or the possible causes.
In our study, most patients were treated concurrently, and following an almost identical protocol of surgical intervention plus chemotherapy, but with differing adjuvant endocrine therapies. There was no difference in age, tumor size, tumor grade, degree of lymph node involvement, or risk of recurrence between the two cohorts. Wherever possible we attempted breast-conserving surgery unless there were positive margin, in which case radical mastectomy was performed. As the women who received breast-conserving surgery always had a significantly lower tumor load, other factors should also considered, such as the tumor-breast ratio and tumor location. Similarly, as BCS is the marriage of breast conserving surgery and radiation therapy, the side effects of radiotherapy should not be ignored. In China, breast-conserving surgery costs are more expensive than modified radical mastectomy because of the surgery costs, concomitant radiotherapy, and the additional pathology required. These factors were explained to each of the patients, and the type of surgery was then based on input from both patients’ and doctors’. In spite of the issues around cost and side effects and in light of the traditional bias towards breast-conserving surgery, some patients elected for radical mastectomy.
Inclusion of only one center in our study may be related to the clustering of surgeries between the two cohorts, which may explain why there was a nearly 13% difference in local treatment modality between the two groups and possibly reflects the fact that doctors influenced patients during the talk before surgery. Among young women, those who received BCS are more likely to experience local recurrence, while long-term survival was similar for those who received BCS compared to those who underwent modified radical mastectomy
. In our study, BCS was higher in the toremifene group but the risk of recurrence was significantly lower. The study also benefited from a large patient population, with few lost to follow-up, and a long follow-up period (median >50 months).
Compliance with treatment was suboptimal in both arms of the study, with 23 women on tamoxifen 20 women on toremifene ceasing therapy after a few months (p = 0.961; Figure
1). Many turned to traditional Chinese medicine and refused any further consultation. These patients were not included in the final analysis. However, patients who discontinued tamoxifen and toremifene within 5 years because of menopause or other unavoidable reasons were still included, in accordance with intent-to-treat analysis.