A Double-blind Randomized Controlled Trial of Toremifen Therapy for Mastalgia

Abstract

Hypothesis: Toremifen is effective in reducing breast pain and does not increase the incidence of adverse events as a therapy for moderate to severe mastalgia. Design and Patients:In a double-blind randomized controlled trial, patients with moderate to severe mastalgia received toremifen citrate, 30 mg daily, or a placebo tablet for 3 menstrual cycles and were followed up for breast pain score and adverse events. The serum levels of estradiol, progesterone, and prolactin were examined before treatment and correlated with the response rate to toremifen treatment.Results: Seventy-two (69.2%) of 104 patients receiving toremifen and 29 (31.9%) of 91 receiving placebo responded to the treatment, with reduction in breast pain score of more than 50% (PϽ.001). Among the patients with cyclical mastalgia, the response rate for toremifen was 76.7% (59/77), whereas the response rate for pla-cebo was 34.8% (23/66; PϽ.001). In contrast, the response rate of patients with noncyclical mastalgia was 48.1% (13/27) for toremifen and 24.0% (6/25) for placebo (P=.09). Adverse events were observed in 44 (42.9%) of 104 patients receiving placebo and 46 (50.5%) of 91 patients receiving toremifen (P=.45). A positive correlation between baseline breast pain score and serum estradiol level was observed in patients with cyclical mastalgia (r =0.35, P=.003).Conclusions: Toremifen effectively relieves moderate and severe cyclical mastalgia and tends to exert a positive therapeutic effect on noncyclical mastalgia. In addition, toremifen therapy does not increase the incidence of intolerable adverse event. Therefore, it is a feasible therapy for mastalgia, especially cyclical mastalgia.

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study

“…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 [40]. 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 [41].…”

Potential of Selective Estrogen Receptor Modulators as Treatments and Preventives of Breast Cancer

“…Toremifene is effective to treat mastalgia in some small phase II trials [126, 127], and is also effective at decreasing prostate cancer incidences in a high-risk population [128]. In addition, a recent multicenter randomized phase III trial showed that toremifene increased bone density and improved lipid profile in men receiving androgen deprivation therapy for prostate cancer [129, 130].…”

Clinical management of idiopathic mastalgia: a systematic review

“…4 In a randomised controlled trial (RCT) (n = 195), levels of serum oestradiol in women with untreated cyclical mastalgia were higher than in women with noncyclical mastalgia. 5 The role of elevated oestrogen in mastalgia is plausible due to its physiological effect on normal breast tissue (stimulates cellular proliferation). In contrast, a smaller study of women with benign breast disease (n = 17) found that oestradiol, progesterone, thyroid hormone and thyrotropin levels were normal.…”

“…However, this mechanism conflicts with literature that suggests elevated levels of oestrogen cause mastalgia. 5,25 Breast size It has been suggested that the weight of breasts creates weakness and strain on the suspensory ligaments, thus creating discomfort. No research has directly explored the role of breast size and mastalgia; however, a survey examined the role of mastalgia on exercise behaviour in 1397 women who ran the 2012 London Marathon and identified, as secondary outcomes, that one-third of women who did experience breast pain had larger breast size.…”

“…59 Similarly, Toremifene (a SERM licensed in the US for use in metastatic breast cancer) provided improvement in mastalgia symptoms in 64% of cases compared to 26% on placebo 60 (n = 62), but when compared with Ormeloxifene (89%), its effects were significantly lower (n = 195). 5 Luteinizing hormone-releasing hormone (LHRH) agonists induce medical castration, thus reducing circulating oestradiol and progesterone to almost negligible levels. The main concern with LHRH agonists is their menopausal sideeffects, including risk of osteoporosis, and the invasive method of delivery (injected subcutaneously).…”