Risk of Ipsilateral Breast Tumor Recurrence in Patients Treated with Tamoxifen or Anastrozole Following Breast-conserving Surgery with or without Radiotherapy

Background: It is unknown whether anastrozole (Ana) is superior to tamoxifen (Tam) with regard to local control after breast-conserving surgery without radiotherapy (RT). Patients and Methods: Two hundred and ninety-two breast cancer patients who had undergone breast-conserving surgery and been treated with Tam or Ana, with or without RT, were retrospectively analyzed. Ipsilateral breast tumor recurrence (IBTR)-free survival rates were compared according to the treatment drug and RT. Results: In the Tam group, IBTR-free survival rates did not significantly differ according to the use or absence of RT (p=0.08), whereas in the Ana group, a significant difference (5-year IBTR-free survival rate, 98.8% in the RT group vs. 65.7% in the no RT group, p<0.0001) was found. In addition, multivariate analysis showed that RT use was an independent prognostic factor for IBTR-free survival (p=0.01) among the patients treated with Ana. Conclusion: Caution is needed when RT is omitted for patients undergoing breast-conserving surgery and receiving Ana for adjuvant treatment. Due to improved disease-free survival, aromatase inhibitors (AI) have become standard adjuvant therapy for postmenopausal women with hormone receptor-positive early breast cancer (1-3). Isolated local recurrences as first events after initial AI administration were significantly fewer than those after tamoxifen (Tam) treatment according to a meta- analysis of randomised trials comparing AI with Tam in an adjuvant setting (4). There seemed to be greater decreases in isolated local recurrence (30%) than in distant recurrence (16%), although this apparent heterogeneity of effect between recurrence sites was not significantly different (p=0.08). Radiotherapy (RT) is an integral component of the multidisciplinary management of breast cancer. RT significantly reduces locoregional recurrence and improves overall survival for patients undergoing breast-conserving surgery (BCS) (5). BCS without radiation is associated with significantly higher local recurrence rates and possibly a higher mortality risk. Several trials have investigated whether RT could be safely omitted for selected patients showing specific favorable treatment response and disease characteristics (6, 7). Unfortunately, most of these trials were unsuccessful in that RT continued to provide a significant benefit. Despite robust benefits of RT for local control, previous studies have suggested underutilization as well as disparities in the use of adjuvant RT among patients with breast cancer. Data from the Surveillance, Epidemiology, and End Results registry indicate that about 12% of patients treated with BCS for invasive breast cancer do not receive RT (8). The reasons for omission of RT among women undergoing BCS are unclear, but are probably multifactorial. Patients cite reasons such as inability to find a radiation facility close to home, inability to bear the cost of relocating for radiation treatment at a facility far from home, difficulty finding transportation to and from a radiation facility on a daily basis and extremely advanced age or physical handicap. Accelerated partial breast irradiation may allow some patients with barriers to standard treatment to receive appropriate adjuvant radiation therapy (9) and several trials are now ongoing, but as yet accelerated irradiation is not standard care. For patients who did not receive RT, AI was selected due to superior local control compared to Tam in several randomised trials. However, there is limited existing evidence regarding local control in breast cancer patients receiving BCS and treated with AI without RT because most