Visceral Metastases From Hormone Receptor Positive Breast Cancer Are As Sensitive To Endocrine Therapy As Non-Visceral Metastases

Background: There remains a perception among many clinicians that visceral metastases (VMs) from hormone receptor positive (HR) breast cancer (BC) respond less well to endocrine therapy (ET) than non-VMs and so should receive chemotherapy as first line treatment. Patients u0026 Methods: Four phase 3 randomised controlled trials (RCTs) of first line ET, all with tamoxifen (TAM) as their control arm) have been reviewed – Exemestane (Exe), fulvestrant 250mg (F250) and two with anastrozole (Ana); the latter, were study 27 in the Rest of the World (ROW) u0026 study 30 in North America (NA). All reported objective response (OR), clinical benefit (CB), time to progression (TTP) / progression free survival (PFS): all have been published (1-5). Only HR positive tumors were included in this review. Data have been analysed both for Tam control arms alone and also for the four different endocrine agents combined. Results: CB u0026 OR for TAM alone in each study individually and then combined are shown in the Table. The OR and CB rates were similar for non-VMs versus VMs in all studies except study 30 (NA) where CB rates were 59% for non-VM and 33% for VM (Test for heterogeneity of CB rates was p=0.047). For the four studies combined, the CB rates for non-VM versus VMs were 64% and 57% respectively (p=0.06) while the OR rates were 34% versus 30% respectively (p= 0.28). When all endocrine agents were combined the OR rate between non-VMs and VMs was significantly different (p = 0.038) as was the CB rate (p = 0.0015). Rates of CB and OR in study 30 (NA) again appear different between non-VMs and VMs (data not shown). The Median Duration of CB on Tam appear similar between non-VMs versus VMs, both for each study individually and when combined (see Table); when combined the Medians were 420 versus 418 days respectively with a Hazard Ratio (HR)=0.952 (0.748-1.211) (p=0.69). When all endocrine therapies for the combined four studies were assessed the HR for DoCB between non-VMs and VMs was 0.922 (0.779-1.093) (p=0.35). For the TTP the HR of non-VMs versus VMs on Tam alone was 0.851 (0.715-1.011) (p=0.07) and for all endocrine therapies the HR was 0.821 (0.727-0.926) (p=0.001). Conclusions: HR+VMs which achieve clinical benefit on ET remain controlled for as long as non-VMs as shown by the DoCB results for both Tam and all endocrine therapies combined. There was no significant difference in OR rates between VMs and non-VMs with Tamoxifen. There was when all endocrine agents were combined and the difference appears to be primarily due to one study (30 – NA). There is no confirmed explanation for these differences. TTP differences appear to be due primarily to the difference in initial CB rates in study 30 (see Table). HR+ VMs have hormone sensitivity similar to non-visceral mets – they respond as well and for as long as non-VMs. In the absence of visceral crisis (ie immediately life-threatening disease) ET would appear to be the treatment of choice for VMs in the same way as it is for non-VMs. Citation Format: John FR Robertson, Robert Paridaens, Jan Bogaerts, Yuri Rukazenkov, Christine Campbell, Ian Bradbury. Visceral metastases from hormone receptor positive breast cancer are as sensitive to endocrine therapy as non-visceral metastases [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-13-02.