Abstract P1-13-02: Visceral metastases from hormone receptor positive breast cancer are as sensitive to endocrine therapy as non-visceral metastases
Authors: Robertson John FR , Paridaens Robert , Bogaerts Jan , Rukazenkov Yuri , Campbell Christine , Bradbury Ian 
Published: May 2015

Abstract
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 & 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) & 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 & 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.
Clinical Outcome by VM and Non VM (Tamoxifen only patients) N (%)StudiesExeAna (EUR)Ana (NA)F250Combined N = 168N = 144N = 162N = 209N=683Without VM (55%)N = 88N = 71N = 82N = 135N=376CB (%)66 (75)42 (59)47 (59)87 (64)242 (64)OR (%)41 (47)26 (37)15 (19)45 (33)127 (34)TTP (Median in days)287254305234277DoCB (Median in days)343360445451420With VM (45%)N = 80N = 73N = 80N = 74N=307CB (%)64 (80)38 (52)27 (33)46 (62)175 (57)OR (%)36 (45)21 (29)13 (16)21 (28)91 (30)TTP (Median in days)340230152281238DoCB (Median in days)376505411339418
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.