Abstract PS11-12: Statin use significantly improves outcome in luminal B relative to luminal A breast cancers
Authors: Redfern Andrew David , Spalding Lisa J , Anderson Robin L , Martin Hilary 
Published: February 2021

Abstract
Cholesterol and statins may have a role in breast cancer progression where statins have been found to associate with reduced breast cancer recurrence risk in early breast cancer patients. Links between breast cancer progression and intra-tumoural cholesterol metabolism have been described, indicating possible underlying cancer biology. Here we set out to explore whether statin use correlated with differences in baseline tumour characteristics including biological tumour sub-type and whether outcomes were impacted by statin use, both overall and within sub-types. Two cohorts of invasive breast cancer patients from a single institution in Western Australia were studied; one comprised of cases across all sub-types (n=417) and one of hormone receptor positive cases only (n=1766), with available data on tumour biology, statin use, and relapse. Statin prescription data was available on 2183 patients, of whom 454 were taking a statin at some point from diagnosis through the end of the follow-up period. Of the patients where statin type was known, 38% were taking a hydrophilic and 62% a lipophilic statin. Although tumour stage did not vary by statin usage, those on a statin had less frequent high grade tumours (12.7 v 18.7%, p=0.025), and were more frequently estrogen receptor positive (96.1 v 93.1, p=0.022) although other receptor expressions did not differ. Finally, luminal A tumours were more common in statin users, at the expense of luminal B and HER2-enriched cancers (81.4 v 74.0, p=0.018) (Table 1).
Overall breast cancer events were more common in statin non-users compared to users (16.7 v 9.3%, HR 1.80, p&lt;0.0001). Due to the influence of the larger hormone receptor positive cohort, the majority of patients had luminal tumours. Looking to the influence of statins on events within sub-types, users compared to non-users experienced substantially less breast cancer events in luminal B cancers (8.8% v 22.3%, p=0.012 ) and modestly reduced events in luminal A cancers (8.3 v 12.6%, p=0.0326). Considering HER2 positive luminal B cancers relative to those afforded luminal B status by virtue of being high grade, the former group showed significantly less events in statin users v non-users (0 v 19.9%, p=0.0047) whereas no significant protection was observed in the latter (18.2 v 24.6%, p=0.294). Low numbers of HER2 positive hormone receptor negative cases precluded analyzing whether protection extended to all HER2 positive tumours, although none of these patients relapsed. No significant differential effect was found by statin type.
In conclusion, statin usage after early breast cancer afforded substantial protection to HER2 positive hormone receptor positive patients, an effect that may extend to all HER2 positive cases. Further validation is warranted. Such patients could be considered for trials exploring statins as agents protecting against relapse.
Table 1: Breast tumour demographics comparing statin users to non-users.Statin UseCasesCasesMedian sizeLN positiveLN positiveInvasive GradeInvasive gradeInvasive GradeER +iveER +ivePR -ivePR -iveHER2 +iveHER2 +iveSub-typeSub-typeSub-typen%mmn%n%n%n%n%n%lum A1117(74.0)Grade 144827.6Lum B336(22.3)NO1729(79.0)18607/1787(34.0)Grade 286753.51601/1719(93.1)1348/1565(86.1)144/1498(9.6)HER2 enrich7(0.5)Grade 330718.9TNBC50(3.3).lum A337(81.4)Grade 113130.2lum B68(16.4)YES454(21.0)17151/475(31.8)Grade 224757.0440/458(96.1)363/428(84.8)32/421(7.6)HER2 enrich1(0.2)Grade 35512.7TNBC8(1.9).p (Fishers)NS0.3820.0250.0220.4820.2510.018
Citation Format: Andrew David Redfern, Lisa J Spalding, Robin L Anderson, Hilary Martin. Statin use significantly improves outcome in luminal B relative to luminal A breast cancers [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-12.