Patients (pts) with pT1aN0M0 breast cancers (BCs) have an excellent outcome across all biologic subtypes. HER2 overexpression occurs in 15-20% of primary BCs, and is associated with poor prognosis. Women with BCs diagnosed in the interval between scheduled screening rounds have poorer stage-specific survival than women with screen-detected (SD) tumors, and an association has been reported between interval cancers (ICs) and HER2 overexpression. We aimed to determine, in a general population of pT1aN0M0 BCs with known screening status, if HER2-positive status maintains its negative prognostic value only in tumors diagnosed as ICs.
All incident pT1aN0M0 BCs (n = 874), systematically collected by the Cancer Registries of Emilia Romagna Region (northern Italy) and diagnosed in women aged 50-69 from 2003 to 2009 were evaluated. Pts unexposed to screening, with unknown HER2 status and/or treated with adjuvant trastuzumab were excluded from analysis.
Twenty percent of BCs were HER2-positive. Fifty-three percent were SD tumors, while 18% were ICs. BCs with high histologic grade (odds ratio [OR] =2.2; 95%CI, 1.1–5.7), hormone receptor negative (OR =2.6; 95%CI, 1.4–4.9), or HER2-positive status (OR =2.4; 95% CI, 1.2–5.5) were more likely to be diagnosed as ICs. With a median follow-up of 115 months, the 8-year invasive disease-free survival (iDFS) for ICs was lower than that for SD tumors: 92% (95%CI, 88% to 94%) vs. 97% (95%CI, 95% to 99%; P = 0.01). Eight-year iDFS rates were 88% (95%CI, 82% to 94%) and 96% (95%CI, 94% to 98%) in pts with HER2-positive and HER2-negative tumors, respectively (P = 0.0004). Notably, HER2-positive ICs showed poorer iDFS than HER2-positive SD tumors (78% vs. 95%, respectively; P = 0.003). An interaction between IC detection and HER2-positive status was found for poorer iDFS after adjusting for prognostic variables (P = 0.0074).
In a general population of pT1aN0M0 early BCs with known screening status, IC detection may identify pts with HER2-positive pT1aN0M0 tumors in whom the rate of recurrence justifies consideration for conventional anti-HER2 adjuvant treatment.
Clinical trial identification
Legal entity responsible for the study
University Hospital of Parma
“Alessandro Liberati Programme” for young investigators; Programma di ricerca Regione-Università 2010-2012 – Regione Emilia-Romagna (Italy)
All authors have declared no conflicts of interest.