Molecular Classification of Screen Detected Breast Cancers.
Gelareh Farshid, Adrienne Walker, Glenda Battersby. BreastScreen SA, Wayville, SA, Australia; SA Pathology, Adelaide, SA, Australia
Background: Detection by mammographic screening confers a survival advantage of approximately 20% compared to symptomatic breast cancers. The improved prognosis is only partly explained by stage migration. The distribution of the molecular subtypes of screen detected breast cancers has been studied little, with varying findings regarding HER2 amplification. We wished to assess a large series of cases with whole section immunohistochemistry and in situ hybridization to ascertain the possible role of molecular profile in the improved prognosis associated with screening.
Design: For invasive breast cancers diagnosed during 2007-08 in our statewide screening program we analyzed patient and tumour related variables including ER, PR and HER2. Molecular subtypes were defined as luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2 (ER-, PR-, and HER2+) and basal-like (triple negative). Results were compared with the findings in previous studies in our population.
Results: During this time 698 invasive cancers were diagnosed (mean age 61.7 +/- 8.1 yrs), mean diameter 15.3mm (+/- 10.8). 114 cases (16.3%) were node positive. The carcinoma was stage I in 67.6%, IIA in 21.7%, IIB in 8.8%, III in 1.3% and IV in 0.4%. For the 682 cases with established biomarker status, 578 (84.8%) were luminal type A, 41 (6.0%) luminal type B, 23 (3.4%) HER2 subtype and 40 (5.9%) were triple negative. The proportion of ER positive cancers is substantially higher than that of symptomatic cancers in our population (89.8% vs. 68.8%), while the 9.4% rate of HER2 positivity is significantly lower than the national average of 15.4% for all breast cancers.
Conclusions: The molecular profile of screen-detected breast cancers is different from that of symptomatic cancers. Since HER2 amplification is a prognostic factor even for small breast cancers, these differences, particularly the relative paucity of HER2 amplification, may account for some of the survival advantages attributable to mammographic detection. The observation of very low rates of HER2 positivity in this cohort suggests that HER2 amplification may not be an early genetic event, but be acquired later in the progression of the disease. It is also possible that HER2 negative cancers, prevalent in screening, are less likely to present as symptomatic tumors. The finding of significant differences in the biomarker profiles of screen detected versus symptomatic cancers has implications for laboratory quality assurance programs in setting target ranges for positive results.
Tuesday, March 1, 2011 8:15 AM
Platform Session: Section C, Tuesday Morning