Abstract CS1-2: Small Tumor – Aggressive Biology: When They Collide!
Authors: Piccart MJ , Azim HA 
Published: August 2014

Abstract
Historically, tumor stage was the main stay in determining the prognosis and the need for adjuvant therapy in patients with operable breast cancer (BC). Patients with a tumor size &lt; 1cm (pT1a, b) and negative nodal involvement (pN0) were regarded to have very favorable prognosis. This in turn was reflected in the way these patients were managed. Since a decade or more, it became obvious that BC is not a single disease, but a group of molecularly distinct subtypes. The appreciation of the biological diversity of BC subtypes has urged the question on the relevance of tumor stage in the decision-making, nowadays. In other words, should patients with early-stage disease continue to receive “milder” or even no systemic therapy being historically known to have favorable prognosis, even if they are of aggressive nature?
Evidence in this regards mainly rely on retrospective data as these patients are often excluded from randomized trials. Data based on analyzing untreated cohorts have shown that the 5-year relapse-free survival of patients with pT1a, b pN0 disease is rather favorable, in the range of 90%. However, obvious differences in outcome were observed according to BC subtype. Patients with ER-positive disease often have an even more favorable outcome reaching up to 95% unlike those with HER2 and t tumors in which 5-year RFS ranges around 75–80%. This calls for integrating biological information in managing these patients.
Patients with ER-positive disease are composed of at least two subtypes, luminal-A and luminal-B.; the latter being more aggressive. It is unlikely that this differs in patients with pN0 disease. This was demonstrated by the Mammaprint®, which separate pT1a, b patients into two distinct groups with different outcome.
Few data suggested that the addition of trastuzumab particularly in patients with pT1b is worthwhile. This is further endorsed by guidelines like NCCN and St Gallen. However, it is important to note that the exact magnitude of benefit of trastuzumab in these patients is unknown. It is plausible to assume that the relative risk reduction on relapse will be similar to that in patients with more advanced tumors, which is in the range of 50%. On the basis that these patients have an absolute risk of relapse in the range of 20–25%, it appears reasonable to consider trastuzumab, particularly in patients with pT1b, which were shown to experience more BC-related events compared to patients with pT1a.
A similar argument exists on the added value of chemotherapy for patients with TN disease. Based on the recent EBCTCG overview, the relative risk reduction on the risk of relapse by administering chemotherapy does not exceed 30%. Acknowledging the absolute risk of relapse of the pT1a, b pN0 patients, the absolute benefit from offering chemotherapy appears to be modest; especially for those with pT1a.
Hence, the appreciation of BC heterogeneity on the molecular level is vital and should be considered in managing patients with very small tumors. As these patients have “relatively” low risk of relapse, it is important to consider absolute risk reductions that are foreseen by the addition of chemotherapy ± trastuzumab. This would help refining management strategies and hence improve counseling of patients diagnosed with these relatively indolent, yet challenging tumors.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr CS1-2.