Abstract CS1-1: Treatment on the Edges: Discordance between Stage and Biology
Authors: Albain KS 
Published: August 2014

Abstract
This Clinical Science Forum addresses one of the mort vexing issues that faces a clinician when guiding patients in adjuvant therapy decisions – what to do for treatment “on the edges”? That is, when there is discordance between stage/risk of relapse and biology, which should most influence the choice of therapy? The first presentation will address bad stage or high risk disease but “good” biology, and the second talk will consider good stage/traditionally lower risk disease but a “bad” biologic profile. This abstract provides an overview of the first scenario.
Historically, in the era predating knowledge about biologic subtypes and without systemic adjuvant therapy, surgical series reported probable cures in patients with large and even locally advanced tumors, as well as in a subset with positive nodes. This data base serves as a backdrop for more modern series in which there is a wide range of long-term survival potential for patients with tumors that have adverse prognostic features. Currently, it is considered standard of care to offer systemic adjuvant chemotherapy, endocrine therapy and/or HER2 targeted treatments to all such patients – with the particular therapeutic choice based on tumor biology. In particular, it is not wise to withhold therapy in these higher risk (“bad stage”) scenarios when the disease is triple negative or HER2-positive.
However, across the luminal subtypes, there is great variation in outcome even when tumors are large and or nodes are positive. Some of these patients will require only endocrine therapy despite the high risk status, whereas others need more creative therapeutic therapies to circumvent multi-pathway drivers of tumor growth and progression. Subsets defined by high levels of expression of the estrogen receptor and low proliferation have a better outcome and often are cured with endocrine therapy alone. Refinement of prediction of which groups may do very well with this approach alone has been possible with the advent of multigene assays such as the 21 gene Recurrence score or the 70 gene assay. In fact, it can be argued that many patients in the high risk (“bad stage”) breast cancer group are over-treated with chemotherapy. For example, in SWOG S8814, a study in postmenopausal, ER+, node positive disease, the 10 year breast cancer specific survival was over 90% in those with a low 21 gene RS assay and this outcome did not vary whether the adjuvant treatment was tamoxifen alone or anthracycline-based therapy followed by tamoxifen. Similar findings were reported for higher risk, node-negative patients in NSABP B20. The current status of the three large prospective studies designed to validate and refine prediction of chemotherapy benefit will be updated (TAILORx, RxPONDER and MINDACT).
Finally, there is the other group of patients with high risk (“bad stage”) ER-positive disease whose risk remains high with tumor biology relatively resistant to standard chemotherapy and insufficient efficacy of the endocrine therapy. In this group, optimizing inhibition of cross talk with other pathways that take over driving tumor growth - despite the endocrine therapy blockade - is mandatory. Only then can “bad stage” be turned into an excellent outcome.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr CS1-1.