15IN - Which luminal BC need chemotherapy?

Date 30 September 2012
Event ESMO Congress 2012
Session Optimizing treatment in luminal breast cancer
Topics Breast Cancer, Early Stage
Presenter Matthew Ellis
Authors M.J. Ellis
  • Siteman Cancer Center Breast Cancer Program, Washington University School of Medicine, 63110 - St Louis/US


Estrogen Receptor positive (ER+) HER2- breast cancer is the largest subset of breast cancers and the most chemotherapy resistant. For small ER+ node negative breast cancers with favorable genomic or clinical risk profiles this is an irrelevant concern as management with endocrine therapy alone is the standard of care. However multiple studies have shown that once HER2+ ER+ are removed from a node positive ER+ population, adjuvant chemotherapy, whether anthracycline or anthracycline/taxane-based has limited efficacy. To investigate new approaches to the treatment of ER+ HER- higher stage tumors we have therefore focused on the neoadjuvant setting. This is because the most critical question in the management of ER+ HER2- tumors is whether the patent has an endocrine therapy sensitive tumor. Endocrine therapy resistance in the neoadjuvant setting can be identified in a straightforward manner using the Ki67 proliferation index. Tumors that have an elevated Ki67 (above 10%) at 2 to 4 weeks after starting an aromatase inhibitor (AI) are defined in our prospective studies as endocrine therapy resistant. This cut-point was established because if Ki67 is >10% the tumor is very unlikely to fall into the lowest relapse risk category at post neoadjuvant endocrine therapy surgery (preoperative endocrine prognostic index zero or PEPI-0 (defined as ER+ Stage 1 or 2A, Ki67 < 2.7%) and therefore not suitable for continued neoadjuvant endocrine therapy (since one of the objectives of our studies is to avoid chemotherapy in AI sensitive tumors). We have recently completed a successful pilot of triaging 35 patients with an early on treatment high Ki67 values to chemotherapy with the efficacy results to be reported at the San Antonio Breast Cancer Symposium. The ALTERNATE trial is based on these principles (ALTernate approaches for clinical stage II or III Estrogen Receptor positive breast cancer NeoAdjuvant TrEatment) and will screen over 2000 patients to identify up to 400 cases of ER+ HER2- AI resistant breast cancer who will be suitable candidates for investigational neoadjuvant approaches to improve outcomes in this understudied group of high risk patients. Patients with PEPI-0 disease will be managed without adjuvant chemotherapy with a prospective plan to demonstrate that the 5 year relapse rate is 5% or less.


The author has declared no conflicts of interest.