Old idea, new lens.

Top Line: In the 90s, the state of systemic therapy for breast cancer was such that ablative chemo followed by stem cell rescue was being explored.

The Study: In 1993 a Dutch phase 3 trial, the largest of its kind, began accruing women 55 years and younger with stage III breast cancer who would be randomized to “standard” versus “high-dose” chemo. Standard (my, how that has changed) meant 5FU + epirubicin + cyclophosphamide x 5 cycles, while high-dose was the same thing except the fifth cycle was substituted with 12x the cyclophosphamide + thiotepa + carbo followed by autologous stem cell transplant. For breast cancer. In the end there were 885 enrollees who proved to have no difference in survival outcomes: now, at 20 years, 45% are alive after high-dose and 42% after standard-dose chemo. Here’s where things get interesting. This was initially analyzed in an era when all breast cancer was seen as pretty much the same stage for stage. Now there’s a secondary analysis to elucidate any difference in long term outcomes across the current paradigm of biologic subtypes. Indeed, at 20 years, survival for triple-negative breast cancer beat the odds with 53% still alive after high-dose chemo compared to only 37% after standard-dose. A similar clear discrepancy was seen among those with ≥10 axillary nodes involved (N3) where 45% were still alive after high-dose chemo and 30% after standard-dose.

TBL: As crazy as it may sound, modern explorations of ablative chemo with autologous stem cell rescue could prove to be beneficial for the as-of-yet largely untargetable triple-negative subset of breast cancer. | Steenbruggen, JAMA Oncol 2020