Introduction: Chemotherapy for early stage breast cancer is associated with a plethora of side effects including fatigue, alopecia, neuropathy, cardiotoxicity, myelosuppression, gastrointestinal symptoms, fertility issues, memory impairment, and mouth sores. As a result, a significant number of patients (pts) require treatment interruptions, dose and drug modifications and discontinuation after therapy initiation. During neoadjuvant therapy (NAT) in breast cancer, treatment interruptions may impact rates of pathologic complete response (pCR) and ultimately increase risk of recurrence. Here we present an analysis of the impact of treatment modifications on treatment response and pCR rates using SimBioSys TumorScope (TS) – a commercially available multiscale biophysical model that simulates tumor response to various therapy regimens in three-dimensional space over time.
Methods: A retrospective review of patients receiving NAT at University of Chicago from Jan 2010 – March 2020 was performed. Pts must have had a pretreatment breast MRI. Baseline characteristics were compared between cohorts of pts receiving standard dose / schedule regimens (SR) and interrupted, reduced, or modified regimens (MR). For the MR cohort, the previously validated TS tool was used to simulate response to the full dose / uninterrupted version of treatment regimens.
Results: 141 pts met study inclusion criteria. 39 pts (28%) received a MR and 102 (72%) received a SR. 6 pts (17%) had early discontinuation of doxorubicin & cyclophosphamide, 15 pts (43%) had early discontinuation of a taxane, 5 pts (14%) had anti-HER2 therapy discontinued and 13 pts (37%) had dose reductions throughout therapy. There was no significant difference in age between MR & SR cohorts (median 52.5 yrs vs 51.4 yrs). Both groups had identical distribution of molecular subtypes. However, African American patients constituted a greater proportion of patients in the MR cohort (59% vs 46%). As expected, a significantly lower proportion of patients that achieved pCR in the MR group, compared to the S group (p = 0.03, OR = 0.44). The TS tool was used to simulate response if patients were to receive full dose / standard schedule treatment. Amongst this population, an additional 7pts (5%) would have been able to achieve pCR had they not had a treatment interruption
Discussion: While common, treatment modification or discontinuation has the potential to impair responses. We found that African American patients were more likely to have treatment modifications in this cohort, which may contribute to poorer outcomes in this patient population. In this proof of concept study, TS can be used to estimate the impact of variable dosing on pCR; allowing clinicians and patients to make better informed decisions on the impact of regimen modifications on response to NAT