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. 2021 May 20;13(10):2492.
doi: 10.3390/cancers13102492.

Patterns of Recurrence after Neoadjuvant Therapy in Early Breast Cancer, according to the Residual Cancer Burden Index and Reductions in Neoadjuvant Treatment Intensity

Christoph Suppan  1 , Florian Posch  1 , Hannah Deborah Mueller  1 , Nina Mischitz  1 , Daniel Steiner  1 , Eva Valentina Klocker  1 , Lisa Setaffy  2 , Ute Bargfrieder  2 , Robert Hammer  3 , Hubert Hauser  3 , Philipp J Jost  1   4 , Nadia Dandachi  1 , Sigurd Lax  2   5 , Marija Balic  1
Affiliations

Patterns of Recurrence after Neoadjuvant Therapy in Early Breast Cancer, according to the Residual Cancer Burden Index and Reductions in Neoadjuvant Treatment Intensity

Christoph Suppan et al. Cancers (Basel). .

Abstract

Background: The prognostic performance of the residual cancer burden (RCB) score is a promising tool for breast cancer patients undergoing neoadjuvant therapy. We independently evaluated the prognostic value of RCB scores in an extended validation cohort. Additionally, we analyzed the association between chemotherapy dose reduction and RCB scores.

Methods: In this extended validation study, 367 breast cancer patients with available RCB scores were followed up for recurrence-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). We also computed standardized cumulative doses of anthracyclines and taxanes (A/Ts) to investigate a potential interaction between neoadjuvant chemotherapy dose reduction and RCB scores.

Results: Higher RCB scores were consistently associated with adverse clinical outcomes across different molecular subtypes (HR for RFS = 1.60, 95% CI 1.33-1.93, p < 0.0001; HR for DDFS = 1.70, 95% CI 1.39-2.05, p < 0.0001; HR for OS = 1.67, 95% CI 1.34-2.08, p < 0.0001). The adverse impact prevailed throughout 5 years of follow-up, with a peak for relapse risk between 1-2 years after surgery. Clinical outcomes of patients with RCB class 1 did not differ substantially at 5 years compared to RCB class 0. A total of 180 patients (49.1%) underwent dose reduction of neoadjuvant A/T chemotherapy. We observed a statistically significant interaction between dose reduction and higher RCB scores (interaction p-value = 0.042).

Conclusion: Our results confirm RCB score as a prognostic marker for RFS, DDFS, and OS independent of the molecular subtype. Importantly, we show that lower doses of cumulative neoadjuvant A/T were associated with higher RCB scores in patients who required a dose reduction.

Keywords: RCB; early breast cancer; neoadjuvant systemic therapy.

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Conflict of interest statement

C.S. received travel expenses, consulting fees, and honoraria from Amgen, Astra Zeneca, Eli Lilly, Novartis, Pfizer, Roche, and Samsung. M.B. has received honoraria, consulting fees research funds, and/or travel expenses from Amgen, Astra Zeneca, Daichii, Eli Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, and Samsung. P.J.J. has a consulting or advisory role and received honoraria, research funding, and/or travel/accommodation expenses from Abbvie, Bayer, Boehringer, Novartis, Pfizer, Servier, Roche, BMS, and Celgene.

Figures

Figure 1
Figure 1
Consort diagram for the study showing number of patients included and reasons for exclusion.
Figure 2
Figure 2
Kaplan–Meier RFS (A), DDFS (B), and OS (C) functions by RCB class. The numbers below the Kaplan–Meier plot form a risk table, whereas the round brackets contain the number of events occurring within the respective report.
Figure 3
Figure 3
Estimated recurrence rates within 5 years of definitive surgery, according to RCB class (A) and subtype (B). Rate curves were predicted with a flexible parametric survival model on the log(cumulative hazard) scale, allowing subtype to vary by time since definitive surgery.
Figure 4
Figure 4
Interaction of cumulative A + T doses by dose reduction. Lower doses of cumulative neoadjuvant A/T are associated with higher RCB scores in patients who required a dose reduction.
See this image and copyright information in PMC

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