Abstract P2-07-04: Prognostic value of residual cancer burden (RCB), neo-bioscore and neoadjuvant response index (NRI) to evaluate response to neoadjuvant trastuzumab-based therapy in HER2-positive breast cancer (BC)
Authors: Steenbruggen TG , van Seijen M , Janssen LM , van Ramshorst MS , van Werkhoven E , Lips EH , Vrancken-Peeters M-JT , Horlings HM , Wesseling J , Sonke GS 
Published: May 2019

Intro Pathological complete response (pCR) to neoadjuvant systemic therapy is associated with favorable long-term outcome. As pCR is not an optimal surrogate marker for outcome, other tools were developed to predict long-term outcome more accurately, including the RCB4, NRI3, and Neo-Bioscore5. We evaluated the prognostic value of these tools in a cohort of patients with HER2+ BC with the aim of selecting a group of patients with residual disease but a similar long-term outcome as patients achieving pCR.

Methods We included all patients with stage II-III HER2+ BC who were treated with trastuzumab-based neoadjuvant therapy and surgery in the Netherlands Cancer Institute between November 2004 and December 2016. Patients were identified from the institutes' tumor registry and data was collected from the patients' records. To assess RCB scores surgical specimens (breast and axilla tissue) of patients without pCR were retrospectively reviewed. NRI and Neo-Bioscore were calculated based on original pathology reports.

Primary endpoint was recurrence-free interval (RFI), defined as time since diagnosis of BC till locoregional or distant recurrence or death from BC, whatever came first. Cox proportional models were used with transformations of RCB, NRI, and Neo-Bioscore. In addition, we evaluated at which cut-off point the NRI could select patients with a similar good prognosis as patients who achieved a pCR, defined by the same lower bound of the 95%CI of the 5-year RFI estimate for the pCR-group.

Results 283 women were included, 149 (53%) with HER2+/ER+ BC. 28% received dual HER2-blockade. Median follow-up was 66 months (range 11-148). 157 patients (55%) achieved a pCR in breast and axilla; predicted 5-year RFI for this group was 91% (95%CI 86-96), HR no-pCR vs pCR 2.19, 95%CI 1.07-4.47. Table 1 shows the predicted 5-year RFI and HR for RCB classes. The HR of an RFI event increases gradually for lower NRI values compared to NRI of 1 and gets more steep near NRI values of 0. Patients with a NRI of ≥0.80-0.99 have a 5-year RFI estimate of 90% (95%CI 86-96), HR 1.1 (95%CI 0.6-1.9) compared to patients with NRI of 1 (which is pCR). Table 2 shows the predicted 5-year RFI and HR for the Neo-Bioscore.

Table 1RCB classes, estimated 5-year RFI and HRRCBn% 5-year RFI95% CIHR95% CI016392.688.397.111113990.385.295.61.330.672.6526278.469.488.53.181.427.1131135.316.476.113.605.3034.81

Table 2Neo-Bioscore classes, predicted 5-year RFI and HRNeo-Bioscoren% 5-year RFI95% CIHR95% CI01998.795.510011115392.486.099.36.100.9240.5229384.977.493.012.670.76210.4037289.983.896.58.200.62108.2041974.962.989.222.331.76283.445329.410.384.095.206.271446.64610.601.00406.2619.558442.21

Conclusions We show that in a HER2+ BC cohort the RCB and NRI are able to identify a subgroup of patients with limited residual disease after neoadjuvant therapy with similar good prognosis as patients with pCR and therefore may not benefit from additional adjuvant therapy.

References

1 Cortazar Lancet 2014

2 FDA Regist 2014

3 Rodenhuis Ann Oncol 2010

4 Symmans JCO 2007

5 Jeruss JCO 2008

6 Mittendorf JAMA Oncol 2016

Citation Format: Steenbruggen TG, van Seijen M, Janssen LM, van Ramshorst MS, van Werkhoven E, Lips EH, Vrancken-Peeters M-JT, Horlings HM, Wesseling J, Sonke GS. Prognostic value of residual cancer burden (RCB), neo-bioscore and neoadjuvant response index (NRI) to evaluate response to neoadjuvant trastuzumab-based therapy in HER2-positive breast cancer (BC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-07-04.