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. 2025 Feb:79:103829.
doi: 10.1016/j.breast.2024.103829. Epub 2024 Oct 28.

The INFLUENCE 3.0 model: Updated predictions of locoregional recurrence and contralateral breast cancer, now also suitable for patients treated with neoadjuvant systemic therapy

M C Van Maaren  1 , T A Hueting  2 , D J P van Uden  3 , M van Hezewijk  4 , L de Munck  5 , M A M Mureau  6 , P A Seegers  7 , Q J M Voorham  7 , M K Schmidt  8 , G S Sonke  9 , C G M Groothuis-Oudshoorn  10 , S Siesling  11 ; NABOR project group
Affiliations

The INFLUENCE 3.0 model: Updated predictions of locoregional recurrence and contralateral breast cancer, now also suitable for patients treated with neoadjuvant systemic therapy

M C Van Maaren et al. Breast. 2025 Feb.

Abstract

Background: Individual risk prediction of 5-year locoregional recurrence (LRR) and contralateral breast cancer (CBC) supports decisions regarding personalised surveillance. The previously developed INFLUENCE tool was rebuild, including a recent population and patients who received neoadjuvant systemic therapy (NST).

Methods: Women, surgically treated for nonmetastatic breast cancer, diagnosed between 2012 and 2016, were selected from the Netherlands Cancer Registry. Cox regression with restricted cubic splines was compared to Random Survival Forest (RSF) to predict five-year LRR and CBC risks. Separate models were developed for NST patients. Discrimination and calibration were assessed by 100x bootstrap resampling.

Results: In the non-NST and NST group, 49,631 and 10,154 patients were included, respectively. Age, mode of detection, histology, sublocalisation, grade, pT, pN, hormonal receptor status ± endocrine treatment, HER2 status ± targeted treatment, surgery ± immediate reconstruction ± radiation therapy, and chemotherapy were significant predictors for LRR and/or CBC in non-NST patients. For NST patients this was similar, but excluding (y)pT and (y)pN status, and including presence of ductal carcinoma in situ, axillary lymph node dissection and pathologic complete response. For non-NST patients, the Cox and RSF models were integrated in the online tool with 5-year AUCs of 0.77 (95%CI:0.77-0.77) and 0.68 (95%CI:0.67-0.68)] for LRR and CBC prediction, respectively. For NST patients, the RSF model performed best (AUCs 0.77 (95%CI:0.76-0.78) and 0.73 (95%CI:0.69-0.76) for LRR and CBC, respectively). Regarding calibration, observed-predicted differences were all <1 %.

Conclusion: This INFLUENCE 3.0 models showed moderate performance in LRR and CBC prediction. The models have been made available as online tool to enable clinical decision support regarding personalised follow-up.

Keywords: Breast cancer; Contralateral breast cancer; Follow-up; Locoregional recurrence; Prediction; Surveillance.

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Conflict of interest statement

Declaration of coompeting interest Tom A. Hueting declares employment at Evidencio. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of patient selection. ∗a second primary breast tumour diagnosed within 90 days of the first.
Fig. 2
Fig. 2
Mean hazard ratios and 95 % confidence intervals of 100 bootstrap samples on which the Cox regression model predicting LRR in the non-NST cohort is developed. ∗ As age is modeled using restricted cubic splines, the interpretation of the coefficients is not straightforward, as the effect of age on risk of LRR is a function of multiple regression coefficients. Abbreviations: LRR = locoregional recurrence, NST = neoadjuvant systemic treatment, HR = hazard ratio, LCL = lower confidence limit, UCL = upper confidence limit, pT = pathological tumour classification, pN = pathological nodal classification, HER2 = human epidermal growth factor 2, RT = radiation therapy.
Fig. 3
Fig. 3
For optimism corrected area under the curves for the non-NST and NST cohorts separately. The left panels show AUCs for prediction of LRR, using the Cox and RSF models. The right panels show AUCs for prediction of CBC, using the Cox and RSF models. Abbreviations: NST = neoadjuvant systemic treatment, LRR = locoregional recurrence, CBC = contralateral breast cancer, AUC = area under the receiver operating characteristic curve, CI = confidence interval.
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