Nomograms for predicting recurrence of HER2-positive breast cancer with different HR status based on ultrasound and clinicopathological characteristics

Abstract

Purpose: This study aimed to identify ultrasound and clinicopathological characteristics related to recurrence in HER2-positive (HER2+) breast cancer, and to develop nomograms for predicting recurrence.

Methods: In this dual-center study, we retrospectively enrolled 570 patients with HER2+ breast cancer. The ultrasound and clinicopathological characteristics of hormone receptor (HR)-/HER2+ patients and HR+/HER2+ patients were analyzed separately according to HR status. Eighty percent of the original samples from HR-/HER2+ and HR+/HER2+ patients were extracted by bootstrap sampling as the training cohorts, while the remaining 20% were used as the external validation cohorts. Informative characteristics were screened through univariate and multivariable Cox regression in the training cohorts and used to develop nomograms for predicting recurrence. The predictive accuracy was calculated using Harrell's C-index and calibration curves.

Results: Three informative characteristics (axillary nodal status, calcification, and Adler degree) were identified in HR-/HER2+ patients, and another three (histological grade, axillary nodal status, and echogenic halo) in HR+/HER2+ patients. Based on these, two separate nomograms were constructed to assess recurrence risk. In the training cohorts, the C-index was 0.740 (95% CI: 0.667-0.811) for HR-/HER2+ nomogram, and 0.749 (95% CI: 0.679-0.820) for HR+/HER2+ nomogram. In the validation cohorts, the C-index was 0.708 (95% CI: 0.540-0.877) for HR-/HER2+ group, and 0.705 (95% CI: 0.557-0.853) for HR+/HER2+ group. The calibration curves also indicated the excellent accuracy of the nomograms.

Conclusions: Ultrasound performance of HER2+ breast cancers with different HR status was significantly different. Nomograms integrating ultrasound and clinicopathological characteristics exhibited favorable performance and have the potential to serve as a reliable method for predicting recurrence in heterogeneous breast cancer.

Keywords: HER2; breast cancer; nomogram; recurrence‐free survival; ultrasound.

FIGURE 1

A flow chart of included HER2+ patients. A total of 570 patients were included in the study, among these, there were 224 HR− (ER− and PR−) patients and 346 HR+ (ER+ or PR+) patients.

FIGURE 2

Workflow of extracting informative characteristics from ultrasound images and clinicopathological information to develop two nomograms.

FIGURE 3

(A–D) The informative characteristics with a frequency greater than 600 in the 1000 training subsets of HR−/HER2+ group, and their corresponding Kaplan–Meier plots for RFS. (B–D) Axillary nodal status, calcification, and Adler degree were strongly associated with RFS in HR−/HER2+ patients. (E–H) The informative characteristics with a frequency greater than 600 in the 1000 training subsets of HR+/HER2+ group, and their corresponding Kaplan–Meier plots for RFS. (F–H) Histological grade, axillary nodal status, and echogenic halo were highly associated with RFS in HR+/HER2+ patients.

FIGURE 4

(A, C) The box plots comparing rad‐score between the recurrence and non‐recurrence groups in HR−/HER2+ and HR+/HER2+ patients, respectively. (B, D) The survival curves of RFS with low‐risk and high‐risk were evaluated in the HR−/HER2+ and HR+/HER2+ groups, respectively.

FIGURE 5

Nomogram for HR−/HER2+ patients RFS with calibration curves. (A) Nomogram of HR−/HER2+ for 3 and 5‐years; (B, C) Calibration curves for 3 and 5‐years in the training cohorts; (D, E) Calibration curves for 3 and 5‐years in the validation cohorts.

FIGURE 6

Nomogram for HR+/HER2+ patients RFS with calibration curves. (A) Nomogram of HR+/HER2+ for 3 and 5‐years; (B, C) Calibration curves for 3 and 5‐years in the training cohorts; (D, E) Calibration curves for 3 and 5‐years in the validation cohorts.

FIGURE 7

(A–C) A 59‐year‐old HR−/HER2+ breast cancer patient with axillary lymph node involvement who recurred in the 12th month after surgery. (A) The ultrasound showed calcification (white arrows) and low Adler degree. The IHC result of the patient: (B) HER2+ and (C) ER−, original magnification ×400. (D–F) A 67‐year‐old patient with HR+/HER2+ breast cancer that has not yet relapsed, with uninvolved axillary lymph node and a histological grade of 1. (D) The ultrasound showed hyperechoic halo (green arrows). The IHC result of the patient: (E) HER2+ and (F) ER+, original magnification ×400.