Deep neural network provides personalized treatment recommendations for de novo metastatic breast cancer patients

Abstract

Background: It has long been controversial whether surgery should be performed for de novo metastatic breast cancer (dnMBC). The choice and timing of the primary tumor resection for dnMBC patients need to be individualized, but there was no tool to assist clinicians in decision-making. Methods: A 1:1:2 propensity score matching (PSM) was applied to examine the prognosis of dnMBC patients who underwent neoadjuvant systemic therapy followed by surgery (NS), surgery followed by chemotherapy (SC), and chemotherapy without surgery (CW). Then, two deep feed-forward neural network models were constructed to conduct personalized treatment recommendations. Results: The PSM-adjusted data showed that not all the dnMBC patients could benefit from surgery, and the advantages of NS and SC were different among various subgroups. Patients with stage T1-2, and pathological grade II tumors can be operated on directly, whereas those with stage T3-4, pathological grade III/IV diseases require NS. However, patients with grade I diseases, over 80 years of age, or with brain metastases could not benefit from surgery, regardless of whether they received neoadjuvant systemic therapy. Our deep neural network models exhibited high accuracy on both the train and test sets, one model can assist in deciding whether surgery is requested for dnMBC patient, if the surgery is necessary, another model can determine whether neoadjuvant systemic therapy is needed. Conclusion: This study investigated the prognosis of dnMBC patients, and two artificial intelligence (AI) assisted surgery decision-making models were developed to assist clinicians in delivering precision medicine while improving the survival of dnMBC patients.

Keywords: deep neural network; dnMBC; neoadjuvant systemic therapy; surgery.

Figure 1

The flowchart detailing the procedure of carrying out the study and statistical analysis. SEER: the Surveillance, Epidemiology, and End Results database; dnMBC: de novo metastatic breast cancer; PSM: propensity score matching; Cox: concordance index; K-M: Kaplan-Meier; NS: neoadjuvant systemic therapy followed with surgery, SC: surgery followed with chemotherapy, CW: chemotherapy without surgery; NST: neoadjuvant systemic therapy.

Figure 2

PSM-adjusted OS and BCSS of patients with dnMBC. Kaplan-Meier (K-M) survival analysis: A. OS of patients with dnMBC; B. BCSS of patients with dnMBC; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery; dnMBC: de novo metastatic breast cancer.

Figure 3

PSM-adjusted OS and BCSS of patients with dnMBC (Stratified by molecular subtype). Kaplan-Meier (K-M) survival analysis: OS of dnMBC patients with (A) HR+/HER2- subtype, (B) HR+/HER2+ subtype, (C) HR-/HER2+ subtype, (D) HR-/HER2- subtype; and BCSS of dnMBC patients with (E) HR+/HER2- subtype, (F) HR+/HER2+ subtype, (G) HR-/HER2+ subtype, (H) HR-/HER2- subtype. OS: overall survival; BCSS: breast cancer-specific survival; dnMBC: de novo metastatic breast cancer; HR: hormone receptor; HER2: human epidermal growth factor receptor 2; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery.

Figure 4

PSM-adjusted OS and BCSS of patients with dnMBC (Stratified by T stage). Kaplan-Meier (K-M) survival analysis: OS of dnMBC patients with (A) T1 stage, (B) T2 stage, (C) T3 stage, (D) T4 stage; and BCSS of dnMBC patients with (E) T1 stage, (F) T2 stage, (G) T3 stage, (H) T4 stage. OS: overall survival; BCSS: breast cancer-specific survival; dnMBC: de novo metastatic breast cancer; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery.

Figure 5

PSM-adjusted OS and BCSS of patients with dnMBC (Stratified by grade). Kaplan-Meier (K-M) survival analysis: OS of dnMBC patients with (A) grade I (well differentiated), (B) grade II (moderately differentiated), (C) grade III/IV (poorly differentiated); BCSS of dnMBC patients with (D) grade I (well differentiated), (E) grade II (moderately differentiated), (F) grade III/IV (poorly differentiated). OS: overall survival; BCSS: breast cancer-specific survival; dnMBC: de novo metastatic breast cancer; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery.

Figure 6

PSM-adjusted OS and BCSS of patients with dnMBC (Stratified by age). Kaplan-Meier (K-M) survival analysis: OS of dnMBC patients aged (A) 40-, (B) 40-49, (C) 50-59, (D) 60-69, (E) 70-79, (F) 80+; BCSS of dnMBC patients aged (G) 40-, (H) 40-49, (I) 50-59, (J) 60-69, (K) 70-79, (L) 80+. OS: overall survival; BCSS: breast cancer-specific survival; dnMBC: de novo metastatic breast cancer; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery.

Figure 7

PSM-adjusted OS and BCSS of patients with dnMBC (Stratified by brain metastases). Kaplan-Meier (K-M) survival analysis: A. OS of dnMBC patients without brain metastases; B. OS of dnMBC patients with brain metastases; C. BCSS of dnMBC patients without brain metastases; D. BCSS of dnMBC patients with brain metastases. OS: overall survival; BCSS: breast cancer-specific survival; dnMBC: de novo metastatic breast cancer; PSM: Propensity score matching; BH: Multiple comparisons were corrected by the Benjamini & Hochberg method; NS: neoadjuvant systemic therapy followed with surgery; SC: surgery followed with chemotherapy; CW: chemotherapy without surgery.

Figure 8

K-M survival analyses comparing the differences in OS between the patients who received the recommendation and anti-recommendation therapy on the train and test sets (deep neural network model 1). A. K-M survival analyses on train set; B. K-M survival analyses on test set; HR: hazard ratio; 95%CI: 95% confidence interval.

Figure 9

K-M survival analyses comparing the differences in OS between the patients who received the recommendation and anti-recommendation therapy on the train and test sets (deep neural network model 2). A. K-M survival analyses on train set; B. K-M survival analyses on test set; HR: hazard ratio; 95%CI: 95% confidence interval; NST: neoadjuvant systemic therapy.