Skip to main content
Top

28-04-2024 | Breast Cancer | RESEARCH ARTICLE

Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning

Authors: Enzhao Zhu, Linmei Zhang, Yixian Liu, Tianyu Ji, Jianmeng Dai, Ruichen Tang, Jiayi Wang, Chunyu Hu, Kai Chen, Qianyi Yu, Qiuyi Lu, Zisheng Ai

Published in: Clinical and Translational Oncology

Login to get access

Abstract

Background

The survival advantage of neoadjuvant systemic therapy (NST) for breast cancer patients remains controversial, especially when considering the heterogeneous characteristics of individual patients.

Objective

To discern the variability in responses to breast cancer treatment at the individual level and propose personalized treatment recommendations utilizing deep learning (DL).

Methods

Six models were developed to offer individualized treatment suggestions. Outcomes for patients whose actual treatments aligned with model recommendations were compared to those whose did not. The influence of certain baseline features of patients on NST selection was visualized and quantified by multivariate logistic regression and Poisson regression analyses.

Results

Our study included 94,487 female breast cancer patients. The Balanced Individual Treatment Effect for Survival data (BITES) model outperformed other models in performance, showing a statistically significant protective effect with inverse probability treatment weighting (IPTW)-adjusted baseline features [IPTW-adjusted hazard ratio: 0.51, 95% confidence interval (CI), 0.41–0.64; IPTW-adjusted risk difference: 21.46, 95% CI 18.90–24.01; IPTW-adjusted difference in restricted mean survival time: 21.51, 95% CI 19.37–23.80]. Adherence to BITES recommendations is associated with reduced breast cancer mortality and fewer adverse effects. BITES suggests that patients with TNM stage IIB, IIIB, triple-negative subtype, a higher number of positive axillary lymph nodes, and larger tumors are most likely to benefit from NST.

Conclusions

Our results demonstrated the potential of BITES to aid in clinical treatment decisions and offer quantitative treatment insights. In our further research, these models should be validated in clinical settings and additional patient features as well as outcome measures should be studied in depth.
Appendix
Available only for authorised users
Literature
2.
go back to reference Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, et al. NCCN guidelines® insights: breast cancer, version 4.2023. J Natl Compr Canc Netw. 2023;21:594–608.CrossRefPubMed Gradishar WJ, Moran MS, Abraham J, Abramson V, Aft R, Agnese D, et al. NCCN guidelines® insights: breast cancer, version 4.2023. J Natl Compr Canc Netw. 2023;21:594–608.CrossRefPubMed
3.
go back to reference Giordano SH, Hortobagyi GN, Kau SW, Theriault RL, Bondy ML. Breast cancer treatment guidelines in older women. J Clin Oncol. 2005;23:783–91.CrossRefPubMed Giordano SH, Hortobagyi GN, Kau SW, Theriault RL, Bondy ML. Breast cancer treatment guidelines in older women. J Clin Oncol. 2005;23:783–91.CrossRefPubMed
4.
go back to reference Barry PA, Schiavon G. Primary systemic treatment in the management of operable breast cancer: best surgical approach for diagnosis, biological evaluation, and research. J Natl Cancer Inst Monogr. 2015;2015:4–8.CrossRefPubMed Barry PA, Schiavon G. Primary systemic treatment in the management of operable breast cancer: best surgical approach for diagnosis, biological evaluation, and research. J Natl Cancer Inst Monogr. 2015;2015:4–8.CrossRefPubMed
5.
go back to reference Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94.CrossRefPubMed Mauri D, Pavlidis N, Ioannidis JP. Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst. 2005;97:188–94.CrossRefPubMed
6.
go back to reference Gallagher KK, Ollila DW. Indications for neoadjuvant systemic therapy for breast cancer. Adv Surg. 2019;53:271–92.CrossRefPubMed Gallagher KK, Ollila DW. Indications for neoadjuvant systemic therapy for breast cancer. Adv Surg. 2019;53:271–92.CrossRefPubMed
7.
go back to reference Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMed Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRefPubMed
8.
go back to reference Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020;26:2838–48.CrossRefPubMedPubMedCentral Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020;26:2838–48.CrossRefPubMedPubMedCentral
9.
go back to reference Brown L, Naffouje SA, Sam C, Laronga C, Catherine Lee M. Neoadjuvant systemic therapy in geriatric breast cancer patients: a national cancer database (NCDB) analysis. Breast Cancer Res Treat. 2022;196:441–51.CrossRefPubMed Brown L, Naffouje SA, Sam C, Laronga C, Catherine Lee M. Neoadjuvant systemic therapy in geriatric breast cancer patients: a national cancer database (NCDB) analysis. Breast Cancer Res Treat. 2022;196:441–51.CrossRefPubMed
10.
go back to reference Cantini L, Trapani D, Guidi L, Boscolo Bielo L, Scafetta R, Koziej M. Neoadjuvant therapy in hormone receptor-positive/HER2-negative breast cancer. Cancer Treat Rev. 2024;123:102669.CrossRefPubMed Cantini L, Trapani D, Guidi L, Boscolo Bielo L, Scafetta R, Koziej M. Neoadjuvant therapy in hormone receptor-positive/HER2-negative breast cancer. Cancer Treat Rev. 2024;123:102669.CrossRefPubMed
11.
go back to reference Conforti F, Pala L, Sala I, Oriecuia C, De Pas T, Specchia C, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ. 2021;375:e066381.CrossRefPubMedPubMedCentral Conforti F, Pala L, Sala I, Oriecuia C, De Pas T, Specchia C, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ. 2021;375:e066381.CrossRefPubMedPubMedCentral
14.
go back to reference Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543–6.CrossRefPubMed Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA. Evaluating the yield of medical tests. JAMA. 1982;247:2543–6.CrossRefPubMed
15.
go back to reference Shibue K. Artificial intelligence and machine learning in clinical medicine. N Engl J Med. 2023;388:2398.PubMed Shibue K. Artificial intelligence and machine learning in clinical medicine. N Engl J Med. 2023;388:2398.PubMed
16.
go back to reference Hosny A, Parmar C, Coroller TP, Grossmann P, Zeleznik R, Kumar A, et al. Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study. PLoS Med. 2018;15:e1002711.CrossRefPubMedPubMedCentral Hosny A, Parmar C, Coroller TP, Grossmann P, Zeleznik R, Kumar A, et al. Deep learning for lung cancer prognostication: A retrospective multi-cohort radiomics study. PLoS Med. 2018;15:e1002711.CrossRefPubMedPubMedCentral
18.
go back to reference Hankey BF, Ries LA, Edwards BK. The surveillance, epidemiology, and end results program: a national resource. Cancer Epidemiol Biomarkers Prev. 1999;8:1117–21.PubMed Hankey BF, Ries LA, Edwards BK. The surveillance, epidemiology, and end results program: a national resource. Cancer Epidemiol Biomarkers Prev. 1999;8:1117–21.PubMed
19.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–7.CrossRef
20.
go back to reference Künzel SR, Sekhon JS, Bickel PJ, Yu B. Metalearners for estimating heterogeneous treatment effects using machine learning. Proc Natl Acad Sci U S A. 2019;116:4156–65.CrossRefPubMedPubMedCentral Künzel SR, Sekhon JS, Bickel PJ, Yu B. Metalearners for estimating heterogeneous treatment effects using machine learning. Proc Natl Acad Sci U S A. 2019;116:4156–65.CrossRefPubMedPubMedCentral
21.
go back to reference Yao L, Chu Z, Li S, Li Y, Gao J, Zhang A. A survey on causal inference. ACM Trans Knowledge Discov Data. 2020;15:1–46.CrossRef Yao L, Chu Z, Li S, Li Y, Gao J, Zhang A. A survey on causal inference. ACM Trans Knowledge Discov Data. 2020;15:1–46.CrossRef
22.
go back to reference Li F, Morgan KL, Zaslavsky AM. Balancing covariates via propensity score weighting. J Am Stat Assoc. 2014;113:390–400.CrossRef Li F, Morgan KL, Zaslavsky AM. Balancing covariates via propensity score weighting. J Am Stat Assoc. 2014;113:390–400.CrossRef
23.
go back to reference Johansson FD, Shalit U, Kallus N, Sontag DA. Generalization bounds and representation learning for estimation of potential outcomes and causal effects. J Mach Learn Res. 2020;23:50. Johansson FD, Shalit U, Kallus N, Sontag DA. Generalization bounds and representation learning for estimation of potential outcomes and causal effects. J Mach Learn Res. 2020;23:50.
24.
go back to reference Schrod S, Schäfer A, Solbrig S, Lohmayer R, Gronwald W, Oefner PJ, et al. BITES: balanced individual treatment effect for survival data. Bioinformatics. 2022;38:i60–7.CrossRefPubMedPubMedCentral Schrod S, Schäfer A, Solbrig S, Lohmayer R, Gronwald W, Oefner PJ, et al. BITES: balanced individual treatment effect for survival data. Bioinformatics. 2022;38:i60–7.CrossRefPubMedPubMedCentral
25.
go back to reference Nagpal C, Goswami M, Dufendach KA, Dubrawski AW (2022) Counterfactual phenotyping with censored time-to-events. In Proceedings of the 28th ACM SIGKDD conference on knowledge discovery and data mining, Washington DC Nagpal C, Goswami M, Dufendach KA, Dubrawski AW (2022) Counterfactual phenotyping with censored time-to-events. In Proceedings of the 28th ACM SIGKDD conference on knowledge discovery and data mining, Washington DC
26.
go back to reference Katzman J, Shaham U, Cloninger A, Bates J, Jiang T, Kluger Y. DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network. BMC Med Res Methodol. 2016;18:24.CrossRef Katzman J, Shaham U, Cloninger A, Bates J, Jiang T, Kluger Y. DeepSurv: personalized treatment recommender system using a Cox proportional hazards deep neural network. BMC Med Res Methodol. 2016;18:24.CrossRef
27.
go back to reference Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39:1–13.CrossRefPubMedPubMedCentral Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39:1–13.CrossRefPubMedPubMedCentral
28.
go back to reference Groenwold RHH, Palmer TM, Tilling K. To adjust or not to adjust? when a “confounder” is only measured after exposure. Epidemiology. 2021;32:194–201.CrossRefPubMedPubMedCentral Groenwold RHH, Palmer TM, Tilling K. To adjust or not to adjust? when a “confounder” is only measured after exposure. Epidemiology. 2021;32:194–201.CrossRefPubMedPubMedCentral
29.
go back to reference Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J. 2009;51:171–84.CrossRefPubMed Austin PC. Some methods of propensity-score matching had superior performance to others: results of an empirical investigation and Monte Carlo simulations. Biom J. 2009;51:171–84.CrossRefPubMed
31.
go back to reference Lusivika-Nzinga C, Selinger-Leneman H, Grabar S, Costagliola D, Carrat F. Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination. BMC Med Res Methodol. 2017;17:160.CrossRefPubMedPubMedCentral Lusivika-Nzinga C, Selinger-Leneman H, Grabar S, Costagliola D, Carrat F. Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination. BMC Med Res Methodol. 2017;17:160.CrossRefPubMedPubMedCentral
32.
go back to reference Krzyzi’nski M, Spytek M, Baniecki H, Biecek P. SurvSHAP(t): time-dependent explanations of machine learning survival models. Knowl Based Syst. 2022;262:110234.CrossRef Krzyzi’nski M, Spytek M, Baniecki H, Biecek P. SurvSHAP(t): time-dependent explanations of machine learning survival models. Knowl Based Syst. 2022;262:110234.CrossRef
33.
go back to reference Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457–65.CrossRefPubMedPubMedCentral Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29:3457–65.CrossRefPubMedPubMedCentral
34.
go back to reference Pan H, Wang J, Shi W, Xu Z, Zhu E. Quantified treatment effect at the individual level is more indicative for personalized radical prostatectomy recommendation: implications for prostate cancer treatment using deep learning. J Cancer Res Clin Oncol. 2024;150:67.CrossRefPubMedPubMedCentral Pan H, Wang J, Shi W, Xu Z, Zhu E. Quantified treatment effect at the individual level is more indicative for personalized radical prostatectomy recommendation: implications for prostate cancer treatment using deep learning. J Cancer Res Clin Oncol. 2024;150:67.CrossRefPubMedPubMedCentral
35.
go back to reference Zhu E, Shi W, Chen Z, Wang J, Ai P, Wang X, et al. Reasoning and causal inference regarding surgical options for patients with low-grade gliomas using machine learning: a SEER-based study. Cancer Med. 2023;12:20878–91.CrossRefPubMedPubMedCentral Zhu E, Shi W, Chen Z, Wang J, Ai P, Wang X, et al. Reasoning and causal inference regarding surgical options for patients with low-grade gliomas using machine learning: a SEER-based study. Cancer Med. 2023;12:20878–91.CrossRefPubMedPubMedCentral
36.
go back to reference Zhu E, Chen Z, Ai P, Wang J, Zhu M, Xu Z, et al. Analyzing and predicting the risk of death in stroke patients using machine learning. Front Neurol. 2023;14:1096153.CrossRefPubMedPubMedCentral Zhu E, Chen Z, Ai P, Wang J, Zhu M, Xu Z, et al. Analyzing and predicting the risk of death in stroke patients using machine learning. Front Neurol. 2023;14:1096153.CrossRefPubMedPubMedCentral
39.
go back to reference Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen international consensus guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216–35.CrossRefPubMed Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen international consensus guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216–35.CrossRefPubMed
40.
go back to reference Curigliano G, Burstein HJ, Gnant M, Loibl S, Cameron D, Regan MM, et al. Understanding breast cancer complexity to improve patient outcomes: the St Gallen international consensus conference for the primary therapy of individuals with early breast cancer 2023. Ann Oncol. 2023;34:970–86.CrossRefPubMed Curigliano G, Burstein HJ, Gnant M, Loibl S, Cameron D, Regan MM, et al. Understanding breast cancer complexity to improve patient outcomes: the St Gallen international consensus conference for the primary therapy of individuals with early breast cancer 2023. Ann Oncol. 2023;34:970–86.CrossRefPubMed
42.
go back to reference Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, et al. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? results of a prospective study. Ann Surg Oncol. 2016;23:3467–74.CrossRefPubMedPubMedCentral Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, et al. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? results of a prospective study. Ann Surg Oncol. 2016;23:3467–74.CrossRefPubMedPubMedCentral
43.
go back to reference Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5:66.CrossRefPubMed Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5:66.CrossRefPubMed
44.
go back to reference She Y, Jin Z, Wu J, Deng J, Zhang L, Su H, et al. Development and validation of a deep learning model for non-small cell lung cancer survival. JAMA Netw Open. 2020;3:e205842.CrossRefPubMedPubMedCentral She Y, Jin Z, Wu J, Deng J, Zhang L, Su H, et al. Development and validation of a deep learning model for non-small cell lung cancer survival. JAMA Netw Open. 2020;3:e205842.CrossRefPubMedPubMedCentral
Metadata
Title
Determining individual suitability for neoadjuvant systemic therapy in breast cancer patients through deep learning
Authors
Enzhao Zhu
Linmei Zhang
Yixian Liu
Tianyu Ji
Jianmeng Dai
Ruichen Tang
Jiayi Wang
Chunyu Hu
Kai Chen
Qianyi Yu
Qiuyi Lu
Zisheng Ai
Publication date
28-04-2024
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-024-03459-8
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine