{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T11:01:03Z","timestamp":1794394863441,"version":"4.9.0"},"reference-count":35,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institut de Recherche sur le Cancer"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Chronic post-surgical pain (CPSP) affects 25\u201360% of women after breast cancer surgery. Prospective data from the Middle East and North Africa (MENA) region remain scarce. This study estimated 3-month CPSP incidence in a Moroccan cohort, developed two internally validated prediction models, and quantified the mediated effects of regional anaesthesia and ketamine through prevention of severe acute postoperative pain. Methods: Prospective cohort of 862 women undergoing curative breast cancer surgery (Institut National d\u2019Oncologie, Rabat; NCT04676438). CPSP was defined as a visual analogue scale (VAS) \u2265 3\/10 AND Brief Pain Inventory (BPI) interference \u2265 3\/10 at three months. Two logistic regression models were developed (Model A: 7 preoperative variables; Model B: 11 perioperative variables) and internally validated by 1000-bootstrap optimism correction. Counterfactual mediation analysis quantified effects mediated through severe acute pain. Results: CPSP incidence was 39.1% (95% confidence interval (CI) 35.9\u201342.4%), with 22.6% neuropathic-predominant. Model A showed limited discrimination (area under the curve (AUC) 0.58), with pain catastrophising as the dominant predictor. Model B demonstrated superior performance (AUC 0.694; Brier score 0.209) with net clinical benefit across the 15\u201355% range of clinically plausible decision thresholds. In counterfactual mediation analysis, an estimated 58.2% and 53.7% of the RA and ketamine effects, respectively, were mediated through severe acute pain, under the framework\u2019s no-unmeasured-confounding assumption. Perioperative ketoprofen independently reduced chronification risk (adjusted odds ratio (aOR) 0.66). Conclusions: In this single-centre Moroccan cohort, 39% of women developed CPSP at three months. Two validated models enable risk stratification at distinct clinical decision points. Regional anaesthesia and ketamine were associated with lower CPSP risk, in a pattern consistent with mediation through prevention of severe acute pain under the model\u2019s assumptions; ketoprofen was independently associated with lower chronification risk. These observational findings are hypothesis-generating and require confirmation before informing changes to analgesic protocols.<\/jats:p>","DOI":"10.3390\/cancers18152433","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"2433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chronic Post-Surgical Pain at 3 Months After Breast Cancer Surgery: Incidence, Predictors, and an Internally Validated Risk Model"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-7898","authenticated-orcid":false,"given":"Abdelilah","family":"Ghannam","sequence":"first","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Centre D\u2019Etudes Doctorales Sciences de la Vie et de la Sant\u00e9, Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Rabat 10000, Morocco"},{"name":"Anesthesia & Intensive Care Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-2026","authenticated-orcid":false,"given":"Mohammed Anass","family":"Majbar","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Surgical Oncology Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"},{"name":"Equipe de Recherche en Oncologie Translationnelle (EROT), Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-0700","authenticated-orcid":false,"given":"Youssef","family":"Motiaa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy of Tangier, Abdelmalek Essaadi University, Tangier 90000, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-1609","authenticated-orcid":false,"given":"Halima","family":"Abahssain","sequence":"additional","affiliation":[{"name":"Oncology and Medical Specialties Department, Valenciennes General Hospital, 59300 Valenciennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2818-839X","authenticated-orcid":false,"given":"Aiman","family":"El Fassi","sequence":"additional","affiliation":[{"name":"Anesthesia & Intensive Care Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oussama","family":"Ssouni","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Anesthesia & Intensive Care Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-4701","authenticated-orcid":false,"given":"Yassine","family":"El Bouazizi","sequence":"additional","affiliation":[{"name":"Centre D\u2019Etudes Doctorales Sciences de la Vie et de la Sant\u00e9, Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Rabat 10000, Morocco"},{"name":"Surgical Oncology Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1478-7919","authenticated-orcid":false,"given":"Zakaria Houssain","family":"Belkhadir","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Anesthesia & Intensive Care Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brahim","family":"Elahmadi","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Anesthesia & Intensive Care Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-9446","authenticated-orcid":false,"given":"Amine","family":"Souadka","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Impasse Souissi, Rabat 10100, Morocco"},{"name":"Surgical Oncology Department, National Institute of Oncology, CHU Ibn Sina, Rabat 10100, Morocco"},{"name":"Equipe de Recherche en Oncologie Translationnelle (EROT), Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V de Rabat, Rabat 10100, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 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