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Preoperative Germline Genetic Testing and Surgical Timing in Breast Cancer: Implementation of National Reimbursement Programs: A Retrospective Cohort Study.

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Title: Preoperative Germline Genetic Testing and Surgical Timing in Breast Cancer: Implementation of National Reimbursement Programs: A Retrospective Cohort Study.
Authors: Vlad IC; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Vlad CI; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Balacescu O; Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Gata VA; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Morariu DS; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Miclaus M; Department of Oncogenetics, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Muntean AL; Department of Medical Education, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania., Catana A; Department of Oncogenetics, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.; Department of Molecular Sciences, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania., Antone N; Department of Medical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania., Achimas-Cadariu P; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.
Source: Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2026 Jul 19; Vol. 62 (7). Date of Electronic Publication: 2026 Jul 19.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: MDPI Country of Publication: Switzerland NLM ID: 9425208 Publication Model: Electronic Cited Medium: Internet ISSN: 1648-9144 (Electronic) Linking ISSN: 1010660X NLM ISO Abbreviation: Medicina (Kaunas) Subsets: MEDLINE
Imprint Name(s): Publication: 2018- : Basel, Switzerland : MDPI
Original Publication: Kaunas : Lietuvos gydytojų sąjunga
MeSH Terms: Breast Neoplasms*/surgery , Breast Neoplasms*/genetics , Breast Neoplasms*/diagnosis , Genetic Testing*/methods , Genetic Testing*/statistics & numerical data , Genetic Testing*/standards , Genetic Testing*/economics, Preoperative Care/methods ; Humans ; Female ; Retrospective Studies ; Middle Aged ; Cohort Studies ; Adult ; Time Factors ; Aged ; Germ-Line Mutation
Abstract: Background and Objectives: Over recent decades, germline genetic testing has become increasingly integrated into breast cancer care, yet its precise effect on the timing of surgical workflows remains incompletely defined. This study investigates the implementation of nationally reimbursed genetic testing programs and examines how the scheduling of multigene germline testing relates to surgical timing. Materials and Methods: In this retrospective cohort analysis, we examined 502 breast cancer cases from the institutional registry of the "Ion Chiricuță" Oncology Institute (IOCN), with a mean age of 52 years, a high rate of neoadjuvant therapy (82.3%) and a majority of them in T2 (52%) and N1 (43%), N2 (29%) clinical stage: 263 patients from an earlier private-practice pay testing era (pre-reimbursement) as a comparison sample and 239 patients from the period when reimbursement programs were in operation. We then evaluated the benefits of state-funded genetic testing initiatives, computing three intervals: diagnosis to genetic test, genetic test to surgery, and diagnosis to surgery. Patients were categorized by timing of multigene testing (preoperative vs. postoperative), receipt of neoadjuvant systemic therapy (NACT), mutation status, and funding source for testing (national PNS program funded by the Romanian Ministry of Health; PNRR European Recovery and Resilience Facility funds; or self-funded private testing). Nonparametric statistics (Mann-Whitney U, Spearman correlation) and effect-size metrics (Cliff's delta, Theil-Sen slope) were employed. Results: The median diagnosis-to-surgery interval was 203 days (IQR 179-230). Patients tested preoperatively had longer intervals than those tested postoperatively (216 vs. 182.5 days; p = 0.000153; Cliff's δ = -0.486), a pattern driven by shared pathways involving NACT rather than by testing-induced delays. NACT was the principal determinant of surgical timing (211 vs. 43 days; p = 302.55 × 10-11). Within the preoperative subgroup, time to multigene testing correlated strongly with time to surgery (Spearman ρ = 0.54; p = 4.75 × 10-7; Theil-Sen slope = 0.37, 95% CI = 0.22-0.53). However, the no-NACT group included only four patients. The presence of a pathogenic variant did not significantly change surgical timing (p = 0.982). The PNS national reimbursement program achieved the highest preoperative integration rate for multigene genetic testing after adjustment for NACT confounder (76.7%), outperforming PNRR (61%) and private practice (56%). Conclusions: While genetic testing timing correlates with surgical workflow, neoadjuvant systemic therapy pathways and program structure exert greater influence than testing per se. Structured national programs enhance preoperative testing uptake without causing delays beyond those inherent to NACT pathways.
Contributed Indexing: Keywords: BRCA1; BRCA2; breast cancer; genetic testing; neoadjuvant systemic therapy; precision oncology; surgical timing; surgical workflow
Entry Date(s): Date Created: 20260728 Date Completed: 20260729 Latest Revision: 20260731
Update Code: 20260731
PubMed Central ID: PMC13413821
DOI: 10.3390/medicina62071397
PMID: 42512939
Database: MEDLINE
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  Data: Preoperative Germline Genetic Testing and Surgical Timing in Breast Cancer: Implementation of National Reimbursement Programs: A Retrospective Cohort Study.
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  Data: <searchLink fieldCode="AU" term="%22Vlad+IC%22">Vlad IC</searchLink>; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Vlad+CI%22">Vlad CI</searchLink>; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Balacescu+O%22">Balacescu O</searchLink>; Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Gata+VA%22">Gata VA</searchLink>; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Morariu+DS%22">Morariu DS</searchLink>; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Miclaus+M%22">Miclaus M</searchLink>; Department of Oncogenetics, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Muntean+AL%22">Muntean AL</searchLink>; Department of Medical Education, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Catana+A%22">Catana A</searchLink>; Department of Oncogenetics, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.; Department of Molecular Sciences, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Antone+N%22">Antone N</searchLink>; Department of Medical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.<br /><searchLink fieldCode="AU" term="%22Achimas-Cadariu+P%22">Achimas-Cadariu P</searchLink>; Department of Oncology, University of Medicine and Pharmacy 'Iuliu Hațieganu', 400347 Cluj-Napoca, Romania.; Department of Surgical Oncology, The Oncology Institute 'Prof. Dr. Ion Chiricuță', 400015 Cluj-Napoca, Romania.
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  Data: <searchLink fieldCode="JN" term="%229425208%22">Medicina (Kaunas, Lithuania)</searchLink> [Medicina (Kaunas)] 2026 Jul 19; Vol. 62 (7). <i>Date of Electronic Publication: </i>2026 Jul 19.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22MDPI%22">MDPI </searchLink><i>Country of Publication: </i>Switzerland <i>NLM ID: </i>9425208 <i>Publication Model: </i>Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1648-9144 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%221010660X%22">1010660X </searchLink><i>NLM ISO Abbreviation: </i>Medicina (Kaunas) <i>Subsets: </i>MEDLINE
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  Data: <searchLink fieldCode="MM" term="%22Breast+Neoplasms%22">Breast Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Breast+Neoplasms+surgery%22">surgery</searchLink> <br /><searchLink fieldCode="MM" term="%22Breast+Neoplasms%22">Breast Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Breast+Neoplasms+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Breast+Neoplasms%22">Breast Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Breast+Neoplasms+diagnosis%22">diagnosis</searchLink> <br /><searchLink fieldCode="MM" term="%22Genetic+Testing%22">Genetic Testing*</searchLink>/<searchLink fieldCode="MM" term="%22Genetic+Testing+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Genetic+Testing%22">Genetic Testing*</searchLink>/<searchLink fieldCode="MM" term="%22Genetic+Testing+statistics+%26+numerical+data%22">statistics & numerical data</searchLink> <br /><searchLink fieldCode="MM" term="%22Genetic+Testing%22">Genetic Testing*</searchLink>/<searchLink fieldCode="MM" term="%22Genetic+Testing+standards%22">standards</searchLink> <br /><searchLink fieldCode="MM" term="%22Genetic+Testing%22">Genetic Testing*</searchLink>/<searchLink fieldCode="MM" term="%22Genetic+Testing+economics%22">economics</searchLink><br /><searchLink fieldCode="MH" term="%22Preoperative+Care%22">Preoperative Care</searchLink>/<searchLink fieldCode="MH" term="%22Preoperative+Care+methods%22">methods</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Retrospective+Studies%22">Retrospective Studies</searchLink> ; <searchLink fieldCode="MH" term="%22Middle+Aged%22">Middle Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Cohort+Studies%22">Cohort Studies</searchLink> ; <searchLink fieldCode="MH" term="%22Adult%22">Adult</searchLink> ; <searchLink fieldCode="MH" term="%22Time+Factors%22">Time Factors</searchLink> ; <searchLink fieldCode="MH" term="%22Aged%22">Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Germ-Line+Mutation%22">Germ-Line Mutation</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Background and Objectives: Over recent decades, germline genetic testing has become increasingly integrated into breast cancer care, yet its precise effect on the timing of surgical workflows remains incompletely defined. This study investigates the implementation of nationally reimbursed genetic testing programs and examines how the scheduling of multigene germline testing relates to surgical timing. Materials and Methods: In this retrospective cohort analysis, we examined 502 breast cancer cases from the institutional registry of the "Ion Chiricuță" Oncology Institute (IOCN), with a mean age of 52 years, a high rate of neoadjuvant therapy (82.3%) and a majority of them in T2 (52%) and N1 (43%), N2 (29%) clinical stage: 263 patients from an earlier private-practice pay testing era (pre-reimbursement) as a comparison sample and 239 patients from the period when reimbursement programs were in operation. We then evaluated the benefits of state-funded genetic testing initiatives, computing three intervals: diagnosis to genetic test, genetic test to surgery, and diagnosis to surgery. Patients were categorized by timing of multigene testing (preoperative vs. postoperative), receipt of neoadjuvant systemic therapy (NACT), mutation status, and funding source for testing (national PNS program funded by the Romanian Ministry of Health; PNRR European Recovery and Resilience Facility funds; or self-funded private testing). Nonparametric statistics (Mann-Whitney U, Spearman correlation) and effect-size metrics (Cliff's delta, Theil-Sen slope) were employed. Results: The median diagnosis-to-surgery interval was 203 days (IQR 179-230). Patients tested preoperatively had longer intervals than those tested postoperatively (216 vs. 182.5 days; p = 0.000153; Cliff's δ = -0.486), a pattern driven by shared pathways involving NACT rather than by testing-induced delays. NACT was the principal determinant of surgical timing (211 vs. 43 days; p = 302.55 × 10<superscript>-11</superscript>). Within the preoperative subgroup, time to multigene testing correlated strongly with time to surgery (Spearman ρ = 0.54; p = 4.75 × 10<superscript>-7</superscript>; Theil-Sen slope = 0.37, 95% CI = 0.22-0.53). However, the no-NACT group included only four patients. The presence of a pathogenic variant did not significantly change surgical timing (p = 0.982). The PNS national reimbursement program achieved the highest preoperative integration rate for multigene genetic testing after adjustment for NACT confounder (76.7%), outperforming PNRR (61%) and private practice (56%). Conclusions: While genetic testing timing correlates with surgical workflow, neoadjuvant systemic therapy pathways and program structure exert greater influence than testing per se. Structured national programs enhance preoperative testing uptake without causing delays beyond those inherent to NACT pathways.
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  Data: <i>Keywords: </i>BRCA1; BRCA2; breast cancer; genetic testing; neoadjuvant systemic therapy; precision oncology; surgical timing; surgical workflow
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  Data: <i>Date Created: </i>20260728 <i>Date Completed: </i>20260729 <i>Latest Revision: </i>20260731
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        Value: 10.3390/medicina62071397
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        Text: English
    Subjects:
      – SubjectFull: Preoperative Care methods
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Retrospective Studies
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      – SubjectFull: Time Factors
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      – SubjectFull: Aged
        Type: general
      – SubjectFull: Germ-Line Mutation
        Type: general
      – SubjectFull: Breast Neoplasms surgery
        Type: general
      – SubjectFull: Breast Neoplasms genetics
        Type: general
      – SubjectFull: Breast Neoplasms diagnosis
        Type: general
      – SubjectFull: Genetic Testing methods
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      – SubjectFull: Genetic Testing statistics & numerical data
        Type: general
      – SubjectFull: Genetic Testing standards
        Type: general
      – SubjectFull: Genetic Testing economics
        Type: general
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      – TitleFull: Preoperative Germline Genetic Testing and Surgical Timing in Breast Cancer: Implementation of National Reimbursement Programs: A Retrospective Cohort Study.
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              Text: 2026 Jul 19
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              Y: 2026
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