{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:47:43Z","timestamp":1785415663942,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["CUP F77G22000340001 (2023_DDE_SCM_ADAQ_RICERCA)"],"award-info":[{"award-number":["CUP F77G22000340001 (2023_DDE_SCM_ADAQ_RICERCA)"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CUP F77G22000340001 (2023_DDE_SCM_ADAQ_RICERCA)"],"award-info":[{"award-number":["CUP F77G22000340001 (2023_DDE_SCM_ADAQ_RICERCA)"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Introduction: Antipsychotic (AP) medications are widely prescribed beyond psychotic disorders, yet their long-term safety profile regarding breast cancer (BC) risk remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the association between AP exposure and incident BC. Eligible studies reported adjusted odds ratios (ORs) with 95% confidence intervals for any AP, prolactin-increasing antipsychotics (PIAPs), or prolactin-sparing antipsychotics (PSAPs). Study quality was assessed using the modified Newcastle-Ottawa Scale (mNOS), and certainty of evidence was graded with the GRADE framework. Random-effect models were used to pool effect estimates by exposure category, duration, and cumulative Defined Daily Dose (DDD). Results: Nine high-quality observational studies encompassing 108 effect estimates were included. Most studies achieved mNOS scores of 9, yet GRADE certainty ranged from very low to moderate, with the overall body of evidence graded as low certainty due primarily to residual confounding. Any AP exposure was associated with a modestly increased BC risk, particularly with long-term use: use for &gt;5 years yielded pooled ORs around 1.5\u20131.6, while short-to-medium duration (1\u20135 years) showed smaller increases (pooled ORs in the range 1.2\u20131.3). For PIAPs, both longer duration (&gt;5 years) and higher cumulative exposure (&gt;1000\u20132000 DDDs) were consistently associated with ORs\/HRs in the 1.3\u20131.6 range, suggesting a possible dose\u2013response pattern. Histological analyses indicated stronger associations for ductal than lobular BC, and elevated risks were observed across age strata, including women aged &lt;55 and \u226570 years. Discussion: This meta-analysis suggests that chronic exposure to prolactin-increasing antipsychotics is associated with a potentially clinically relevant increase in BC risk, whereas prolactin-sparing agents do not show a clear signal of harm. However, the certainty of this association is limited by inconsistently measured confounders and by the observational nature of the data. These findings support a cautious, individualized approach in which clinicians preferentially consider PSAPs when appropriate, discuss BC risk as part of shared decision-making, and integrate tailored screening strategies for women requiring long-term PIAP therapy. Further high-quality pharmacoepidemiologic studies with better confounder control and mechanistic integration are needed to refine risk estimates and inform preventive neuropsychopharmacology.<\/jats:p>","DOI":"10.3390\/medsci14020205","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:53:23Z","timestamp":1776696803000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Breast Cancer Risk in over 1.3 Million Women on Antipsychotic Therapy: Life-Saving Drugs or Hidden Trigger for Breast Cancer?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8430-337X","authenticated-orcid":false,"given":"Enrico Altiero","family":"Giusto","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Section of Experimental Medicine and Laboratory of Technologies for Advanced Therapy (LTTA), University of Ferrara, 44121 Ferrara, Italy"},{"name":"Azienda Ospedaliero-Universitaria S. Anna, Via Aldo Moro 8, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5210-8601","authenticated-orcid":false,"given":"Vittorio","family":"Oteri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Endocrinology Section, Garibaldi-Nesima Hospital, University of Catania, Via Palermo, 636, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Guido","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3885-0395","authenticated-orcid":false,"given":"Delia Anamaria","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Department of Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-2514","authenticated-orcid":false,"given":"Jacopo","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37122 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-7405","authenticated-orcid":false,"given":"Carlotta","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Experimental Medicine and Laboratory of Technologies for Advanced Therapy (LTTA), University of Ferrara, 44121 Ferrara, Italy"},{"name":"Biomedical Research Center, Kansai Medical University, 10-15, Fumizono-cho Moriguchi-shi, Osaka 570-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-6508","authenticated-orcid":false,"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Section of Experimental Medicine and Laboratory of Technologies for Advanced Therapy (LTTA), University of Ferrara, 44121 Ferrara, Italy"},{"name":"Maria Cecilia Hospital, GVM Care & Research, Via Corriera 1, 48033 Cotignola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9404-3655","authenticated-orcid":false,"given":"Francesco","family":"Fiorica","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Section of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37122 Verona, Italy"},{"name":"Department of Clinical Oncology, Section of Medical Oncology, AULSS 9 Scaligera, 37122 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Haddad, N., Farhat, N., Go, J., Chen, Y., Gravel, C.A., Momoli, F., Mattison, D.R., McNair, D., Alami, A., and Krewski, D. 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