{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:00:59Z","timestamp":1775538059227,"version":"3.50.1"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While benign mammary hyperplasia frequently undergoes spontaneous regression, clinicians currently lack validated serological biomarkers for personalized surveillance strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate whether the serum prolactin-to-estradiol ratio [PER; prolactin (ng\/mL) \u00f7 estradiol (pg\/mL)] can predict radiological regression in benign hyperplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study (January 2020\u2013December 2024) enrolled women (18\u201355\u202fyears) with biopsy-confirmed ductal or lobular hyperplasia. Baseline fasting prolactin and estradiol were measured using duplicate electrochemiluminescence immunoassays (WHO-traceable) from routine clinical samples. Follow-up biopsies were performed only when imaging triggers were met. Multivariable logistic regression and interval-censored Cox models assessed associations with demographic, reproductive, and lesion covariates. Performance was evaluated using C-statistics, calibration, ROC analysis, and decision curves.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 1,645 participants completing follow-up (94.7%), 790 (45.5%) demonstrated radiological regression. Patients with regression had significantly lower mean PER compared to non-regressors (0.161\u202f\u00b1\u202f0.086 vs. 0.232\u202f\u00b1\u202f0.136;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), reflecting a composite hormonal environment of reduced prolactin and relatively elevated estradiol. PER demonstrated a strong inverse dose\u2013response relationship with regression probability (adjusted OR per 0.1-unit increase\u202f=\u202f0.15; 95% CI: 0.10\u20130.22) and time-to-regression (adjusted HR per 0.1-unit decrease\u202f=\u202f1.76; 95% CI: 1.54\u20132.01), with regression rates declining from 60.3% in the lowest PER tertile to 28.0% in the highest. At the optimal cutoff of PER \u22640.185, discriminative performance reached an AUC of 0.664, significantly outperforming clinical variables alone (AUC 0.529), with net clinical benefit confirmed across a broad range of decision thresholds. Predictive effects remained consistent across age, menstrual phase, and histological subtype (all interaction\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;gt;\u202f0.08), with a modest but significant BMI interaction (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.042).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Low PER independently and reliably predicts spontaneous regression of benign breast hyperplasia. External validation studies and point-of-care assay development are needed before clinical implementation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1814991","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T04:15:27Z","timestamp":1775535327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Predicting radiological regression in benign breast hyperplasia: the prolactin-to-estradiol ratio as a prognostic biomarker"],"prefix":"10.3389","volume":"13","author":[{"given":"Kun","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Medicine, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huayu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guizhou Medical University","place":["Kaili, Guizhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.4048\/jbc.2020.23.e40","article-title":"Breast Cancer risk prediction in Korean women: review and perspectives on personalized breast cancer screening","volume":"23","author":"Kim","year":"2020","journal-title":"J Breast Cancer"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1001\/archinternmed.2010.152","article-title":"Influence of race and sex on prevalence and recurrence of colon polyps","volume":"170","author":"Penn","year":"2010","journal-title":"Arch Intern 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