The Association of Postpartum Status with Breast Cancer Prognosis, Clinicopathological Features, and Tumor Microenvironment Remodeling: A Systematic Review of Epidemiological Evidence | ||
| Journal of Integrated Maternal and Pediatric Care | ||
| Articles in Press, Accepted Manuscript, Available Online from 19 September 2026 | ||
| Document Type: Protocol | ||
| Authors | ||
| Samane Heydari* 1; Sadegh Safaei2 | ||
| 1Mother and Newborn Health Research Center, Comprehensive Research Institute for Maternal and Child Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| 2Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran | ||
| Abstract | ||
| Postpartum breast cancer (PPBC) is associated with poorer survival, higher metastatic rates, and distinct tumor biology versus breast cancer in nulliparous women or those with a longer delivery interval. Lactation, weaning, and postpartum mammary involution may create a pro-metastatic microenvironment, but evidence linking these exposures to prognosis and tumor-immune-stromal features has not been synthesized. The review will follow PRISMA and MOOSE guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science will be searched from inception using terms for breast cancer, postpartum status, lactation, involution, prognosis, and tumor microenvironment. Eligible studies will be observational (cohort, case–control, cross-sectional) studies of women with breast cancer defining a postpartum subgroup (by time since last childbirth, parity, lactation, or weaning), including a comparator (nulliparous women or longer birth interval), and reporting at least one prognostic outcome (overall, distant metastasis-free, or disease-free survival, or recurrence), an aggressive clinicopathological feature, molecular/immune profile, or a treatment response. We will exclude experimental studies without human endpoints, risk-factor/incidence studies, reviews, and case reports. Two reviewers will independently screen, extract data, and assess risk of bias using the Newcastle–Ottawa Scale. If ≥3 studies report comparable estimates for the same exposure–outcome pairing, we will perform a random-effects meta-analysis using restricted maximum likelihood; random-effects models were pre-specified because of anticipated clinical and methodological heterogeneity. If <3 studies are available, findings will be synthesized narratively. Sensitivity analyses may fit a fixed-effect model, but this will not replace the primary random-effects analysis. Heterogeneity will be assessed with I² and Cochran’s Q, with I² informing interpretation rather than model choice. | ||
| Keywords | ||
| Breast Neoplasms; Survival Analysis; Postpartum Period; Lactation; Parity | ||
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