Postpartum breast cancer (PPBC) is associated with poorer outcomes than general BC, yet no screening strategy exists for lactating women. Emerging studies suggest that breast milk (BM) contains molecular and genomic material that may reflect BC etiology. Moreover, previous proteomic studies reported significant protein alteration in the BM of BC patients, and that protein dysregulation in BM is linked to cancer pathways. These studies suggested that systematic collection and analysis of BM may enable early detection, risk stratification, and mechanistic insight for PPBC. Hence, we propose a multimodal approach for early detection of PPBC using BM from mice, organoids, and humans.
We will develop multi-omics sequencing assays to measure ctDNA, proteomics, microRNAs, and microbiota composition in breast milk. The assay will be optimised using MMTC-PyMT mouse model and patient-derived BC organoids of different receptor status.
A prospective observational cohort study will be conducted in breastfeeding participants aged 18–45 years regardless of BC history. The BM will be either self-collected with self-examination instructions or clinician-collected and examined three monthly. High-risk participants based on results from physical examination, BM analysis, or personal concerns will be imaging investigated. End point is lost to follow-up, ceasing breast feeding, or death whichever occurs first.
Differential analysis will be performed in cases diagnosed with BC vs healthy controls for proteomic profiles, ctDNA mutation prevalence and variant allele frequencies, microRNA expression patterns, and microbiome composition. Multivariate modelling will be used to correlate molecular signatures with BC status, tumour subtype, lactation variables. We will report temporal changes in BM-derived molecular markers before clinical diagnosis and their correlation.
This project will establish the first BM bank revealing ethiology of PPBC. Characterisation of the breast tissue microenvironment through milk analysis, including inter-breast differences, will allow the development of a future BC screening programs for high-risk postpartum populations.