HR negative

P2, N=46, Active, not recruiting, Virginia Commonwealth University | Trial completion date: Mar 2026 --> Mar 2027

Nodal positivity rates are substantial for T1-T2 HER2+ and triple-negative tumors, even for T1a/b tumors. Among T1c tumors, HR-HER2+ subtype and age of 50 years or younger independently predicted increased nodal positivity, supporting NST especially for these patients.

Compared with IHC 3+ IDC, IHC 2+/FISH+ IDC demonstrated lower pCR rates and inferior RFS in hormone receptor-negative subset following neoadjuvant trastuzumab/ pertuzumab-containing therapy. Pathologic response correlated inversely with HER2/CEP17 ratio and HER2 copy number. Reassessment of HER2 expression with more sensitive quantitative methods, particularly in IHC 2+/FISH+ tumors, may improve therapeutic stratification.

sTILs vary markedly across breast cancer subtypes and correlate with aggressive pathological features, particularly TNBC, high-grade, hormone receptor negativity, and high proliferative index. Incorporating standardized sTIL assessment into routine reporting may help identify tumors with active immune microenvironments.

Given that our cases were identified in a relatively short time period, it is likely that GLI1-rearranged tumours are more common in the female genital tract than is realised and a high index of suspicion is required to initiate appropriate testing and establish the diagnosis. In the absence of readily available appropriate molecular testing, GLI1 immunohistochemistry can serve as an acceptably accurate surrogate biomarker for GLI1 rearrangement, since we found that GLI1 immunohistochemistry showed strong, diffuse nuclear staining in 6 GLI1-rearranged gynaecologic tumours stained for this study, whereas this was consistently negative, or at most weak/focal, in an array of 135 morphologic mimics.

CDC25A is an independent prognostic biomarker of clinical outcome in breast cancer. Further functional studies are warranted to validate CDC25A as a potential prognostic and therapeutic biomarker in breast cancer.

P3, N=11000, Active, not recruiting, University College, London | Not yet recruiting --> Active, not recruiting

P1/2, N=104, Recruiting, Consorzio Oncotech | Not yet recruiting --> Recruiting

Current evidence suggests that pregnancy itself does not inevitably worsen breast cancer prognosis when treatment is not compromised. However, breast cancers diagnosed soon after childbirth represent a distinct high-risk subgroup. These findings support full-intensity, guideline-based therapy during pregnancy and highlight the need for special attention and further research focused on postpartum breast cancer.

Conclusion P53 expression is associated with aggressive clinicopathological features like large tumour size, high Ki-67 index and the HER2-enriched subtype, suggesting its role in tumour progression and aggressiveness. Further, large multicentric studies with survival analysis are needed to confirm its clinical validity.

Our findings demonstrate that BRCA1 protein loss delineates a distinct aggressive tumor biology within high-risk breast cancers. We emphasize that BRCA1 IHC is a complementary biomarker and cannot supplant germline genetic testing for clinical decision-making regarding targeted therapies.

ER/PR expression in PASH is less frequent than previously reported by some studies. However, the frequency of fat necrosis and associated fibrocystic changes in PASH support a chronic, hormone-related process. Consistent CD34 positivity and absence of markers seen in histologic mimics aid in the diagnosis of PASH in challenging cases. PASH does not appear to impart increased cancer risk.