Relative to HR+/HER2- subtype, local recurrence was greater in HER2+ metastases (HR 3.20, 95% CI 1.78-5.75, p < 0.001), while patients with TNBC demonstrated higher rates of new brain metastases after initial treatment (HR 3.16, 95% CI 1.99-5.02, p < 0.001) and shorter time to salvage whole brain radiation (WBRT) (HR 3.79, 95% CI 1.36-10.56, p = 0.01) and salvage stereotactic radiation (HR 1.86, 95% CI 1.11-3.10, p = 0.02).
The authors searched for patients who had breast carcinoma recurrences or metastases diagnosed between 2010 and 2018 by fine-needle aspiration or by the drainage of body cavity fluids with HER2 IHC and/or FISH performed on formalin-fixed CBs.
The aim of this study was to analyze the association of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS).
Due to the heterogeneity of breast cancer and possible discordance in HER2 status between primary tumors and distant metastases, assessment of HER2 expression by noninvasive imaging is important.
<b>Conclusion:</b> Our findings confirm the clinical benefits and safety of retreatment therapy with trastuzumab for HER2-positive patients with metastatic cancer of the breast that had progressed during trastuzumab-based treatment regimens.
It was shown that elevated TMED3 markedly correlated with ER, PR, Her-2 status, and lymph nodes metastases in addition to significant association with poor overall prognosis.
This retrospective, exploratory study included patients (≥ 18 years old) treated at our center (2005-2009) who had ER+ , HER2-negative invasive breast cancer and synchronous nodal metastases with available tumor blocks from both sites.
The impact of following factors on 5-year disease-free survival (DFS) and overall survival (OS) was studied: age, sex, preoperative 7th nerve palsy, skin infiltration, pT, pN, surgical margin, type of parotidectomy and neck dissection, histology (SDC de novo vs. SDC ex pleomorphic adenoma, SDCexPA), intra/periparotid lymph nodes metastases, perineural invasion (PNI), extraparenchymal extension (EPE), and overexpression HER2.
Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC.
The ERBB2 mutation status was determined by next generation sequencing and/or pyrosequencing in n = 106 ILBCs, including n = 86 primary or locally recurrent tumors and n = 20 metastases from visceral organs, soft tissue, or skin.
Mechanistically, GPAA1 enhanced the levels of metastasis-associated GPI-anchored proteins to increase tumour metastasis and intensified lipid raft formation, which consequently promoted the interaction between EGFR and ERBB2 as well as downstream pro-proliferative signalling.
Consistently, tRF3E levels significantly decrease in the blood of patients with epidermal growth factor receptor 2 (HER2)-positive BC reflecting tumor status (control > early cancer > metastatic cancer). tRF3E down-regulation was recapitulated in Δ16HER2 transgenic mice, representing a BC preclinical model.
TBCP-1 tumours maintain a HER2-positive phenotype in vivo and give rise to a high incidence of spontaneous and experimental metastases in the brain and other organs.
Trastuzumab duocarmazine shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer, with a manageable safety profile.
For metastasis studies, 7 patient-derived xenograft tumours (PDX: BB3RC32, ER+ PR+ HER2-; BB2RC08, ER+ PR+ ER2-; BB6RC37, ER- PR- HER2- and BB6RC39, ER+ PR+ HER2+), MDA-MB-231-luc2, T47D-luc2 or MCF7-Luc2 cells were injected into the 4th mammary ducts and metastases monitored by luciferase imaging and confirmed on histological sections.
This is a retrospective study in which FISH analysis of Her-2/Neu was carried out simultaneously on archived material of 50 cases previously diagnosed as invasive duct carcinoma and the corresponding nodal metastases from the Pathology Department, NCI.
Local recurrences (7.5%) and distant metastases (25.6%) occurred most often in HER2 positive disease and the least often in luminal A (3.7% and 9.5%, respectively).
Sixty-seven percent of breast cancers overexpressed human epidermal growth factor receptor 2 (HER2); 53% of pituitary metastases from breast cancers appeared ≥10 years after diagnosis of the primary tumor.
Four endophenotypes were identified with LCA: 1) "Favourable biology" had entirely local disease with favourable biology, 2) "HGHR-" had the highest incidence of HR- receptor status and highest grade but few metastases and relatively good outcomes, 3) "HR+ bone" had isolated bone metastases and uniform receptor status (HR+/HER2-), and 4) "Distant organ spread" had high metastatic burden and poor survival.
Furthermore, median time between the end of adjuvant treatment and second histology of the metachronous metastases accounted for 15 days (range 2-165 days) and 478 days (range 7-2739 days) was observed in the group of patients with decreased or unchanged HER2 expression, respectively.
This study lends support to the diagnosis of the liver among patients at high risk of liver metastases, including those with HER2-positive and other systemic metastases.
A prior site of disease (including intracranial metastases) was HER2+ for 13% of evaluable patients: 3 of 11 patients with colorectal cancer and no patients with esophageal or pancreatic cancer.
Targeted therapy such anti-HER2 agents have a lower efficacy in this setting compared to metastases elsewhere; however, novel therapies are emerging in this regard.