[Clinicopathological features of breast cancer with HER2 low expression: a real-world retrospective study].

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis.

BACKGROUND: Given the use of tamoxifen as standard treatment for hormone receptor-positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor-positive breast cancer in premenopausal women. METHODS: Premenopausal patients with hormone receptor- positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints. RESULTS: Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025). CONCLUSIONS: In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor-positive breast cancer in premenopausal women were similar.

Expression of preosteoblast markers and Cbfa-1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone.

In giant cell tumour of bone (GCT), mononuclear stromal cells, which represent the neoplastic component of this lesion, regulate the formation of multinucleated osteoclast-like giant cells which are the characteristic hallmark of this tumour. However, the origin of stromal tumour cells has not yet been clearly defined. In this study, we evaluated several osteoblast markers including collagen type I, bone sialoprotein (BSP), osteonectin and osteocalcin in GCT using immunohistochemical techniques. Amongst the 13 GCT specimens and 7 GCT stromal cell (GCTSC) cultures studied, majority of the GCTSC synthesized type I collagen, BSP and osteonectin proteins but did not produce the differentiated osteoblast marker, osteocalcin. We further examined the regulation of several important osteogenic genes such as Cbfa-1, osterix and osteocalcin, and regulation of ALP activity in GCTSC in culture by bone morphogenetic protein 2 (BMP-2). Real-time PCR analysis indicated that Cbfa-1, osterix and osteocalcin mRNA were present in primary cultures of GCTSC. The addition of BMP-2 upregulated Cbfa-1 and osterix gene expression within 12 h and the enhancement was still observed at 24 h. ALP activity was minimal in untreated GCTSC in cultures. The number of ALP-positive GCTSC was significantly increased following treatment with BMP-2 or combinations with beta-glycerophosphate and ascorbic acid. In contrast, BMP enhancement of osterix mRNA level and ALP activity was also seen in SaOS2 osteoblast-like cells, but not in the primary culture of normal human skin fibroblasts. In summary, our data suggest that GCT stromal tumour cells may have an osteoblastic lineage and retain the ability to differentiate into osteoblasts.