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In China, 60% of breast cancer patients were premenopausal women at the time of diagnosis. Compared with postmenopausal women, premenopausal women have strong ovarian function and secrete estrogen to promote breast cancer growth. Ovarian function suppression (OFS) has been used in the treatment of breast cancer for decades, and a large body of evidence-based medical research confirmed that the application of OFS alone or combination therapy can reduce the recurrence risk and improve survival in premenopausal women with breast cancer. The long-term follow-up data of OFS studies have been published successively. SOFT and TEXT study reported the follow-up results of 12 and 13 years, the STO-5 study reported the follow-up data of 20 years, and the ASTRRA study based on Asian populations reported the follow-up data of 8 years. It is further confirmed that the application of OFS for patients with early breast cancer could significantly reduce the recurrence risk over ten years and improve the possibility of cure. MonarchE study and NATALEE study demonstrated that the application of CDK4/6 inhibitors in combination with endocrine therapy and gonadotropin releasing hormone analog (GnRHa) in premenopausal patients with early breast cancer has further improved the survival benefits. Committee of Breast Cancer Society, China Anti-Cancer Association in the field of breast cancer treatment in China jointly discussed and formulated the "Expert consensus on clinical applications of ovarian function suppression for Chinese women with early breast cancer (2024 edition)" based on the "Expert consensus on clinical applications of ovarian function suppression for Chinese women with early breast cancer (2021 edition)". The consensus recommends that medical castration with GnRHa is the first choice for OFS in premenopausal hormone receptor-positive early breast cancer. CDK4/6 inhibitors in combination with endocrine therapy and GnRHa benefit the premenopausal hormone receptor-positive breast cancer population, including patients with node-positive breast cancer, and patients with node-negative breast cancer who meet one of any criteria (G3, G2 and Ki-67 proliferation index ≥20%, G2 and 21-gene assay recurrence score ≥26, G2 and Prosigna PAM50 high risk, G2 and MammaPrint high risk, G2 and EndoPredict high risk). Chemotherapy eligibility (high risk of recurrence) in the 2023 St. Gallen consensus will also be as one of the risk factors to determine whether OFS is applicable for premenopausal hormone receptor positive breast cancer patients. Adjuvant endocrine therapy plan is decided based on the status of ovarian function before chemotherapy for hormone receptor-positive breast cancer. If ovarian protection is considered, GnRHa concurrent chemotherapy is recommended, which does not affect the survival benefit of patients. If ovarian protection is not considered, it is recommended that GnRHa can be used with start of chemotherapy or sequentially after chemotherapy, the latter is more recommended. Endocrine therapy for perimenopausal patients is recommended to refer to the premenopausal regimen. The recommended duration of GnRHa in adjuvant endocrine therapy intermediate- and high-risk patients is 5 years. After 5 years' endocrine therapy combined with GnRHa, if they are not menopausal and well tolerated, they may consider continuing 2 to 5 years of endocrine therapy combined with GnRHa or using selective estrogen receptor modulators (SERM) alone for 2 to 5 years. Adding GnRHa to the adjuvant treatment regimen is safe and tolerable. It is recommended to fully communicate with patients about the use of the drug and possible adverse events before use. Safety management can improve patient adherence. For patients undergoing medical castration, it is not routinely recommended to monitor estrogen levels during medical castration. However, estrogen testing may be performed for clinical decision making when incomplete ovarian suppression is suspected (including changes in usage such as lack of injection experience by the injection provider, changes in dosage forms, or certain physiological changes that may indicate the recovery of ovarian function, such as symptoms of menopause fluctuating periodically). For premenopausal breast cancer patients, whether hormone receptor-positive or hormone receptor-negative, it is recommended to use GnRHa drugs to protect ovarian function, reduce the risk of premature ovarian failure, and reduce fertility damage. It is recommended to start using GnRHa at least 1 week before chemotherapy, once every 28 d, until 2 weeks after the last dose of chemotherapy. Clinical trials conducted on patients with hormone receptor-positive breast cancer are not recommended to include only postmenopausal people. Premenopausal people under GnRHa application conditions should also be explored to clarify the actual effect of experimental drugs on these patients. In addition, this consensus also adds a full management path for OFS drug application in patients with early/locally advanced breast cancer, in order to further assist clinical decision-making. [ABSTRACT FROM AUTHOR]

Background and purpose: Systematic treatment for breast cancer largely depends on the status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). Discordance in ER, PR and HER2 status between primary breast cancer and distant metastases has been observed in a proportion of patients in previous studies. Liver is one of the frequent metastatic sites of breast cancer. Currently, limited data are available on the receptor conversion between primary breast cancer and matched liver metastases. This study aimed to investigate the prevalence, risk factors and prognostic impact of receptor conversion between primary breast cancer and paired liver metastases. Methods: The data of breast cancer patients who had pathologically confirmed liver metastases from January 2013 to May 2020 at Fudan University Shanghai Cancer Center were retrospectively collected. A total of 353 patients with ER, PR and HER2 status available on both primary breast cancer and matched liver metastases were finally included in this study. ER, PR and HER2 status were interpreted according to the most updated American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. The evolution of receptor status and phenotype from primary to metastatic breast cancer was illustrated using Sankey diagrams. Kappa coefficient and McNemar's test were used to assess the agreement on receptor status between primary breast cancer and liver metastases. The Kaplan-Meier curves were plotted and survival differences across each group were assessed by log-rank test. Multivariate analyses were performed based on the COX proportional hazard regression model. Results: The total discordance rate of ER, PR and HER2 was 19.5%, 39.4% and 4.8%, respectively (Kappa coefficient: 0.569, 0.258 0.876). In de novo stage IV patients, the discordance rate of ER, PR and HER2 was 15.2%, 28.3% and 2.2%, respectively. Multivariate analysis showed that previous endocrine therapy before liver re-biopsy was an independent risk factor of PR discordance. None of the variables of interest was found to be associated with discordance in ER or HER2 status. Additionally, 37.9% of the HER2-0 tumors converted to HER2-low. A trend of increase in triple-negative and decrease in hormone receptor (HR)+/HER2- cases were observed in liver metastases. Patients with HR+/HER2- primary breast cancer who converted to triple-negative in liver metastases had a significantly shorter overall survival (OS) than those with consistent HR+/HER2- subtype. Patients with the same subtype in liver metastases shared similar OS. Conclusion: This study confirmed discordance in ER, PR and HER2 status between primary breast cancer and liver metastases. The prognosis of breast cancer patients was determined mainly by the subtype in metastases rather than that in primary disease. Our study underlined the necessity of liver re-biopsy in de novo stage IV patients with liver metastases. Over one-third of HER2-0 patients converted to HER2-low in liver metastases after reassessment, which enabled them to be treated with new antibody-drug conjugate (ADC). [ABSTRACT FROM AUTHOR]

Breast cancer is one of the common malignant tumors in the world. About 6% of the patients are de novo stage Ⅳ breast cancer, which is incurable. Traditionally, the role of surgery has been confined to relieving symptoms, improving quality of life and reducing tumor load. Nowadays, a multidisciplinary team is a prerequisite for optimal management, and patients with oligometastatic lesion always live for a long time. R0 resection of the primary and metastatic foci can extend the time of progressionfree survival (PFS), which may bring survival benefits. Therefore, whether to perform surgery has become a hot clinical issue. This article deeply discussed extensively the surgical value in de novo stage Ⅳ breast cancer patients. [ABSTRACT FROM AUTHOR]

With the improvement of comprehensive treatment of breast cancer and the continuous development of anti-tumor drugs, the survival time of breast cancer patients, especially advanced breast cancer, has been further extended. In recent years, the treatment of advanced breast cancer has ushered an era of fine classification and precise tiered therapy. In 2022, many breakthroughs have been made in the field of advanced breast cancer research. With changes in the treatment of each subtype, some treatment schemes affecting clinical practice have been incorporated into treatment guidelines. The treatment for hormone-receptor-positive advanced breast cancer focuses on patients who have failed treatment with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Novel anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADC) in advanced HER2 positive breast cancer are the focus of research. More research evidence is needed for immunotherapy in advanced triple-negative breast cancer (TNBC), and the treatment with ADC targeting Trop-2 has been effective. Treatment with ADC in HER2-low breast cancer are changing clinical practice. In this article, we summarized the research progress of different types of advanced breast cancer in this year, in order to better guide the individualized treatment and improve the prognosis of advanced breast cancer patients. [ABSTRACT FROM AUTHOR]

Background and purpose: The novel centrosomal regulatory protein Sec23 homolog B (SEC23B) regulates autophagy in cells, thereby providing energy and nutrients that contribute to tumor growth and distant metastasis. However, whether this role is involved in the mechanism of infiltrative metastasis in breast cancer is unclear. The aim of this study was to investigate the molecular mechanism by which SEC23B promotes breast cancer infiltration and metastasis. Methods: The association between SEC23B expression and breast cancer prognosis and metastasis was analyzed using Kaplan-Meier Plotter database and HCMDB database. MCF-7 cells were divided into vector group (control) and SEC23B overexpression plasmid group (SEC23B), and MDA231-LM2 cells were divided into SEC23B knockdown group (sh-SEC23B) and control group (sh-NC). Western blot was used to detect the expressions of SEC23B, autophagy-associated proteins [dead bone fragment 1 (SQSTM1, p62), microtubule-associated-protein light-chain-3 (LC3)] and extracellular-regulated protein kinases (ERK)/mammalian target of rapamycin (mTOR) pathway proteins in breast cancer cells. Cell migration was assessed by transwell assay and wound healing assay, and autophagic granules in cells were detected by immunofluorescence staining. In addition, an in vivo intraperitoneal tumor model was constructed to study the effect of SEC23B on breast cancer cell metastasis in vivo. Results: The overall survival of breast cancer patients with high SEC23B expression was significantly shorter than that of patients with low SEC23B expression. The expression of SEC23B in metastatic breast cancer was significantly higher than that in breast cancer without metastasis. SEC23B protein levels were lower in primary breast cancer cells (MCF-7, BT-549, MDA-MB-468 and MDA-MB-453) than in metastatic breast cancer cells (MDA231- LM2 and ZR-75-30). Compared with the control group, the SEC23B group significantly accelerated cell migration (P<0.001). Compared with the sh-NC group, the sh-SEC23B group significantly reduced cell migration (P<0.001). Compared with the control group, the expression level of LC3A/B and the formation of autophagy particles in the SEC23B group were significantly increased, while the expression of p62 protein and the phosphorylation levels of mTOR and ERK were decreased. Compared with the sh-NC group, the LC3A/B expression level and the formation of autophagy particles were significantly decreased in the sh-SEC23B group, and the phosphorylation levels of mTOR and ERK were increased, especially under starvation conditions. In in vivo experiments, tumor weight was significantly lower in the sh-SEC23B group compared with the sh-NC group (P<0.01), and there was an increase in necrotic tissue and a decrease in tumor metastasis in lung tissue in mice. sh-SEC23B group mice had a significantly lower number of lung metastatic tumors and LC3 immunohistochemical staining than the sh-NC group (P<0.01). Conclusions: SEC23B induces breast cancer autophagy and promotes cancer cell metastasis by inhibiting ERK/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: Internal mammary lymph node irradiation (IMNI) improves survival in patients with internal mammary lymph node (IMLN) high-risk metastatic breast cancer. The purpose of this study was to study the advantages of internal mammary sentinel lymph node (IMLN) biopsy (IM-SLNB) for assessing prognosis and directing individualized IMNI. Methods: This study evaluated patients recruited in three prospective clinical trials (NCT01642511, NCT03541278, and NCT03024463) from November 2011 to December 2021, assessed for prognostic risk variables based on IMSLN metastatic status and prognosis between subgroups. In patients who received regional lymph node irradiation, the implementation status, survival benefit, and influence of IMNI on radiation-induced lung injury (RILI) were studied. The primary endpoint was disease-free survival (DFS), with overall survival (OS) and RILI as secondary endpoints. Results: The study enrolled 537 patients and had a 60-month median follow-up. Patients with IMSLN metastasis had a significantly worse 5-year DFS and OS (DFS: 95.1% vs 71.4%, OS: 99.1% vs 90.1%, both P<0.05), and IMSLN metastatic status was an independent risk factor for DFS and OS (both P<0.05). Adding IMNI did not improve DFS (P = 0.099) or OS (P = 0.486) in patients with negative IMSLN, while it did increase the risk of RILI (OR = 3.678, P<0.05). However, adding IMNI improved 5-year DFS (87.3% vs 52.5%, P = 0.040) for patients with positive IMSLN but had no effect on OS (P = 0.603). Conclusion: This study discovered that IMSLN metastatic status has significant prognostic importance. Patients with IMSLN metastasis who receive IMNI have significantly improved prognosis, and patients without IMSLN metastasis have a much lower risk of RILI by being exempt from IMNI without worse prognosis. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women worldwide with rising prevalence. The human epidermal growth factor receptor 2 (HER2) is crucial to the biological behavior and pathogenic mechanism of breast cancer. Approximately 45%- 55% of all subtypes of breast cancer have low expression of HER2, which are classified as HER2 immunohistochemistry staining 1+ or 2+ and in situ hybridization (ISH) negative. Although in most cases, HER2 low expression (HER2-low) breast cancer is still classified as HER2 negative or triple negative in clinical practice, HER2-low differs from HER2 not detected (HER2-0) breast cancer not only in HER2 expression levels, there are also differences in terms of estrogen receptor (ER) status, primary tumor volume, lymph node involvement, and pathologic complete response (pCR) following neoadjuvant therapy and disease-free survival (DFS). In clinical trials targeting early-stage HER2-low breast cancer, the NSABP B-31 and N9831 trials demonstrated the possibilities for breast cancer patients to benefit from adjuvant trastuzumab therapy; however, in phase III prospective randomized controlled study NSABP B-47, trastuzumab did not alter invasive disease-free survival (iDFS), 5-year interval without distant recurrence, or overall survival (OS) in patients with HER2-low breast cancer. Recent years have seen the emergence of clinical trials for targeted treatments for advanced HER2-low breast cancer, focusing mostly on trastuzumab, lapatinib, and antibody-drug conjugate (ADC), such as trastuzumab emtansine (T-DM1), DS-8201 (also known as trastuzumab deruxtecan, T-DXd, Enhertu), and SYD985. Phase III trial CALGB9840 demonstrated a lack of therapeutic effect of trastuzumab and a narrow therapeutic window that could not be overcome by changing the dose of lumretuzumab in HER2 non-over-expressed breast cancer, respectively. Two randomized phase III trials (EGF30001 and EGF100151) both found that receiving lapatinib did not improve progression-free survival (PFS) in patients with HER2-low breast cancer. T-DM1 sensitivity was initially observed in patients with HER2-low breast cancer in the single-arm phase II studies 4258g and 4374g, but results were still uncertain because of the small number of patients. The phase III clinical study DESTINY-Breast04 proved the safety and efficacy of DS-8201 (5.4 mg/kg) in HER2-low metastatic breast cancer. The phase I clinical trial proved the efficacy and safety of 1.2 mg/kg SYD985 intravenously in HER2-low breast cancer. Additionally, there are currently ongoing clinical trials for several novel anti-HER2 therapeutics, including novel ADC drugs (RC48-ADC, ARX788, A166, etc.), bispecific antibodies (KN026, ZW25, ertumaxomab, etc.), and breast cancer vaccines (nelipepimut-S, GP2, AE37, etc.). In this paper, we will review the major clinical trials of targeted therapies for HER2-low breast cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast cancer is the most common malignancy in women, and it is also the cancer with the highest number of new cases worldwide in 2020. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for approximately 20% of all breast cancers, which indicates higher rate of recurrence and metastasis and a poor prognosis. Therefore, it is of great significance to explore the biomarkers related to HER2-positive breast cancer. This study aimed to investigate the expression of circ-0003910 in HER2-positive breast cancer tissues and cells, and to clarify the effect of circ-0003910 on the migration and invasion of breast cancer cells. Methods: Circular RNA (circRNA) microarray was used to screen circRNA differentially expressed in HER2-positive breast cancer cells, and significantly overexpressed circRNA was selected as the research target. Fluorescence in situ hybridization (FISH) assay was used to detect the subcellular localization of circ-0003910. BaseScope assay was used to analyze the expression and clinical significance of circ-0003910 in breast cancer tissues. Circ-0003910 overexpressed and knockdown breast cancer cells were constructed by transfection of cloned plasmid and siRNA in vitro. The effect of circ-0003910 on the migration and invasion ability of breast cancer cells was detected by transwell assay. The molecular mechanism of circ0003910 promoting the migration and invasion of breast cancer cells was preliminarily explored by TMT quantitative proteomics techniques. Results: CircRNA microarray analysis showed that a total of 1 843 differentially expressed circRNAs were screened in HER2-positive breast cancer cells (fold change≥2, P<0.05), including 845 upregulated circRNAs and 998 downregulated circRNAs. Compared with normal breast epithelial cells, the differential expression ratio of circ-0003910 in HER2-positive breast cancer cells was 24.39. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) results showed that the expression of circ0003910 was higher in HER2-positive breast cancer cells than in other molecular types of breast cancer cells, and BaseScope assay verified that circ-0003910 was mainly located in the cytoplasm of HER2-positive breast cancer tissue cells. Overexpression of circ0003910 promoted the migration and invasion of breast cancer cells, while circ-0003910 knockdown produced the opposite effects. Proteomics identification showed that 197 proteins were changed after overexpression of circ-0003910, of which 104 proteins were upregulated and 93 proteins were downregulated. GO and KEGG enrichment analysis suggested that circ-0003910 may be involved in biological processes such as cell adhesion molecule synthesis, transcriptional dysregulation in cancer, and protein digestion and absorption. Conclusion: Circ-0003910 is upregulated in breast cancer cells and can promote the migration and invasion of breast cancer cells, which may be a new biomarker and target for the treatment of metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Bone metastasis is one of the most serious complications in advanced breast cancer patients. Severe osteodynia, pathological fracture and other complications in bone metastasis of breast cancer can seriously affect the quality of life and shorten life span. In recent years, with the further understanding of the mechanism of bone metastases and the cross-talk between tumor cells and bone microenvironment, development and application of many new effective drugs have made significant progress in the treatment of bone metastasis of breast cancer. This article reviewed the mechanism of bone metastasis of breast cancer and current treatment advances. [ABSTRACT FROM AUTHOR]