Breast Journal最新文献

Background: Triple-negative breast cancer, a subtype of breast cancer, is characterized by a poor prognosis. Recent studies have shown that miRNA30b acts as an oncogene and is vital for the proliferation of malignancies across various systems. This study aimed to elucidate the impact of miRNA30b on the proliferation, migration, and invasion capabilities of breast cancer cells in vitro.

Methods: Triple-negative breast cancer cell lines MDA-MB-231 were transiently transfected with miRNA30b inhibitor, mimic, or the negative control by Lipofectamine 2000. Successful transfection was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Functional assays, including CCK8, clone formation, scratch, and transwell assays, were conducted to evaluate the proliferation, invasion, and migration ability of MDA-MB-231 cells in each group. The target protein of miRNA30b was determined using an online prediction data website, and the dual-luciferase assay confirmed whether there was a binding site between miRNA30b and ADAM12. The effect was further verified by Western blot analysis.

Results: MDA-MB-231 cells were transfected with miRNA30b inhibitor, mimic, and negative control. miRNA30b expression was downregulated in the cells. Relative to the negative control group, miRNA30b expression significantly increased in the mimic group and decreased in the miRNA30b inhibitor group, with the differences being statistically significant. The miRNA30b mimic group exhibited a significant increase in miRNA30b expression and a corresponding promotion of cell proliferation, colony formation, and migration. Conversely, the miRNA30b inhibitor group displayed significantly reduced miRNA30b expression and suppressed cell proliferation, colony formation, and migration abilities compared to the negative control cells. Bioinformatics software predicted ADAM12 as a potential target of miRNA30b. Dual-luciferase assays confirmed the presence of a binding site between miRNA30b and ADAM12. Western blot analysis revealed that overexpression of miRNA30b downregulated ADAM12 expression in MDA-MB-231 cells.

Conclusions: miRNA30b could promote proliferation, migration, and invasion of TNBC cell lines MDA-MB-231. The effect of miRNA30b on triple-negative breast cancer would be achieved partly at least through inhibiting the expression of ADAM12.

Purpose: We aimed to investigate whether estrogen receptor (ER) status affects the predictive role of the human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) score on the efficacy of neoadjuvant treatment for HER2-positive breast cancer.

Methods: This retrospective study comprised 167 individuals diagnosed with HER2-positive invasive breast cancer who had undergone neoadjuvant treatment and surgery. Uni- and multivariable logistic regression analyses were performed on the relationship between the HER2 IHC score and total pathological complete response (tpCR), breast pathological complete response (bpCR), or axillary partial response (apCR). Subgroup analyses were used to investigate whether the relationship between the HER2 IHC score and tpCR, bpCR, or apCR differed by ER or PR status.

Results: The overall tpCR rate for HER2-positive breast cancers treated with neoadjuvant treatment was 41.32% (69 of 167). The tpCR, bpCR, and apCR rates were greater in the HER2 IHC 3+ group (tpCR: IHC 3 + 47.69% vs. IHC 2 + 18.92%, p = 0.009). Significant interactions between HER2 IHC score and tpCR or bpCR were found in subgroup analyses based on ER status (tpCR: p for interaction = 0.001; bpCR: p for interaction = 0.001). Among ER-positive patients, the HER2 IHC 2+ group had substantially decreased tpCR, bpCR, and apCR rates than the HER2 IHC 3+ group (tpCR rate: p = 0.003; bpCR rate: p = 0.002; apCR rate: p = 0.002). For ER-negative individuals, the tpCR, bpCR, and apCR rates did not differ significantly among the HER2 IHC 3+ versus HER2 IHC 2+ groups. Similarly, interactions between HER2 IHC score and tpCR, bpCR, or apCR were found in subgroup analyses based on PR status.

Conclusion: HER2 IHC 2+ may indicate a decreased tpCR rate, bpCR rate, and apCR rate to neoadjuvant treatment in HR-positive patients having HER2-positive breast cancer, but not in HR-negative patients.

Background. Breast cancer is an important cause of cancer-related death in women worldwide and represents the second most frequent cause of brain metastases after lung cancer. The aim of this study was to determine the characteristics and outcomes of triple-negative breast cancer (TNBC) patients with brain metastasis (BM). Methods. We retrospectively reviewed a cohort of patients diagnosed with TNBC at the “Instituto Nacional de Enfermedades Neoplasicas” (period 2000–2014) to evaluate patients who developed BM. Survival rates were assessed by the Kaplan–Meier method, and prognostic factors were identified with the Cox regression analysis. Results. Of a total of 2007 TNBC patients, 193 (9.62%) developed BM. Of these, 169 stages I–III patients with a median age of 45 years (range:21–78) were included. The stage in this cohort was 4 (2.4%) clinical stage (CS) I, 23 (13.6%) with CS II and 142 (84.0%) with CS III. Most of these patients presented ECOG ≥2 (68.6%). The most common symptom was headache (74.0%), followed by nausea-vomiting (46.7%). Imaging showed that 80 patients (53.0%) had ≥1 metastatic brain lesion. Regarding the treatment of BM in this cohort, 132 patients (84.6%) received radiotherapy (RT), 2 (1.5%) surgery, and 6 (4.5%) surgery plus RT. The overall survival (OS) rate of BM was 59.8%, 37.3%, and 15.0% at 3, 6, and 12 months, respectively. A multivariate analysis showed RT to be the only factor with a positive impact on the OS of BM (hazard ratio (HR) = 0.48, 95% confidence interval (CI):0.30-0.77, and p = 0.002), while ECOG ≥2 was associated with a worse OS (HR = 1.69, 95%CI:1.15–2.48, and p = 0.007). Conclusion. Despite the poor prognosis of TNBC patients who develop BM, RT showed a benefit in OS rates, while ECOG ≥2 was the only prognostic factor associated with a worse OS. These results may be useful for multidisciplinary teams for treatment planning in patients with TNBC and BM.

Introduction. Breast cancer is currently the most frequently detected cancer in women and the primary cause of cancer-related deaths globally. The incidence of breast cancer has significantly increased in countries across sub-Saharan Africa, counting Ethiopia. There are multiple determinants of breast cancer, a few of these can be changeable whereas others are not. Evidence suggests that breastfeeding, which is a changeable determinant, reduces breast cancer risk. However, there is a lack of evidence specifically linking the duration of breastfeeding to breast cancer risk. To date, no study has been conducted on the association between the duration of breastfeeding and the likelihood of breast cancer among Ethiopian women. Objective. The aim of this study was to evaluate the relationship between breastfeeding duration and breast cancer risk in Ethiopian mothers who had breastfed, taking into account other significant determinants. Methods. A hospital-based case-control study was carried out in Bahir Dar, Ethiopia, involving 203 women (70 cases and 133 controls). Face-to-face interviews were performed using a standardized, validated questionnaire that assessed various sociodemographic, reproductive, lifestyle, and dietary characteristics. Differences between cases and controls were evaluated using the chi-square test. The associations among factors were examined through bivariate and multivariable binary logistic regression, with results presented as odds ratios and 95% confidence intervals. Results. The multivariable investigation revealed that an inverse relationship between breastfeeding duration and breast cancer risk. Mothers who breastfed for a longer period had a 93% lower risk of breast cancer (AOR = 0.07; 95% CI: 0.021–0.21) compared to those who breastfed for a shorter duration. Younger mothers had a 95% lower likelihood of developing breast cancer (AOR = 0.05; 95% CI: 0.003–0.91) than older mothers. Additionally, mothers with sedentary behaviour were 10.53 times more likely to develop breast cancer (AOR = 10.53; 95% CI: 5.21–21.36) than those who were moderately or highly active. Mothers who experienced chest therapy were 6.43 times more likely to develop breast cancer (AOR = 6.43; 95% CI: 3.20–13.90) compared to those who had not. Conclusions. Interventions such as breastfeeding counselling and promoting the recommended duration of breastfeeding are crucial in minimizing the risk of breast cancer. Enhancing physical activity should also be viewed as a vital approach for lowering breast cancer risk. Additionally, healthcare professionals need to limit exposure to chest radiation therapy to reduce the likelihood of breast cancer.

Introduction. Disease recurrence in patients with the early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast tumor subtype is particularly challenging to manage due to its complex and very heterogeneous biological nature. Namely, due to primary and secondary resistance, one-quarter of patients with early-stage disease will experience disease recurrence. This variability in the timing of recurrence highlights the need to better identify key biomarkers that could predict therapeutic outcomes and guide personalized treatment strategies for these patients. Mutations in the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene are highly prevalent (30–40%) in HR+/HER2− advanced breast cancer. They lead to activation of the PI3K/AKT/mTOR pathway, promoting cell growth, and proliferation, and are associated with poor prognosis in advanced breast cancer. Our aim was to examine the association between and impact of PIK3CA mutation status on disease-free survival (DFS) in HR+/HER2− early breast cancer patients. Methods. This cohort study was multicentric and retrospective in nature and was conducted at five Croatian institutions from July 2020 to December 2021. The study included initially early and locally advanced operable HR+/HER2− breast cancer patients who were diagnosed with disease recurrence during adjuvant hormonal treatment or within the first six years of follow-up. Results. A total of 186 patients were included, 40.9% of whom tested positive for the PIK3CA mutation. Primary and adjuvant treatment, particularly adjuvant endocrine treatment, were similar between the two groups. After adjustment for 14 relevant covariates, we found that patients with a positive PIK3CA status and the H1047 PIK3CA mutation had a significantly lower hazard of disease recurrence than patients with no PIK3CA mutation (HR 0.65; 95% CI 0.45; 0.95; p = 0.024; false discovery rate, FDR <10%). Conclusions. This study highlights the potential impact of PIK3CA mutations on disease recurrence during or following adjuvant endocrine therapy and potentially opens the door for further investigation of possibly more personalized treatment strategies.

Breast cancer is the leading cause of death and morbidity among women. A major challenge for clinical management of breast cancer is the dissemination of breast cancer cells from the primary tumor site via lymphatic drainage, resulting in metastatic tumor spread. Recent studies have found that high expression of the microRNA miR-146a-5p is associated with better survival outcomes for breast cancer patients. However, the mechanisms for this prognostic benefit are not fully elucidated, including whether or not miR-146a-5p plays a role in suppression of lymphatic dissemination. In this study, we investigated the role and uncovered functional mechanisms of miR-146a-5p in breast cancer. We found that high expression of miR-146a-5p is associated with better clinical outcomes, specifically in the patients with N0 breast cancer. In culture, miR-146a-5p overexpression in MCF-7 breast cancer cells suppressed cell migration and lymphangiogenesis in lymphatic endothelial cells. When implanted in the mammary fat pad of mice, we observed that miR-146a-5p overexpressing MCF-7 suppressed lymphatic dissemination but had no effect on tumor progression in the primary site. This suppression was associated with fewer disseminated cancer cells and reduced lymphangiogenesis in the draining and distal lymph nodes. In conclusion, these results suggest that miR-146a-5p can exhibit a protective role against breast cancer metastasis, and it can be a therapeutic target for breast cancer.

Background. Despite excellent prognosis of early breast cancer, the patients face problems related to decreased quality of life and mental health. There is a need for easily available interventions targeting modifiable factors related to these problems. The aim of this study was to test the use of a new digital supportive intervention platform for early breast cancer patients. Material and Methods. Ninety-seven early breast cancer patients answered questions on wellbeing, exercise, and sociodemographic factors before systemic adjuvant treatment at the Helsinki University Hospital. Based on these answers and predictive algorithms for anxiety and depression, they were guided onto one or several digital intervention paths. Patients under 56 years of age were guided onto a nutrition path, those who exercised less than the current guideline recommendations onto an exercise path, and those at risk of mental health deterioration onto an empowerment path. Information on compliance was collected at 3 months on the amount of exercise and quality of life using EORTC-C30 scale, anxiety and depression using HADS scale at baseline and 12 months, and log-in information at 3 and 12 months. Results. Thirty-two patients followed the empowerment path, 43 the nutrition path, and 75 the exercise path. On a scale of 1–5, most of the participants (mean = 3.4; SD 0.815) found the interventions helpful and would have recommended testing and supportive interventions to their peers (mean = 3.70; SD 0.961). During the 10-week intervention period, the mean number of log-ins to the empowerment path was 3.69 (SD = 4.24); the nutrition path, 4.32 (SD = 2.891); and the exercise path, 8.33 (SD = 6.293). The higher number of log-ins to the empowerment (rho = 0.531, P = 0.008, and n = 24) and exercise paths (rho = 0.330, P = 0.01, and n = 59) was related to better global quality of life at one year. The number of log-ins correlated to the weekly amount of exercise in the exercise path (cc 0.740, P value <0.001, and n = 20). Conclusion. Patients’ attitudes towards the interventions were positive, but they used them far less than was recommended. A randomized trial would be needed to test the effect of interventions on patients’ QoL and mental health.

Breast cancer (BC), a globally prevalent malignancy, shows significant variability in incidence across different geographical regions. In this study, we examined the expression of the tumor suppressor gene BRCA1 and the tumor marker CA15-3 in women diagnosed with BC, focusing on different cancer grades. Our research, conducted at the Baqiyat Elah Hospital in Tehran in 2021, involved collecting blood and serum samples from BC patients. These samples underwent BRCA1 gene expression analysis and CA15-3 tumor marker assessment. Using the AJCC grading system, we categorized BC patients into various grades. Our findings revealed that BRCA1 gene expression was present in 28.57% of patients, while 71.43% showed negative expression. Both BRCA1 expression and CA15-3 levels significantly increased with advanced cancer stages (P < 0.001). These results suggest the potential utility of BRCA1 gene expression and CA15-3 tumor marker assessment in BC prognosis and management, particularly concerning staging and disease progression. This study provides valuable insights into the biology of BC and the development of prognostic markers for improved patient outcomes.

Background and Purpose. Occult breast cancer (OBC) is a rare condition. Due to the small number of patients in previous studies, the benefits of treatment with mastectomy are still discussed. This study aims to determine the clinicopathological characteristics, treatment, and prognosis of OBC presenting with locoregional lymph node metastasis (LNM). Materials and Methods. This study included patients registered in the national Danish Breast Cancer Group (DBCG) database between 2001 and 2015, with locoregional LNM as well as a bilateral negative mammography, ultrasonography, and physical examination of the breasts. Overall survival (OS) and invasive disease-free survival (IDFS) were compared by treatment groups, ALND + RT (axillary lymph node dissection and radiotherapy) or ALND + MAST ± RT (axillary lymph node dissection, mastectomy with or without radiotherapy). Results. In total, 56 patients were included in the study, of which 37 were treated by ALND + RT, 16 by ALND + MAST ± RT, and the remaining three patients receiving different treatments. The median follow-up for the 53 OBC patients sorted by treatment group was 12.2 years (interquartile range: 10.1 years; 15.3 years). There was no significant difference in OS or IDFS between the treatment groups, except for a subgroup of 46 (out of 53) patients without verified in situ lesions before treatment, where ALND + RT treatment showed an improved OS (log-rank p = 0.05). Conclusion. Treating OBC patients with ALND and radiotherapy resulted in a similar outcome as treatment with ALND and mastectomy. This supports omission of mastectomy in favor of radiotherapy of the breast in these patients.

Purpose. Endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i-based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2– MBC after progression on CDK4/6 inhibitors. Methods. We collected data from 32 patients with HR+/HER2– MBC treated with anlotinib plus chemotherapy after progressing on CDK4/6i at Jiangsu Cancer Hospital from March 2020 to October 2023. The median follow-up was 9.1 months (range, 2.0–19.7 months) as of the data cutoff date in October 2023. The primary endpoint was median progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and adverse events. Results. The median PFS (mPFS) of all patients was 7.6 months (95% confidence interval (CI), 5.75–9.45). There was no significant difference in mPFS between patients who responded to prior CDK4/6i treatment and those who did not (8.3 months vs. 6.8 months, p = 0.580). Besides, the ORR was 34.4% and DCR was 93.8%. The most frequently observed adverse events were anemia (50.0%), neutropenia (40.6%), thrombocytopenia (34.4%), and epistaxis (34.4%). Dose interruption or reductions due to adverse events occurred in 2 (6.3%) and 5 (15.6%) patients, respectively. Conclusions. The study preliminarily demonstrates that anlotinib combined with chemotherapy may be an optional recommendation for patients with HR+/HER2– metastatic breast cancer who have progressed after CDK4/6i.