Journal of Breast Cancer最新文献

Phyllodes tumors (PT) are fibroepithelial neoplasms that are treated by complete surgical excision. The effectiveness of adjuvant therapies, including radiotherapy and chemotherapy, for PT remains unclear, and the use of neoadjuvant chemotherapy (NAC) is yet to be established. We report a case of a 15-year-old girl with acute lymphatic leukemia (ALL) who was incidentally diagnosed with a 50-mm borderline PT in the left breast using computed tomography, ultrasonography, and histological examination following needle biopsy. Lumpectomy was performed after administration of anthracycline-based chemotherapy for ALL, resulting in tumor size reduction. Histopathological examination of the excised specimen demonstrated decreased mitotic activity and stromal cellularity post-chemotherapy. To our knowledge, this is the first study to report the histopathological differences in pre- and post-chemotherapy borderline PT samples. Our findings suggest that NAC may induce changes in borderline PT, potentially affecting diagnosis and treatment decisions. Hence, further investigation is warranted in this regard.

Breast density is an independent risk factor for breast cancer, although variability exists in measurements. This study sought to evaluate the agreement between radiologists and automated breast density assessment software and assess the impact of breast density measures on breast cancer risk estimates using the Breast Cancer Surveillance Consortium (BCSC) model (v.2). A retrospective database search identified women who had undergone mammography between December 2021 and June 2022. The Breast Imaging Reporting and Data System (BI-RADS) breast composition index assigned by a radiologist (R) was recorded and analyzed using three commercially available software programs (S1, S2, and S3). The agreement rate and Cohen's kappa (κ) were used to evaluate inter-rater agreements concerning breast density measures. The 5-year risk of invasive breast cancer in women was calculated using the BCSC model (v.2) with breast density inputs from various density estimation methods. Absolute differences in risk between various density measurements were evaluated. Overall, 1,949 women (mean age, 53.2 years) were included. The inter-rater agreement between R, S1, and S2 was 75.0-75.6%, while that between S3 and the others was 60.2%-63.3%. Kappa was substantial between R, S1, and S2 (0.66-0.68), and moderate (0.49-0.50) between S3 and the others. S3 placed fewer women in mammographic density d (14.9%) than R, S1, and S2 (40.5%-44.0%). In BCSC risk assessment (v.2), S3 assessed fewer women with a high 5-year risk of invasive breast cancer than the other methods, resulting in an absolute difference of 0% between R, S1, and S2 in 75.0%-75.6% of cases, whereas the difference between S3 and the other methods occurs in 60.2%-63.3% of cases. Breast density assessment using various methods showed moderate-to-substantial agreement, potentially affecting risk assessments. Precise and consistent breast density measurements may lead to personalized and effective strategies for breast cancer prevention.

Purpose: A widely distributed cell cycle inhibitor, p27, regulates cyclin-dependent kinase-cyclin complexes. Although the prognostic value of p27 has been established for various types of carcinomas, its role in luminal breast cancer remains poorly understood. This study aimed to explore the functional enrichment of p27 and identify potential drug targets in patients with luminal-type breast cancer.

Methods: Clinicopathological data were collected from 868 patients with luminal-type breast cancer. Additionally, publicly available data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset (1,500 patients) and the Gene Expression Omnibus database (855 patients) were included in the analysis. Immunohistochemical staining for p27, differential gene expression analysis, disease ontology analysis, survival prediction modeling using machine learning (ML), and in vitro drug screening were also performed.

Results: Low p27 expression correlated with younger age, advanced tumor stage, estrogen receptor/progesterone receptor negativity, decreased cluster of differentiation 8+ T cell count, and poorer survival outcomes in luminal-type breast cancer. The METABRIC data revealed that reduced cyclin-dependent kinase inhibitor 1B (CDKN1B) expression (encoding p27) was associated with cell proliferation-related pathways and epigenetic polycomb repressive complex 2. Using ML, p27 emerged as the second most significant survival factor after N stage, thereby enhancing survival model performance. Additionally, luminal-type breast cancer cell lines with low CDKN1B expression demonstrated increased sensitivity to specific anticancer drugs such as voxtalisib and serdemetan, implying a potential therapeutic synergy between CDKN1B-targeted approaches and these drugs.

Conclusion: The integration of ML and bioinformatic analyses of p27 has the potential to enhance risk stratification and facilitate personalized treatment strategies for patients with breast cancer.

Purpose: Although numerous studies have identified potential risk factors for ipsilateral lymphedema development in patients with breast cancer following axillary node dissection, the risk factors for lymphedema in patients undergoing sentinel node biopsy without axillary dissection remain unclear. In this study, we aimed to determine the real-world incidence and risk factors for lymphedema in such patients.

Methods: We conducted a single-center, retrospective review of medical records of patients with breast cancer who underwent sentinel node biopsy alone. The development cohort (5,051 patients, January 2017-December 2020) was analyzed to identify predictors of lymphedema, and a predictive model was subsequently created. A validation cohort (1,627 patients, January 2014-December 2016) was used to validate the model.

Results: In the development cohort, 49 patients (0.9%) developed lymphedema over a median follow-up of 56 months, with most cases occurring within the first three years post-operation. Multivariate analysis revealed that a body mass index (BMI) of 30 kg/m² or above, radiation therapy (RTx), chemotherapy, and more than three harvested lymph nodes significantly predicted lymphedema. The predictive model showed an area under the curve of 0.824 for systemic chemotherapy, with the number of harvested lymph nodes being the most significant factor. Patients were stratified into four risk groups, showing lymphedema incidences of 3.3% in the highest-risk group and 0.1% in the lowest-risk group. In the validation cohort, the incidences were 1.7% and 0.2% for the highest and lowest risk groups, respectively.

Conclusion: The lymphedema prediction model identifies RTx, chemotherapy, BMI ≥ 30 kg/m², and more than three harvested lymph nodes as significant risk factors. Although the overall incidence is low, the risk is notably influenced by the extent of lymph node removal and systemic therapies. The model's high negative predictive value supports its application in designing tailored lymphedema surveillance programs for early intervention.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus.

Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumor-killing effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts.

Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDA-MB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells.

Conclusion: Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic."

Methods: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression.

Results: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy.

Conclusion: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

Purpose: Controversies persist regarding contraindications for nipple-sparing mastectomy (NSM). This study aimed to assess the accuracy of subareolar frozen section analysis and identify risk factors for nipple-areola complex (NAC) recurrence post NSM.

Methods: Consecutive cases of primary invasive breast cancer undergoing NSM at our single center from January 2015 to December 2020 were retrospectively reviewed.

Results: The nipples were retained in 126 patients (127 breasts), and the areola was retained with nipple excision for five breasts. Frozen section analysis demonstrated a sensitivity of 81.8% and specificity of 95.3%. The NAC recurrence rate was 4.3% over a median follow-up period of 48 (30-105) months. An atypical ductal hyperplasia (ADH) at the margin emerged as an independent factor for NAC recurrence in multivariate Cox regression analysis (hazard ratio, 25.464; 95% confidence interval, 1.841-352.145; p = 0.016). Kaplan-Meier survival analysis revealed no statistically significant reduction in overall survival rates (log-rank test, p = 0.660).

Conclusion: Frozen sections of subareolar tissue are reliable and re-excision may be necessary when ADH is detected at the nipple margin in NSM. The NAC recurrence rate was low, and the outcome was favorable following wide local excision.

Breast cancer remains a significant health concern for women, with a significant number of women facing unresectable, symptomatic, and advanced disease that severely affects their quality of life. Palliative radiotherapy (RT) is a well-established modality for managing such cases and alleviating symptoms. Recent advancements in systemic therapies and the resulting increase in long-term survival rates have not only heightened the need for retreatment in certain patients, but have also emphasized the importance of achieving durable local control. Additionally, inconsistencies in RT referral timing and variations in disease severity and extent contribute to diverse RT objectives and expected outcomes. The optimal dose fractionation for RT remains underexplored. Furthermore, a deeper understanding of breast radiobiology, along with the introduction of ultra- and moderately hypofractionated regimens and the widespread adoption of conformal techniques such as intensity-modulated RT, has diversified the approaches in RT dose and target volume. This review aimed to provides a comprehensive summary of the current evidence on the efficacy, outcomes, and toxicity profiles of palliative RT for symptomatic breast cancer. It highlights the need for more optimized regimens and further research to address the evolving treatment landscape and differing expectations of patients and physicians regarding RT.

Purpose: The interval between neoadjuvant chemotherapy (NAC) and surgery for locally advanced breast cancer (LABC) remains controversial. At the same time, the prognostic effect of delayed surgery in patients with poor responses is currently unclear.

Methods: Data was collected from patients who had poor responses to NAC and underwent modified radical surgery from January 2013 to December 2018. The interval from completion of NAC to surgery was divided into two groups: a longer (greater than four weeks) or shorter (four weeks or less) interval. The associations of these interval groups with overall survival (OS) and recurrence-free survival (RFS) were evaluated by multivariable Cox models adjusting for the existing prognostic factors. Propensity score matching (PSM) was used to minimize election bias.

Results: A total of 1,229 patients (mean age, 47.2 ± 8.9 years; median follow-up duration, 32.67 [6.57-52.63] months) were included. The 5-year OS rates were 73.2% and 60.8% in the shorter (n = 171) and longer interval group (n = 1,058), respectively, while the 3-year RFS rates were 80.8% and 71.7%, respectively. In multivariate Cox analysis, the longer interval was associated with an increased risk of mortality (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.01-2.02; p = 0.046) and recurrence (HR, 1.50; 95% CI, 1.12-1.99; p = 0.006). There was an interaction between the molecular subtype and the surgery interval for OS (p_interaction = 0.014) and RFS (p_interaction = 0.027). After PSM, no significant difference in OS (p = 0.180) and RFS (p = 0.069) was observed between the two groups.

Conclusion: Among LABC patients with a poor response, those with a longer interval between NAC and surgery had worse OS and RFS. The results indicate that these patients should receive modified radical surgery timely, which may in turn improve their prognosis.

Purpose: This study evaluated the effectiveness of different surveillance intensities on morbidity and mortality in women with breast cancer.

Methods: This retrospective study included patients who had undergone breast cancer surgery in the Republic of Korea between 2009 and 2011. The patients were divided into two groups based on the intensity of their postsurgical surveillance: intensive surveillance group (ISG) and less-intensive surveillance group. Surveillance intensity was measured based on the frequency and type of follow-up diagnostic tests conducted, including mammography, ultrasonography, computed tomography, magnetic resonance imaging, bone scans, and positron emission tomography scans.

Results: We included 1,356 patients with a median follow-up period of 121.2 months (range, 12.8-168.0 months). The analysis revealed no significant difference in the overall survival (OS) between the two groups within five years of surgery. However, patients with ISG exhibited significantly better breast cancer-specific survival (BCSS) and distant metastasis-free survival (DMFS) within the same period. Five years after surgery, the differences in survival outcomes between the groups were not statistically significant.

Conclusion: Intensive surveillance did not demonstrate a significant improvement in OS for patients with breast cancer beyond five years postoperatively. However, within the first five years, intensive surveillance was associated with better BCSS and DMFS. These findings suggest that personalized surveillance strategies may benefit specific patient subsets, particularly in the early years after treatment. Further nationwide randomized studies are warranted to refine surveillance guidelines and optimize outcomes in patients with breast cancer.