Breast Cancer Research and Treatment最新文献

Purpose: As breast cancer survival rates improve, cardiovascular disease (CVD) has become a critical concern among survivors due to co-morbidities and the cardiotoxic effects of cancer treatments. The risk of developing CVD in this population may surpass the risk of cancer recurrence. This review aims to analyze existing research on the use of statins in breast cancer survivors, focusing on their potential role in mitigating cardiovascular risk and cancer recurrence.

Methods: The review begins by exploring the shared mechanisms underlying the development of both heart disease and breast cancer. It then examines the evidence for the role of statins in reducing cancer therapy-related cardiac dysfunction (CTRCD) and breast cancer recurrence, highlighting findings from the literature on their anti-inflammatory and lipid-lowering effects.

Results: The analysis reveals that statins may offer benefits beyond their traditional cardiovascular applications. Evidence suggests that statins could reduce the risk of CTRCD and potentially lower the risk of breast cancer recurrence.

Conclusions: Statins demonstrate promising potential in providing dual benefits for breast cancer survivors by mitigating CVD risk and possibly reducing the likelihood of cancer recurrence. However, additional studies are required to better understand the specific role of statins in breast cancer prevention and survivorship care.

Purpose: To generate a model for predicting nodal response to neoadjuvant systemic treatment (NAST) in biopsy-proven node-positive breast cancer patients (cN+) that incorporates tumor microenvironment (TME) characteristics and could be used for planning the axillary surgical staging procedure.

Methods: Clinical and pathologic features were retrospectively collected for 437 patients. Core biopsy (CB) samples were reviewed for stromal content and tumor-infiltrating lymphocytes (TIL). Orange Datamining Toolbox was used for model generation and assessment.

Results: 151/437 (34.6%) patients achieved nodal pCR (ypN0). The following 5 variables were included in the prediction model: ER, Her-2, grade, stroma content and TILs. After stratified tenfold cross-validation, the logistic regression algorithm achieved and area under the ROC curve (AUC) of 0.86 and F1 score of 0.72. Nomogram was used for visualization.

Conclusions: We developed a clinical tool to predict nodal pCR for cN+ patients after NAST that includes biomarkers of TME and achieves an AUC of 0.86 after tenfold cross-validation.

Purpose: Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes.

Methods: Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment.

Results: 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment.

Conclusion: In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study. Patients first received Trametinib monotherapy (2 mg daily; Part I) then at progression transitioned to Trametinib (1.5 mg) plus Uprosertib (50 mg; Part II).

Results: Between October 2013 and January 2017, 37 patients were enrolled to Part I. Subsequently, 19 patients entered Part II. Of the 37 patients receiving Trametinib monotherapy, 2 patients achieved partial response (PR) for an ORR of 5.4% (2/37) and an additional 6/37 (16.2%) achieved stable disease (SD). The clinical benefit rate (PR+SD) for patients receiving monotherapy was 21.6% (8/37). Of the 19 patients in Part II, 3 patients achieved PR for an ORR to Part II of 15.8% (3/19) and an additional 3 achieved SD. Median progression-free survival (PFS) was 7.7 weeks for Part I and 7.8 weeks for Part II. Circulating tumor DNA (ctDNA) clearance at C2D1 of Trametinib monotherapy was associated with improved PFS and overall survival.

Conclusion: In patients with mTNBC, Trametinib monotherapy demonstrated limited efficacy and addition of Uprosertib was associated with numerically greater objective responses but no difference in PFS. Translational analyses suggest ctDNA clearance as a potential early biomarker of response.

Purpose: Chemotherapy in combination with trastuzumab is the standard neoadjuvant and adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Assessing the regimens administered to patients with HER2-positive BC in the real world is lacking. We evaluated neoadjuvant and adjuvant regimen patterns among HER2-positive BC patients (2007 to 2021) identified in a health insurance claims database.

Methods: Female BC patients ≥ 18 years who received chemotherapy, surgery, and trastuzumab were chosen from Optum's de-identified Clinformatics® Data Mart database. Summary statistics, Joinpoint models, Kaplan-Meier survival curves, and Cox regression models were used to analyze the data.

Results: We identified 6474 patients (median age 60 years), 71.7% were White, 10.9% were Black, 8.6% were Hispanic, 4.1% were Asian, and 4.7% had unknown race/ethnicity. About 33.8% received neoadjuvant therapy and neoadjuvant therapy use increased with an annual percent change of 10.24% (P < .001). The three most common regimens were adjuvant docetaxel, carboplatin, and trastuzumab (TCH; 29.0%); adjuvant paclitaxel and trastuzumab (17.7%); and neoadjuvant TCH with pertuzumab followed by adjuvant trastuzumab (17.7%). The 5-year overall survival (OS) was 96% (95% CI, 95-96%). Patients had an increased risk of death if they were ≥ 59 years at diagnosis, had a health maintenance organization or other insurance plan, had dual Medicare/Medicaid eligibility, had a mastectomy, did not receive 18 cycles of trastuzumab, or received regimens not recommended by the National Comprehensive Cancer Network.

Conclusion: Treatment regimen patterns for HER2-positive BC evolved in correspondence with the U.S. Food and Drug Administration's approval of new drugs for this cancer and National Comprehensive Cancer Network treatment guidelines.

Purpose: In early-stage, triple-negative breast cancer (TNBC), immune cell infiltration contributes to cancer cell survival, tumor invasion, and metastasis. High TNBC glucocorticoid receptor (GR) expression in early-stage TNBC is associated with poor long-term outcomes; it is unknown if high GR expression is associated with an immunosuppressed tumor microenvironment. We hypothesized that high tumor GR expression would be associated with an immune-suppressed tumor microenvironment, which could thus account for the poor prognosis observed in GR-positive TNBC.

Methods: Formalin fixed-paraffin embedded tissue (n = 47) from patients diagnosed with early-stage TNBC from The University of Chicago (2002-2014) were evaluated for both tumor cell anti-GR immunohistochemistry and for infiltrating immune cells by immunofluorescence. Multiplexed antibodies were used to enumerate CD8+, FOXP3+, and BATF3+ immune cells infiltrating within pan-cytokeratin positive tumor cell regions of interest, and nonparametric tests compared absolute counts of each of these tumor-infiltrating immune cell types.

Results: The average age of patients represented in this study was 52 years, and 63% self-identified as Black. There was no significant association between tumor GR expression and age, race, or clinical stage at diagnosis. Compared to GR-low tumors, high GR expression in early-stage, treatment-naïve TNBC was associated with relatively increased numbers of immunosuppressive FOXP3 + regulatory T cells (p = 0.046) and BATF3+immune cells (p = 0.021). While there was a positive correlation with high GR expression and CD8+ cell infiltration, it was not significant (p = 0.068). The ratio of CD8+/FOXP3+cells was also not significant (p = 0.24).

Conclusions: These data support the hypothesis that in early-stage TNBC, high GR expression is significantly associated with infiltration of immunosuppressive regulatory T cells, suggesting a tumor-intrinsic role in shaping the immunosuppressive immune cell milieu. Furthermore, suppression of GR activity may regulate the tumor immune microenvironment and improve long-term outcomes in GR-high TNBC.

Purpose: After breast cancer diagnosis and treatment, the majority of women will gain weight. The aim of this study was to describe the experiences of weight management among Australian women with breast cancer.

Methods: This is a secondary analysis of data from a qualitative study evaluating the feasibility of novel interventions for weight management after breast cancer. Participants were recruited via email invitation from a breast cancer consumer organization and breast cancer centre in Australia. Eligible participants had received treatment for breast cancer, and were fluent in English. Discussions were audio-recorded, transcribed verbatim and analysed using thematic analysis with the constant comparison method.

Results: Thirty-seven women provided data in five focus groups and one semi-structured interview. Four themes were identified: Timing, milestones and turning points; Making sense of the journey; Factors leading to weight gain; and Information and health professional support. Varying trajectories of weight gain were described, the most common being gradual or fluctuating weight gain. Weight gain was attributed to a number of related factors including becoming postmenopausal, and the impact of treatment effects. Achieving a sense of autonomy and agency assisted with weight management. An overall lack of information and support relating to weight management was highlighted.

Conclusions: There is a need for a coordinated and systematic approach to weight management after breast cancer. Further research on the role of supportive care and systems-level support is warranted to mitigate the significant public health burden of excess weight after breast cancer treatment.

Purpose: This study aims to investigate the factors influencing the malignant risk of BI-RADS 4B calcification-only lesions detected on Contrast-Enhanced Mammography (CEM) and to develop a predictive model for stratifying malignant risk.

Methods: A retrospective analysis was conducted on 131 calcification-only lesions of BI-RADS 4B identified on low-energy (LE) images of CEM from 125 females between March 2017 and April 2023 at three institutions. The patients were grouped as training (95 lesions) and external validation sets (36 lesions). On LE images, morphological features of the calcifications, including morphology, distribution and size, were evaluated. On recombined images, the presence and types of enhancement were assessed as qualitative variables, and the grey values from lesion areas and background were measured as quantitative variables. Multivariate logistic regression analysis was used to construct a predictive model. The discrimination of the model was assessed by the receiver operating characteristic (ROC) curve and confirmed by the external validation set.

Results: Of the 131 lesions, 43 were malignant. The morphology, distribution, the presence and types of enhancement and the grey values of calcifications showed significant differences between benign and malignant lesions. The nomogram was developed based on morphology and the presence of enhancement, with areas under the ROC curve of 0.859 (95% confidence interval [CI]: 0.769, 0.949) and 0.856 (95% CI: 0.729, 0.983) in the training and external validation sets, respectively.

Conclusion: On CEM, the presence of enhancement and morphology were identified as independent predictors of malignant calcifications of BI-RADS 4B. The predictive model demonstrated favorable performance.

Purpose: The cyclin D1 gene (CCND1) encodes a key cell-cycle regulatory protein. Resistance to endocrine therapy is reportedly observed more often in patients with CCND1-amplified tumors. CCND1 amplification is known to be a driving event in breast cancer, but contradictory findings are reported for its association with prognosis. This study therefore investigated the prognostic value of CCND1 amplification in hormone receptor (HR)-positive breast cancer patients.

Methods: A cohort of 894 unselected breast cancer patients from the Bavarian Breast Cancer Cases and Controls (BBCC) study was included. The CCND1 amplification rate was evaluated in tissue microarrays using fluorescence in situ hybridization. A CCND1/CEP11 ratio ≥ 2.0 was considered amplified. Statistical analysis was conducted on cases with ratios based on a range of 20-100 nuclei analyzed per case. A univariable Cox regression model was fitted with disease-free survival (DFS) and overall survival (OS).

Results: CCND1 gene status was assessable in 511 patients. The CCND1 amplification rate was 12.9% (66 patients). Most patients with CCND1 amplification had luminal B-Like-(51.5%, n = 34) or luminal A-Like tumors (25.8%, n = 17), 13 patients with HER2-positive disease (19.7%) and only two patients had triple-negative tumors (3.0%). Survival analysis, focused on HR-positive, HER2-negative patients, showed no statistically significant differences in the DFS and OS with and without CCND1 amplification (P = 0.20 and 0.14, respectively, in the unadjusted analysis).

Conclusions: CCND1 amplification is a recurring event in breast cancer, occurring most frequently in luminal B-like and HER2-amplified subtypes. A trend toward less favorable outcomes was observed among CCND1-amplified HR-positive, HER2-negative tumors.