Breast Cancer Research and Treatment最新文献

Purpose: Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy.

Methods: This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.

Results: Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).

Conclusion: Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive breast cancer (BC) subtype with higher incidence and mortality rates in non-Hispanic Black (NHB) women than non-Hispanic Whites. Studies assessing disparities between NHB and Hispanic women, the two largest US racial/ethnic minorities, are lacking. This study evaluates disparities in the treatment and outcomes between NHB and Hispanic women with non-metastatic TNBC.

Methods: This observational, population-based study using the SEER database included adult, female patients diagnosed with non-metastatic TNBC between 2010 and 2015 and identified as NHB or Hispanic. Logistic regression analysis was used to examine the adjusted odds of receiving breast cancer-directed treatment. Kaplan-Meier and cumulative incidence of death curves were plotted to assess overall survival (OS) and risk of breast cancer-related death, respectively. Multivariate regression analyses with Cox and Fine-Gray methods were calculated to assess factors associated with OS and breast cancer-related death, respectively.

Results: There were 3426 Hispanic and 5419 NHB patients with non-metastatic TNBC. Hispanics had better 5-year OS relative to NHB (76% vs. 72%). No differences in the odds of receiving chemotherapy or surgery between cohorts was seen. However, the odds of undergoing breast-conserving surgery (BCS) and receiving radiation was higher in NHB than Hispanics, (OR, 1.22; 95% CI, 1.10-1.36) and (OR, 1.50; 95% CI, 1.36-1.66), respectively. Lack of radiation therapy was associated with increased BC-related death in NHB relative to Hispanics (sHR, 1.40; 95% CI, 1.19-1.65). Nevertheless, this difference was not seen when radiation was given, (sHR, 1.03; 95% CI, 0.87-1.23).

Conclusions: We found racial disparities in treatment and outcomes between NHB and Hispanics. NHB were more likely to receive radiation therapy and have BCS. Still, after adjusting for demographic and treatment-related factors, NHB had worse OS and BCSS relative to Hispanics. Additional research is needed to understand the drivers of these disparities.

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.

Purpose: To evaluate patient-reported health-related quality-of-life (QoL) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced/metastatic breast cancer (ABC) treated with palbociclib in the longitudinal real-world study, POLARIS.

Methods: Data were prospectively collected from adult patients with HR+/HER2- ABC treated with palbociclib plus endocrine therapy (ET) in routine clinical practice. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30) and reported at baseline and months 6, 12, and 18. Data were expressed as absolute scores at a given time and change from baseline for global QoL and functional/symptom scales. Global Heath Status (GHS)/QoL scores were also determined across 6 patient subgroup categories (e.g., age, visceral disease status). Additionally, the proportions of patients with scores below (functional scales) or above (symptom scales) EORTC-validated thresholds reflecting clinical importance of a health problem were determined.

Results: Among patients treated with palbociclib plus ET (N = 1250) who completed questionnaires at any of the study timepoints, mean GHS/QoL scores at months 6 (69.3), 12 (70.1), and 18 (69.9) were higher than baseline (64.0). Similar trends were observed for functional and symptom scales. Mean GHS/QoL scores over time were consistent across the evaluated subgroups. Decreases in the proportions of patients with clinically important functional impairment/symptoms were observed for most functional/symptom scales from baseline through month 18.

Conclusion: Findings from this real-world study indicate patients with HR+/HER2- ABC treated with palbociclib plus ET maintain their QoL for at least 18 months.

Clinical trial registration: NCT03280303; registered 12 September 2017.

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: 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.

Background: Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers.

Purpose: The current investigation aims to explore the connection of the functional TNF-α^-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices.

Methods: The ARMS-PCR method was used for genotyping TNF-α^-308G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI); 163 with breast cancer (BC) and 144 controls (C).

Results: The TNF-α^-308G > A SNP was distributed among different groups in a unique pattern; in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (OR_AA: 14.67 [95% CI = 3.78-56.91] and OR_A: 0.27 [95% CI = 0.19-0.39], respectively; P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (OR_GA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively).

Conclusion: This research is the first to correlate TNF-α^-308G > A (rs1800629) SNP in Egyptian BC patients. The A allele, GA & AA genotypes, and the Overdominant model of the TNF-α^-308G > A gene variants were recorded as prognostic risk factors for BC carcinogenesis.

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.