Breast Cancer Research and Treatment最新文献

Background: Atypical breast lesions are high-risk findings found on some core needle biopsies that may represent concurrent malignancy. Clinical management remains uncertain due to wide variability in reported upgrade rates and an incomplete understanding of contributing risk factors. Risk prediction models have been developed to estimate likelihood of malignant upgrade (from atypia to malignancy), but these models are highly variable in performance and predictor selection. This systematic review evaluates existing models predicting upgrade to malignancy in high-risk breast lesions, focusing on clinical applicability.

Methods: A qualitative systematic review was conducted following PRISMA guidelines. Searches in MEDLINE, Embase, and Scopus identified studies that developed risk prediction models estimating breast malignancy upgrade after atypia diagnosis. Studies analyzing multiple risk factors and providing quantitative risk estimates were included. Extracted data included study characteristics, statistical methods, key predictors, and model performance. Prediction model Risk of Bias Assessment Tool (PROBAST) was used for quality assessment.

Results: Of the 3202 studies screened, 17 met inclusion criteria. Sample sizes ranged from 20 to 525, with reported upgrade rates from 14.9 to 67.3%. Common predictors of upgrade included lesion size, histology, and radiologic-pathologic concordance. Discriminatory performance varied (AUROC 0.514-0.909), and calibration was rarely assessed, limiting reliability. Most studies lacked external validation and exhibited a high risk of bias.

Conclusion: Current risk prediction models for malignant upgrade for high-risk lesions demonstrate significant variability and limitations in widespread use. While they may supplement clinical judgment, further external validation and improved calibration are needed before they can reliably guide management.

Purpose: Male breast cancer (mBC) is rare and accounts for ~ 1% of all breast cancer cases in the United States (US), and mBC incidence has risen in recent years. This study sought to examine mBC mortality disparities across racial/ethnic groups and associated socioeconomic determinants at the national level.

Methods: This retrospective study analyzed the 2010-2021 National Cancer Database. Patients were eligible if they were ≥ 18 years, were male sex, and had stage I-IV disease, with available data on receptor status. Overall survival (OS) was modeled using Cox regression adjusting for demographic, socioeconomic, and clinicopathologic factors.

Results: Of 20,470 mBC (mean age, 66.2 [SD, 12.6] years), 2.5% were Asian or Pacific Islander, 13.8% Black, 4.0% Hispanic, and 78.2% White. After controlling for clinicopathologic characteristics, Black patients had worse OS than White patients (adjusted hazard ratio [AHR], 1.22; 95% CI, 1.12-1.32); however, when further adjusting for socioeconomic factors, this difference was no longer significant (AHR, 1.09; 95% CI, 0.99-1.21). Hispanic patients (AHR, 0.76; 95% CI, 0.62-0.94) had a lower mortality risk. OS varied across tumor stages and molecular subtypes. In the triple-negative mBC cohort, Asian or Pacific Islander patients had worse OS than White patients (AHR, 2.35; 95% CI, 1.21-4.55), warranting further investigation. Additionally, lower median household income, lack of health insurance, Medicaid/Medicare, and comorbidities were associated with a higher mortality risk.

Conclusion: Our findings highlight elevated mortality risks of mBC among Black patients, among Asian or Pacific Islander patients with TNBC, and associations with household income and insurance status. Interventions addressing socioeconomic inequities that impact access to cancer care programs and services may help reduce racial/ethnic disparities and improve mBC survival outcomes.

Purpose: Up to 30% of patients with hormone receptor-positive (HR +) breast cancer do not start adjuvant endocrine therapy (AET) as prescribed. AET non-initiation is associated with increased recurrence and decreased survival. We conducted a single-arm, open-pilot study to assess the feasibility and acceptability of a nurse-led, culturally sensitive intervention ('INITIATE') to optimize AET initiation.

Methods: From 9/2022 to 8/2024, we recruited 35 patients with stage I-IIIB, HR + breast cancer who delayed or reported hesitancy to start AET. INITIATE included two virtual sessions delivered in English or Spanish with an oncology nurse. Feasibility was defined by enrollment rates (> 50% eligible patients), intervention attendance (≥ 70% of patients attending one of two sessions), and retention (> 70% completing the 3-month questionnaire). At baseline, 1 month, and 3 months post-baseline, patients self-reported sociodemographics, AET initiation, intervention acceptability (Client Satisfaction Questionnaire-3), and other psychosocial outcomes. We conducted semi-structured, qualitative exit interviews to gather additional feedback. We computed descriptive statistics for the quantitative outcomes and conducted a rapid qualitative analysis of the interview data.

Results: We enrolled 45.5% (35/77) of eligible patients; 82.9% (29/35) attended at least one intervention session, and 77.1% (27/35) completed the 3-month assessment. Most patients (68.6%) were White, and 37.1% identified as a racial or ethnic minority. Qualitatively, patients reported that INITIATE helped them understand the importance of taking AET and improved their coping skills. Ninety-six percent reported high acceptability, and 88.9% started their AET by three months post-baseline.

Conclusion: INITIATE is mostly feasible and acceptable and demonstrates promise for promoting AET initiation among patients with HR + breast cancer.

Purpose: To evaluate differences in clinical outcomes, treatments received, recurrence, and sociodemographic characteristics in patients with triple-negative breast cancer (TNBC) classified as invasive lobular carcinoma (TNBC-ILC) or invasive carcinoma of no special type (TNBC-NST).

Methods: Using national registry data, we conducted a retrospective, population-based cohort study of 6449 women diagnosed with primary TNBC (stratified by histological subtype) in Sweden (2007-2021). Clinical and treatment data were analyzed using descriptive statistics, logistic regression, machine learning (Boruta/XGBoost), and Cox proportional hazards models adjusted for patient age, tumor size, grade, nodal status, comorbidities, and receipt of adjuvant chemotherapy (ACT).

Results: TNBC-ILC accounted for 2.7% of all TNBC cases and affected older patients (median age 70 vs 62 years). Compared to TNBC-NST, TNBC-ILC had lower Ki-67, fewer high-grade tumors, higher T stage, and greater socioeconomic vulnerability. Machine learning identified age and post-operative tumor size as key predictive features of TNBC-ILC. ACT was administered to 40% of TNBC-ILC versus 59% of TNBC-NST cases (P < 0.001), with a survival benefit observed only in TNBC-NST. TNBC-ILC patients aged 50-64 years were less likely to receive ACT. Despite lower proliferative activity, TNBC-ILC was associated with worse overall (OS; adj-HR 1.39, 95% CI 1.04-1.86) and disease-specific survival (DSS; adj-HR 1.98, 95% CI 1.41-2.79), particularly in patients ≥ 50 years of age. TNBC-ILC patients ≥ 75 years had the poorest 5-year survival (DSS 55%; OS 42%).

Conclusions: TNBC-ILC is a distinct subgroup with older age, lower grade and Ki-67, undertreatment, and poorer survival, emphasizing the need for age- and subtype-specific treatment strategies.

Purpose: Breast cancer-related lymphedema (BCRL) disproportionately impacts patients facing socioeconomic challenges. The influence of socioeconomic disparities on preventive procedures such as immediate lymphatic reconstruction (ILR) is unclear. We sought to determine the impact of area deprivation index (ADI) on BCRL incidence and patient-reported outcomes (PROs) following ILR.

Methods: We retrospectively studied consecutive patients who underwent ILR following ALND between 2017 and 2024 across multiple hospitals within a hospital network. Patients were stratified into quartiles based on ADI (Q1 = least deprived, Q4 = most deprived). BCRL prevalence and condition-specific (LYMPH-Q) quality-of-life performance was compared and correlated across quartiles via multivariable regression, including subgroup analysis by ethnicity.

Results: We identified 172 patients with follow-up time of 23.1 ± 15.2 months. Patients residing in the most deprived neighborhoods (ADI Q4) demonstrated significantly higher BCRL rates compared to those from less deprived neighborhoods (Q1-3) (16.3% vs. 3.9%; p = 0.006). In multivariable regression, residence in the most deprived neighborhoods remained independently associated with a significantly higher risk of BCRL (OR 5.10, 95% CI 1.30-20.30; p = 0.021). Subgroup analysis revealed that Black patients in the highest ADI quartile reported significantly worse LYMPH-Q function scores (median 62.0 vs 100.0; p = 0.020), compared to Black patients residing in less deprived areas. ADI was not significantly associated with surgical complications or unplanned reoperations.

Conclusions: Neighborhood socioeconomic disadvantage significantly increases BCRL risk following ILR and is associated with significantly worse patient-reported functional outcomes among Black patients. Targeted interventions addressing neighborhood-level factors are critical to mitigate these disparities and ensure equitable outcomes.

Purpose: To assess associations of 3D morphometry of breast calcifications, determined using high-resolution microCT, with underlying histopathology and evaluate the potential for classifying tissue calcifications as an aid in optimizing identification and diagnosis of the most severe pathology in a biopsy.

Methods: We compared morphometry of calcifications in tissue blocks (n = 156) of benign breast disease (n = 74), ductal carcinoma in situ (n = 39), and ductal carcinoma in situ with invasive breast cancer (n = 43) using (10 µm) microCT. Matched sections were reviewed microscopically to define lesion(s) in which calcifications were embedded. 3D reconstructions of calcifications were reviewed independently by two masked radiologists to assess the need for biopsy and calcification morphology. Calcification morphometry was compared to pathologic diagnosis using linear mixed models.

Results: A total of 12,216 calcifications (IQR 9-66 per specimen) were analyzed. Individual breast cancer-associated calcifications were significantly larger than benign breast disease-associated calcifications (p_adjusted = 0.012) and calcification volume was positively associated with grade of ductal carcinoma in situ (P_trend = 0.009). Structure model index revealed more cylindrical shape in breast cancer calcifications versus benign breast disease calcifications (p_adjusted = 0.008). Re-analysis by the specific microscopic lesion containing the calcification, rather than the most severe diagnosis per biopsy, strengthened associations. Radiologists agreed on biopsy recommendation in 92% of microCT images, while achieving sensitivities of 53.1% and 54.3%. and specificities of 50.0% and 54.1%.

Conclusion: Our analysis provides proof-of-concept that morphometry of tissue calcifications varies by lesion type, suggesting that future studies may enable development of a pathologic classification linked to diagnosis and mammographic findings.

Purpose: Triple-negative breast cancers (TNBCs) are associated with a high frequency of PTEN loss, which can lead to activation of the mTOR pathway and tumor proliferation but may be reversible with the mTOR inhibitor everolimus. A prior phase II single-arm trial of carboplatin and everolimus in patients with advanced TNBC demonstrated good tolerability and preliminary efficacy.

Patients and methods: A phase II randomized trial in patients with advanced TNBC, with 0-3 prior lines of therapy, was conducted. Patients were randomized 2:1 to receive carboplatin and everolimus or carboplatin alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety.

Results: Between 2015 and 2022, 59 patients were randomized to carboplatin/everolimus (n = 38) or carboplatin alone (n = 21). The median age of the population was 62 years and 68% had received at least one prior line of therapy. Median PFS was significantly improved in patients who received carboplatin/everolimus (4.7 months) versus carboplatin alone (4.2 months; HR:0.49; 95% CI: 0.25-0.98; p = 0.0390). OS was 17.6 months with the combination and 14.6 months with carboplatin alone (HR:1.17; 95% CI: 0.59-2.30; p = 0.6593). The most common adverse events (AEs) on the combination included thrombocytopenia, anemia, leukopenia, and neutropenia.

Conclusion: The combination of carboplatin and everolimus in this study reduced the risk of progression or death by 52%. The regimen was well tolerated and provides a promising treatment option for patients with advanced TNBC.

Introduction: This study examines the intermittent discontinuation of palbociclib based on its availability and its clinical outcomes during the Lebanese economic crisis in patients with metastatic Breast Cancer (BC) HR+ between the years 2019 and 2023.

Methods: This study carries out a retrospective analysis on 46 patients treated with palbociclib - Letrozole during the years 2019 and 2023 in Lebanon. It used descriptive tables and figures to summarize demographic, clinical, and outcome characteristics. It analyzed the data using Student T test for parametric variables, Wilcoxon and Kruskal-Wallis tests for non-parametric variables, and Chi-squared and Fisher tests for qualitative variables. Pearson's correlation and regression models were used to associate between the intermittent administration of palbociclib and its clinical outcomes.

Results: Our sample had a mean age of 59.33 +/-13.27 years. 87% had ductal carcinomas and 13% had lobular carcinomas. 52.2% of patients had treatment for their metastases prior to palbociclib, and a discontinuation was observed in 63.1 %. Intermittent discontinuation is associated with advanced age (p=0.048) and statistically reduces PFS (p=0.026). The intermittent drug intake also affects PFS (p=0.03) but has no effect on the disease progression.

Conclusion: This study is the only research in the world focused on intermittent intake of palbociclib. The intermittent discontinuation of palbociclib is influenced by age and affects the PFS. These results highlight the significance of adherence and protocol compliance.

Background: Health-related quality of life (HRQoL) has long been recognized as a critical area of cancer research as it reflects patients' well-being, but less is known if HRQoL predicts survival outcomes in survivors of early stage breast cancer.

Aims: We assessed racial disparities in HRQoL and the impact of HRQoL on survival outcomes in breast cancer survivors.

Methods: This study included a total of 721 breast cancer survivors from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort who completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) instrument in 2020. We examined racial differences in FACT-B scores and patient characteristics correlated with FACT-B and its subscales using multiple linear regression. We used Cox regression to assess the associations between HRQoL assessments and survival outcomes.

Results: Functional well-being score was lower in Black survivors than in White survivors (mean score: 19.6 vs. 20.9, P = 0.003). Being married was associated with a higher HRQoL score. Having a recurrence before interview and comorbidities worsened physical and emotional well-being. The total FACT-B score were significant predictors of both all-cause [hazard ratio (HR) = 0.68 per standard deviation, 95% CI 0.48-0.95] and breast cancer-specific mortality (HR = 0.57, 95% CI 0.37-0.88). Physical and functional well-being subscales were found to be associated with all-cause and breast cancer-specific mortality, and recurrence-free survival. Emotional well-being predicted breast cancer-specific mortality.

Conclusions: Our findings highlighted racial disparities in HRQoL and HRQoL associated with survival outcomes in breast cancer, suggesting the need to reduce the disparities and examine the long-term impact of HRQoL on health outcomes in future studies.

Purpose: Metastatic breast cancer (MBC) is incurable, despite therapeutic advances, especially in hormone receptor positive (HR+) and human epidermal growth factor-2 negative (HER2-) disease. Specialist palliative care (SPC) is recommended to alleviate distress and reduce overly aggressive end-of-life (EoL) care. This study determined rates of SPC, hospice utilization, and aggressive EoL care in patients with HR+/HER2- MBC.

Methods: A retrospective review was performed of patients with treatment naïve HR+/HER2- MBC treated with endocrine therapy and/or cyclin-dependent kinase 4 and 6 inhibitors at Duke Cancer Institute between January 2012 and December 2017. Variables pertaining to SPC and hospice use and EoL care outcomes up to March 2024 were collected. SPC and hospice utilization and EoL care data were analyzed with descriptive statistics.

Results: Of 102 patients, 85 died during the study period, and over half (55%) received aggressive EoL care. Half had some form of SPC, and rates of aggressive EoL care were comparable between those who engaged with SPC and those who did not. The most common indicators of aggressive EoL care included multiple ED visits (28%) and hospital admissions (23%) in the last 30 days of life as well as in-hospital location of death (24%). Although 72% enrolled in hospice care, 9% of patients were on hospice for ≤ 3 days.

Conclusion: This real-world study demonstrates that many patients with HR + /HER2- MBC receive aggressive EoL care despite some engaging with SPC and many enrolling in hospice. Interventions to decrease aggressive EoL care are needed for this population.