Breast Cancer Research and Treatment最新文献

Purpose: Circulating tumor DNA (ctDNA) enables early detection of ESR1 mutations in hormone receptor-positive, HER2-negative metastatic breast cancer. Building on the PADA-1, the SERENA-6 trial demonstrated significant progression-free survival and quality-of-life benefits from ctDNA-guided early endocrine switching before radiologic progression.

Methods: We examine the evolving clinical utility of liquid biopsy in this setting and review evidence from trials evaluating biomarker-guided treatment adaptation. We also compare imaging- versus biomarker-guided strategies.

Conclusion: This review outlines the key challenges to validating and implementing ctDNA-guided early endocrine switching in routine clinical practice and discusses its potential to reshape monitoring and decision-making in metastatic hormone receptor-positive, HER2-negative breast cancer.

Purpose: Chemotherapy-induced alopecia (CIA) affects approximately 65% of patients receiving chemotherapy and has a negative impact on quality of life (QoL). Scalp cooling (SC) is the only FDA-cleared intervention for CIA. This systematic review and meta-analysis evaluated SC adverse events (AEs), reasons for discontinuation, and scalp metastasis incidence.

Methods: Meta-analyses using random-effects models estimated pooled prevalences of SC AEs, SC discontinuation, and reasons for discontinuation. A generalized linear mixed model was used to estimate the incidence of scalp metastasis.

Results: Sixty-seven studies met the inclusion criteria. The most common AEs were generalized chills (42%, 95% confidence interval (CI) 26-58%), cap heaviness (35%, 95% CI 18-52%), and headache (30%, 95% CI 21-39%). The SC discontinuation rate was 18% (95% CI 13-23%). The most common reasons for discontinuation were progressive alopecia (15%, 95% CI 10-20%) and reasons unrelated to SC (9%, 95% CI 5-13%). The most frequent AEs leading to SC discontinuation were headache (4%, 95% CI 2-6%), cold intolerance (4%, 95% CI 3-5%), and general discomfort (4%, 95% CI 2-7%). Secondary analysis of scalp metastases yielded an incidence of 0.15% (95% CI 0.05-0.47%). Analysis of FDA Manufacturer and User Facility Device Experience (MAUDE) database medical device reports revealed that user error contributed to cold thermal injuries. Prevalence estimates were limited by significant heterogeneity between studies, reflecting variations in study methodology and real-world SC practices.

Conclusion: SC is generally well tolerated with minimal safety concerns. Clinical comfort strategies like supportive medications and improved patient education could enhance SC tolerability and support its implementation.

Purpose: This study aims to evaluate the impact of lymph node status on survival outcomes in female breast cancer patients underwent immediate breast reconstruction (IBR) after mastectomy.

Methods: Data from 8418 cases (2010-2017) receiving IBR were divided into regional lymph node negative (LN-) and positive (LN+) groups. Propensity score matching (PSM) was used to balance covariates between groups. Subgroup Cox regression analysis was performed to assess overall survival (OS) and breast cancer-specific survival (BCSS), considering sociodemographic, oncological, and treatment-related factors.

Results: Inpatients underwent IBR, the LN+  group exhibited significantly poorer OS and BCSS than the LN- group, both before and after PSM. Higher income, specific tumor characteristics, and implant-based reconstruction were related to better survival outcomes. Subgroup analysis revealed that in LN- group, lower income, HR-, HER2- status, and higher tumor grade were OS/BCSS risk factors. In the LN+  group, advanced T stage independently predicted worse OS/BCSS, and contralateral breast removal was associated with a decrease in OS risk.

Conclusions: Caution is warranted when recommending IBR for patients with N2-3, and implant-based reconstruction may represent a more favorable option in selected cases. LN+  status is a significant adverse prognostic factor in IBR patients. Personalized treatment strategies based on LN status are essential for optimizing survival outcomes.

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.