Breast Cancer Research and Treatment最新文献

Background: To compare the risks of cardiovascular events, fractures, and all-cause mortality between denosumab and zoledronic acid in patients with breast cancer bone metastases.

Patients and methods: We identified female patients with breast cancer and bone metastases who received denosumab or zoledronic acid between April 2014 and August 2023 from a nationwide database of routinely collected administrative claims data in Japan. After adjusting for potential confounders using propensity score overlap weighting, we estimated the incidence of outcomes (per 10,000 person-years) and hazard ratios (HRs) using Cox proportional hazards models.

Results: Among the eligible 4350 patients, 2953 received denosumab and 1397 received zoledronic acid. The participants' median age was 76 years (interquartile range, 68 to 81). The adjusted incidence of composite cardiovascular disease was 118 in the denosumab group and 152 in the zoledronic acid group (HR 0.80, 95% confidence interval, 0.67 to 0.95). Heart failure was less frequent in patients administered denosumab [65 vs. 92; HR, 0.69 (0.55 to 0.87)] than in those administered zoledronic acid, whereas the rates of stroke and myocardial infarction were similar between the two groups. Denosumab was also associated with lower risks of any fracture [237 vs. 298; HR 0.80 (0.71 to 0.90)], hip (31 vs. 43), vertebral (135 vs. 168), and non-vertebral (114 vs. 142) fractures. Overall, 471 all-cause mortality events occurred in the denosumab group and 610 in the zoledronic acid group [HR 0.75 (0.69 to 0.82)].

Conclusion: In patients with breast cancer bone metastases, denosumab was associated with lower risks of cardiovascular events, fractures, and mortality than those with zoledronic acid.

Purpose: Seroma formation is one of the most common complications after mastectomy. Seromas can lead to repeated aspirations, increase the risk of infection, and potentially delay oncologic treatment. Several strategies have recently been employed to prevent seromas, but there is no definitive standard. We aim to determine whether perioperative glucocorticoids (GC) are safe and effective in preventing seromas in patients undergoing mastectomy.

Methods: We performed a systematic search in five databases on November 12, 2024. Eligible studies included women who underwent mastectomy and received perioperative GCs. Results are reported as risk ratios (RR), odds ratios (OR), or mean differences (MDs) with 95% confidence intervals (CIs), and are presented as forest plots. A random-effects model was used to pool effect sizes.

Results: Altogether, 13 studies (12 RCTs and 1 case-control study) with 1011 patients were included; all were eligible for meta-analysis. The rate of seroma formation was significantly lower in the GC groups compared to the placebo groups (RR = 0.56, CI 0.38; 0.82, p = 0,008). Total volume of drainage (MD = -213.36 ml, CI -312.5; -114.22, p = 0.001) and days to drain removal (MD =-3.01 days, CI -4.06; -1.96, p = 0.001) were also lower in the GC groups. The rate of wound infection showed a higher trend in the intervention groups (RR = 1.26, CI 0.82; 1.92, p = 0.224), although the results did not reach statistical significance, CONCLUSIONS: Our results suggest that perioperative glucocorticoid administration may reduce seroma formation in patients undergoing mastectomy. A potential increase in wound infection rates was also observed, but this requires further investigation.

Purpose: To quantify the proportion of HER2-negative metastatic breast cancers with low or ultralow levels of HER2 expression and identify facilitators and barriers to HER2 testing and reporting in US community settings.

Methods: Analysis of electronic medical record data from a retrospective cohort of patients diagnosed with HER2-negative breast cancer from 2018 to 2023 within the Guardian Research Network, classifying HER2 status by immunohistochemistry (IHC) score. Analysis of responses to surveys of community-based pathologists and oncologists, supplemented by qualitative analysis of one-to-one interview transcripts.

Results: The retrospective study identified 13,824 patients diagnosed with HER2-negative breast cancer from seven healthcare organizations, with 13,100 patients included in the final cohort. Patients were classified as HER2 IHC 0 (32%), 1 + (35%), 2 + (18%), and 3 + (1%); 15% of patients did not have a documented IHC score. Surveys and interviews with 63 community-based pathologists and oncologists found that most pathologists (93%) reported discrete IHC scoring on pathology reports, but 16% had difficulty assigning scores between IHC 0 and IHC 1 + . Barriers included inadequate standards, increased interpretation time, and workflow disruptions. Digital pathology was used by 39% of pathologists, with improved accuracy, higher efficiency, and reduced subjectivity stated as advantages, and high costs and lack of practice standards as barriers to adoption.

Conclusion: While innovative testing tools were viewed favorably by pathologists and oncologists, cost and need for training were barriers to adoption. Improving documentation practices, standardizing protocols, and adopting tools such as digital pathology could enhance the accuracy and consistency of HER2 testing.

Purpose: Small cell neuroendocrine carcinoma (SCNEC) is a very rare, highly aggressive subtype of breast cancer. There are no standard recommendations for the management of mammary SCNEC, and the use and response to neoadjuvant chemotherapy are not well studied. Etoposide is an agent not included in guidelines for the management of breast cancer but traditionally used in the treatment of small cell carcinoma of the lung.

Methods: We searched for institutional and consultation cases of breast SCNEC and identified those treated with neoadjuvant chemotherapy. Clinical, pathologic, and genetic findings of two patients with SCNEC of the breast treated with etoposide are described. Additionally, we performed a literature review of all known cases of mammary SCNEC treated with neoadjuvant chemotherapy to date.

Results: These two women were the sole patients who underwent neoadjuvant etoposide-based chemotherapy followed by surgery for breast SCNEC at our institution in the past 25 years. Both patients achieved excellent imaging and pathologic responses, with no evidence of residual carcinoma in the subsequent breast excisions.

Conclusion: Etoposide may be considered as a therapeutic option in the neoadjuvant setting of breast SCNEC. More reports on this very rare breast cancer subtype and response to treatment are needed.

Purpose: There have been few studies on the relationship between chronic inflammatory diseases and breast cancer outcome. We evaluated the relationship between chronic inflammatory diseases and survival among breast cancer patients in the U.S. military health system (MHS), a universal healthcare system.

Methods: The study used the Military Cancer Epidemiology database (MilCanEpi), which linked databases from the Department of War's Central Cancer Registry (CCR) and the Military Health System (MHS) Data Repository (MDR). A total of 33 chronic inflammatory diseases were identified. A time-dependent Cox proportional hazard regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of death associated with chronic inflammatory diseases while adjusting for potential confounders.

Results: The final data included 14,258 patients with histologically confirmed primary breast cancer. Among them, 7883 had a diagnosis of chronic inflammatory diseases at or after breast cancer and 6375 had no diagnosis at any time in the data. A diagnosis of chronic inflammatory diseases was independently associated with a significantly increased risk of all-cause death after adjustment for confounders (adjusted HR = 1.76, 95% CI = 1.56-1.98). Notably, the increased risk of death associated with the inflammatory diseases persisted among stage-IV patients who usually died of breast cancer. The association was also observed regardless of age, comorbidity, hormone receptor status, timing of disease diagnosis relative to breast cancer diagnosis, or other characteristics.

Conclusion: Chronic inflammation, characterized by chronic inflammatory diseases, was independently associated with increased all-cause death among breast cancer patients in MHS. Future research with cancer-specific death as the outcome is warranted.

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.