Breast Cancer Research and Treatment最新文献

Purpose: Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate (ADC) approved for the treatment of HER2-positive metastatic breast cancer (MBC). Despite its efficacy, eventual resistance and disease progression are common, and no prospective studies exist to guide therapy in T-DXd-resistant HER2-positive MBC.

Methods: This retrospective study analyzed patients with HER2-positive MBC who received cancer-directed therapies following treatment with T-DXd at Memorial Sloan Kettering Cancer Center.

Results: Eighty-one eligible patients were identified, who received 199 lines of therapy collectively. Post-T-DXd therapies included other ADCs, chemotherapy, HER2-targeted antibodies, hormone-based therapy, tyrosine kinase inhibitors (TKIs), and clinical trials. The median overall survival (OS) after stopping T-DXd treatment was 19 months, with a median progression-free survival (mPFS) of 3.7 months per subsequent treatment line. Chemotherapy was the most common treatment (42% of treatment lines; mPFS 3.4 months). No single therapeutic approach was clearly superior, although subsets of patients appeared to benefit from hormone therapy or TKIs. In a multivariate analysis including treatment type, treatment line, hormone receptor (HR) status, presence of brain metastases, and reason for T-DXd cessation, patients who discontinued T-DXd due to toxicity, rather than disease progression, had significantly better outcomes on subsequent therapy lines (HR 0.35; p < 0.001).

Conclusion: Our study indicates that patients emerge from T-DXd treatment with highly refractory disease. These findings highlight the urgent need for optimized treatment strategies and novel therapeutic options for this patient population.

Purpose: Prior studies have shown favorable post-surgical outcomes for patients with breast cancer treated at higher-volume hospitals. However, the impact of hospital volume on the management and outcomes for patients with locally advanced breast cancer (LABC) is unknown.

Methods: This retrospective study included 42,980 patients from the National Cancer Database (NCDB) with LABC treated between 2010 and 2017 at 1306 cancer-accredited centers. Centers were categorized as high-, medium-, and low-volume centers based on the number of patients with LABC seen annually. We assessed the association between hospital volume, receipt of trimodality therapy (TMT), and overall survival (OS), adjusting for demographic, clinical, and treatment variables.

Results: High-volume centers treated a median of 18.6 patients (range 15.4, 90.7) per year compared to 8.0 and 2.9 patients at medium- and low-volume centers, respectively. High-volume centers included more academic/research centers; served younger, higher-income, and racially diverse patients; and achieved higher rates of timely (within 60 days of diagnosis) neoadjuvant systemic therapy (NST) initiation and pathologic complete response (pCR) compared to low-volume centers (all P < .001). Treatment at high-volume centers (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82, 0.97; P < .001) and receipt of recommended TMT (HR, 0.52; 95% CI 0.50, 0.54; P < .001) were independently associated with improved 5-year OS.

Conclusion: Higher hospital volume was associated with improved survival outcomes in patients with LABC, influenced by greater adherence to guideline-concordant care. Efforts should focus on enhancing the capacity of low-volume centers to replicate high-volume care standards, addressing access and outcomes for vulnerable populations.

Introduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited therapeutic options. Mesothelin (MSLN), a tumor-associated antigen with potential targeted drugs, has been reported to be positive in some TNBC patients. However, there is a lack of studies on the clinicopathological characteristics of MSLN-expressing TNBC.

Materials and methods: We first demonstrated the significance of MSLN through pan-cancer analysis. We utilized local cohort to demonstrated that MSLN is associated with an immunosuppressive microenvironment and patients with high MSLN expression have poorer response to neoadjuvant chemotherapy combined with immunotherapy. Moreover, MSLN-expressing TNBC exhibit extensive lymphovascular tumor thrombi. Furthermore, spatial transcriptomics investigated T1N3-stage TNBC and identified MSLN as a highly expressed target in this aggressive subtype, public single-cell data identified MSLN-expressing tumor sub-cluster and their characteristics.

Conclusion: This study provides novel insights into the role of MSLN in TNBC and lays the foundation for future therapeutic strategies targeting MSLN in this aggressive breast cancer subtype.

Introduction: Limited data is available on patients diagnosed with breast cancer at age 85 and older, and there is no consensus on mammographic screening guidelines for older women, including those with a history of breast cancer. We sought to describe characteristics of presentation in this patient population and to determine whether differences exist between older women with a history of breast cancer and those without.

Methods: A retrospective review was conducted of all female patients aged 85 and older who consulted a breast surgeon for a diagnosis of new or recurrent breast cancer.

Results: From January 1, 2009 to September 30, 2024, 132 patients with newly diagnosed or recurrent breast cancer were identified. Mean age was 88.3 years (range 85-99). Ninety patients (68.2%) were diagnosed with breast cancer for the first time and the remainder (42; 31.8%) had a history of breast cancer. 57.1% of patients with a history of breast cancer were diagnosed on screening imaging compared to 31.1% with no prior history, who more commonly were diagnosed based on symptoms. In patients with a history of breast cancer, there was a mean time of 14.6 years from index cancer to ipsilateral breast tumor recurrence and 19.2 years from index cancer to contralateral cancer event.

Discussion: Roughly one-third of patients had a prior breast cancer and were significantly more likely to be diagnosed on screening studies compared to women who did not have a history of breast cancer. Women without a history of breast cancer were more likely to be symptomatic at the time of diagnosis and more likely to be diagnosed at a later disease stage. In patients with a prior breast cancer, second breast cancer events tended to happen late, which raises the question of how long screening should continue after a breast cancer diagnosis in older patients and whether guidelines should distinguish between those with a prior history of breast cancer and those without.

Purpose/objectives: For patients undergoing neoadjuvant chemotherapy (NAC), many clinical factors were identified to be associated with failure. Yet, for patients achieving pathologic complete response (pCR), it remains unknown what factors are associated with any subsequent failures. Our goal is to assess the patterns and predictors of locoregional failure (LRF), distant failure (DF), and invasive disease-free survival (IDFS) post-NAC, with a particular focus on those who achieved pCR.

Methods/materials: Between 2000 and 2021, we retrospectively reviewed 1115 consecutive patients in a single-institution database following NAC. Multivariable analysis was performed using the Cox proportional hazards model to identify the independent predictors of LRF, DF, and IDFS for the entire cohort and stratified by type of breast surgery. A univariable analysis was conducted to ascertain the independent predictors of any failure (IDFS) among patients who achieved pCR in both the breast and axilla.

Results: The median follow-up was 8.0 years [interquartile range: 4.1-12.4 years]. For the entire cohort, the 15-year cumulative incidence rates were 9.7% for LRF and 27.4% for DF, and the 15 year IDFS was 69.6%. The 15-year IDFS rates were 73.6% and 67.2% in breast-conserving surgery (BCS) and mastectomy cohorts, respectively (HR = 0.76, p = 0.03). On multivariable analysis, we found that LVI, ECE, number of malignant LNs post-NAC, triple-negative disease (TNBC), and tumor size were associated with IDFS for mastectomy patients, while achieving pCR in the breast was associated with a decreased risk for any failure. For BCS patients, the number of malignant LNs post-NAC, and TNBC were associated with IDFS, while achieving pCR in the axilla was associated with a decreased risk for any failure. On univariable analysis, we found that cT3-4 vs. cT1-2 pre-NAC was significantly associated with inferior IDFS among patients who achieved pCR in both the breast and axilla (n = 209). Patients with cN0 pre-NAC had a lower, albeit non-significant, risk of IDFS events. In patients with cN-positive disease pre-NAC who achieved pCR in both the breast and axilla (n = 117), RNI or PMRT (n = 95) did not significantly impact IDFS compared to those without RNI or PMRT (n = 22), with a median time to IDFS post-pCR of 7.1 years vs. 7.8 years, respectively.

Conclusion: We identified predictors of failure in this cohort, including among patients who achieved pCR. The median time to failure after pCR is around 7 years with or without adjuvant RNI/PMRT, highlighting the need to wait for mature results from the B51 trial and warranting further follow-up.

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.