Breast Cancer最新文献

Background: Although the demand for care immediately after mastectomy is rising, and such medical services are referred to as post-acute care (PAC), there is limited evidence on the factors influencing PAC choices among these patients in Korea.

Methods: A total of 106,670 patients diagnosed with breast cancer and undergoing mastectomy were extracted from the Central Cancer Registry data from 2012 to 2019 using Public Cancer Library data of KCURE. PAC was defined as utilization of long-term care hospital (LTCH), hospital-based nursing care (HBNC), or HBC (hospital-based care) within 2 months post-surgery. Multinomial logistic regression was used to identify factors associated with different types of PAC utilization.

Results: The utilization patterns of different types of PAC within 2 months after mastectomy were associated with age, income, cancer severity, and particularly the region of residence (Metropolitan; HBNC, OR 0.16, 95% CI 0.10-0.26; LTCH, OR 2.35, 95% CI 2.21-2.50; HBC, OR 2.17, 95% CI 1.97-2.39), as well as the location (capital areas; HBNC, OR 12.46, 95% CI 4.97-31.25; LTCH, OR 1.21, 95% CI 1.15-1.28; HBC, OR 1.90, 95% CI 1.74-2.07) and type of the hospital (tertiary hospital; HBNC, OR 13.70, 95% CI 7.86-23.86; LTCH, OR 1.45, 95% CI 1.37-1.53; HBC, OR 3.38, 95% CI 3.00-3.80) where the surgery was performed.

Conclusion: In this study, we found the factors associated with PAC utilization on mastectomy patients. Our study found that middle-aged breast cancer patients, residents of metropolitan or rural areas, and those who underwent surgery at hospitals in capital area were particularly associated with higher utilization of inpatient-related PAC services. Breast cancer patients with higher income, older adults, metropolitan residents, patients who underwent breast cancer surgery at metropolitan hospitals, and those treated at tertiary hospitals were strongly associated with higher utilization of HBNC services. Identifying factors that determine the use of PAC has meaningful implications for patients and healthcare systems.

Although the prognosis of breast cancer has significantly improved compared to other types of cancer, there are still some patients who expire due to recurrence or metastasis. Therefore, it is necessary to develop a method to identify patients with poor prognosis at the early stages of cancer. In the process of discovering new prognostic markers from genes of unknown function, we found that the expression of C1orf50 determines the prognosis of breast cancer patients, especially for those with Luminal A breast cancer. This study aims to elucidate the molecular role of C1orf50 in breast cancer progression. Bioinformatic analyses of the breast cancer dataset of TCGA, and in vitro analyses, reveal the molecular pathways influenced by C1orf50 expression. C1orf50 knockdown suppressed the cell cycle of breast cancer cells and weakened their ability to maintain the undifferentiated state and self-renewal capacity. Interestingly, upregulation of C1orf50 increased sensitivity to CDK4/6 inhibition. In addition, C1orf50 was found to be more abundant in breast cancer cells than in normal breast epithelium, suggesting C1orf50's involvement in breast cancer pathogenesis. Furthermore, the mRNA expression level of C1orf50 was positively correlated with the expression of PD-L1 and its related factors. These results suggest that C1orf50 promotes breast cancer progression through cell cycle upregulation, maintenance of cancer stemness, and immune evasion mechanisms. Our study uncovers the biological functions of C1orf50 in Luminal breast cancer progression, a finding not previously reported in any type of cancer.

Purpose: The aim of this study was to examine the clinical utility of tumor-infiltrating lymphocytes (TILs) evaluated by "average" and "hot-spot" methods in breast cancer patients.

Methods: We examined 367 breast cancer patients without neoadjuvant chemotherapy (NAC) by average and hot-spot methods to determine the consistency of TIL scores between biopsy and surgical specimens. TIL scores before NAC were also compared with the pathological complete response (pCR) rate and clinical outcomes in 144 breast cancer patients that received NAC. TIL scores evaluated by the two methods were predicted from clinicopathological data using random forest regression.

Results: Surgical specimens showed higher TIL scores than biopsy specimens using the hot-spot method (p < 0.001), while biopsy and surgical specimens showed similar TIL scores using the average method. There was a linear relationship between the pCR rate and TIL scores determined using hot-spot (p < 0.001) and average methods (p = 0.001). Patients without pCR and low TILs by the average method had significantly worse overall survival compared to other patients (p = 0.02). The root mean squared errors of the predicted TIL score for the test set were 19.662 (hot-spot) and 10.955 (average).

Conclusion: The average method may have an advantage for breast cancer patients receiving NAC, since the TIL score using this method is more consistent between biopsy and surgical specimens, and it associates better with clinical outcomes. Our exploratory study showed that machine learning from clinicopathological data may better predict TIL scores assessed by the average, rather than hot-spot, method.

Background: In Japan, despite 5 years since CGP tests were covered by insurance in 2019, low drug accessibility rates remain a critical issue. We evaluated drug accessibility in 3776 breast cancer from the C-CAT database using two criteria: the proportion first linked to PMDA-approved drugs with phase III trial evidence for breast cancer through CGP tests but not existing Companion diagnostics [CDx] (*), and the proportion first linked to PMDA-approved drugs including based on phase I and II trial evidence (**). Additionally, cases linked to investigational drugs for non-PMDA-approved drugs were counted.

Methods: We identified the top 100 genetic alterations in Japanese breast cancer via CGP tests, listing corresponding drugs from C-CAT reports. Drug accessibility was re-evaluated through simulations with updated evidence levels by a member of the expert panel at Osaka University (EP-EL in OUH).

Results: Results showed the proportion improved to 28.4% under the newest EP-EL in OUH, including 3.4% for HER2-negative cases eligible for HER2-targeted therapy due to ERBB2 amplification and 25.0% for ER-positive, HER2-negative cases eligible for capivasertib-fulvestrant therapy due to PIK3CA, AKT1, and PTEN alterations (*). However, in part, initial false negatives for HER2 status and practical difficulties in using CGP tests as a CDx for capivasertib exist. Including mutations like TMB-H, MSI-H, BRAF V600E mutation, and NTRK fusions raised the proportion to 37.9% (**), but lacking drugs with phase III trials evidence.

Conclusion: These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.

Background: Circulating tumor DNA (ctDNA) enables non-invasive evaluation and is considered a promising tool for diagnosis, treatment selection, risk stratification, and disease monitoring. However, while the utility of ctDNA has been demonstrated in advanced-stage cancers, its detection in early breast cancer (EBC) remains limited. This study investigated the characteristics of EBC patients associated with higher ctDNA detectability.

Methods: A total of 101 patients with EBC were enrolled. Formalin-fixed paraffin-embedded samples (FFPEs) were obtained from biopsy tissue, and plasma samples were collected before and after neoadjuvant chemotherapy (NAC). Forty-seven breast cancer-related genes were analyzed using next-generation sequencing. The diagnostic performance of ctDNA was evaluated, and logistic regression analyses were conducted to assess the impact of clinical and molecular factors on ctDNA status.

Results: The most frequently identified gene was TP53 (FFPE, 66.7%; ctDNA, 46.4%), followed by PIK3CA (FFPE, 36.2%; ctDNA, 17.4%). The diagnostic performance of the three most common genes showed a sensitivity range of 11.1-58.7%, specificity of 78.3-100%, and diagnostic accuracy of 65.2-78.3%. The triple-negative breast cancer (TNBC) subtype exhibited the strongest association with ctDNA detection (odds ratio [OR] 209.50, p = 0.005) in multivariate analysis. Also, those who exhibited ctDNA clearance after NAC had a higher pathological complete response rate compared to those without clearance (38.5% vs. 11.1%, p = 0.238).

Conclusions: Our study highlights that ctDNA analysis can complement genetic testing from a single tissue biopsy in breast cancer patients. Furthermore, ctDNA analysis may be particularly important in patients with TNBC.

Antibody-drug conjugates (ADCs) are an emerging class of anticancer therapy that combines the specificity and long circulation half-life of monoclonal antibodies with the cytotoxic potency of the payload connected through a chemical linker. The optimal management of toxicities is crucial for improving quality of life in patients undergoing ADCs and for avoiding improper dose reductions or discontinuations. This article focuses on the characteristics and management of nausea and vomiting (NV) induced by three ADCs: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan (SG), and datopotamab deruxtecan (Dato-DXd). We summarize the proposed mechanism of NV, clinical study data on NV, and recommendations from clinical guidelines. We also discuss three prospective studies evaluating prophylactic antiemetic therapy in patients receiving T-DXd, along with future perspectives.

Breast cancers (BCs) are frequently linked to an immunosuppressive microenvironment that facilitates tumor evasion of anti-cancer immunity. The cells that suppress the immune system such as regulatory B cells (Bregs), regulatory T cells (Tregs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), play a crucial role in immune resistance. Also, tumor progression and immune evasion of cancers are facilitated by cytokines and factors released by tumor cells or immunosuppressive cells. Targeting these regulatory cells therapeutically, whether through elimination, inactivation, or reprogramming, has resulted in hopeful anti-tumor reactions. Yet, the substantial diversity and adaptability of these cells, both in terms of appearance and function, as well as their variation over time and depending on where they are in the body, have posed significant challenges for using them as reliable biomarkers and creating focused therapies that could target their creation, growth, and various tumor-promoting roles. The immunotherapy approaches in BC and their effectiveness in treating certain subtypes are still in their initial phases. In this review, we thoroughly outlined the characteristics, roles, and possible treatment options for these immune-suppressing cells in the tumor environment.

Background: Triple-negative breast cancer (TNBC) is a serious disease with limited treatment options. We explored the significance of androgen receptor (AR) expression and tumor-infiltrating lymphocytes (TILs) in predicting neoadjuvant chemotherapy (NAC) resistance in TNBC, hypothesizing that AR/TIL classification using pretreatment biopsies can identify NAC-resistant subgroups and improve the understanding of apocrine differentiation.

Methods: This retrospective study included 156 consecutive patients with TNBC treated with NAC. AR immunostaining was defined positive if ≥ 1% of the tumor cell nuclei were stained. Stromal TIL levels were assessed, with high levels defined as ≥ 50%. Apocrine differentiation was detected using an anti-15-PGDH antibody. The pathological response to NAC was evaluated.

Results: Overall, 36% (n = 56) of the patients achieved a pathological complete response (pCR). AR⁺/TIL^low tumors had a high non-pCR rate (76%, 42/55) and were resistant to NAC. Kaplan-Meier plots showed significant differences in overall survival (OS) and distant metastasis-free survival (DMFS) among the four AR/TIL subgroups (OS: p = 0.013; DMFS: p = 0.0016). All 11 cases with some degree of apocrine differentiation were AR⁺/TIL^low, 15-PGDH-positive, and NAC-resistant. AR⁺/TIL^low status was significantly associated with a high likelihood of non-pCR (OR = 0.26, p = 0.009). Multivariate analysis confirmed pCR as an independent predictor of better prognosis (OS, HR = 0.13, p = 0.006; DMFS, HR = 0.15, p = 0.002), whereas AR⁺/TIL^low status was not significantly associated with OS or DMFS.

Conclusions: AR/TIL classification using pretreatment biopsies identified TNBC subgroups with distinct NAC responses and prognoses. AR⁺/TIL^low TNBC, including apocrine differentiation cases, were NAC-resistant, highlighting the need for alternative therapies.

Background: In Japan, biennial mammography screening has been recommended for the early detection of breast cancer (BC) in women aged 40 years or above since 2004 by the Ministry of Health, Labor and Welfare. The purpose of this study is to estimate the economic impact of BC screening on work productivity, using a new measure called the productivity-adjusted life-year (PALY).

Methods: We used a dynamic life table modeling approach to estimate the work productivity of female patients aged 40-64 years diagnosed with BC in 2019 over the year of diagnosis and the subsequent 5 years. Changes in life-years, PALYs, and gross domestic product (GDP) were assessed by changing the screening detection rate from the current (34.2%) to an ideal (100%) percentage. Each input for modeling was obtained from the most recent public database available.

Results: BC patients were estimated to lose 1903 in life-years, 3596 in PALYs, and US$281 million in GDP at the current screening detection rate compared with the ideal detection rate. On the other hand, the following gains are expected when the current screening detection rate was increased to 40-80%; life-years gain; 168-1325, PALYs gain; 317-2503, GDP gain: US$25-196 million.

Conclusion: This study has used modeling to show that detecting BC without screening is associated with a lower work productivity and an economic and life-years loss. Encouraging BC screening may be beneficial to maintaining work productivity after diagnosis.