Cancer survivors have an elevated risk of developing subsequent primary cancer, with breast cancer being one of the most common sites. Our study aimed to determine the incidence, patterns of, and risk factors for diagnosis of a subsequent primary breast cancer (SPBC) among survivors of adult non-breast cancers. Adult females diagnosed with a non-breast cancer in Alberta, Canada between 2000 and 2021 who survived ≥ 180 days were followed until SPBC diagnosis, death, or censoring on December 31, 2021. The incidence of SPBC was compared to the cancer-free general population using standardized incidence ratios (SIRs) and incidence rate differences (IRDs). Exploratory analyses of the association between sociodemographic/clinical factors and SPBC risk was conducted according to cancer type using Fine-Gray models adjusting for competing risk of death. The study included 59,687 female cancer survivors, with 1113 incident SPBC cases. Overall, there was an increased risk of SPBC among survivors compared to the cancer-free general population (SIR = 1.15 [95% CI: 1.09-1.22], 10-year cumulative incidence = 2.0%). Significantly elevated SPBC risk was found among survivors of kidney, endometrial, and colorectal cancers, as well as obesity-related cancers combined. The increased risk of SPBC was primarily driven by early-stage and hormone receptor positive diagnoses. Depending on the primary cancer site, risk factors for SPBC included overweight/obese body mass index, diabetes, and cancer treatment. History of cancer should prompt discussion of breast cancer awareness, screening, and risk reduction. Future research is needed to inform personalized risk assessment for survivors of adult non-breast cancers.
This annual report of the National Clinical Database-Breast Cancer Registry (NCD-BCR) by the Japanese Breast Cancer Society presents nationwide breast cancer statistics for patients registered in Japan in 2023. Among 107,372 patients with breast cancer at 1317 institutions, 99.3% were females with a median age of 62 years. The distribution of the clinical stages was as follows: stage 0 (15.5%); stage I (42.1%); stage II (31.1%); stage III (7.0%); and stage IV (2.1%). Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity was observed in 78.9%, 70.0%, and 13.3% of patients, respectively. Among 102,717 patients without distant metastases, 41.2% underwent breast-conserving surgery, 76.5% underwent sentinel lymph node biopsy, and 6.0% underwent breast reconstruction. The distribution of radiotherapy was as follows: 75.2% received whole-breast irradiation, 15.7% chest-wall irradiation, and 20.7% regional irradiation. Among the 13,061 patients with pT1abN0M0 breast cancer, comprising 10,819 hormone receptor [HR]-positive/HER2-negative, 1479 HER2-positive and 763 HR-negative/HER2-negative individuals, 92.4% of HR-positive/HER2-negative patients received endocrine therapy, 46.9% of HER2-positive patients received chemotherapy and/or anti-HER2 therapy, and 31.2% of HR-negative/HER2-negative patients received chemotherapy. This annual report provides a nationwide overview of contemporary systemic therapy patterns in small breast cancer and highlights size‑dependent and subtype‑specific use of systemic therapy in Japan, reflecting a risk‑adapted treatment strategy.
Romosozumab was associated with increases in bone mineral density in postmenopausal women with hormone receptor-positive breast cancer and cancer treatment-induced bone loss (CTIBL). No clinical signals of fracture occurrence or cancer recurrence were observed; however, these findings are based on a small retrospective case series and require confirmation in larger prospective studies. Cancer treatment-induced bone loss (CTIBL) is a major complication in postmenopausal women with hormone receptor-positive breast cancer receiving aromatase inhibitor therapy. Although antiresorptive agents are commonly used, some patients continue to experience progressive bone loss or fragility fractures. Romosozumab, a monoclonal antibody against sclerostin, has demonstrated efficacy in postmenopausal osteoporosis; however, clinical data in patients with cancer remain limited. We retrospectively analyzed 22 postmenopausal women with clinically non-metastatic (Stage I-III) hormone receptor-positive breast cancer who received romosozumab for CTIBL at a single institution. Romosozumab was administered for 12 months in patients with progressive bone loss, new fragility fractures, or high fracture risk. All patients received concomitant calcium and/or active vitamin D supplementation. Changes in bone mineral density (BMD), bone turnover markers, and tumor markers (CA15-3, CEA) were evaluated. Differences in skeletal response were also evaluated between treatment-naïve patients and those with prior exposure to bone-modifying agents. Clinical outcomes, including new fragility fractures and cancer recurrence, were assessed during follow-up. The mean age of the patients was 66.8 years, and the mean duration of aromatase inhibitor therapy prior to treatment was 35.3 months to 36.9 months. After 12 months of romosozumab treatment, lumbar spine BMD increased by 11.5% (P < 0.001), and total hip BMD increased by 4.1% (P = 0.002). Changes in bone turnover markers were observed, consistent with the known mechanism of action of romosozumab. No new fragility fractures were observed during the treatment period. During a mean follow-up period of 38.3 months (including the 12-month treatment period), tumor markers remained stable, and no clinical evidence of cancer recurrence was observed. In this small retrospective case series, romosozumab was associated with increases in BMD in postmenopausal women with hormone receptor-positive breast cancer and CTIBL. No clinical signals suggestive of short-term oncological deterioration were observed; however, given the limited sample size, retrospective design, and lack of a control group, these findings should be interpreted with caution. Further prospective studies with larger cohorts and longer follow-up are required to better define the efficacy and safety of romosozumab in this population.
TP53 mutation is a critical driver of breast cancer, yet its relationship with treatment outcomes for breast cancer remains unclear. This study investigates the association between TP53 mutation and response to CDK4/6 inhibitors (CDK4/6i) and immune checkpoint inhibitors (ICI) in breast cancer using real-world data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) cohort, focusing on age-related differences. METABRIC (n = 1355) was used for initial survival analysis, and gene set enrichment analysis (GSEA) was performed to identify pathways enriched in TP53-mutated ER-positive/HER2-negative breast cancers. Clinical and genomic data of metastatic breast cancer (mBC) patients in Japan were analyzed in the C-CAT (n = 1668) cohort. Treatment duration was used as a real-world surrogate endpoint reflecting treatment exposure and potential clinical benefit. Patients were stratified by age into four groups: Adolescents and Young Adults (AYA; 15-39 years), perimenopausal (40-54 years), menopausal (55-64 years), and older (≥ 65 years). TP53 mutations were associated with poor prognosis in the METABRIC cohort. GSEA showed TP53-mutated tumors were enriched with gene sets related to cell proliferation and immune response, while TP53 wild-type tumors enriched for estrogen response pathways. In the C-CAT cohort, TP53 mutations were linked to shorter CDK4/6i treatment duration with similar trends observed for both abemaciclib and palbociclib. However, TP53 mutations were not associated with ICI treatment duration. Patients in the AYA group had the shortest treatment duration, with TP53 mutation prevalence decreasing with age. In age-stratified analyses, TP53 mutation was associated with shorter treatment duration in perimenopausal, menopausal, and older groups but not in the AYA group. However, formal interaction testing did not detect a significant interaction between TP53 mutation and age group. TP53 mutation is associated with shorter CDK4/6i treatment duration, highlighting the importance of considering both genomic and age-related clinical context when interpreting treatment duration in ER-positive/HER2-negative breast cancer.
Cell-free DNA (cfDNA) offers a minimally invasive approach to capture genomic and epigenetic dynamics during cancer progression. We performed targeted sequencing of 26 gene loci transcriptionally regulated during the acquisition of therapy resistance in breast cancer and analyzed blood-derived cfDNA from 150 breast cancer samples (105 primary and 45 recurrent). Recurrent samples exhibited increased genomic variant counts in both coding and noncoding regions, accompanied by shorter cfDNA fragment lengths. Furthermore, cfDNA fragmentation profiles were variable in recurrent samples, with frequently amplified loci such as ERBB2 and concurrent reductions at loci, including RERE and SYNPO2. Notably, nucleosome occupancy-derived scores from RERE and SYNPO2 distinguished recurrent from primary cancer with high accuracy (area under the curve = 0.826). Using a machine-learning approach, integration of these cfDNA features accurately predicted breast cancer relapse. Collectively, these findings demonstrate that cfDNA-based profiling focused on transcriptional alterations provides a sensitive strategy for detecting breast cancer recurrence. cfDNA-based (epi)genomic profiling captures transcriptionally regulated chromatin and nucleosome remodeling during the acquisition of therapy resistance and relapse, enabling minimally invasive, mechanistically informed detection of breast cancer recurrence. Targeting transcriptionally relevant genomic loci provide clinically actionable biomarkers to monitor therapy resistance and guide precision treatment decisions in real time.
Adjuvant olaparib significantly improves invasive disease-free and overall survival in high-risk human epidermal growth factor receptor 2 (HER2)-negative, early breast cancer patients carrying germline breast cancer susceptibility gene 1/2 (gBRCA) pathogenic variants (PVs). Timely gBRCA testing as a companion diagnostic for adjuvant olaparib is essential. However, its real-world uptake remains unclear. We enrolled patients with invasive HER2-negative early breast cancer who underwent curative surgery during 2023 in Japan. Eligibility was based on the OlympiA trial criteria. Estrogen receptor (ER)-positive patients required ≥ 4 positive nodes after surgery or non-pathological complete response (non-pCR) with clinical and pathologic stage (CPS) and estrogen receptor status and histologic grade (EG) score ≥ 3 following neoadjuvant chemotherapy (NAC). ER-negative patients required invasive tumor > 2 cm or ≥ 1 nodal metastasis after surgery, or non-pCR after NAC. The primary outcome was gBRCA testing rate; secondary outcomes included a proportion of patients with gBRCA PVs and a proportion of patients starting adjuvant olaparib. We also explored factors associated with not undergoing testing. Of 824 patients enrolled from 46 facilities, 691 were analyzed after random sampling and exclusions. The testing rate was 63.2% (95% confidence interval 59.5-66.9). Among 254 untested patients, 168 (66%) were not informed-mainly due to physician oversight in recognizing eligibility (57%) or physician-perceived patient ineligibility (40%). Of 69 informed but untested patients, reasons included psychological distress (46%), testing cost (35%), and familial concerns (12%). Of 42 patients (9.6%) with gBRCA PVs, 32 received olaparib. Multivariable analysis (female only) showed that age ≥ 65 years, postmenopausal status, major comorbidities, upfront surgery, absence of family history of hereditary breast and ovarian cancer-related cancers, and absence of bilateral or multiple primary breast cancers were associated with lower testing rates. Greater physician awareness of companion diagnostic is needed to ensure timely gBRCA testing and equitable access to adjuvant olaparib.
Contemporary breast cancer treatment emphasizes both oncological outcomes and preservation of health-related quality of life. However, few studies have examined how different surgical procedures affect patients' postoperative daily life. This study aimed to clarify the impact of various surgical approaches on the postoperative daily lives of Japanese patients with breast cancer. This multicenter cross-sectional survey (administered once between 2022 and 2024) was conducted among 561 Japanese women who had undergone mastectomy (MT), breast-conserving surgery (BCS), or immediate breast reconstruction (IBR) for breast cancer between August 2013 and July 2021. Participants completed a study-specific questionnaire assessing the perceived impact of surgery on daily-life domains, including clothing selection, employment, housework, hobbies, partner relationships, and sexual activity. We also performed an exploratory analysis of write-in responses provided by participants who selected 'Other' to identify additional factors. Clinical and treatment variables were retrospectively abstracted from medical records. Multivariable analyses were conducted to identify factors associated with postoperative impact on daily life. The MT group reported more impairment in clothing selection (45.5%) and a significantly higher proportion reporting onsen-use difficulty in the 'Other' write-in field (7.9%; exploratory endpoint) than BCS (13.1% and 0.6%, respectively) and IBR (16.0% and 2.1%, respectively) groups. Other domains showed no significant differences. MT remained a significant independent predictor in multivariable analyses. The impact of breast cancer surgery on postoperative daily life varied by procedure type. MT most affected clothing selection and onsen use. Providing information on procedural differences in potential impacts may support shared decision-making.
Genome-wide association studies (GWAS) have identified over 200 genetic risk loci for breast cancer, yet their target genes remain largely unknown. We conduct multi-ancestry transcriptome-wide association studies (TWAS) to discover potential breast cancer susceptibility genes. We develop ancestry-specific genetic models to predict levels of gene expression, alternative splicing, and 3' UTR alternative polyadenylation using genomic and transcriptomic data from 652 normal female tissue samples and apply these models to GWAS data of 178,534 cases and 248,300 controls for association analyses. We identify 290 genes associated with breast cancer risk, including 103 previously unreported and 46 not located at known GWAS loci, and 39 genes show distinct associations with breast cancer risk by estrogen-receptor status. Single-cell RNA sequencing and in vitro experiment data provide additional functional evidence for 169 genes. These genes are enriched in pathways implicated in breast carcinogenesis. Our study uncovers insights into breast cancer genetics and biology.
The impact of progesterone receptor (PR) status on the prognosis of breast cancer after isolated locoregional recurrence (ILRR) remains unclear. This study assessed the prognostic impact of the PR status of ILRR tumors in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The study utilized data from the Japanese National Clinical Database (2004-2015), including 1,625 patients with ER+/HER2- ILRR. All participants were patients aged between 20 and 75 years at diagnosis who underwent curative surgery for ER+/HER2- primary breast cancer. Patients were classified into three groups based on the PR status of primary (p) and recurrent (r) tumors. We compared the overall survival (OS) and breast cancer-specific survival (BCSS) among the three groups using the Kaplan-Meier method with the log-rank test. ER and PR were considered positive if immunohistochemistry staining was positive in > 1% of tumor cells. For the ER expression levels in ILRR tumors, 1-10% were considered as ER-low positive. Patients with PR- ILRR (pPR-/rPR- and pPR+/rPR-) had significantly worse OS and BCSS than those with PR+ ILRR (pPR+/rPR+). Factors associated with worse outcomes included lymph node metastasis, a shorter disease-free interval, ER-low positivity, and no surgery for ILRR tumor. This study highlights PR-negativity in ER+/HER2- ILRR tumors as a poor prognostic factor after ILRR, independent of the PR status of the primary breast cancer, emphasizing the need for tailored treatment strategies.
It is ideal to remove areas where breast cancer existed before neoadjuvant chemotherapy (NAC) in breast-conserving surgery (BCS) after NAC to ensure a pathological response. However, this becomes challenging, particularly when NAC is effective. It is also important to determine the appropriate resection line to maintain breast cosmesis in the absence of residual cancer cells. We aimed to identify magnetic resonance imaging (MRI) findings that enable the removal of the original cancer extent without additional margins outside the cancer boundary in BCS after NAC using an MRI projection mapping system (PMS). We enrolled 36 women with breast cancer in the study. Contrast-enhanced MRI was performed in the prone and supine positions before NAC. Supine unenhanced MRI with skin markers for registration was performed after NAC, one day before surgery. A maximum intensity projection image visualizing both the tumor extent before NAC and skin markers was projected onto the breast using PMS, and BCS was performed. We compared the clinical, pathological, and MRI findings between patients who required additional margins and those who did not undergo BCS using MRI-PMS. Nineteen of the 36 patients did not require additional margins for BCS after NAC using MRI-PMS. These patients had a higher tumor diameter reduction rate and a lower signal ratio between the tumor bed and normal tissue after NAC than those who required additional margins. This study indicates that MRI-PMS allows BCS without additional margins and may facilitate the conservation of normal breast tissue in patients with a greater diameter reduction rate or a lower signal ratio between the tumor bed and normal tissue after NAC.
Apocrine morphology is a distinctive histopathological feature of breast cancer associated with unique clinical behavior, particularly in estrogen receptor (ER)-negative tumors. However, its molecular basis remains unclear and its relevance in ER-positive breast cancer has not been systematically examined. We performed an integrative analysis of breast cancer patients from the SEER database (n = 226,584) and The Cancer Genome Atlas (TCGA; n = 1017), incorporating clinicopathological, transcriptomic, and genomic data. Apocrine carcinoma was associated with favorable prognosis in ER-negative but worse survival in ER-positive breast cancer. Molecular and AR-related classifications did not fully recapitulate apocrine morphology. In ER-negative tumors, apocrine morphology correlated with lower proliferation and reduced predicted chemotherapy sensitivity. Conversely, in ER-positive tumors, apocrine morphology was associated with increased proliferation, enhanced immune-related signaling, and greater genomic instability. In conclusion, apocrine morphology represents an ER-dependent biological state with distinct prognostic and molecular implications.
Bevacizumab is an anti-angiogenic agent that inhibits tumor vascularization and thereby suppresses tumor growth. Tumor-infiltrating lymphocytes (TILs), particularly CD8-positive TILs, play a critical role in the antitumor immune response. However, little is known about the effect of bevacizumab-containing chemotherapy on CD8-positive TIL dynamics. This study aimed to evaluate changes in CD8-positive TILs before and after treatment in patients with advanced breast cancer receiving bevacizumab in combination with chemotherapy. Thirty patients with initially inoperable advanced breast cancer who responded to first-line bevacizumab-containing chemotherapy and subsequently became eligible for surgery were included. CD8-positive TILs were assessed by immunohistochemistry in biopsy samples obtained before treatment and in surgical specimens collected after treatment. Stromal CD8-positive TILs were classified as low, intermediate, or high, based on their proportion among total stromal TILs. Of the 30 patients, 20 had luminal-like breast cancer and 10 had triple-negative breast cancer. Before treatment, CD8-positive TIL expression was low in 16 patients (64.0%), intermediate in 6 (24.0%), and high in 3 (12.0%). After treatment, 10 patients (33.3%) showed low expression, 11 (36.7%) had intermediate expression, and 9 (30.0%) had high expression, indicating an increase in CD8-positive TIL levels. The high pathological response (a pathological response grade of 2 or higher) rate was 36.7%, and patients with increased CD8-positive TILs tended to show higher pathological response and better overall survival, although these differences did not reach statistical significance. In contrast, the ypT stage was significantly lower in cases with high post-treatment CD8-positive TIL expression, suggesting that immune activation after bevacizumab may contribute to local tumor regression. Bevacizumab-containing chemotherapy appears to enhance CD8-positive TIL infiltration in primary breast tumors, which may contribute to improved local tumor regression and better therapeutic outcomes.
It is important that axillary surgery is optimized for de-escalation in the era of sentinel lymph node biopsy for early breast cancer. Several randomized trials of clinically node-negative breast cancer have demonstrated the non-inferiority of regional lymph node recurrence and distant metastasis in women aged ≥ 50 years with small tumors of the luminal subtype who did not undergo axillary surgery compared with those who underwent sentinel lymph node biopsy. Tailored axillary surgery has been attempted to personalize axillary management in patients with clinically node-positive breast cancer treated with neoadjuvant chemotherapy. Image-guided localization, such as clipping, has been shown to accurately diagnose lymph node involvement and reduce the rate of false negatives for sentinel lymph node biopsy. This technique also reduces regional lymph node recurrence, although regional nodal irradiation and adjuvant therapy are usually required for this purpose. In this review, we aimed to facilitate the optimization of axillary surgery for patients with clinically node-negative and node-positive breast cancer by discussing the findings of randomized trials and our own experiences at the Japanese Society for Sentinel Node Navigation Surgery.
The heat shock protein beta-1 (HSPB1/HSP27) is highly expressed and phosphorylated in cancer tissues. However, the precise role of HSPB1 in cancer remains unclear. In this study, we report the unexpected findings elucidating the essential role of HSPB1 in adapting amino acid deficiency by upregulating amino acid transporter SLC7A5 function. HSPB1 regulates estrogen receptor-positive (ER+) breast cancer cell proliferation in a SLC7A5-dependent manner. In response to cellular stress, which is specified as amino acid-deficient conditions, HSPB1 was phosphorylated at Ser 78 residue by stress MAPK p38. SLC7A5 is associated with phosphorylated HSPB1 for its functional activation, leading to upregulated amino acid incorporation. In addition, HSPB1 and SLC7A5 overexpression increased acetylated α-tubulin levels. SLC7A5 overexpression did not change acetyl-CoA level, but SLC7A5 knockdown decreased ATAT1 and induced HDAC6 upregulation. Furthermore, HSPB1 and SLC7A5 induced paclitaxel and tamoxifen resistance. Therefore, the HSPB1-SLC7A5 axis contributes to the acquisition of tolerance to both tamoxifen and paclitaxel in breast cancer cells, uncovering a novel therapeutic target against drug resistance in breast cancer.
Postmastectomy pain syndrome (PMPS) is a prevalent chronic pain condition that occurs after breast cancer surgery, often impairing quality of life in survivors of breast cancer. Despite its prevalence, no standardized treatment has been established. Acupuncture has been reported to be an efficacious intervention for the management of chronic pain and may be an effective treatment for PMPS. This study aims to explore the effectiveness and safety of integrative treatment of acupuncture-based intervention for PMPS. This is a single-center, single-arm, prospective interventional study. Eligible participants are patients with breast cancer who experience chronic postoperative pain in the chest, neck, or shoulder with a numerical rating scale (NRS) score ≥4, are at least 6 months postcurative treatment, have no evidence of disease recurrence, and are not receiving anticancer treatment at enrollment. Participants will receive the intervention once weekly for 12 sessions, followed by a 4-week observation period. The primary end point is the change in the average pain NRS score from baseline to week 16. The study commenced in October 2023 and is scheduled to continue through March 31, 2027. The first participant was enrolled on October 24, 2023. As of the manuscript submission, 24 patients have been enrolled. This study will explore the potential role of an integrative treatment of acupuncture-based intervention in the management of PMPS. The results will contribute to the evidence base for acupuncture in PMPS and inform the design of future clinical studies.
Nipple discharge (ND) is one of its major symptoms of breast cancer. However, the low volume of NDs has limited their diagnostic capability. This study aimed to identify extracellular vesicles (EVs) miRNAs in ND using cellulose nanofiber (CNF) sheets to develop clinical biomarkers. Patients with ND from two independent institutions between 2023 and 2024 were included. ND-EVs were isolated from 23 samples [normal, n = 8; intraductal papilloma, n = 1; ductal carcinoma in situ (DCIS), n = 8; invasive ductal carcinoma, n = 6] using CNF sheets. Additionally, miRNAs were also analyzed from intracystic fluid, tumor tissue, and tissue surface EVs from the same patients, and miRNA sequencing was performed. miRNA sequencing for ND-EVs revealed distinct clustering between cancer and normal groups, identifying miR-342-3p, miR-20b-5p, and miR-550a-5p as candidate biomarkers. ND-EV miRNA profiles reflected tumor tissue characteristics, especially in DCIS. Four additional miRNAs (miR-92b-3p, miR-375-3p, miR-182-5p, miR-96-5p) were commonly upregulated in DCIS tissue, tissue surface, and ND-EVs. These miRNAs were validated by qRT-PCR. ROC curve analyses demonstrated that combining the five miRNAs yielded high diagnostic performance, with AUCs of 0.902 for breast cancer and 0.938 for DCIS. A subset of three miRNAs also showed robust discrimination ability. ND-EV miRNAs collected via CNF sheets show great potential as noninvasive biomarkers for early breast cancer detection.
To map global practice patterns and disparities in the use of preoperative breast magnetic resonance imaging (MRI) for early breast cancer (EBC) among members of the Senologic International Society (SIS) and SIS Working Group. A cross-sectional, web-based survey was distributed to SIS members worldwide. The questionnaire captured respondent demographics, center characteristics, local/national breast MRI use, guideline perceptions and personal practice, specific indications for MRI, and decision-making influences. We analyzed 114 responses from 17 countries. Significant variations were observed. While 36/46 (78.3%) of Japanese respondents perceived national guidelines as recommending preoperative MRI, only 18/60 (30%) of Europeans did. Overall, 96/114 (84.2%) of all respondents believed preoperative MRI provided a patient benefit, with none believing it caused harm. The most frequent indications in the total cohort were invasive lobular carcinoma (106/114, 93.0%), mammographic/sonographic suspicion of multifocality/multicentricity (96/114, 84.2%) and planned neoadjuvant therapy (89/114, 78.1%), while in Japan ductal carcinoma in situ (DCIS) or accompanying DCIS component was the most frequent indication (45/46, 97.8%). Half of respondents stated that national guidelines recommend preoperative breast MRI for EBC (57/114, 50%). Furthermore, 30/57 (52.6%) of these "guideline-positive" respondents reported performing more MRIs than advised while most guidelines recommending only selected preoperative indications such as invasive lobular histopathology, dense breasts, suspicion of multifocality/multicentricity or imaging inconsistencies. Key influencing factors included specialty, reimbursement, and time to access preoperative MRI. This SIS-based international survey revealed heterogeneous global adoption of preoperative breast MRI for EBC, highlighting a significant gap between evidence-based guidelines and real-world practice. Clinical decisions are heavily influenced by geography, culture and resources, and belief in patient benefit. These findings highlight the need to tailor guidelines to local contexts, and strengthen awareness and dissemination efforts, together with further research to clarify the role of MRI in the modern multidisciplinary management of EBC.
This study aimed to investigate patient characteristics and treatment patterns and completion rates over a 2-year follow-up period among Japanese patients with early breast cancer (EBC) who received adjuvant therapy with abemaciclib in real-world clinical practice. This retrospective observational study used a Japanese administrative claims database to examine patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative EBC who received abemaciclib adjuvant therapy from December 2021-November 2024. Results were summarized descriptively. Of the 2042 eligible patients, 439 (median age [min-max] of 55 [26-84] years, with 99.3% being females) had a ≥2-year follow-up (median duration of follow-up: 890 days). Among these, 70.6% completed 2 years of abemaciclib+ endocrine therapy [ET], 21.9% discontinued abemaciclib but continued ET, and 7.5% discontinued both within 2 years. A dose of 300 mg/day was initiated in 92.3% of patients and dose reduction occurred in 58.3% of patients in 2-year follow-up group. Anti-diarrheal agents and probiotics were frequently prescribed initially, with rates declining over time. This study demonstrates that adjuvant abemaciclib+ET is being used at the labeled dosage in most Japanese patients. Furthermore, 2-year completion rates in patients with 2-year follow-up were comparable to the clinical trial data from monarchE (69%). Abemaciclib is a medicine used together with hormone (endocrine) therapy after surgery to reduce the risk of breast cancer coming back in people with hormone receptor–positive, human epidermal growth factor receptor 2-negative early breast cancer. While clinical trials have shown this treatment to be effective, there is limited information on its long-term use in routine clinical practice in Japan.This study used anonymized health insurance claims data from a large Japanese database to describe patient characteristics, treatment patterns, dose modification patterns, and 2-year treatment completion rates, among adults who received abemaciclib combined with endocrine therapy after surgery between December 2021 and November 2024.Among 2,042 eligible patients, 439 patients were followed for at least two years. Most patients were women, and the average age was 55 years. Of those with two years of follow-up, 70.6% completed two years of treatment with abemaciclib together with endocrine therapy, 21.9% stopped abemaciclib, but continued endocrine therapy, and 7.5% stopped both abemaciclib and endocrine therapy within two years. Most patients started abemaciclib at the recommended dose of 300 mg/day, and more than half required a dose reduction during treatment in the 2-year follow-up group. Medicines used to manage side effects, such as treatments for diarrhea, were commonly prescribed early and decreased over time.
Accurate identification and localization of axillary lymph node involvement in breast cancer before therapeutic interventions, such as neo-adjuvant chemotherapy or surgery, are for optimal disease management. This study evaluates the concordance between charcoal-based localization of axillary lymphadenopathy and sentinel lymph node biopsy. In this cohort study, 70 patients with breast cancer and up to three metastatic axillary lymph nodes were enrolled at Omid Hospital's radiology department. Nodes were marked with 0.2-0.3 mL charcoal injection under ultrasound guidance. After completion of neoadjuvant chemotherapy, preoperative lymphoscintigraphy was performed. The frequency of positive lymph nodes identified by charcoal staining was compared with the sentinel lymph node findings during surgery. Post-surgical pathology identified charcoal in 89 nodes across 64 patients, yielding a detection rate of 91.4% (95% CI: 85-98%). Among the 64 patients with charcoal- contained nodes, 56 were SLNs containing charcoal, and 8 were non-SLNs, resulting in a concordance rate of 87.5% (95% CI: 79.4%-96%). A chi-square test confirmed a significant association between charcoal-tattooed nodes and SLNs concordance (χ² = 12.3, p < 0.001). This study demonstrated that ultrasound-guided charcoal tattooing of metastatic axillary lymph nodes before Neoadjuvant chemotherapy is a safe, low-cost, and effective technique for localization of limited nodal involvement in breast cancer patients, with high concordance with sentinel lymph node biopsy.
Bone metastasis is a critical factor in the morbidity and mortality of breast cancer patients, yet the specific contributions of the bone marrow microenvironment to this process remain incompletely understood. We investigated the influence of bone marrow cell populations on intraosseous tumor growth following the injection of E0771 breast cancer cells into the bone. Kinetic analysis revealed a progressive reduction in CD19+CD20+B220+ immature B cells as the tumor burden increased. Depletion of CD20+ immature B cells, but not CD19+CD20-B220+ pro/pre-B cells, significantly increased the intraosseous tumor burden along with upregulation of the proliferation marker Ki-67. To simulate the bone cavity environment, we employed anchorage-independent in vitro co-cultures of tumor cells with B-cell populations. Using this co-culture system, pro/pre-B cells, but not immature B cells, enhanced tumor cell proliferation with upregulation of Ki-67. Mechanistically, pro/pre-B cells enhanced tumor cell proliferation through the production of soluble factors and promoted stem cell-like properties, as indicated by increased expression of the stem cell marker CD44. By analyzing clinical datasets from breast cancer patients, we found that high CD20 expression correlated with longer overall survival, thereby supporting a positive correlation between increased immature B cells and better control of disease progression. Collectively, these results indicate contradictory roles for CD20- pro/pre-B cells and CD20+ immature B cells in controlling the tumor microenvironment in bone.