Status of incremental costs of first-line treatment recommended in Japanese clinical guidelines for metastatic breast cancer patients.

BACKGROUND: The increasing incidence and prevalence of breast cancer alongside diagnostic and treatment technology advances have produced a debate about the financial burden cancer places on the healthcare system and concerns about access. METHODS: This study was conducted at 51 hospitals belonging to the Breast Cancer Study Group of the Japan Clinical Oncology Group using a web-based survey. The survey period conducted from July 2021 to June 2022. The study population included patients with metastatic breast cancer who received the related treatment as their first-line therapy. The proportion of patients who selected that regimen as their first-line treatment was tabulated. The total cost increase for each current standard therapy in comparison to conventional treatments was calculated. RESULTS: A total of 702 patients (pts) were surveyed. Of those enrolled, 342 (48.7%) received high-cost treatment [estimated monthly drug costs exceeding ~500 000 Japanese Yen (JPY)]. Of these, 16 pts (4.7%) were receiving very high-cost treatment, amounting to more than 1 000 000 JPY per month. Fifty three (15.5%) of the patients who received high-cost treatment were 75 years of age or older. Of these, 1 pt (0.3%) were receiving very high-cost treatment. Analyses of incremental costs by current drugs showed that abemaciclib was costly with total additional cost of 6 365 670 JPY per patient. The total additional cost of the regimen per patient that included palbociclib was the second highest at 4011248 JPY, followed by atezolizumab at 3209033 JPY. CONCLUSIONS: The findings indicate that evaluating the financial implications of high-cost treatments requires considering not only drug prices but also analysis of total cost increase.

Efficacy and impact of SARS-CoV-2 vaccination on cancer treatment for breast cancer patients: a multi-center prospective observational study.

PURPOSE: Vaccination is an essential strategy to prevent infection in the SARS-CoV-2 pandemic. However, there are concerns about vaccine efficacy and the impact of vaccination on cancer treatment. Additionally, the emergence of novel variants may affect vaccination efficacy. This multi-center, prospective, observational study investigated the efficacy and impact of vaccination against SARS-CoV-2 variants on treatment among breast cancer patients in Japan. METHODS: Patients with breast cancer scheduled to be vaccinated with the SARS-CoV-2 vaccine from May to November 2021 were prospectively enrolled (UMIN000045527). They were stratified into five groups according to their cancer treatment: no treatment, hormone therapy, anti-human epidermal growth factor receptor (HER)2 therapy, chemotherapy, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Serum samples for assessing serological responses were collected before the first vaccination and after the second vaccination. RESULTS: Eighty-five breast cancer patients were included. The overall seroconversion rate after second vaccination was 95.3% and the lowest seroconversion rate was 81.8% in the patients under chemotherapy. The overall positivity rate of neutralizing antibodies against the wild-type, α, Δ, κ, and omicron variants were 90.2%, 81.7%, 96.3%, 84.1%, and 8.5%, respectively. Among the patients under chemotherapy or CDK4/6 inhibitors, various degrees of decreased neutralizing antibody titers against SARS-CoV-2 variants were observed. Withdrawal or reduction of systemic therapy because of vaccination was observed in only one patient. CONCLUSION: Our data support SARS-CoV-2 vaccination for breast cancer patients. However, a reduction in neutralizing antibody titers was suggested during chemotherapy and CDK4/6 inhibitors, raising concerns about the impact on long-term infection prevention.

Low RAI2 expression is a marker of poor prognosis in breast cancer.

PURPOSE: Retinoic acid-induced 2 (RAI2) has been shown to be a putative suppressor of the early hematogenous dissemination of tumor cells to the bone marrow in breast cancer. Here, we investigated the associations of RAI2 mRNA and protein expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: Invasive breast cancer tissues (n = 604) were analyzed for RAI2 mRNA expression. We examined the associations of clinicopathological factors with the expression levels of RAI2 mRNA in these samples. We also analyzed RAI2 protein expression by immunohistochemistry in invasive breast cancer tissues (n = 422). RESULTS: We identified significant positive associations between low expression of RAI2 mRNA and shorter disease-free survival (DFS), breast-cancer-specific survival (BCSS), and overall survival (OS) in breast cancer patients. We also identified significant positive associations between negative for RAI2 protein expression and shorter DFS, BCSS, and OS in breast cancer patients. Low RAI2 mRNA and negative for RAI2 protein expression were positively associated with larger tumor size, higher tumor grade, and ERα-negativity. Multivariate analyses indicated that not only RAI2 mRNA but also RAI2 protein expression were independent risk factors for both DFS and BCSS in breast cancer patients. The median follow-up periods were 10.3 and 9.3 years for the RAI2 mRNA and protein expression analyses, respectively. CONCLUSIONS: Our findings suggest that RAI2 has a role in the metastasis of breast cancer, and that RAI2 expression could be a promising candidate biomarker of prognosis in breast cancer patients.

Compression therapy using surgical gloves does not prevent paclitaxel-induced peripheral neuropathy: results from a double-blind phase 2 trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design. METHODS: The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome. RESULTS: Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0). CONCLUSION: Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN. TRIAL REGISTRATIONS: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan ( UMIN000027944 ). Registered 26 June 2017.

Differences in baseline risk estimated by physicians and patients with early breast cancer.

BACKGROUND: Physicians recommend adjuvant therapy to patients based on baseline risk. A common recognition for baseline risk between patients and physicians is critical for successful adjuvant therapy. We prospectively investigated the differences in estimated baseline risk between physicians and patients with early breast cancer. METHODS: This analysis was performed at a single institution in Japan. Early breast cancer patients over 18 years old were enrolled after surgery. After explaining the pathological results, physicians asked each patient about an estimated baseline risk. Differences in estimated baseline risk were defined as the baseline risk estimated by patients minus the baseline risk estimated by physicians. The primary endpoint was that the number of patients who estimate baseline risk higher than physicians was higher than those who estimate a lower baseline risk. The secondary endpoints were differences in estimated baseline risk by stage, subtype and the influence of patient factors to differences in estimated baseline risk. RESULTS: From July 2017 to December 2018, 262 patients were enrolled. Among the 262 patients, 190 estimated a higher baseline risk than physicians, 53 estimated a lower baseline risk and 19 estimated the same. Overall, patients estimated a significantly higher baseline risk than physicians (P < 0.001). Differences in estimated baseline risk was significantly smaller in patients who knew the term 'baseline risk' than patients who did not (P = 0.0037). Differences in estimated baseline risk were also significantly smaller in patients with stage II breast cancer than patients with stage I (P = 0.0239). However, there were no statistically significant differences of differences in estimated baseline risk according to other factors. CONCLUSIONS: Patients with early breast cancer estimated a significantly higher baseline risk than physicians. Physicians should accurately explain baseline risk to patients for shared decision making.

Patient-reported outcomes and objective assessments with arm measurement and bioimpedance analysis for lymphedema among breast cancer survivors.

PURPOSE: Lymphedema (LE) decreases the quality of life of breast cancer patients. Objective quantification of PRO may improve the discordance between patient-reported outcomes (PROs) and objective assessments of LE by establishing a standard follow-up for LE. This study determined the prevalence of subjective and objective LE and evaluated the correlation between objective assessment and PRO of LE in primary breast cancer patients undergoing breast and axilla surgery. METHODS: Breast cancer patients who underwent sentinel lymph node biopsy (SN) or axillary lymph node dissection (ALND) more than 1 year after surgery were enrolled. We prospectively evaluated LE using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and two objective assessments (arm circumference and bioimpedance) and analyzed their correlations. RESULTS: Between November 2018 and January 2019, 631 patients (SN; n = 415, ALND; n = 216) were enrolled. The median age, body mass index, and duration from surgery was 56 years, 21.9 kg/m2, and 3.8 years, respectively. The prevalences of subjective and objective LE were 4.1% and 1.4% in the SN group and 51.8% and 24.1% in the ALND group, respectively. The objective assessments were weakly positively correlated with PRO-CTCAE. Arm circumference measurement correlated better than bioimpedance overall and was most strongly correlated with "frequency" (r = 0.485, p < 0.01). CONCLUSIONS: LE occurred in few SN patients. The prevalence of subjective LE was higher than that of objective LE. Arm circumference measurements better reflected PRO than did bioimpedance. These results underscore the limitation of LE detection by subjective or objective methods alone.

Impact of BMI for clinical outcomes in Japanese breast cancer patients.

OBJECTIVE: The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. METHODS: Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, >30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. RESULTS: From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1-149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38-4.28; P < 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15-6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11-3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15-11.04; P < 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52-13.34; P < 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02-4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. CONCLUSION: Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

Sentinel lymph node biopsy may be unnecessary for ductal carcinoma in situ of the breast that is small and diagnosed by preoperative biopsy.

BACKGROUND: Current guidelines do not recommend that sentinel lymph node biopsy is routinely performed for ductal carcinoma in situ; thus, indications for sentinel lymph node biopsy in patients with ductal carcinoma in situ remain controversial. In this study, we investigated whether sentinel lymph node biopsy can be safely omitted when ductal carcinoma in situ has been diagnosed by preoperative biopsy. METHODS: We retrospectively analysed sentinel lymph node metastasis rates and upstaging to invasive cancer in surgical specimens, performed receiver operating characteristic analysis for ductal carcinoma in situ lesion size and assessed correlations with preoperative clinicopathological factors of 277 patients with ductal carcinoma in situ diagnosed by preoperative biopsy at our institution. RESULTS: Among 277 patients with sentinel lymph node biopsy, six (2.2%) had sentinel lymph node metastasis. All six were upstaged to invasive cancer by pathological examination of surgical specimens. In total, 69 patients (24.9%) were upstaged to invasive cancer. The mean size of ductal carcinoma in situ lesions on preoperative imaging was significantly larger for the 69 upstaged patients (50.0 mm) than for the non-upstaged patients (34.4 mm; P < 0.0001). Of the 277 patients with sentinel lymph node biopsy, 117 (42.2%) had preoperative ductal carcinoma in situ lesions <31.8 mm, which was identified as the optimal cut-off size by receiver operating characteristic analysis. Of these 117 patients, 96 (82.1%, 95% confidence interval: 73.9-88.5%) could be safely omitted from sentinel lymph node biopsy because all of them remained as ductal carcinoma in situ and had negative sentinel lymph nodes at surgery. CONCLUSIONS: Size of ductal carcinoma in situ lesions on preoperative diagnostic imaging is a predictor of diagnosis of invasive cancer on pathological examination of surgical specimens. Sentinel lymph node biopsy may be unnecessary in ductal carcinoma in situ diagnosed by preoperative biopsy in patients with small lesions.

Occult breast cancer may originate from ectopic breast tissue present in axillary lymph nodes.

PURPOSE: Occult breast cancer (OBC) is classified as a carcinoma of unknown primary, and involves axillary lymphadenopathy and is histologically consistent with metastatic breast cancer. OBC has been conventionally considered as a metastatic lymph node lesion, the origin of which is an undetectable breast tumor. Therefore, OBC patients would usually have undergone axillary lymph node dissection, and mastectomy or whole breast radiotherapy (WBRT). However, majority of OBC reports have been based on cases that were diagnosed during a period when diagnostics was still relatively primitive, and when magnetic resonance imaging was not yet a standard preoperative assessment. Therefore, there have been many false negatives in the breast based on preoperative assessment. METHODS: We herein hypothesize that the origin of OBC is ectopic breast tissue present in axillary lymph nodes (ALNs). If our hypothesis is true, mastectomy and WBRT may be unnecessary for OBC patients. RESULTS: Our hypothesis is supported by several findings. First, advances in radiological imaging have suggested that a primary breast tumor is absent in OBC patients. Second, proliferative breast lesions arising from ectopic breast present in ALNs have been reported. Lastly, cellular subtypes in OBC based on immunohistochemistry are of various types including ordinary breast cancer and the prognosis is not worse than stage II breast cancer. CONCLUSION: It is important to distinguish between "primary" OBC in ALNs and "metastatic" OBC from micro-primary breast tumor. Further studies are required to determine if omission of mastectomy and WBRT is acceptable.

[Three Poor Performance Status(PS)Cases of Metastatic Breast Cancer Controlled with Adjustment of Dosing Interval and Dosage of Bevacizumab and Paclitaxel].

A standard symptomatic therapy regimen of bevacizumab(BV)plus paclitaxel(PTX)was planned for use in 3 cases of metastatic breast cancer. Due to poor patient performance status(PS)because of malignant pleural effusion and ascites, the initial standard regimen was determined to be unsuitable. However, adjustment and fine-tuning of the BV plus PTX interval and dosage were found to be effective in improving symptoms, and consequently obtained good efficacy. Adverse effects were managed with drug withdrawal and symptomatic therapy. The 3 clinical cases all included females aged 62-76 years old, with a median age of 67.6. One case was classified as PS 3, and 2 were classified as PS 4. The main deciding factors for initiating the regimen of BV plus PTX were 2 cases of malignant pleural effusion and 1 case of malignant ascites, which contributed to worsening of the overall PS. With adjustment and fine-tuning of the BV plus PTX interval and dosage, we were able to safely achieve symptomatic improvement in 3 metastatic breast cancer cases, in which the overall PS grade was unsuitable for standard chemotherapy.

A novel system to provide information via online YouTube videos and an evaluation of current online information about hereditary breast cancer.

BACKGROUND: The internet, especially YouTube, has become a prominent source of health information. However, the quality and accuracy of medical content on YouTube vary, posing concerns about misinformation. This study focuses on providing reliable information about hereditary breast cancer on YouTube, given its importance for decision-making among patients and families. The study examines the quality and accessibility of such content in Japanese, where limited research has been conducted. METHODS: A nonprofit organization called BC Tube was established in May 2020 to create informative videos about breast cancer. The study analyzed 85 YouTube videos selected using the Japanese keywords "hereditary breast cancer" and "HBOC", categorized into six groups based on the source of upload: BC Tube, hospitals/governments, individual physicians, public-interest organizations/companies, breast cancer survivors, and others. The videos were evaluated based on various factors, including content length, view counts, likes, comments, and the presence of advertisements. The content was evaluated using the PEMAT and DISCERN quality criteria. RESULTS: BC Tube created high-quality videos with high scores on PEMAT understandability, significantly outperforming other sources. Videos from public-interest organizations/companies received the most views and likes, despite their lower quality. Videos from medical institutions and governments were of superior quality but attracted less attention. CONCLUSIONS: Our study emphasizes the importance of promoting accessible, easy-to-understand, and widely recognized medical information online. The popularity of videos does not always correspond to their quality, emphasizing the importance of quality evaluation. BC Tube provides a peer-reviewed platform to disseminate high-quality health information. We need to develop high-quality online health information and encourage the promotion of evidence-based information on YouTube.

Characterizing user demographics in posts related to breast, lung and colon cancer on Japanese twitter (X).

Various cancer-related information is spreading on social media. Our study aimed to examine the account types associated with cancer-related tweets (currently known as posts) on Twitter (currently known as X) in Japan, specifically focusing on breast, lung, and colon cancer. Using the Twitter application programming interface, we collected tweets containing keywords of the three cancers type in August-September 2022. The accounts were categorized into seven types: Survivor, Patient's family, Healthcare provider, Public organization, Private organization, News, and Other according to account name and texts. We analyzed the sources of the top 50 most liked and retweeted tweets. Out of 7753 identified tweets, breast cancer represented the majority (62.8%), followed by lung cancer (20.8%) and colon cancer (16.3%). Tweets came from 4976 accounts. Account types varied depending on the cancer type, with breast cancer topics more frequently from Survivor (16.0%) and lung cancer from Patient's family (16.3%). Healthcare provider and Public organization had minimal representation across three cancer types. The trends in the top 50 tweets mirrored the distribution of accounts for each cancer type. Breast cancer-related tweets had the highest frequency. There were few from public organizations. These findings emphasize the need to consider the characteristics of cancer-related information sources when sharing and gathering information on social media.

Fact-Checking Cancer Information on Social Media in Japan: Retrospective Study Using Twitter.

BACKGROUND: The widespread use of social media has made it easier for patients to access cancer information. However, a large amount of misinformation and harmful information that could negatively impact patients' decision-making is also disseminated on social media platforms. OBJECTIVE: We aimed to determine the actual amount of misinformation and harmful information as well as trends in the dissemination of cancer-related information on Twitter, a representative social media platform. Our findings can support decision-making among Japanese patients with cancer. METHODS: Using the Twitter app programming interface, we extracted tweets containing the term "cancer" in Japanese that were posted between August and September of 2022. The eligibility criteria were the cancer-related tweets with the following information: (1) reference to the occurrence or prognosis of cancer, (2) recommendation or nonrecommendation of actions, (3) reference to the course of cancer treatment or adverse events, (4) results of cancer research, and (5) other cancer-related knowledge and information. Finally, we selected the top 100 tweets with the highest number of "likes." For each tweet, 2 independent reviewers evaluated whether the information was factual or misinformation, and whether it was harmful or safe with the reasons for the decisions on the misinformation and harmful tweets. Additionally, we examined the frequency of information dissemination using the number of retweets for the top 100 tweets and investigated trends in the dissemination of information. RESULTS: The extracted tweets totaled 69,875. Of the top 100 cancer-related tweets with the most "likes" that met the eligibility criteria, 44 (44%) contained misinformation, 31 (31%) contained harmful information, and 30 (30%) contained both misinformation and harmful information. Misinformation was described as Unproven (29/94, 40.4%), Disproven (19/94, 20.2%), Inappropriate application (4/94, 4.3%), Strength of evidence mischaracterized (14/94, 14.9%), Misleading (18/94, 18%), and Other misinformation (1/94, 1.1%). Harmful action was described as Harmful action (9/59, 15.2%), Harmful inaction (43/59, 72.9%), Harmful interactions (3/59, 5.1%), Economic harm (3/59, 5.1%), and Other harmful information (1/59, 1.7%). Harmful information was liked more often than safe information (median 95, IQR 43-1919 vs 75.0 IQR 43-10,747; P=.04). The median number of retweets for the leading 100 tweets was 13.5 (IQR 0-2197). Misinformation was retweeted significantly more often than factual information (median 29.0, IQR 0-502 vs 7.5, IQR 0-2197; P=.01); harmful information was also retweeted significantly more often than safe information (median 35.0, IQR 0-502 vs 8.0, IQR 0-2197; P=.002). CONCLUSIONS: It is evident that there is a prevalence of misinformation and harmful information related to cancer on Twitter in Japan and it is crucial to increase health literacy and awareness regarding this issue. Furthermore, we believe that it is important for government agencies and health care professionals to continue providing accurate medical information to support patients and their families in making informed decisions.

Low TINAGL1 expression is a marker for poor prognosis in breast cancer.

PURPOSE: Tubulointerstitial nephritis antigen-like 1 (TINAGL1) was reported to suppress tumor metastasis and growth in triple-negative (TN) breast cancer. We aimed to determine the associations of TINAGL1 expression with clinicopathological factors and prognosis in breast cancer patients with long-term follow-up. METHODS: A total of 599 consecutive primary invasive breast cancer patients with available tissue specimens from surgery in our hospital were included in the study. TINAGL1 mRNA expression was examined in all 599 tissue specimens using a TaqMan real-time PCR system. TINAGL1 protein expression was further examined in 299 patients with available tissue specimens for immunohistochemical staining. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median follow-up period was 12.0 years. In the total patients, low TINAGL1 mRNA expression was associated with significantly shorter disease-free survival (DFS) and overall survival than high expression (P = 0.003 and P = 0.01, respectively). Furthermore, hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer patients with low TINAGL1 mRNA expression had a worse prognosis. Multivariate analysis identified low TINAGL1 mRNA expression, combined with lymph node positivity, as an independent poor prognostic factor for DFS in invasive breast cancer patients (HR 1.41; 95% CI 1.02-1.96; P = 0.036). TINAGL1 mRNA expression also varied with menopausal status, with low TINAGL1 mRNA expression being positively associated with poor prognosis in premenopausal patients, but not in postmenopausal patients. CONCLUSION: Our findings demonstrate that TINAGL1 may be a promising candidate biomarker and therapeutic target in breast cancer patients.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Low HECTD1 mRNA expression is associated with poor prognosis and may be correlated with increased mitochondrial respiratory function in breast cancer.

HECT domain E3 ubiquitin ligase 1 (HECTD1) has been reported to be a negative regulator of epithelial-mesenchymal transition and to decrease breast cancer invasion and metastasis. However, the clinical significance and detailed role of HECTD1 in breast cancer remain elusive. We investigated the role of HECTD1 in two large breast cancer cohorts at our institution and The Cancer Genome Atlas using mRNA expression and bioinformatics analysis. We also examined the prognostic significance of HECTD1 mRNA expression by multivariate analysis and HECTD1 protein expression by immunohistochemistry using our cohort. HECTD1 mRNA expression was significantly lower in breast cancer tissues compared with those in adjacent normal tissues (P<0.001). HECTD1 mRNA expression levels also differed among breast cancer subtypes. Decreased HECTD1 mRNA expression was significantly associated with aggressive tumor characteristics, including large tumor size and high histological grade. HECTD1 mRNA expression was inversely associated with mitochondrial cellular respiratory function (oxidative phosphorylation (P<0.001, FDR q-value <0.001) the respiratory chain complex (P<0.001, FDR q-value <0.001) and reactive oxygen species (P<0.001, FDR q-value <0.001), but not with epithelial-mesenchymal transition, in breast cancer tissues. Low expression of HECTD1 mRNA was associated with shorter disease-free survival (log-rank: P=0.013) and overall survival (log-rank: P=0.038) in breast cancer patients. Multivariate analysis also identified low HECTD1 mRNA expression level as an independent risk factor for disease-free (hazard ratio: 1.54, 95% confidence interval: 1.11-2.13, P=0.009) and overall (hazard ratio: 1.50, 95% confidence interval: 1.01-2.24, P=0.046) survival among breast cancer patients. There was no association of HECTD1 protein expression with HECTD1 mRNA expression and prognosis. In conclusion, we identified low expression of HECTD1 mRNA as an independent poor prognostic factor in breast cancer and showed that HECTD1 mRNA expression was inversely correlated with genes involved in mitochondrial cellular respiratory function in breast cancer.

Surgical treatment trends and identification of primary breast tumors after surgery in occult breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

BACKGROUND: Occult breast cancer (OBC) is classified as carcinoma of an unknown primary site, and the adequate therapy for OBC remains controversial. This retrospective study aimed to reveal the transition in breast cancer therapy and the frequency of primary breast tumors after resection in clinical OBC (cT0N+) patients using the Japanese Breast Cancer Registry database. METHODS: We enrolled OBC patients with cT0N+ from the registry between 2010 and 2018. On the basis of the period of diagnosis, OBC patients were divided into the following two groups: 2010-2014 and 2015-2018. We described the transition in treatments and tumor characteristics. After breast resection, the frequency of pathological identification of primary tumors and tumor sizes was assessed. RESULTS: Of the 687,468 patients registered, we identified 148 cT0N+ patients with a median age of 61 years. Of these patients, 64.2% (n = 95) received breast surgery (2010-2014: 79.1%, 2015-2018: 50.0%). Axillary lymph node dissection was performed in 92.6% (n = 137, 2010-2014: 91.6%, 2015-2018: 93.4%). The breast tumor size in the resected breast was 0-7.0 cm (median: 0 cm, 2010-2014: 0-7.0 cm [median: 0 cm], 2015-2018: 0-6.2 cm [median: 0 cm]). The pathological identification rate of the primary tumor was 41.1% (n = 39, 2010-2014: 40.4%, 2015-2018: 42.1%). CONCLUSIONS: Breast surgery for cT0N+ decreased between 2010 and 2018. Despite the high identification rate of primary tumors, most tumors were small, and there was no significant change in the identification rate or invasive diameter of the identified tumors after 2010.

Granulocyte colony-stimulating factor-associated aortitis in a woman with breast cancer: a case report.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is increasingly used to prevent chemotherapy-associated febrile neutropenia. Generally, aortitis is not considered a side effect of G-CSF and is thought to be extremely rare. Aortitis is an inflammation of the aorta and occurs mainly in connective tissue diseases (Takayasu arteritis, giant cell arteritis, etc.) and infectious diseases (bacterial endocarditis, syphilis, etc.). We report herein a rare case of G-CSF associated with aortitis in a woman with breast cancer. CASE PRESENTATION: Here, we present a case involving a 63-year-old woman with luminal type stage IIa breast cancer. The patient's treatment was initiated with docetaxel and cyclophosphamide, with pegfilgrastim (PEG-G) as support. After PEG-G administration on day 3, the patient developed an intermittent fever of up to 39.4 °C on day 10 and visited our outpatient clinic on day 13 with persistent high fever. Laboratory tests revealed a high neutrophil count (14,000/µL) and a high C-reactive protein (CRP) level (42.8 mg/dL) without any other abnormalities. Contrast-enhanced computed tomography scanning revealed soft tissue thickening with weak enhancement around the wall of the thoraco-abdominal aorta, aortic arch and left subclavian artery. The patient did not respond to antimicrobial agents. On the basis of these observations, the patient was diagnosed with PEG-G-induced aortitis, and her condition rapidly improved without corticosteroids. CONCLUSIONS: Clinicians should be aware of aortitis as a potential complication in patients undergoing G-CSF chemotherapy. In cases with persistent high fever after PEG-G administration, and in the absence of infection, aortitis should be suspected.