記述言語：英語   出版者・発行元：Cancer Science  

Approximately 5%–10% of breast cancers are hereditary, caused by germline pathogenic variants (GPVs) in breast cancer predisposition genes. To date, most studies of the prevalence of GPVs and risk of breast cancer for each gene based on cases and noncancer controls have been conducted in Europe and the United States, and little information from Japanese populations is available. Furthermore, no studies considered confounding by established environmental factors and single-nucleotide polymorphisms (SNPs) identified in genome-wide association studies (GWAS) together in GPV evaluation. To evaluate the association between GPVs in nine established breast cancer predisposition genes including BRCA1/2 and breast cancer risk in Japanese women comprehensively, we conducted a case-control study within the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (629 cases and 1153 controls). The associations between GPVs and the risk of breast cancer were assessed by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models adjusted for potential confounders. A total of 25 GPVs were detected among all cases (4.0%: 95% CI: 2.6–5.9), whereas four individuals carried GPVs in all controls (0.4%). The OR for breast cancer by all GPVs and by GPVs in BRCA1/2 was 12.2 (4.4–34.0, p = 1.74E-06) and 16.0 (4.2–60.9, p = 5.03E-0.5), respectively. A potential confounding with GPVs was observed for the GWAS-identified SNPs, whereas not for established environmental risk factors. In conclusion, GPVs increase the risk of breast cancer in Japanese women regardless of environmental factors and GWAS-identified SNPs. Future studies investigating interactions with environment and SNPs are warranted.

DOI： 10.1111/cas.15312

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PubMed

記述言語：日本語   出版者・発行元：特定非営利活動法人　日本乳癌検診学会  

［背景・目的］ブレスト・アウェアネスは乳癌の早期発見につながる効率的かつ効果的な乳房の健康行動であるが，未だ広く国民に知れわたっていない生活習慣であり，積極的な啓発運動が求められている。われわれは YouTube を活用して，動画での乳癌情報提供の仕組みを確立しており，ブレスト・アウェアネスに関する動画を発信している。今回，どのようなブレスト・アウェアネスの情報がより多くの方々に届けられるかを明らかにするために，われわれのブレスト・アウェアネス関連動画を比較検討した。［方法］ブレスト・アウェアネスの啓発のために，複数の乳腺科医による十分な議論，ピアレビュー，非医療者の視聴を経て，科学的妥当性，表現や内容の理解しやすさに配慮して動画を６本作成し，YouTube チャンネル『乳がん大事典【BC Tube 編集部】』に投稿した。２０２０年７月から２０２１年６月までのこれらの動画の視聴回数・維持率を比較検討した。［結果］対象期間の全６動画の視聴回数は計７．７万回であった。そのなかで最も視聴回数が多かったのは「乳癌症状のまとめ短編」で２．９万回再生，視聴維持率も他の動画よりも高く，４７．２％であった。「ブレスト・アウェアネス」を解説した動画の視聴回数は０．５万回，視聴維持率３７．２％であった。［結語］「ブレスト・アウェアネス」を解説した動画よりも，症状について，さらに簡潔にまとめた動画のほうがより視聴されていた。ブレスト・アウェアネスが「自分の乳房の意識化するプロセス」を指すとおり，視聴者が「自分事と捉える」「自分の乳房を意識できる」よう，簡潔かつアクセスしやすいプラットフォームを確立し，行動変容につなげることが肝要である。さらに，社会の風潮に合わせて発信する内容や方法を改良し続ける必要がある。

DOI： 10.3804/jjabcs.31.31

CiNii Research

記述言語：日本語   出版者・発行元：Japanese Journal of Clinical Oncology  

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.

DOI： 10.1093/jjco/hyab152

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記述言語：英語  

DOI： 10.1097/SLA.0000000000005185

PubMed

記述言語：英語   出版者・発行元：International Journal of Cancer  

Although alcohol consumption is reported to increase the incidence of breast cancer in European studies, evidence for an association between alcohol and breast cancer in Asian populations is insufficient. We conducted a pooled analysis of eight large-scale population-based prospective cohort studies in Japan to evaluate the association between alcohol (both frequency and amount) and breast cancer risk with categorization by menopausal status at baseline and at diagnosis. Estimated hazard ratios (HR) and 95% confidence intervals were calculated in the individual cohorts and combined using random-effects models. Among 158 164 subjects with 2 369 252 person-years of follow-up, 2208 breast cancer cases were newly diagnosed. Alcohol consumption had a significant association with a higher risk of breast cancer in both women who were premenopausal at baseline (regular drinker compared to nondrinker: HR 1.37, 1.04-1.81, ≥23 g/d compared to 0 g/d: HR 1.74, 1.25-2.43, P for trend per frequency category: P =.017) and those who were premenopausal at diagnosis (≥23 g/d compared to 0 g/d: HR 1.89, 1.04-3.43, P for trend per frequency category: P =.032). In contrast, no significant association was seen in women who were postmenopausal at baseline or at diagnosis, despite a substantial number of subjects and long follow-up period. Our results revealed that frequent and high alcohol consumption are both risk factors for Asian premenopausal breast cancer, similarly to previous studies in Western countries. The lack of a clear association in postmenopausal women in our study warrants larger investigation in Asia.

DOI： 10.1002/ijc.33478

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記述言語：英語   出版者・発行元：日本疫学会  

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05=282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

DOI： 10.2188/jea.je20190296

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CiNii Research

記述言語：英語  

DOI： 10.1007/s12282-020-01065-4

PubMed

記述言語：英語   出版者・発行元：Cancer Research  

A genetic variant on aldehyde dehydrogenase 2 (ALDH2 rs671, Glu504Lys) contributes to carcinogenesis after alcohol consumption. Somewhat conversely, the ALDH2 Lys allele also confers a protective effect against alcohol-induced carcinogenesis by decreasing alcohol consumption due to acetaldehyde-related adverse effects. Here, we applied a mediation analysis to five case–control studies for head and neck, esophageal, stomach, small intestine, and colorectal cancers, with 4,099 cases and 6,065 controls, and explored the potentially heterogeneous impact of alcohol drinking on digestive tract carcinogenesis by decomposing the total effect of the ALDH2 Lys allele on digestive tract cancer risk into the two opposing effects of the carcinogenic effect (direct effect) and the protective effect (indirect effect mediated by drinking behavior). Alcohol was associated with an increased risk of most digestive tract cancers, but significant direct effects were observed only for upper gastrointestinal tract cancer risk, and varied substantially by site, with ORs (95% confidence interval) of 1.83 (1.43–2.36) for head and neck cancer, 21.15 (9.11–49.12) for esophageal cancer, and 1.65 (1.38–1.96) for stomach cancer. In contrast, a significant protective indirect effect was observed on risk for all cancers, except small intestine cancer. These findings suggest that alcohol is a major risk factor for digestive tract cancers, but its impact as a surrogate for acetaldehyde exposure appears heterogeneous by site. Meanwhile, the behavior-related effect of the ALDH2 Lys allele results in a decreased risk of most digestive tract cancers.

DOI： 10.1158/0008-5472.CAN-19-2685

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記述言語：英語   出版者・発行元：Breast Cancer Research and Treatment  

Purpose: Addition of carboplatin (CBDCA) to neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) has improved pathological complete response (pCR) rates in previous studies. We present long-term survival outcomes (disease-free survival [DFS], pre-planned secondary endpoint; overall survival [OS], post hoc exploratory endpoint) of our randomized study of the addition of CBDCA to NAC for HER2-negative breast cancer. Methods: Patients with stage II/III, HER2-negative breast cancer (N = 179) were randomly assigned to receive CP–CEF (four 3-week cycles of CBDCA [area under the curve, 5 mg/mL/min, day 1] and weekly paclitaxel [wPTX, 80 mg/m2, day 1, 8, 15] followed by four 3-week cycles of cyclophosphamide, epirubicin, and 5-fluorouracil [CEF, 500/100/500 mg/m2]) or P–CEF (four cycles of wPTX followed by four cycles of CEF) as NAC. DFS and OS were analyzed at each population of pCR status and assigned treatment arm. Results: Of 179 patients, 154 were available for long-term follow-up. At a median follow-up of 6.6 years (range, 0.7–8.0 years), patients who achieved pCR [n = 42, 23.5% (CP–CEF: n = 28, P–CEF: n = 16)] had longer DFS and OS than non-pCR patients [DFS; HR 0.15 (0.04–0.61), P = 0.008, OS; log-rank P = 0.003]. Addition of carboplatin to NAC significantly improved DFS and OS in the subset of patients with TNBC [DFS: HR, 0.22 (0.06–0.82), P = 0.015; OS: HR, 0.12 (0.01–0.96), P = 0.046], but not in the subset of patients with hormone receptor-positive disease or among all patients. Conclusions: Addition of carboplatin to neoadjuvant chemotherapy significantly improved DFS and OS in patients with TNBC but not in those with hormone receptor-positive, HER2-negative breast cancer.

DOI： 10.1007/s10549-020-05580-y

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記述言語：日本語   出版者・発行元：Breast Cancer Research and Treatment  

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.

DOI： 10.1007/s10549-019-05443-1

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記述言語：英語  

DOI： 10.1038/s41598-019-54839-y

PubMed

記述言語：英語  

DOI： 10.1111/tbj.13473

PubMed

記述言語：英語  

DOI： 10.1007/s00595-019-01775-z

PubMed

記述言語：英語  

DOI： 10.1186/s40792-019-0635-4

PubMed

記述言語：日本語   出版者・発行元：Breast Journal  

Skin-sparing mastectomy (SSM) with immediate reconstruction is standard surgical treatment for early breast cancer with widespread ductal carcinoma in situ (DCIS). The local recurrence rate after SSM is up to 7.0%. We investigated prediction of the pathological margin using contrast-enhanced MRI, and evaluated the cut-off point to obtain the safety margin. We performed SSM with immediate reconstruction in 216 early breast cancer patients with widespread DCIS and/or invasive cancer from January 2014 to December 2015. Forty cases were retrospectively reviewed after excluding those with >15 mm between skin and tumor, determined by preoperative contrast-enhanced MRI, or involving reconstructive surgery for local recurrence, immeasurable lesion by preoperative contrast-enhanced MRI, or neoadjuvant chemotherapy. We defined a positive pathological margin as <1 mm from the cancer nest. We reviewed the distance between skin and tumor by MRI and pathological examination. To identify the cut-off for predicting a positive pathological margin, we performed sensitivity analysis using an ROC curve. The margin-positive rate by pathological examination was 27.5% (n = 11/40), with a moderate correlation of MRI margin and pathological margin (r = 0.44). The best cut-off point for margin positivity was 5 mm of MRI margin, with sensitivity and specificity of 54% and 86%, respectively (P = 0.009). This is the first prediction of pathological margin by preoperative contrast-enhanced MRI in early breast cancer patients with SSM. Care is required for SSM if the MRI margin is less than 5 mm due to pathological margin positivity.

DOI： 10.1111/tbj.13194

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記述言語：英語  

DOI： 10.1007/s10549-018-4898-4

PubMed

担当区分：筆頭著者  

DOI： 10.1007/s12282-018-0856-6

記述言語：英語  

DOI： 10.1007/s12282-018-0852-x

PubMed

記述言語：英語  

DOI： 10.1007/s12282-018-0850-z

PubMed

記述言語：英語  

DOI： 10.1093/jjco/hyy088

PubMed

記述言語：英語  

DOI： 10.1007/s12282-016-0742-z

PubMed