Publications by authors named "Seigo Nakamura"

167 Publications

On-tissue polysulfide visualization by surface-enhanced Raman spectroscopy benefits patients with ovarian cancer to predict post-operative chemosensitivity.

Redox Biol 2021 May 2;41:101926. Epub 2021 Mar 2.

Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au-S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.
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http://dx.doi.org/10.1016/j.redox.2021.101926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010883PMC
May 2021

Novel Anti-FOLR1 Antibody-Drug Conjugate MORAb-202 in Breast Cancer and Non-Small Cell Lung Cancer Cells.

Antibodies (Basel) 2021 Feb 1;10(1). Epub 2021 Feb 1.

Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

Antibody-drug conjugates (ADCs), which are currently being developed, may become promising cancer therapeutics. Folate receptor α (FOLR1), a glycosylphosphatidylinositol-anchored membrane protein, is an attractive target of ADCs, as it is largely absent from normal tissues but is overexpressed in malignant tumors of epithelial origin, including ovarian, lung, and breast cancer. In this study, we tested the effects of novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 in breast cancer and non-small cell lung cancer (NSCLC) cell lines. FOLR1 expression, cell proliferation, bystander killing effects, and apoptosis were evaluated in seven breast cancer and nine NSCLC cell lines treated with MORAb-202. Tumor growth and FOLR1 expression were assessed in T47D and MCF7 orthotopic xenograft mouse models after a single intravenous administration of MORAb-202 (5 mg/kg). MORAb-202 was associated with inhibited cell proliferation, with specific selectivity toward FOLR1-expressing breast cancer cell lines. Eribulin, the payload of MORAb-202, was unleashed in HCC1954 cells, diffused into intercellular spaces, and then killed the non-FOLR1-expressing MCF7 cells in co-culture systems. In orthotopic xenograft mouse models, FOLR1-expressing T47D tumors and non-FOLR1-expressing MCF7 tumors were suppressed upon MORAb-202 administration. The novel anti-FOLR1 antibody-eribulin conjugate MORAb-202 has potential antitumor effects in breast cancer.
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http://dx.doi.org/10.3390/antib10010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930947PMC
February 2021

The disease sites of female genital cancers of BRCA1/2-associated hereditary breast and ovarian cancer: a retrospective study.

World J Surg Oncol 2021 Feb 2;19(1):36. Epub 2021 Feb 2.

Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, Tokyo, Japan.

Disease sites of female genital tract cancers of BRCA1/2-associated hereditary breast and ovarian cancer (HBOC) are less understood than non-hereditary cancers. We aimed to elucidate the disease site distribution of genital cancers in women with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+) of HBOC. For the primary disease site, the proportion of fallopian tube and peritoneal cancer was significantly higher in BRCA2+ (40.5%) compared with BRCA1+ (15.4%) and BRCA- (no pathogenic variant, 12.8%). For the metastatic site, the proportion of peritoneal dissemination was significantly higher in BRCA1+ (71.9%) than BRCA- (55.1%) and not different from BRCA2+ (71.4%). With one of the most extensive patients, this study supported the previous reports showing that the pathogenic variants of BRCA1/2 were involved in the female genitalia's disease sites.
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http://dx.doi.org/10.1186/s12957-021-02151-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856749PMC
February 2021

Pathogenicity assessment of variants for breast cancer susceptibility genes based on BRCAness of tumor sample.

Cancer Sci 2021 Mar 2;112(3):1310-1319. Epub 2021 Feb 2.

Division of Cancer Genomics, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.

Genes involved in the homologous recombination repair pathway-as exemplified by BRCA1, BRCA2, PALB2, ATM, and CHEK2-are frequently associated with hereditary breast and ovarian cancer syndrome. Germline mutations in the loci of these genes with loss of heterozygosity or additional somatic truncation at the WT allele lead to the development of breast cancers with characteristic clinicopathological features and prominent genomic features of homologous recombination deficiency, otherwise referred to as "BRCAness." Although clinical genetic testing for these and other genes has increased the chances of identifying pathogenic variants, there has also been an increase in the prevalence of variants of uncertain significance, which poses a challenge to patient care because of the difficulties associated with making further clinical decisions. To overcome this challenge, we sought to develop a methodology to reclassify the pathogenicity of these unknown variants using statistical modeling of BRCAness. The model was developed with Lasso logistic regression by comparing 116 genomic attributes derived from 37 BRCA1/2 biallelic mutant and 32 homologous recombination-quiescent breast cancer exomes. The model showed 95.8% and 86.7% accuracies in the training cohort and The Cancer Genome Atlas validation cohort, respectively. Through application of the model for variant reclassification of homologous recombination-associated hereditary breast and ovarian cancer causal genes and further assessment with clinicopathological features, we finally identified one likely pathogenic and five likely benign variants. As such, the BRCAness model developed from the tumor exome was robust and provided a reasonable basis for variant reclassification.
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http://dx.doi.org/10.1111/cas.14803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935793PMC
March 2021

BRCAness as a prognostic indicator in patients with early breast cancer.

Sci Rep 2020 12 3;10(1):21173. Epub 2020 Dec 3.

The Third Department of Breast Cancer, China Tianjin Breast Cancer Prevention, Treatment and Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Huanhu West Road, Hexi District, Tianjin, China.

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P < 0.001), nuclear grade III (76.1% vs. 48.4%, P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P < 0.001). Five-year disease free survival (DFS) (54.0% vs. 88.0%, P < 0.001) and overall survival (OS) (76.3% vs. 93.1%, P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184-7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618-11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.
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http://dx.doi.org/10.1038/s41598-020-78016-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713365PMC
December 2020

Innovative use of magnetic resonance imaging-guided focused ultrasound surgery for non-invasive breast cancer: a report of two cases.

Surg Case Rep 2020 Nov 23;6(1):294. Epub 2020 Nov 23.

Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, Japan.

Objective: This report describes the first clinical experience with magnetic resonance imaging-guided focused ultrasound surgery (MRgFUS) using the ExAblate 2100 system for non-invasive breast cancer.

Methods: Two women with non-invasive breast cancer underwent MRgFUS treatment. One week after the MRgFUS treatment, US-guided vacuum-assisted biopsy was performed for the ablated lesions at the same time as breast-conserving surgery.

Results: The patients experienced good cosmetic outcomes and did not experience any severe adverse events, such as skin burns. Pathological examination of the surgical specimens revealed a few degenerated intraductal lesions around the breast biopsy markers.

Conclusion: Performing MRgFUS with the new ExAblate 2100 system appears to be safe and feasible. The histopathological results revealed that adequate ultrasound energy in the appropriate location can induce tumor necrosis.
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http://dx.doi.org/10.1186/s40792-020-01032-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683687PMC
November 2020

The relationship between BRCA-associated breast cancer and age factors: an analysis of the Japanese HBOC consortium database.

J Hum Genet 2021 Mar 12;66(3):307-314. Epub 2020 Oct 12.

Breast Center, Showa University, Tokyo, Japan.

BRCA1/2 pathogenic variant prevalence in Japanese breast cancer is unclear. Here, we analyzed BRCA1/2 pathogenic variant prevalence with a particular focus on age factors, using the Japanese HBOC consortium database. All registered subjects were Japanese individuals who underwent BRCA1/2 genetic testing from January 1996 to July 2017 according to the Japanese HBOC consortium database. Cases were extracted and analyzed for each evaluation item. Overall BRCA1 and BRCA2 pathogenic variant prevalence was 11.2% and 9.0% in the cohort of 2366 proband patients, respectively. The age at onset of breast cancer for patients with BRCA1/2 pathogenic variants was significantly lower than that for patients without a BRCA1/2 pathogenic variant. In both BRCA1/2 patients, ages at onset were not statistically significantly different between two subtype groups (ER-positive vs. TNBC). We analyzed the BRCA1/2 pathogenic variant prevalence among age groups in patients with no family history of breast or ovarian cancer. In the TNBC group, the rate of genetic variants was more frequent among younger patients. Our results demonstrated that early breast cancer onset is associated with a BRCA1/2 pathogenic variant in the Japanese population. Younger TNBC patients were more likely to have a BRCA1/2 pathogenic variant irrespective of a family history of breast or ovarian cancer.
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http://dx.doi.org/10.1038/s10038-020-00849-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843417PMC
March 2021

Response and Prognosis of Docetaxel and Cyclophosphamide as Neoadjuvant Chemotherapy in ER HER2 Breast Cancer: A Prospective Phase II Study.

Clin Breast Cancer 2020 12 18;20(6):462-468. Epub 2020 Sep 18.

Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan; Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan.

Background: Although a docetaxel and cyclophosphomide (TC) regimen without anthracycline as adjuvant therapy became one of the standard regimens especially for ER-positive (ER)/human epidermal growth factor receptor 2-negative (HER2) primary breast cancer, the efficacy of TC as neoadjuvant chemotherapy (NAC) is not known. We conducted the prospective trial to assess the efficacy of a TC regimen in the neoadjuvant setting for stage II to III ER/HER2 primary breast cancer.

Patients And Methods: A TC regimen that included 75 mg/m of docetaxel and 600 mg/m of cyclophosphamide for 4 cycles every 3 weeks was administered as NAC. Primary endpoints are the rate of clinical response (clinical partial response and clinical complete response) and pathologic complete response; secondary endpoints are the disease-free survival and overall survival rates.

Results: Thirty (71.4%) of 42 tumors had clinical response. No patient achieved pathologic complete response. At the median follow-up period of 105.2 months (range, 12.1-119.7 months), the disease-free survival rate was 81.6%, and the distant disease-free survival rate was 86.8%. In terms of survival, only 1 patient died during the study period. The overall survival rate was 97.4% during the study period. Patients who developed distant recurrence had a trend to have progesterone receptor-negative or weakly positive compared with those who did not develop any recurrence (85.7% vs. 45.2%; P = .05).

Conclusions: Our prospective study showed that a TC regimen as NAC achieved a high clinical response rate in stage II to III ER/HER2 breast cancer. A TC regimen without anthracycline as NAC might be one of the options for patients with ER/HER2 breast cancer without high-risk factors including progesterone receptor negativity.
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http://dx.doi.org/10.1016/j.clbc.2020.09.007DOI Listing
December 2020

Incidence of contralateral and ipsilateral breast cancers and prognosis in BRCA1/2 pathogenic variant carriers based on the Japanese HBOC Consortium registration.

J Hum Genet 2021 Apr 9;66(4):379-387. Epub 2020 Oct 9.

Breast Center, Showa University, Tokyo, Japan.

This study aimed to clarify the breast cancer prognosis in Japanese patients with BRCA1/2 pathogenic variant. We analyzed 2235 women with breast cancer who underwent BRCA1/2 genetic testing between 1996 and 2018 using data from the Japanese hereditary breast and ovarian cancer syndrome registry. The cumulative risk for contralateral and ipsilateral breast cancers and time to death since the first breast cancer were stratified based on the BRCA1/2 variant status. The median follow-up was 3.0 years (0.1-34.1 years) after the first breast cancer. The annual average risks of contralateral breast cancer in BRCA1 and BRCA2 and non-BRCA1/2 pathogenic variant carriers were 4.0%, 2.9%, and 1.9%, respectively (P = 0.001). The annual average risks of ipsilateral breast cancer in the three groups were 2.7%, 1.4%, and 1.1%, respectively (P = 0.06). BRCA1 pathogenic variant carriers had significantly higher risks of contralateral (hazard ratio 1.91, P < 0.001) and ipsilateral (hazard ratio 2.00, P = 0.02) breast cancers than non-BRCA1/2 pathogenic variant carriers. The time to death by the BRCA1/2 variant status was not significantly difference (P = 0.28). The prognosis of breast cancer patients who received standard treatment was comparable regardless of the BRCA1/2 variant status.
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http://dx.doi.org/10.1038/s10038-020-00850-5DOI Listing
April 2021

Risk Factors for Ipsilateral Breast Tumor Recurrence in Triple-Negative or HER2-Positive Breast Cancer Patients Who Achieve a Pathologic Complete Response After Neoadjuvant Chemotherapy.

Ann Surg Oncol 2021 May 6;28(5):2545-2552. Epub 2020 Oct 6.

Department of Breast Surgical Oncology, St. Luke's International Hospital, Tokyo, Japan.

Background: Attention has been focused on attempts to eliminate breast surgery for breast cancer patients who achieve a pathologic complete response after neoadjuvant chemotherapy (NAC). However, there are few data on ipsilateral breast tumor recurrence (IBTR) among patients with triple-negative or epidermal growth factor receptor 2-positive (HER2+) tumors who achieve a pathologic complete response after NAC and breast-conserving treatment.

Methods: Using a multi-institutional retrospective database, this study evaluated the risk factors for IBTR among patients with newly diagnosed stages 1 to 3 breast cancer involving triple-negative or HER2+ tumors who achieved ypT0 after NAC and breast-conserving treatment.

Results: During a median follow-up period of 4.8 years (range, 0.1-15.5 years), the 5-year IBTR-free survival rate was 95.5%. The breast cancer subtype was not associated with IBTR-free survival. Patients younger than 40 years at diagnosis had significantly worse IBTR-free survival than those who were 40 years of age or older (5-year IBTR-free survival, 87.7 vs 96.9%; p = 0.002).

Conclusions: This retrospective study demonstrated that age at diagnosis was independently associated with IBTR-free survival. Special caution is needed when clinical trials analyzing omission of breast surgery after NAC are enrolling younger patients (UMIN-CTR No. UMIN000037067).
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http://dx.doi.org/10.1245/s10434-020-09176-0DOI Listing
May 2021

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan.

Clin Breast Cancer 2021 Feb 20;21(1):e48-e52. Epub 2020 Aug 20.

Department of Breast Surgical Oncology, Showa University School of Medicine, Tokyo, Japan; The Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

Background: We studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear.

Patients And Methods: The study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium.

Results: Our study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05).

Conclusions: Patients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.
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http://dx.doi.org/10.1016/j.clbc.2020.08.004DOI Listing
February 2021

How pregnancy and childbirth affect the working conditions and careers of women surgeons in Japan: findings of a nationwide survey conducted by the Japan Surgical Society.

Surg Today 2021 Feb 8;51(2):309-321. Epub 2020 Sep 8.

Department of Breast Surgical Oncology, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.

Purpose: To identify the conflicts between a career as a surgeon and pregnancy and childbirth for women in Japan.

Methods: The Japan Surgical Society conducted a nationwide survey on pregnancy and childbirth among its members who are women. The questionnaire included items regarding demography, working styles, and pregnancy and childbirth, including adverse events and harassment.

Results: The response rate was 29.9% (1068 responses, median age, 37 years). Among the responders, 61% were married and 47% had children (average number of children, 1.7). Half of the respondents reported having experienced sexual harassment and 62% reported having received unwelcome comments about pregnancy. About 20% had undergone fertility treatment. In total, 51% had pregnancies, with miscarriages in 33% of these. The top answer for the best timing for pregnancy and childbirth was after becoming board-certified. Nearly one-third of first-time mothers experienced adverse events during pregnancy and delivery, and 28% quit or changed their job because of their pregnancy and the birth of their first child.

Conclusions: Japanese women who choose a career as a surgeon face obstacles during pregnancy and childbirth. It is vital to share the findings of this study and understand the issues associated with pregnancy and childbirth regardless of gender. Interventions are essential to ensure that every pregnant surgeon has a safe working environment to allow unobstructed development of her career.
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http://dx.doi.org/10.1007/s00595-020-02129-wDOI Listing
February 2021

Risk factors for lymph node metastasis of ovarian, fallopian tube and primary peritoneal cancer in hereditary breast and ovarian cancer syndrome.

Jpn J Clin Oncol 2020 Dec;50(12):1380-1385

Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, Tokyo.

Background: To establish an individualized surgical strategy for lymphadenectomy in ovarian cancer patients with the germline BRCA1 and BRCA2 pathogenic variants (BRCA1+ and BRCA2+), we investigated the clinicopathological characteristics that are involved in the increased risk of lymph node metastasis.

Methods: We retrospectively reviewed the data of Japanese women registered in the database of the Japanese Hereditary Breast and Ovarian Cancer Consortium, who underwent BRCA1 and BRCA2 genetic testing.

Results: We evaluated the predictors of lymph node metastasis in all patients with the information of age at the diagnosis, disease site, histological subtype, 2014 FIGO stage, personal breast cancer history and family history; 233, 153 and 32 patients in the BRCA- (no pathogenic variant), BRCA1+ and BRCA2+ groups, respectively. The prevalence of lymph node metastasis was not markedly different between BRCA- (20.0%), BRCA1+ (18.4%) and BRCA2+ (26.2%). Multivariate analysis revealed an absence of a family history of ovarian cancer as an independent predictor for an increased risk of lymph node metastasis in BRCA1+, and the prevalence of lymph node metastasis was 11.7 and 42.0% in the groups with and without a family history of ovarian cancer, respectively. This subgroup without a family history of ovarian cancer did not show any correlation with a particular variant of BRCA1, including two common variants of c.188 T > A and c.2800C > T.

Conclusions: This study suggested that certain genetic factors related to the penetrance of hereditary breast and ovarian cancer syndrome altered the frequency of lymph node metastasis in BRCA1+ ovarian cancer, and family history may be useful to personalize the indication of lymphadenectomy.
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http://dx.doi.org/10.1093/jjco/hyaa124DOI Listing
December 2020

COVID-19: clinical issues from the Japan Surgical Society.

Surg Today 2020 Aug 11;50(8):794-808. Epub 2020 Jul 11.

Committee for novel coronavirus disease 2019 outbreak of the Japanese Surgical Society, Tokyo, Japan.

In this unprecedented COVID-19 pandemic, several key issues must be addressed to ensure safe treatment and prevent rapid spread of the virus and a consequential medical crisis. Careful evaluation of a patient's condition is crucial for deciding the triage plan, based on the status of the disease and comorbidities. As functionality of the medical care system is greatly affected by the environmental situation, the treatment may differ according to the medical and infectious disease circumstances of the institution. Importantly, all medical staff must prevent nosocomial COVID-19 by minimizing the effects of aerosol spread and developing diagnostic and surgical procedures. Polymerase chain reaction (PCR) screening for COVID-19 infection, particularly in asymptomatic patients, should be encouraged as these patients are prone to postoperative respiratory failure. In this article, the Japan Surgical Society addresses the general principles of surgical treatment in relation to COVID-19 infection and advocates preventive measures against viral transmission during this unimaginable COVID-19 pandemic.
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http://dx.doi.org/10.1007/s00595-020-02047-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351651PMC
August 2020

ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features.

Neurology 2020 09 9;95(11):e1500-e1511. Epub 2020 Jul 9.

From the Department of Neuromuscular Research, National Institute of Neuroscience (Y.S., A.N., S.H., I. Nonaka, S. Noguchi and I. Nishino), Medical Genome Center (Y.S., A. Iida, S.H., S.N., I. Nishino), and Departments of Neurology (M.M.-Y., Y.O.) and Child Neurology (A. Ishiyama and H.K.), National Center Hospital, National Center of Neurology and Psychiatry (NCNP), Tokyo; Integrated Graduate School of Medicine, Engineering, and Agricultural Science (Y.S.), University of Yamanashi; Department of Neurology (S. Nakamura), National Hospital Organization, Shizuoka Medical Center; Department of Neurology and Clinical Neuroscience (S.F. and T.K.), Yamaguchi University Graduate School of Medical Science; Department of Neurology (M.Y. and H.S.), Osaka Toneyama Medical Center; and Department of Neurology (H.S.), Osaka University Graduate School of Medicine, Japan.

Objective: To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease.

Methods: We searched for variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants.

Results: We identified 63 patients from 59 families with biallelic variants of . Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed that myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center.

Conclusions: ADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features.
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http://dx.doi.org/10.1212/WNL.0000000000010237DOI Listing
September 2020

Current status of breast cancer screening in high-risk women in Japan.

Breast Cancer 2020 Jul 6. Epub 2020 Jul 6.

Division of Breast Surgical Oncology, Department of Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

Overseas, the importance for breast MRI screening for high-risk groups has been shown. However, the evidence among Japanese population was lacking. Therefore, we collaborated with the "Study on clinical and genetic characterization of hereditary breast and ovarian cancer and improvement in prognosis using genetic information in Japan" group, as part of the Comprehensive Research Project on the Promotion of Cancer Control, Health and Labour Sciences Research, and have been conducting the study entitled, "Study of the usefulness of MRI surveillance of BRCA1/2 mutation carriers" since 2014. In addition, we found that in the Japanese population also, the pathological and imaging characteristics differ between BRCA1 and BRCA2 mutation carriers, like in non-Japanese populations by the several reports. In high-risk females, risk categories such as BRCA1 or BRCA2 mutation carriers are very important. Furthermore, in the future, the optimal surveillance modalities and examination intervals would also vary according to the age, thinness of the breast (constitution), breast density (individual differences on mammography), etc.; this would be "personalized surveillance", and quality-assured MRI examination is of the essence. This review will present clinical trial data of prospective MRI surveillance in Japan, and summarize the current status of breast cancer screening in high-risk Japanese women.
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http://dx.doi.org/10.1007/s12282-020-01103-1DOI Listing
July 2020

Prevalence of disease-causing genes in Japanese patients with -wildtype hereditary breast and ovarian cancer syndrome.

NPJ Breast Cancer 2020 12;6:25. Epub 2020 Jun 12.

Project for Development of Innovative Research on Cancer Therapeutics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku Tokyo, Japan.

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with -wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of , , and mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.
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http://dx.doi.org/10.1038/s41523-020-0163-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293299PMC
June 2020

Moving a neodymium magnet promotes the migration of a magnetic tracer and increases the monitoring counts on the skin surface of sentinel lymph nodes in breast cancer.

BMC Med Imaging 2020 05 27;20(1):58. Epub 2020 May 27.

Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan.

Background: We suspected that moving a small neodymium magnet would promote migration of the magnetic tracer to the sentinel lymph node (SLN). Higher monitoring counts on the skin surface before making an incision help us detect SLNs easily and successfully. The present study evaluated the enhancement of the monitoring count on the skin surface in SLN detection based on the magnet movement in a sentinel lymph node biopsy (SNB) using superparamagnetic iron oxide (SPIO) nanoparticles.

Methods: After induction of general anesthesia, superparamagnetic iron oxide nanoparticles were injected sub-dermally into the subareolar area or peritumorally. The neodymium magnet was moved over the skin from the injection site to the axilla to promote migration of the magnetic tracer without massage. A total of 62 patients were enrolled from February 2018 to November 2018: 13 cases were subjected to magnet movement 20 times (Group A), 8 were subjected to 1-min magnet movement (Group B), 26 were given a short (about 5 min) interval from injection to 1-min magnet movement (Group C), and 15 were given a long (about 25 min) interval before 1-min magnet movement using the magnetometer's head (Group D). In all cases, an SNB was conducted using both the radioisotope (RI) and SPIO methods. The monitoring counts on the skin surface were measured by a handheld magnetometer and compared among the four groups. Changes in the monitoring count by the interval and magnet movement were evaluated.

Results: The identification rates of the SPIO and RI methods were 100 and 95.2%, respectively. The mean monitoring counts of Group A, B, C, and D were 2.39 μT, 2.73 μT, 3.15 μT, and 3.92 μT, respectively (p < 0.0001; Kruskal-Wallis test). The monitoring counts were higher with longer magnet movement and with the insertion of an interval. Although there were no relationships between the monitoring count on the skin surface and clinicopathologic factors, magnet movement strongly influenced the monitoring count on the skin surface.

Conclusion: Moving a small neodymium magnet is effective for promoting migration of a magnetic tracer and increasing monitoring counts on the skin surface.

Trial Registration: UMIN, UMIN000029475. Registered 9 October 2017.
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http://dx.doi.org/10.1186/s12880-020-00459-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254765PMC
May 2020

[Evaluation of the Benefits of Administering Hand Therapy to Patients with Chemotherapy-Induced Peripheral Neuropathy].

Gan To Kagaku Ryoho 2020 May;47(5):783-788

Dept. of Pharmacology, School of Medicine, Showa University.

Taxanes, which are used to treat breast cancer, damage the microtubules of normal nerve cells, causing numbness of the fingers related to chemotherapy-induced peripheral neuropathy(CIPN); therefore, effective methods for reducing numbness are needed. In 2017, it was reported that physical stimuli related to massage improved finger blood flow volumes, contributing to the regeneration of damaged nerves. We developed a method of hand therapy for breast cancer patients complaining of numbness related to anticancer drug administration, and examined its effects on numbness. Hand therapy was performed by a single therapist who received lectures at the Sophia Phytotherapy College, which is accredited by the Japan Handcare Association. The fingertips to wrist, ankle, metacarpal bones, palm, and elbow were massaged using the bilateral arms/fingers for 15minutes. We investigated the influences of daily living status(Support Team Assessment Sched- ule-Japan: STAS-J), age, body mass index(BMI), severity/site of numbness, type of numbness, type of drug, duration of breast cancer, duration of numbness, and presence or absence of lymph node dissection, and evaluated the severity of numbness using a 10-cm Visual Analog Scale(VAS). The study included 51 breast cancer patients complaining of numbness of the fingers, with a mean age of 59 years. In patients with relatively mild numbness(STAS-J 1), the VAS scores before and after hand therapy were 4.7±1.8 and 1.9±1.3, respectively, showing a marked decrease. In STAS-J 2 patients, the values were 4.9 ±1.4 and 2.1±1.3, respectively, also showing a marked decrease. Thus, this hand therapy reduced numbness in mild- and moderate-status patients. Statistical comparisons were performed between the STAS-J 1/2(mild/moderate numbness)and STAS-J 3/4(severe numbness)groups. Although the severity of numbness was not correlated with age, BMI, type of drug, lymph node dissection, or duration of breast cancer, the proportion of patients with a B1-year history of numbness was significantly larger in the STAS-J 1/2 group. The most frequent site of numbness was from the proximal interphalangeal joints to the fingertips. Concerning the severity of numbness, many patients complained of severe numbness, as represented by that after sitting straight. These results suggest that this hand therapy is effective for reducing numbness in patients receiving taxanes and complaining of mild to moderate numbness.
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May 2020

Liquid biopsy for the detection of clinical biomarkers in early breast cancer: new insights and challenges.

Pharmacogenomics 2020 04 14;21(5):359-367. Epub 2020 Apr 14.

Project for Development of Liquid Biopsy, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.

The widespread use of breast screening programs has contributed to the detection of early stage breast cancer, which is often asymptomatic. Early diagnosis is essential to avoid overtreatment and improve clinical outcomes, as early stage breast cancer is rarely life-threatening if detected quickly. Despite this, tissue biopsy remains the principle method for detecting these cancers. Liquid biopsy has been recently proposed as a promising detection method in oncology that is not only less invasive but also contributes to the early diagnosis of breast cancer. Here, we describe the clinical utility of liquid biopsy as a tool for the early detection of breast cancer.
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http://dx.doi.org/10.2217/pgs-2019-0130DOI Listing
April 2020

Diagnostic performance of coronal view in comparison with transverse view of three-dimensional automated breast ultrasound.

Acta Radiol 2021 Jan 4;62(1):27-33. Epub 2020 Apr 4.

Breast Center, Showa University Hospital, Tokyo, Japan.

Background: Automated breast ultrasound (ABUS) is one of the first ultrasound devices which enables the de-coupling of image acquisition and interpretation. Another feature of ABUS is the coronal view, utilizing three-dimensional volume data reconstructed from two-dimensional transverse images acquired automatically.

Purpose: To assess the diagnostic performance of coronal view interpretation by comparing it with that of the transverse view.

Material And Methods: This was a retrospective, multi-case, observer study using a cancer-enriched dataset of ABUS images at a single institution with approval by an Institutional Review Board. The 100 scan datasets selected between October 2014 and January 2017 included 70 non-cancer cases and 30 malignancies. In the present observer study, two experienced physicians provided their confidence levels regarding the malignancy of each of the 100 scan datasets independently. The reading times for interpretation of coronal and transverse views were recorded.

Results: Area under the receiver operating characteristic curves for two observers with the transverse view (0.856) was improved by use of the coronal view (0.917,  = 0.036). The average reading times were 140.4 s with the coronal view and 148.5 s with the transverse view per scan dataset ( = 0.246).

Conclusion: It is conceivable that the accurate use of the coronal view will lead to improvement in diagnostic performance in breast cancer screening, although this needs to be confirmed with a larger prospective study.
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http://dx.doi.org/10.1177/0284185120913706DOI Listing
January 2021

Effectiveness of a Smartphone Application as a Support Tool for Patients Undergoing Breast Cancer Chemotherapy: A Randomized Controlled Trial.

Clin Breast Cancer 2020 06 26;20(3):201-208. Epub 2020 Feb 26.

Division of Drug Information Analytics, Department of Clinical Pharmacy, Showa University School of Pharmacy, Tokyo, Japan.

Background: Outpatients undergoing cancer chemotherapy experience anxiety related to adverse drug reactions that they can experience at home. We developed a breast cancer patient support system (BPSS) application (app). The BPSS app chronologically and quantitatively records patients' subjective and objective symptoms during breast cancer chemotherapy, with the goal of providing supportive management for adverse drug reactions. The present study examined whether the BPSS app is an effective tool for supporting patients undergoing chemotherapy.

Patients And Methods: A total of 102 patients undergoing chemotherapy at the Showa University Hospital (Tokyo, Japan) were enrolled in the present order- and age-controlled clinical trial and randomized into BPSS or no-BPSS app groups. The patients underwent 4 courses of chemotherapy. The primary outcome was the change in the hospital anxiety and depression scale score, which was assessed directly before and after the 4 courses of chemotherapy. Other outcomes included health literacy (measured using the 14-item health literacy scale (HLS-14), side effects, and app adherence.

Results: Of the 102 patients, 95 completed the present study. No significant improvement was seen in anxiety, depression, or health literacy at the end of treatment between the BPSS and no-BPSS app groups. Overall, 1868 side effects were reported. When the patients' records were compared with the medical staff records, the analysis revealed that the medical staff had underestimated some grade 3 symptoms.

Conclusion: The BPSS app is a feasible tool for patients with breast cancer and might be useful as a support tool for information sharing between patients and medical staff in an effort to optimize chemotherapy and deliver suitable patient care and support.
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http://dx.doi.org/10.1016/j.clbc.2020.01.004DOI Listing
June 2020

High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study.

Breast Cancer 2020 Jul 5;27(4):706-715. Epub 2020 Mar 5.

IOB Institute of Oncology, Quironsalud Group, Madrid, Barcelona, Spain.

Background: Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS).

Methods: The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively.

Results: Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin.

Discussion: This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures.

Trial Registration: www.ClinicalTrials.gov code: NCT00388726.
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http://dx.doi.org/10.1007/s12282-020-01067-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297864PMC
July 2020

BRCAness as an Important Prognostic Marker in Patients with Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy: A Multicenter Retrospective Study.

Diagnostics (Basel) 2020 Feb 21;10(2). Epub 2020 Feb 21.

Department of Breast Surgical Oncology, Showa University School of Medicine, Shinagawa 142-8666, Japan.

Triple-negative breast cancer (TNBC) has several subtypes. The identification of markers associated with recurrence and poor prognosis in patients with TNBC is urgently needed. BRCAness is a set of traits in which dysfunction, arising from gene mutation, methylation, or deletion, results in DNA repair deficiency. In the current study, we evaluated the clinical significance and prognosis of BRCAness in a multicenter retrospective study. Ninety-four patients with TNBC treated with neoadjuvant chemotherapy were enrolled from three university hospitals for this retrospective study. BRCAness was evaluated in 94 core needle biopsy (CNB) specimens prior to neoadjuvant chemotherapy and 49 surgical specimens without pathological complete response (pCR). The samples were assessed using multiplex ligation-dependent probe amplification, and the amplicons were scored. Of the 94 patients, 51 had BRCAness in CNB specimens. There were no significant differences in pCR rates or recurrence between the BRCAness and non-BRCAness groups. Among surgical specimens, the BRCAness group had a significantly shorter recurrence-free survival and overall survival compared with the non-BRCAness group. The BRCAness of surgical specimens was found to be an important marker to predict prognosis in patients with TNBC after neoadjuvant chemotherapy. A clinical trial to assess the clinical impact of carboplatin with BRCAness is planned.
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http://dx.doi.org/10.3390/diagnostics10020119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168149PMC
February 2020

The number of FoxP3-positive tumor-infiltrating lymphocytes in patients with synchronous bilateral breast cancer.

Breast Cancer 2020 Jul 13;27(4):586-593. Epub 2020 Jan 13.

Department of Pathology, Showa University, Tokyo, Japan.

Purpose: In breast cancer, FoxP3-positive tumor-infiltrating lymphocytes (FoxP3+ TILs) vary depending on lymph node status, histological grade, and subtype. All these studies have compared the numbers of FoxP3+ TILs among different hosts, but recruitment of FoxP3+ TILs might depend on each individual's immune environment and each tumor's biological characteristics. In the present study, FoxP3+ TIL numbers were investigated in patients with synchronous bilateral breast cancer (SBBC) to determine the factors that affect FoxP3+ TIL recruitment in the same anti-tumor immune environment.

Methods: Patients diagnosed with SBBC who underwent curative surgery at two institutions were enrolled in this study. Patients who underwent primary systemic therapy or who were diagnosed with ductal carcinoma in situ or who had distant metastases at diagnosis were excluded. The average numbers of Foxp3+ TILs were determined from the scores of five high-power microscopic fields (HPF). The associations between Foxp3+ TIL numbers and the clinicopathological features of bilateral breasts in a single individual were examined.

Results: Nuclear grade (NG) (p = 0.007) and subtype (p = 0.03), but not size (p = 0.18) and axillary lymph node (p = 0.23) were significantly associated with increase of FoxP3 + TIL numbers by univariate analysis. Further, only NG was a statistically significant clinicopathological factor for change in the number of FoxP3+ TILs by multivariate analysis (p = 0.046) CONCLUSIONS: There was no relationship between FoxP3+ TIL numbers and cancer progression as reflected in tumor size and axillary lymph node in patients with SBBC. Aggressive biological factors, especially high NG, were significantly related to enhanced recruitment of FoxP3+ TILs.
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http://dx.doi.org/10.1007/s12282-020-01049-4DOI Listing
July 2020

Factors associated with prolonged overall survival in patients with postmenopausal estrogen receptor-positive advanced breast cancer using real-world data: a follow-up analysis of the JBCRG-C06 Safari study.

Breast Cancer 2020 May 6;27(3):389-398. Epub 2019 Dec 6.

Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, 135-8550, Japan.

Background: Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients.

Methods: OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study.

Results: A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age (< 60 years), longer time from ABC diagnosis to fulvestrant use (≥ 3 years), no prior palliative chemotherapy before fulvestrant use, and progesterone receptor (PgR) negativity (PgR-) were significantly correlated with prolonged OS (median 7.0 years). For cases with histological or nuclear grade data, lower histological or nuclear grades were also correlated with longer OS. In recurrent metastatic cases, long disease-free interval (DFI) was not correlated with longer OS.

Conclusions: In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR-, and lower histological or nuclear grade correlated positively with prolonged OS.
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http://dx.doi.org/10.1007/s12282-019-01029-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196081PMC
May 2020

Multicenter clinical trial on sentinel lymph node biopsy using superparamagnetic iron oxide nanoparticles and a novel handheld magnetic probe.

J Surg Oncol 2019 Dec 30;120(8):1391-1396. Epub 2019 Oct 30.

Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Background: Sentinel lymph node biopsy is a standard staging procedure for early axillary lymph node-negative breast cancer. As an alternative to the currently used radioactive tracers for sentinel lymph node (SLN) detection during the surgical procedure, a number of studies have shown promising results using superparamagnetic iron oxide (SPIO) nanoparticles. Here, we developed a new handheld, cordless, and lightweight magnetic probe for SPIO detection.

Methods: Resovist (SPIO nanoparticles) were detected by the newly developed handheld probe, and the SLN detection rate was compared to that of the standard radioisotope (RI) method using radioactive colloids ( Tc) and a blue dye (indigo carmine). This was a multicenter prospective clinical trial that included 220 patients with breast cancer scheduled for sentinel node biopsy after a clinical diagnosis of negative axillary lymph node from three facilities in Japan.

Results: Of the 210 patients analyzed, SLN was detected in 94.8% (199/210 cases, 90% confidence interval [CI]) with our magnetic method and in 98.1% (206/210 cases, 90% CI) with the RI method. The magnetic method exceeded the threshold identification rate of 90%.

Conclusion: This was the first clinical study to use a novel handheld magnetometer to detect SLN, which we demonstrate to be not inferior to the RI method.
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http://dx.doi.org/10.1002/jso.25747DOI Listing
December 2019

Differences in perception of breast cancer treatment between patients, physicians, and nurses and unmet information needs in Japan.

Support Care Cancer 2020 May 3;28(5):2331-2338. Epub 2019 Sep 3.

Division of Breast Surgery, Department of Surgery, School of Medicine, Showa University, 1-5-8 Hatanodai Shinagawa-ku, Tokyo, 142-8555, Japan.

Purpose: Discrepancies exist between healthcare provider and patient perceptions surrounding breast cancer treatment. Significant treatment changes in the last 10 years have made re-evaluation of these perceptions necessary.

Methods: Physicians and nurses involved in breast cancer treatment, and patients who had received breast cancer chemotherapy (past 5 years), were questioned using an Internet survey. Participants ranked physical concerns (treatment side effects), psychological concerns, priorities for treatment selection, and side effects to be avoided during treatment. Patients were asked about desired treatment information/information sources. Rankings were calculated using the mean value of scores. Spearman's rank correlation was used to determine the concordance of rankings among groups.

Results: Survey respondents included 207 patients, 185 physicians, and 150 nurses. Patients and nurses similarly ranked distressing physical concerns; physician rankings differed. Quality of life (QoL) and treatment response ranked high with physicians and patients when considering future treatment; nurses prioritized QoL. All three groups generally agreed on ranking of psychological concerns experienced during chemotherapy, explanation of treatment options, and how treatment decisions were made, although more patients thought treatment decisions should be made independently. Healthcare providers reported providing explanations of treatment side effects and information on physical/psychological support options while patients felt both were lacking. Concordance was calculated as 0.47 (patient-physician), 0.83 (patient-nurse), and 0.76 (physician-nurse). Patients desired additional information, preferring healthcare providers as the source.

Conclusions: Specific areas for improvement in breast cancer patient care were identified; programs should be implemented to address unmet needs and improve treatment in these areas.
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http://dx.doi.org/10.1007/s00520-019-05029-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083820PMC
May 2020

Taxane-based combinations as adjuvant chemotherapy for node-positive ER-positive breast cancer based on 2004-2009 data from the Breast Cancer Registry of the Japanese Breast Cancer Society.

Breast Cancer 2020 Jan 20;27(1):85-91. Epub 2019 Jul 20.

Division of Breast Surgical Oncology, Department of Surgery, Showa University, Tokyo, Japan.

Background: Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting.

Methods: Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups.

Results: There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1-3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes.

Conclusions: In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1-3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.
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http://dx.doi.org/10.1007/s12282-019-00997-wDOI Listing
January 2020