A randomized trial of the impact of symptom monitoring using an electronic patient-reported outcome app on health-related quality of life in postmenopausal breast cancer patients receiving adjuvant endocrine therapy.

BACKGROUND: Electronic patient-reported outcomes (ePRO) monitoring is a useful communication tool for cancer patients and healthcare providers. In this study, we examined the impact of symptom monitoring using an ePRO app on quality of life (QoL) in postmenopausal breast cancer patients receiving adjuvant endocrine therapy. METHODS: The free app "Welby My Carte ONC" was used in the study. Patients with breast cancer starting adjuvant endocrine therapy were randomly assigned in a 1:1 ratio to ePRO monitoring (ONC) and control groups. The ONC group reported five symptoms extracted from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) (insomnia, joint pain, headache, anxiety, and hot flashes) weekly for 3 months through the app. Reported symptoms were shared with medical personnel. When serious symptoms were reported, these personnel ascertained the patient's health status and provided advice over the phone. The primary endpoint was QoL measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 3 months from enrollment. Differences between groups were tested using analysis of covariance. RESULTS: The study included 125 subjects with mean age of 64 years in the ONC group (n = 61) and 63 years in the control group (n = 64). In the ONC group, the response rate to PRO-CTCAE was about 70% or higher until week 10. The item missing rate was 0. The ONC group reported more symptoms related to joint pain and insomnia. The difference in FACT-B total score between the groups was - 1.55 (95% confidence interval: - 5.91, 2.81), indicating no significant difference. CONCLUSIONS: Symptom monitoring using ePRO early after initiation of adjuvant endocrine therapy after surgery did not improve QoL of breast cancer patients.

High-value breast cancer care within resource limitations.

Breast cancer care is a costly global health issue where effective management depends on early detection and treatment. A breast cancer diagnosis can result in financial catastrophe especially in low- and middle-income countries (LMIC). Large inequities in breast cancer care are observed and represent a global challenge to caregivers and patients. Strategies to improve early diagnosis include awareness and clinical breast examination in LMIC, and screening in high-income countries (HIC). The use of clinical guidelines for the management of breast cancer is needed. Adapted guidelines from HIC can address disparities in populations with limited resources. Locally developed strategies still provide effective guidance in improving survival. Integrated practice units (IPU) with timely multidisciplinary breast care conferences and patient navigators are required to achieve high-value, personalized breast cancer management in HIC as well as LMIC. Breast cancer patient care should include a quality of life evaluation using ideally patient-reported outcomes (PROM) and experience measurements (PREM). Evaluation of breast cancer outcomes must include the financial cost of delivered care. The resulting value perspective should guide resource allocation and program priorities. The value of care must be improved by translating the findings of social and economic research into practice and resolving systemic inequity in clinical breast cancer research. Cancer survivorship programs must be put in place everywhere. The treatment of patients with metastatic breast cancer must require more attention in the future, especially in LMIC.

Potential Usefulness a Coronal View using an Automated Breast Ultrasound System in Detecting Breast Lesions.

Objective: An automated breast ultrasound system (ABUS) combined with screening mammography has increased cancer detection rates; however, supplemental ABUS use has increased recall rates. In this study, we aimed to identify an accurate and efficient method of ABUS interpretation and evaluate the potential usefulness of its coronal view versus the conventional transverse view. Materials and Methods: This retrospective observer study included comprised 114 ABUS cases (40 normal, 35 benign, 39 malignant). Ten physicians from multiple institutions interpreted the anonymized coronal and transverse views independently. The observers scored their confidence in the lesion detection for each case using a continuous scale and recorded reading times for each coronal and transverse view interpretation. Free-response receiver operating characteristic analysis was employed to compare detection accuracies between views; a paired t-test was used to compare the average reading times. Results: Detection accuracy did not differ significantly between the coronal and transverse views (figure of merit=0.740 and 0.745, respectively; p = 0.72). However, the average reading time for the coronal view was significantly shorter than that for the transverse view (149.7 vs. 200.3 seconds per case, p = 0.003). Conclusion: The coronal view obtained with the ABUS was useful for interpretation and associated with significantly shorter reading times compared with the conventional transverse view while maintaining breast lesion detection accuracy.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

BACKGROUND: A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. PATIENTS AND METHODS: Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. RESULTS: Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. CONCLUSION: APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.

Numerous variants of unknown significance (VUSs) exist in hereditary breast and ovarian cancers. Although multiple methods have been developed to assess the significance of BRCA1/2 variants, functional discrepancies among these approaches remain. Therefore, a comprehensive functional evaluation system for these variants should be established. We performed conventional homologous recombination (HR) assays for 50 BRCA1 and 108 BRCA2 VUSs and complementarily predicted VUSs using a statistical logistic regression prediction model that integrated six in silico functional prediction tools. BRCA1/2 VUSs were classified according to the results of the integrative in vitro and in silico analyses. Using HR assays, we identified 10 BRCA1 and 4 BRCA2 VUSs as low-functional pathogenic variants. For in silico prediction, the statistical prediction model showed high accuracy for both BRCA1 and BRCA2 compared with each in silico prediction tool individually and predicted nine BRCA1 and seven BRCA2 variants to be pathogenic. Integrative functional evaluation in this study and the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines strongly suggested that seven BRCA1 variants (p.Glu272Gly, p.Lys1095Glu, p.Val1653Leu, p.Thr1681Pro, p.Phe1761Val, p.Thr1773Ile, and p.Gly1803Ser) and four BRCA2 variants (p.Trp31Gly, p.Ser2616Phe, p.Tyr2660Cys, and p.Leu2792Arg) were pathogenic. This study demonstrates that integrative evaluation using conventional HR assays and optimized in silico prediction comprehensively classified the significance of BRCA VUSs for future clinical applications.

Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06).

BACKGROUND: The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer (AMBC) is unclear. METHODS: We analyzed the data from 94 patients with ER-positive HER2-positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER-positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti-HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first-line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. RESULTS: The TTF was longer in the patients treated with F500 as first- or second-line therapy (n = 20) than in those who received later-line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti-HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. CONCLUSIONS: In patients with ER-positive HER2-positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first- or second-line therapy. In patients who received chemotherapy-free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut-off for indicating clinical outcomes.

Examining the effectiveness of a deep learning-based computer-aided breast cancer detection system for breast ultrasound.

PURPOSE: This study aimed to evaluate the clinical usefulness of a deep learning-based computer-aided detection (CADe) system for breast ultrasound. METHODS: The set of 88 training images was expanded to 14,000 positive images and 50,000 negative images. The CADe system was trained to detect lesions in real- time using deep learning with an improved model of YOLOv3-tiny. Eighteen readers evaluated 52 test image sets with and without CADe. Jackknife alternative free-response receiver operating characteristic analysis was used to estimate the effectiveness of this system in improving lesion detection. RESULT: The area under the curve (AUC) for image sets was 0.7726 with CADe and 0.6304 without CADe, with a 0.1422 difference, indicating that with CADe was significantly higher than that without CADe (p < 0.0001). The sensitivity per case was higher with CADe (95.4%) than without CADe (83.7%). The specificity of suspected breast cancer cases with CADe (86.6%) was higher than that without CADe (65.7%). The number of false positives per case (FPC) was lower with CADe (0.22) than without CADe (0.43). CONCLUSION: The use of a deep learning-based CADe system for breast ultrasound by readers significantly improved their reading ability. This system is expected to contribute to highly accurate breast cancer screening and diagnosis.

Validation of the prognosis of patients with ER­positive, HER2­negative and node­negative invasive breast cancer classified as low risk by Curebest™ 95GC Breast in a multi­institutional registry study.

Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.

Adjuvant olaparib in the subset of patients from Japan with BRCA1- or BRCA2-mutated high-risk early breast cancer from the phase 3 OlympiA trial.

BACKGROUND: The efficacy and safety of olaparib compared with placebo in the subset of patients from Japan in the phase 3 OlympiA trial (NCT02032823) are reported here and contextualized with reference to the global OlympiA population. METHODS: Patients with germline BRCA1 and/or BRCA2 pathogenic variants and HER2-negative, high-risk early breast cancer who had received neoadjuvant or adjuvant chemotherapy and completed local treatment were eligible. Patients were randomized 1:1 to receive olaparib or placebo for 1 year. PRIMARY ENDPOINT: invasive disease-free survival (IDFS). Secondary endpoints: distant disease-free survival (DDFS), overall survival (OS), and safety. Data are reported from the first pre-specified interim analysis (data cut-off [DCO] March 27, 2020) and the second, event driven, pre-specified interim analysis of OS (DCO July 12, 2021) in patients from Japan. RESULTS: 140 patients were randomized in Japan (olaparib, n = 64; placebo, n = 76). At the first pre-specified interim analysis (median follow-up: 2.9 years), hazard ratios (HRs) for adjuvant olaparib compared with placebo were 0.5 for IDFS (95% confidence interval [CI] 0.18-1.24) and 0.41 for DDFS (95% CI 0.11-1.16). At the second pre-specified interim analysis of OS, three deaths occurred in the olaparib group versus six deaths in the placebo group (HR, 0.62 [95% CI 0.13-2.36]). Findings were consistent with those for the global population. No new safety signals were observed. CONCLUSIONS: While this analysis in a Japanese subset of patients was not powered to detect population-related treatment differences, efficacy and safety analysis results were consistent with the global OlympiA population, suggesting the findings from the global study are generalizable to clinical practice in Japan.

The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.

Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed-all-nominated-in-one-BRCA (MANO-B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition.

Risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer: a single-institution 10-year experience.

BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.

Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients.

BACKGROUND: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. METHODS: A total of 47 patients with Stage I-III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. RESULTS: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). CONCLUSIONS: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2-mutation carriers.

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients.

Retrospective study on the effectiveness of medroxyprogesterone acetate in the treatment of ER-positive/HER2-negative post-menopausal advanced breast cancer: an additional analysis of the JBCRG-C06 Safari study.

BACKGROUND: Only old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment. METHODS: This was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan-Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate. RESULTS: From the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer. CONCLUSION: In actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

Risk-reducing mastectomy for women with hereditary breast and ovarian cancer (HBOC): analytical results of data from the Japanese Organization of HBOC.

BACKGROUND: Risk-reducing mastectomy is one option for women with hereditary breast and ovarian cancer to reduce the risk of breast cancer. PATIENTS AND METHODS: We analyzed data of the Japanese Organization of Hereditary Breast and Ovarian Cancer on women who were diagnosed as hereditary breast and ovarian cancer by BRCA germline genetic testing between 2010 and 2019 to reveal the rate and likelihood of risk-reducing mastectomy. RESULTS: There were 412 women with BRCA1, 271 with BRCA2 and 4 with both female pathogenic variants. Ninety (13.1%) received risk-reducing mastectomy. The rates of risk-reducing mastectomy were statistically significantly higher in women with BRCA1 pathogenic variants than BRCA2, in women who had breast cancer than those who did not, in women with a breast cancer family history than in those without, in mothers than in those without children, in women who were receiving surveillance with MRI than those who were not and in women who received risk-reducing salpingo-oophorectomy than in those who did not on univariate analyses. The ages when they received the genetic testing were statistically significantly younger in the women receiving risk-reducing mastectomy than those who did not receive it. The women with BRCA1 pathogenic variants, personal history of breast cancer, mothers, those receiving MRI surveillance and younger women were independently significantly more likely to receive risk-reducing mastectomy based on multivariate analysis. CONCLUSIONS: The rate of risk-reducing mastectomy was not high in Japan; however, risk-reducing surgery was approved by the Japanese National Medical Insurance for hereditary breast and ovarian cancer patients with breast and/or ovarian cancer in 2020, so this rate will increase.

Comparison between a new assay system, Elecsys® Anti-p53, and conventional MESACUP™ for the detection of serum anti-p53 antibodies: A multi-institutional study.

The sensitivity and specificity of a new automated electrochemiluminescence immunoassay system, Elecsys® Anti-p53 (Elecsys), were compared with that of the conventional serum anti-p53 antibody (s-p53-Ab) enzyme-linked immunosorbent assay kit [MESACUP anti-p53 test (MESACUP)]. Elecsys and MESACUP were used to analyze the levels of s-p53-Abs in patients with esophageal, colorectal and breast cancer. A total of 532 controls and 288, 235 and 329 patients with esophageal, colorectal and breast cancer, respectively, were enrolled. Additionally, the sera of patients with benign diseases of the esophagus, colorectal system and breast, patients with autoimmune diseases and healthy volunteers were analyzed as controls. Sensitivity and specificity were compared between the two assay systems. Positive agreement rates were 58.7% in all samples, 71.2% in esophageal samples, 73.6% in colorectal samples and 35.1% in breast samples. Negative agreement rates for the different cancer types were ≥97.1% and the overall agreement rates were ≥92.3%. When the specificities of the two assays were aligned for all samples, Elecsys demonstrated higher sensitivities for all types of analyzed cancer together, as well as for esophageal, colorectal and breast cancer, respectively. Although positive concordance between the two assay systems was low in terms of specificity, Elecsys had a higher sensitivity than the MESACUP.

Diagnostic performance of dedicated breast positron emission tomography.

BACKGROUND: Dedicated breast positron emission tomography (dbPET) has been developed for detecting smaller breast cancer. We investigated the diagnostic performance of dbPET in patients with known breast cancer. METHODS: Eighty-two preoperative patients with breast cancer were included in the study (84 tumours: 11 ductal carcinomas in situ [DCIS], 73 invasive cancers). They underwent mammography (MMG), ultrasonography (US), and contrast-enhanced breast magnetic resonance imaging (MRI) before whole-body PET/MRI (WBPET/MRI) and dbPET. We evaluated the sensitivity of all modalities, and the association between the maximum standard uptake value (SUVmax) level and histopathological features. RESULTS: The sensitivities of MMG, US, MRI, WBPET/MRI and dbPET for all tumours were 81.2% (65/80), 98.8% (83/84), 98.6% (73/74), 86.9% (73/84), and 89.2% (75/84), respectively. For 11 DCIS and 22 small invasive cancers (≤ 2 cm), the sensitivity of dbPET (84.9%) tended to be higher than that of WBPET/MRI (69.7%) (p = 0.095). Seven tumours were detected by dbPET only, but not by WBPET/MRI. Five tumours were detected by only WBPET/MRI because of the blind area of dbPET detector, requiring a wider field of view. After making the mat of dbPET detector thinner, all 22 scanned tumours were depicted. The higher SUVmax of dbPET was significantly related to the negative oestrogen receptor status, higher nuclear grade, and higher Ki67 (p < 0.001). CONCLUSIONS: The sensitivity of dbPET for early breast cancer was higher than that of WBPET/MRI. High SUVmax was related to aggressive features of tumours. Moreover, dbPET can be used for the diagnosis and oncological evaluation of breast cancer.

Differences in age at diagnosis of ovarian cancer for each BRCA mutation type in Japan: optimal timing to carry out risk-reducing salpingo-oophorectomy.

OBJECTIVE: BRCA1 and BRCA2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) by age 40 and 45, respectively. However, the carriers have a different way of thinking about their life plan. We aimed to investigate the distribution of age at diagnosis of ovarian cancer (OC) patients to examine the optimal timing of RRSO in the carriers. METHODS: We examined a correlation between age at diagnosis of OC and common mutation types in 3,517 probands that received BRCA genetic testing. Among them, germline BRCA1 mutation (gBRCA1m), germline BRCA2 mutation (gBRCA2m) and germline BRCA wild-type (gBRCAwt) were found in 185, 42 and 241 OC patients, respectively. RESULTS: The average age at diagnosis of OC in gBRCA1m and gBRCA2m was 51.3 and 58.3 years, respectively, and the difference from gBRCAwt (53.8 years) was significant. The gBRCA2m carriers did not develop OC under the age of 40. The average age was 50.1 years for L63X and 52.8 years for Q934X in BRCA1, and 55.1 years for R2318X and 61.1 years for STOP1861 in BRCA2. The age at diagnosis in L63X or R2318X carriers was relatively younger than other BRCA1 or BRCA2 carriers, however their differences were not significant. With L63X and R2318X carriers, 89.4% (42/47) and 100% (7/7) of women were able to prevent the development of OC, respectively, when RRSO was performed at age 40. CONCLUSION: There appears to be no difference in the age at diagnosis of OC depending on the type of BRCA common mutation. Further analysis would be needed.