Radiation-induced angiosarcoma of the breast: individual participant meta-analysis of Japanese population.

BACKGROUND: Radiation-induced angiosarcoma (RIAS) of the breast is a very rare and poor prognostic disease. According to previous studies, the efficacy of chemotherapy for RIAS is still controversial. However, no study has assessed the prognosis of RIAS and the prognostic impact of preoperative or postoperative chemotherapy in Japanese patients. Our study aimed to assess them in Japanese people using publication data with our three patients. METHODS: Thirty-nine patients diagnosed with RIAS, including 36 patients from 34 published case series, and three patients from our hospital were used for analysis. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. RESULTS: Among the 39 patients, 36 patients (92.3%) underwent surgery. The median DFS and OS periods were 14 months (range 1-75 months) and 23 months (range 4-84 months), respectively. Chemotherapy with taxane-based regimen was administered in 13 cases (33.2%) pre- or post-operatively. DFS was significantly improved with chemotherapy in addition to surgery (p = 0.037). However, addition of chemotherapy to surgery did not improve DDFS (p = 0.09) and OS (p = 0.878). In multivariate analysis, age ≥ 70 years was an independent but poor prognostic factor of DFS. Additionally, a lack of chemotherapy showed a trend to be associated with worse DFS. There was no independent variable contributing to DDFS and OS. CONCLUSIONS: Chemotherapy may have reduced the recurrence rate of RIAS in Japanese patients but did not improve OS. Further data are needed to confirm the efficacy and proper regimen of chemotherapy.

The Efficacy of Short-Term Toe Resistance Training in Chronic Hemodialysis Patients with Type 2 Diabetes.

Resistance training is effective in chronic hemodialysis patients with type 2 diabetes mellitus, but its effect on toe pinch force (TPF) is unknown. This study was a randomized controlled trial conducted at three hospitals to investigate the effect of short-term toe resistance training on TPF in chronic hemodialysis patients with type 2 diabetes. The patients were randomly allocated to intervention (performed aerobic exercise and four toe resistance training exercises) and control (performed aerobic exercise only) groups. After 2 weeks of exercise intervention program, evaluations of TPF and clinical parameters were performed. In addition, the rate of retention of exercise therapy was assessed 6 months after the exercise intervention program was completed. After the exercise intervention program, TPF was significantly higher in the intervention group than in the control group. The intervention group had a significantly higher rate of continuation of exercise therapy. Two weeks of toe resistance training significantly increased the TPF in chronic hemodialysis patients with type 2 diabetes. Toe resistance training was shown to be an effective training method for continuing exercise therapy. Toe resistance training is recommended in clinical practice for chronic hemodialysis patients with type 2 diabetes.

Factors associated with an unfavorable clinical course in hospitalized patients with pelvic inflammatory disease: a retrospective cohort study of 117 patients from a Japanese academic institution.

BACKGROUND: This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID). METHODS: A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93). RESULTS: The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization. CONCLUSIONS: Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID.

Relationship between occlusal force and endothelial function in community-dwelling elderly women: A pilot study.

OBJECTIVE: In this study, age, endothelial function as flow-mediated dilation (FMD), occlusal force, grip strength, and advanced glycation end products (AGEs) were obtained. AGEs were measured as indicators of aging, while grip strength was measured as an indicator of muscle strength. This study aimed to explain the relationship between occlusal force and endothelial function and determine whether occlusal force can be a new indicator in community preventative care projects. MATERIALS AND METHODS: In 38 community-dwelling women (age, 76.7 ± 5.7 years), the occlusal force and grip strength were measured, the endothelial function was evaluated by FMD, and AGEs were obtained. The relationship between occlusal force, measurement items, and factors were investigated independently related to endothelial function. RESULTS: There were significant correlations between occlusal force and grip strength (r = .54, p < .01). The degree of FMD was significantly associated with occlusal force (r = .60, p < .01) and grip strength (r = .35, p < .05) or increase in AGEs (r = -.37, p < .05). Multiple regression analysis revealed that occlusal force was significantly associated with the degree of FMD (p < .01). CONCLUSION: Occlusal force can be an important indicator of endothelial function in the community-dwelling elderly. This study may help understand the general health of the elderly in communities.

Association between mammographic breast composition and breast cancer risk among Japanese women: a retrospective cohort study.

BACKGROUND: Mammographic breast composition is associated with breast cancer risk. However, evidence in a Japanese cohort investigating this association is scarce. Thus, we aimed to compare breast cancer risk between women with and without dense breasts. METHODS: All Japanese women who underwent breast cancer screening at a tertiary care academic hospital-affiliated preventive center at least twice with known baseline mammographic breast composition were included in this study. A single-center retrospective cohort study was conducted among 24,863 women who had 125,566 screening opportunities between April 1, 2005, and March 31, 2015. All women were categorized into two groups based on their baseline breast composition: women with dense breasts (13,815) and women with non-dense breasts (11,048). We compared the demographic characteristics between the two groups. After calculating person-years, Cox proportional hazards analyses were performed to estimate the hazard ratio (HR) of developing breast cancer according to breast composition status. RESULTS: During the study period, 358 breast cancer cases were identified. The dense and non-dense groups differed significantly by age, body mass index, family history of breast cancer, physical activity, history of smoking and alcohol consumption, number of pregnancies, and number of deliveries. After adjusting for these factors, Cox proportional hazards analyses showed that women with dense breasts had a significantly higher HR for developing breast cancer than women without dense breasts. The association was even stronger in younger women (≤ 50 years old), but it did not achieve statistical significance in older women. CONCLUSION: Dense breasts at baseline are a risk factor for developing breast cancer in Japanese women. However, this association was only observed in women aged 50 years or younger at the time of entry into the screening program.

The Association between Chronic Hemodialysis and Toe Pinch Force in Japanese Patients: Cross-Sectional Study.

The purpose of this cross-sectional study was to investigate the effect of chronic hemodialysis on toe pinch force (TPF). A total of 37 chronic hemodialysis patients without type 2 diabetes mellitus (T2DM) (age: 69.4 ± 11.8 years, duration of hemodialysis: 3.5 ± 3.4 years) were enrolled in this study. The TPF in chronic hemodialysis patients without T2DM was compared with that in 34 apparently healthy participants and 37 chronic hemodialysis patients with T2DM. There was no significant difference in clinical profiles between healthy participants and chronic hemodialysis patients with and without T2DM. The TPF in chronic hemodialysis patients without T2DM was lower compared with that in healthy participants (2.70 ± 1.05 kg vs. 3.34 ± 0.99 kg, p = 0.025). In addition, the TPF in patients with T2DM was even lower compared with that in patients without T2DM (2.12 ± 1.01 kg vs. 2.70 ± 1.05 kg, p = 0.042). This study showed a dramatic reduction in TPF in chronic hemodialysis patients, especially in those with T2DM.

Accuracy of morphologic change measurements by ultrasound in predicting pathological response to neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard therapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer (HER2 + ve BC). There are concerns about the accurate imaging modalities to measure residual tumor during or after NAC. Up to now no standard imaging method for monitoring the efficacy of NAC has been established, and few reports showed ultrasonographic change. We aimed to assess the echogenicity in ultrasonography (US) as the predictive marker of pathological complete response (pCR) for not only TNBC, but also HER2 + ve BC. Furthermore, we also investigated the change in depth (D) and width (W) of the tumor as the predictive value of pCR. METHODS: We retrospectively reviewed a consecutive 59 patients with TNBC and 41 patients with HER2 + ve BC who received NAC. In all of 100 patients, echogenicity, D and W of the tumor were measured before (pre-NAC) and after NAC (post-NAC). The tumor echogenicity was measured at representative region of interest (ROI), and calculated as the relative comparative assessment with fat echogenicity (ROI ratio). RESULTS: pCR was significantly associated with higher post-NAC ROI ratio in TNBC (p = 0.010), while there was no association in HER2 + ve BC (p = 0.885). pCR was significantly associated with smaller sizes of post-NAC D and W in TNBC (p = 0.001, 0.003), while no trend was observed in HER2 + ve BC (p = 0.259, 0.435). The area under the curve (AUC) for post-NAC ROI ratio and D were 0.701, 0.755, respectively. Combined with them, AUC became higher up to 0.762. CONCLUSION: TNBC and HER2 + ve BC showed different morphologic features of residual disease. Echogenicity and tumor size after NAC were both useful to predict pCR for TNBC, but not HER2 + ve BC. In future, radiological imaging needs to be analyzed in terms of breast cancer subtypes.

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.

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).

Somatic mutations, clinicopathologic characteristics, and survival in patients with untreated breast cancer with bone-only and non-bone sites of first metastasis.

Background: Bone is the most common site of metastasis of breast cancer. Biological mechanisms of metastasis to bone may be different from mechanisms of metastasis to non-bone sites, and identification of distinct signaling pathways and somatic mutations may provide insights on biology and rational targets for treatment and prevention of bone metastasis. The aims of this study were to compare and contrast somatic mutations, clinicopathologic characteristics, and survival in breast cancer patients with bone-only versus non-bone sites of first metastasis. Methods: Primary tumor samples were collected before treatment from 389 patients with untreated primary breast cancer and distant metastasis at diagnosis. In each sample, 46 or 50 cancer-related genes were analyzed for mutations by AmpliSeq Ion Torrent next-generation sequencing. Fisher's exact test was used to identify somatic mutations associated with bone-only first metastasis. Logistic regression models were used to identify differences in detected somatic mutations, clinicopathologic characteristics, and survival between patients with bone-only first metastasis and patients with first metastasis in non-bone sites only ("other-only first metastasis"). Results: Among the 389 patients, 72 (18.5%) had bone-only first metastasis, 223 (57.3%) had other-only first metastasis, and 94 (24.2%) had first metastasis in both bone and non-bone sites. The most commonly mutated genes were TP53 (N=103), PIK3CA (N=79), AKT (N=13), and PTEN (N=2). Compared to patients with other-only first metastasis, patients with bone-only first metastasis had higher rates of hormone-receptor-positive disease, non-triple-negative subtype, and lower grade (grade 1 or 2; Nottingham grading system) (all three comparisons, p<0.001); had a lower ratio of cases of invasive ductal carcinoma to cases of invasive lobular carcinoma (p=0.002); and tended to have a higher 5-year overall survival (OS) rate (78.2% [95% confidence interval (CI), 68.6%-89.0%] vs 55.0% [95% CI, 48.1%-62.9%]; p=0.051). However, in the subgroup of patients with TP53 mutation and in the subgroup of patients with PIK3CA mutation, OS did not differ between patients with bone-only and other-only first metastasis (p=0.49 and p=0.68, respectively). In univariate analysis, the rate of TP53 mutation tended to be lower in patients with bone-only first metastasis than in those with other-only first metastasis (15.3% vs 29.1%; p=0.051). In multivariate analysis, TP53 mutation was not significantly associated with site of first metastasis (p=0.54) but was significantly associated with hormone-receptor-negative disease (p<0.001). Conclusions: We did not find associations between somatic mutations and bone-only first metastasis in patients with untreated breast cancer. Patients with bone-only first metastasis tend to have longer OS than patients with other-only first metastasis. More comprehensive molecular analysis may be needed to further understand the factors associated with bone-only metastatic disease in breast cancer.

Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer.

Importance: Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective: To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants: Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention: Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures: The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results: Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor-positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor-positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance: This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration: ClinicalTrials.gov Identifier: NCT01036087.

Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: An international collaboration and individual patient meta-analysis.

BACKGROUND: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT. METHODS: Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively. RESULTS: A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively. CONCLUSIONS: BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up. Cancer 2018;124:2923-30. © 2018 American Cancer Society.

Prior systemic treatment increased the incidence of somatic mutations in metastatic breast cancer.

BACKGROUND: Understanding the biology of breast cancer is important for guiding treatment strategies and revealing resistance mechanisms. Our objectives were to investigate the relationship between previous systemic therapy exposure and mutational spectrum in metastatic breast cancer and to identify clinicopathological factors associated with identified frequent somatic mutations. METHODS: Archival tissues of patients with metastatic breast cancer were subjected to hotspot molecular testing by next-generation sequencing. The variables that significantly differed (P < 0.05) in univariate analysis were selected to fit multivariate models. Logistic models were fit to estimate the association between mutation status and clinical variables of interest. Five-fold cross-validation was performed to estimate the prediction error of each model. RESULTS: A total of 922 patients were included in the analysis. In multivariate analysis, previous systemic treatment before molecular testing (N = 186) was associated with a significantly higher rate of TP53 and PIK3CA mutations compared with the lack of systemic treatment (P < 0.001 for both). CONCLUSION: Systemic treatment exposure is an independent risk factor for high rates of TP53 and PIK3CA mutation, which suggests the importance of testing samples after systemic therapy to accurately assess mutations. It is worth testing the gene profile when tumours become resistant to systemic treatments.

Change in sonographic brightness can predict pathological response of triple-negative breast cancer to neoadjuvant chemotherapy.

INTRODUCTION: Ultrasound (US) is conventionally performed to determine effects of neoadjuvant chemotherapy (NAC) on breast cancer. In patients with triple-negative breast cancer (TNBC), higher pathological complete response (pCR) predicts the most favorable survival outcome. We aimed to predict pCR to NAC using echogenicity changes in US region of interest (ROI) in patients with TNBC. METHODS AND MATERIALS: We retrospectively determined clinicopathological characteristics of 52 patients with primary TNBC who underwent NAC. Changes in echogenicity for pCR and non-pCR patients were calculated from ratios of tumor to fat (T/F) in their ROIs, before and after NAC, as [T/F After/T/F Before] and [T/F After - T/F Before]. RESULTS: Of the 52 patients (median age: 52 years; range 26-77 years), 20 (38.5%) achieved pCR, which was significantly associated with change in ROI ratio (P < 0.01). The cut-off values for ROI ratio and ROI difference were 0.8 and 0.3. Sensitivity and specificity were 73.7 and 81.8% for ROI ratio, and 70.0 and 81.3% for ROI difference. Area under the curves (AUCs) for ROI ratio and ROI difference were 0.80 [95% confidence interval (CI) 0.67-0.92] and 0.78 (95% CI 0.64-0.92), respectively. CONCLUSION: Quantification of echogenic changes by converting absolute values of tumor and fat regions can predict pCR and individual differences between tumors after NAC in patients with TNBC.

The Prognostic Effect of Changes in Tumor Stage and Nodal Status After Neoadjuvant Chemotherapy in Each Primary Breast Cancer Subtype.

BACKGROUND: Although the prognostic value of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) depends on the intrinsic subtype of breast cancer, it is not clear whether chemosensitivity itself, shown by a decreasing tumor burden after NAC, contributes to improved prognosis in primary breast cancer patients, especially in patients with non-pCR. The aim of this study was to assess the prognostic effect of changes in tumor stage or nodal status after NAC in each primary breast cancer subtype. PATIENTS AND METHODS: We assessed 719 consecutive patients with primary breast cancer who underwent surgical resection after NAC between 2001 and 2010. The patients were divided into 5 subtypes according to their hormone receptor (HR) status, HER2 status, and nuclear grade (NG; 1/2 = low, and 3 = high). RESULTS: In patients with HR-positive (HR+)/HER2-/NG-low tumors, regardless of change in tumor size, the loss of node positivity after NAC significantly improved disease-free survival (DFS). In patients with HR+/HER2-/NG-high tumors, achievement of tumor downstaging as well as the loss of node positivity improved their DFS. In patients with HR-/HER2- tumors, tumor downstaging and the loss of node positivity significantly improved DFS, despite a non-pCR. In contrast, in patients with HER2+ tumors, changes in tumor stage or nodal status were not associated with prognosis unless pCR was achieved. CONCLUSION: Our results revealed that changes in tumor stage and nodal status after NAC might be prognostic markers in patients with HR+/HER2-/NG-high tumors or HR-/HER2- tumors, even if there are residual tumors in the breast.

Identification of frequent somatic mutations in inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer is an aggressive form of breast cancer that shows distinct clinical features from non-inflammatory breast cancer. Genomic understanding of inflammatory breast cancer will shed light on biological targets for this disease. Our objective was to identify targeted hotspot mutations using multiplex genome sequencing in inflammatory breast cancer and compare the findings with those for patients with non-inflammatory breast cancer to further recognize novel targets. METHODS: We studied 400 patients with metastatic breast cancer who had somatic hotspot mutation testing using a 46- or 50-gene multiplex platform from March 2012 to December 2014. Among this population, 24 patients had inflammatory breast cancer and 376 patients had non-inflammatory breast cancer. We tested a total of 26 samples from 24 patients with inflammatory breast cancer. RESULTS: The average number of mutations per patient was higher in inflammatory breast cancer than in non-inflammatory breast cancer (1.23 vs. 0.65, respectively). Identified somatic mutations in inflammatory breast cancer were TP53 (n = 18, 75%), PIK3CA (n = 10, 41.7%), and ERBB2 (n = 4, 16.7%). TP53 and ERBB2 mutations were significantly more prevalent in inflammatory breast cancer than in non-inflammatory breast cancer (P < 0.01). All patients with ERBB2 mutations had hormone receptor (HR)+ primary tumors. CONCLUSIONS: TP53, PIK3CA, and ERBB2 were detected as three major somatic mutations in metastatic inflammatory breast cancer patients. While the inflammatory breast cancer TP53 and PIK3CA mutations mirrored previously reported data for metastatic non-inflammatory breast cancer, this is the first report of higher frequency of ERBB2 mutation in inflammatory breast cancer, especially in the HR+ subtype. Once validated in a larger cohort of inflammatory breast cancer patients, this novel finding could lead to development of treatments for HR+ inflammatory breast cancer.

Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.

INTRODUCTION: Epidermal growth factor receptor (EGFR) targeted treatment has been evaluated but has not shown a clear clinical benefit for breast cancer. This review article aims to consider the knowledge of the biological background of EGFR pathways in dissecting clinical studies of EGFR targeted treatment in breast cancer. Areas covered: This review focuses on the role of the EGFR pathway and the investigational drugs that target EGFR for breast cancer. Expert opinion: Recent studies have indicated that EGFR targeted therapy for breast cancer has some promising effects for patients with triple-negative breast cancer, basal-like breast cancer, and inflammatory breast cancer. However, predictive and prognostic biomarkers for EGFR targeted therapy have not been identified. The overexpression or amplification of EGFR itself may not be the true factor of induction of the canonical pathway as an oncogenic driver of breast cancer. Instead, downstream, non-canonical pathways related to EGFR may contribute to some aspects of the biological behavior of breast cancer; therefore, the blockade of the receptor could result in sufficient suppression of downstream pathways to inhibit the aggressive behavior of breast cancer. Mechanistic studies to investigate the dynamic interaction between the EGFR pathway and non-canonical pathways are warranted.

[The Role of Preoperative Chemotherapy Depending on Breast Cancer Subtype].

Following the discovery that the prognostic impact of preoperative chemotherapy depends on the primary breast cancer subtype, the treatment strategy for primary breast cancer changed. Pathologic complete response(pCR)with preoperative chemotherapy is predictive of a favorable prognosis in patients with HER2 type or triple-negative type breast cancer, but not in patients with ER-positive/HER2-negative, the so-called Luminal type, breast cancer. However, the role of preoperative chemotherapy in patients with Luminal-B type breast cancer who may need chemotherapy should be further assessed. Recent studies have reported severalsubtypes of triple-negative breast cancer, distinguishable by gene expression analysis, which may respond differently to treatment. Furthermore, novel agents, including pertuzumab or T-DM1 for HER2 type breast cancer, bevacizumab or PARP inhibitors for triple negative-breast cancer, or combination regimens with these novelagents, are expected to achieve higher pCR rates and improve patient prognosis. The tumor microenvironment may also play an important role in predicting treatment response or prognosis. It is important that tailor-made treatment strategies for patients with primary breast cancer, especially for patients who will not respond favorably to current standard therapies, consider both the treatment effects and the medicaleconomic effects.

A nomogram for predicting locoregional recurrence in primary breast cancer patients who received breast-conserving surgery after neoadjuvant chemotherapy.

BACKGROUND: We sought to develop and validate a predictive model of locoregional recurrence (LRR) in patients who underwent breast-conserving therapy (BCT) after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: The clinicopathological characteristics of 520 consecutive primary breast cancer patients with residual tumor who underwent BCT after NAC between 2001 and 2008 were evaluated. Predictive variables of LRR were determined using a multivariate Cox proportional hazards model. The model was validated for discrimination and calibration by bootstrap re-sampling. RESULTS: At a median follow-up period of 51 months, 64 patients (12%) had developed LRR. Clinical stage T3 or T4, lymphovascular invasion, nuclear grade >3, and ≥4 positive lymph nodes metastasis were positively correlated with LRR. The nomogram for predicting LRR developed by using these four-clinicopathologic variables demonstrated high concordance. Patients with score 0-1 derived by the prediction model had significantly low LRR rate compared with patients with score 2 or higher (P < 0.001). CONCLUSIONS: This nomogram may be useful to predict LRR in primary breast cancer patients who underwent BCT after NAC with high reproducibility. This model is useful to conduct a study-identifying patients who may need an additional treatment to standard adjuvant therapy because of a high probability of LRR.

Higher sika deer density is associated with higher local abundance of Haemaphysalis longicornis nymphs and adults but not larvae in central Japan.

Haemaphysalis longicornis (Acari: Ixodidae) is one of the most common and important arthropod disease vectors in Japan, carrying Japanese spotted fever and bovine theileriosis. The recent expansion of sika deer (Cervus nippon, Artiodactyla: Cervidae) populations, the most common wild host of H. longicornis, has also caused concern about increasing the risk of vector-borne diseases in Japan. We used generalized linear mixed model analysis to determine the relative contribution of deer density and other biological and abiotic factors on the abundance of H. longicornis ticks questing at each developmental stage. A total of 6223 H. longicornis adults, nymphs, and larvae were collected from 70 sites in three regions of central Japan. The abundance of questing adult and nymphal ticks was associated with deer density and other biotic and abiotic factors. However, the abundance of questing larvae showed no association with deer density but did show an association with other biotic and abiotic factors. These findings show that a high density of deer along with other biotic and abiotic factors is associated with increased risk of vector-borne diseases through amplified local abundance of questing nymphal and adult H. longicornis. Further, questing larvae abundance is likely regulated by environmental conditions and is likely correlated with survival potential or the distribution of other host species.

Sentinel node biopsy after neoadjuvant chemotherapy in cytologically proven node-positive breast cancer.

INTRODUCTION: Several studies have assessed the feasibility of sentinel lymph node biopsy (SLNB) after NAC in patients with breast cancer, but diagnostic accuracy has varied. We prospectively evaluated the diagnostic accuracy of SLNB in detecting axillary lymph node (ALN) metastases after NAC in patients with cytologically proven positive nodes before chemotherapy. PATIENTS AND METHODS: We studied 95 breast cancer patients with cytologically proven positive nodes and a partial or complete clinical response to NAC in the breast lesions confirmed using magnetic resonance imaging. Patients then underwent SLNB followed by ALN dissection. The identification rate of sentinel lymph nodes (SLNs) and the false negative rate of nodal metastases were assessed. Subgroup analysis was conducted according to several clinical factors. RESULTS: SLNs were successfully identified in 81 (85.3%) of the 95 patients. Among these 81 patients, 51 (63.0%) had ALN metastases on final pathologic examination after NAC. Eight of the 51 patients with ALN metastases had negative results on SLNB (false negative rate, 15.7%). Univariate analysis indicated that the false negative rate was significantly lower only in the HER2-negative group (P = .003). CONCLUSION: SLNB after NAC did not correctly predict the presence or absence of axillary node metastases in patients with breast cancer who had cytologically proven positive nodes before NAC. However, the diagnostic accuracy might be different in cancer subtypes, therapeutic effect of chemotherapy, or sentinel lymph node status after chemotherapy. Well-powered studies are needed to confirm diagnostic accuracy of SLNB after NAC according to subgroup in patients with breast cancer.