長嶋 健

若年者の乳腺葉状腫瘍はまれであり,線維腺腫,特に若年性線維腺腫との鑑別は困難である.これまでは線維腺腫であれば腫瘤摘出術,葉状腫瘍であればマージンをつけた切除が必要とされてきたが,近年,葉状腫瘍に対する手術においても断端陰性であればマージンは不要であるという報告が増加している.症例は11歳,女児.左乳房に7cm大の腫瘤を自覚し受診.画像検査および針生検では若年性線維腺腫もしくは良性葉状腫瘍が疑われ,腫瘤摘出術を施行した.病理結果は良性葉状腫瘍で断端は陰性であった.自験例では良性葉状腫瘍であったことと,腫瘤摘出術によって断端陰性が得られたことより,追加切除は施行せず,術後6年6ヵ月無再発で経過している.若年者の葉状腫瘍に対する治療において,根治性とともに整容性や機能温存へ十分配慮した上での方針決定が望まれる.(著者抄録)

BACKGROUND: Tumors can acquire tolerance to tumor immunity and develop enhanced proliferation. Regulatory B cells (Bregs), whose role in immune tolerance is similar to that of regulatory T cells (Tregs), appear to be involved in tumor immunity. Recently, Bregs were found to induce Tregs against tumor immunity. However, the platform for the coexistence of Bregs and Tregs in cancer patients and its clinical significance remain unclear; thus, they were evaluated in breast cancer patients. METHODS: In 489 breast cancer patients, CD25- and IL10-positive Bregs and Foxp3-positive Tregs were immunohistochemically evaluated in tumor-infiltrating lymphocyte aggregates (TIL aggregates) that consisted of CD19-positive B-cell follicles and CD3-positive T-cell parafollicles. Then the correlations of the localization and existence of these cells with metastasis-free survival (MFS) were evaluated in breast cancer patients. RESULTS: TIL aggregates were observed in marginal regions of tumors in breast cancer patients. In the TIL aggregates, the existence of Bregs was closely related to that of Tregs (p < 0.0001). On multivariate analysis, the coexistence of Bregs and Tregs in TIL aggregates was correlated with MFS in breast cancer patients (p = 0.007). Furthermore, MFS was significantly shorter for patients with the coexistence of Tregs and Bregs in TIL aggregates than in those with Tregs alone without Bregs (p = 0.0475). CONCLUSIONS: The present results suggest that Bregs are related to the induction of Tregs in TIL aggregates and the development of metastasis of breast cancer cells. Bregs are expected to be a new diagnostic and therapeutic target in breast cancer patients.

オンコプラスティックサージェリー(OBS)は、癌を取り除く適切な手術と広範切除に伴う部分再建、全摘後再建および対称性を得るための対側の修正術からなる領域である。OBSの手技は、欠損部修復に乳房内組織を用いるvolume displacement technique(VD)と乳房外組織を用いるvolume replacement technique(VR)に大別され、乳房および腫瘍のサイズと占拠部位によって使い分ける。乳房温存術におけるOBSの概要と諸問題について解説した。

Neoadjuvant chemotherapy (NAC) with anthracyclines followed by taxane chemotherapy has become the standard treatment for patients with locally advanced, operable breast cancer. Recently, the efficacy of nanoparticle albumin-bound paclitaxel (nab-PTX) for metastatic breast cancer was reported. However, there are still few studies of a neoadjuvant regimen including nab-PTX. Thus, the present phase II study evaluated the efficacy and safety of 5-fluorouracil, epirubicin and cyclophosphamide (FEC regimen) followed by nab-PTX as neoadjuvant treatment for operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Women with operable HER2-negative breast cancer (clinical stage T1a-4N1-3) received 4 cycles of FEC (5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days), followed by 4 cycles of nab-PTX at 260 mg/m2 every 21 days. The patients then underwent mastectomy or breast-conserving surgery (BCS). The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included clinical response rate, pathological response rate, BCS rate and safety. A total of 16 patients were evaluated and 3 patients (18%) achieved pCR (1 patient with estrogen receptor-positive cancer and 2 with estrogen receptor-negative cancer). The pCR rate was 12 and 25% in patients with estrogen receptor-positive and -negative cancers, respectively. The clinical response rate was 100% (clinical complete and partial response in 6 and 10 patients, respectively). The BCS rate was 31.25%. Three patients experienced grade 3 neutropenia during FEC therapy, and no grade 3/4 events occurred during nab-PTX therapy. Thus, neoadjuvant therapy with FEC followed by nab-PTX for operable HER2-negative breast cancer was found to be a safe and effective option.

Background We evaluated the relationship between the immunohistochemically determined expression of the cell polarity protein scribble to prognosis in different environments of estrogen receptor (ER) expression and epithelial-to-mesenchymal transition (EMT). Methods We immunohistochemically evaluated the expression level of scribble in primary tumors and lymph node metastases of 225 node-positive breast cancer patients who had received chemotherapy. We then evaluated metastasis-free survival (MFS) in the absence or presence of ER and the EMT-related protein vimentin. Results Among patients with ER-positive tumors, patients with low scribble expression in the primary tumor had a significantly shorter MFS than patients with high scribble expression (p = 0.0225). Furthermore, among patients with vimentin-negative tumors, patients with low expression of scribble in the primary tumor had significantly shorter MFS than patients with high expression of scribble (p = 0.0463). In contrast, among patients with vimentin-positive tumors, patients with high expression of scribble in the primary tumor had significantly shorter MFS than patients with low expression of scribble (p = 0.0343). Moreover, among patients with ER-negative tumors, patients with high expression of scribble in lymph node metastases showed significantly higher expression of E-cadherin in metastases (p = 0.0407) and had significantly shorter MFS than patients with low expression of scribble (p = 0.0064). Conclusions The prognostic significance of cell polarity depended on the ER expression and EMT. Furthermore, the preservation of cell polarity in metastases was associated with mesenchymal-to-epithelial transition and worse prognosis. Cell polarity promotes the diversity of metastasis in combination with malignancy grade in breast cancer patients.

The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

We report a case of breast-conserving surgeryusing real-time virtual sonography(RVS)in a breast cancer patient who received neoadjuvant chemotherapy(NAC). The patient was a 63-year-old woman. Ultrasound(US)showed a lobulated 45 ×40×40mm diameter mass in the C area of the right breast. Histological examination found invasive ductal carcinoma that was negative for estrogen and progesterone receptors and for human epidermal growth factor receptor type 2/neu protein expression, and the Ki-67 index was 50%. The patient was diagnosed with breast cancer clinical stage II A(T2N0M0). The basal-like subtype is more sensitive to anthracycline-based NAC than luminal breast cancers. The patient wanted breastconserving surgery. Therefore, we treated the patient with NAC. First, we obtained US volume data of the tumor as a Digital Imaging and Communication in Medicine(DICOM)file, simplyscanning the skin over the lesion gentlywith the probe. We administered tri-weeklynanoparticle albumin-bound paclitaxel(nab PTX)followed bya fluorouracil, epirubicin, and cyclophosphamide( FEC)regimen. Follow-up computed tomography(CT)and US showed good tumor concentric shrinkage without anysurrounding lesion after NAC. Finally, right breast-conserving surgerywas performed, using RVS to detect the area where the tumor was before NAC in the US image after NAC. Histopathologically, the effect of the chemotherapy was Grade 2a and the surgical margins were negative.

Background: The critical issue related to breast-conserving therapy (BCT) is that cosmetic outcomes deteriorate with long-term follow-up. There is little research for breast density as a predictor of cosmetic outcomes at the late stage after BCT. To improve the long-term quality of life after BCT of breast cancer patients, the correlation of volumetric breast density (VBD) and cosmetic outcome at the late stage after BCT was evaluated. Study design: Breast volume, fibroglandular tissue volume, adipose tissue volume, and VBD were calculated on mammography using image analysis software (Volpara (R)) in 151 patients with BCT. Furthermore, the correlation of breast density and the change of breast volume over time was analyzed on mammography in 99 patients who were followed-up long-term after BCT. Results: On multivariate analysis, VBD was a predictor of cosmetic outcome after BCT with percent breast volume excised (PBVE). Decreased adipose tissue volume and increased fibrosis were more common in patients with VBD &lt; 15%. Furthermore, remnant breast volume continued to decrease over time in low breast density patients during long-term follow-up. 93% of patients with VBD &gt;= 15% and PBVE &lt; 10% had a better cosmetic outcome, while 60% of patients with VBD &lt; 15% and PBVE &gt;= 10% had a worse cosmetic outcome after BCT. Conclusions: While PBVE was involved in cosmetic outcome at the early stage after BCT, VBD was associated with cosmetic outcome at the late stage after BCT. Thus, a combination of VBD and PBVE could predict cosmetic outcome after BCT and contribute to the selection for the appropriate BCT. (C) 2016 Elsevier Ltd. All rights reserved.

Obesity is known to decrease the efficacy of neoadjuvant chemotherapy (NAC) against breast cancer; however, the relationship between actual body composition and NAC outcomes remains unknown. Therefore, we determined the effect of body composition on NAC outcomes. A total of 172 advanced breast cancer patients who underwent surgery after NAC were retrospectively analyzed. Body composition parameters including abdominal circumference (AC), subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle area (SMA) were calculated using computed tomography volume-analyzing software. VFA/SFA ratio was used to evaluate visceral obesity. The associations of body composition parameters with pathological complete remission (pCR) and survival were analyzed. AC, SFA, and VFA were significantly correlated with body mass index (BMI) (all P&lt;0.05; r=0.82, r=0.71, and r=0.78, respectively). AC, SFA, and VFA increased significantly and SMA decreased significantly after menopause (all P&lt;0.05). VFA/SFA ratio increased significantly after menopause, even though BMI remained unchanged. Body composition parameters were not associated with pCR. Distant disease-free survival (DDFS) was significantly worse in the high VFA group than in the low VFA group (P&lt;0.05). Furthermore, in the high VFA group, postmenopausal patients had significantly shorter DDFS than premenopausal patients (P&lt;0.05). VFA was independently associated with DDFS in the multivariate analysis (P&lt;0.05). High visceral fat is associated with worse NAC outcomes in breast cancer patients, especially postmenopausal patients. Interventions targeting visceral fat accumulation will likely improve NAC outcomes.

Although radiofrequency ablation (RFA) is promising for the local treatment of breast cancer, data concerning the longterm results are limited. The present study attempted to evaluate the safety and efficacy of RFA and to clarify patient outcomes after treatment. The study included 26 breast cancer patients treated with RFA between 2006 and 2010. There were no acute complications such as burns. All subjects were followed-up after breast radiation and systemic therapies. At the median follow-up period of 88 months, no local recurrence or distant metastases had occurred. After treatment, a hard lump was formed around the ablated area, which gradually decreased in size in all cases (p<0.001). The lumps were calcified in 9 cases. Nipple retraction persisted in 2 cases. However, it is necessary to recognize that a cosmetic result of RFA was not excellent in all cases, RFA appears to be a safe local treatment technique for breast cancer patients.

A 44 -year-old woman presented at the outpatient department with a chief complaint of swelling in the right breast. MRI showed a huge breast tumor accompanied by solitary enhanced masses in the pectoralis major muscle. After receiving neoadjuvant chemotherapy, she underwent mastectomy (Halsted operation) and axillary dissection. Pathological examination revealed an E-cadherin-positive infiltrating lobular carcinoma (ILC), and the absence of residual tumor in the muscle was confirmed. In cases of solitary metastasis in the muscle, treatment selection is sometimes difficult. Further research is needed to determine whether surgery contributes to local control in cases of advanced ILC with muscle metastasis.

BACKGROUND: To achieve an unnoticeable postoperative scar in patients with little abdominal skin laxity for breast reconstruction by deep inferior epigastric artery perforator (DIEP) flap, we devised a new design called the low-rise scar DIEP flap; the skin paddle of this flap is located lower with a smaller vertical width, and more adipose tissue is elevated to obtain enough volume. The purpose of this report is to evaluate the utility of the low-rise scar DIEP flap compared with that of the conventionally designed flap. METHODS: Twelve patients who underwent low-rise scar DIEP flaps (study group) and 11 patients who underwent conventionally-designed DIEP flaps (control group) were included in the present study. The distance from the umbilicus to horizontal scar was divided by the patient's height. The length of the scar was divided by the abdominal circumference. These ratios were compared between groups. RESULTS: All flaps survived completely and no recipient site complication was observed, except for one case in the control group with small-range fat necrosis. No donor site complication was observed in either group. The distance ratio was significantly larger in study group (<0.01, 0.049 ± 0.004, and 0.028 ± 0.005, respectively). The length ratio was significantly smaller in the study group <0.01, 0.42 ± 0.02 and 0.36 ± 0.02, respectively). The weight of the flap used for reconstruction was 338.8 ± 127.7 g in the study group and 320.5 ± 63.0 g in the control group CONCLUSIONS: A low-rise scar DIEP flap leaves a lower and shorter postoperative scar.

The objective of this study is to investigate interactions between adipocytes and breast cancer cells, and identify the responsible factors for the observed effects. In 27 breast cancer patients undergoing mastectomy, mammary adipose tissue was obtained from the breast quadrant bearing the tumor and corresponding non-tumoral quadrant. Isolated normal breast adipocytes (NBAs) and cancer-associated adipocytes (CAAs) were cultured in collagen gels to mimic the in vivo environment. Immunohistochemistry, qRT-PCR, and cell proliferation assays were performed to analyze adipocyte phenotypes. MCF7 and MDA-MB-231 breast cancer cell lines were co-cultured with adipocytes to detect phenotypic changes. Migration of MCF7 and MDA-MB-231 cells was assessed in NBA- and CAA-conditioned media. Cytokine levels in conditioned media were measured by cytokine array. Migration assays were repeated using conditioned media containing neutralizing antibodies. NBAs and CAAs lost their morphological phenotype in culture, acquiring a spindle-like shape, and CAAs showed higher cell proliferation, suggesting reversion to an immature phenotype. In co-cultures with MCF7 or MDA-MB-231 cells, NBAs exhibited increased cell proliferation, indicating acquisition of the immature phenotype of CAAs. MCF7 and MDA-MB-231 showed higher migration in a CAA-conditioned medium than in an NBA-conditioned medium. Cytokine array analysis of conditioned media revealed higher levels of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in the CAA-conditioned medium. Neutralization experiments using antibodies against IL-6 or MCP-1 showed abrogation of migration-enhancing effects of the CAA-conditioned medium. Adipocytes revert to an immature and proliferative phenotype in the presence of breast cancer cells, and promote cancer cell migration via adipokines including IL-6 and MCP-1.

The aim of the present study was to investigate the relationships between the automated bone scan index (aBSI) and skeletal-related events (SRE) in breast cancer patients with bone metastasis. A computer-aided software (BONENAVI (TM)) that was developed using an Artificial Neural Network (Artificial Neural Network) was used for the present analysis. Forty-five patients diagnosed with bone metastasis due to breast cancer from April 2005 through March 2013 were retrospectively analyzed. Before and after the time of initial treatment, aBSI, Artificial Neural Network score, and hotspot number were calculated, and the relationships between these scores and SRE were analyzed. Twenty cases showed decreased (improved) aBSI values after initial treatment (Group A), and 25 cases showed unchanged/increased (worsened) aBSI values (Group B). Chi-square analysis revealed a significant difference in incident numbers of SRE between the two groups-one case in Group A and 12 in Group B (P &lt; 0.001). Event-free survival was significantly shorter in Group B (hazard ratio: 8.31, 95% CI: 1.33-12.14, log-rank test; P &lt; 0.05). The groupswere also divided by the results of 2 radiologists' visual scan interpretations, and no significant differenceswere shown in the number of SRE (P = 0.82, P = 0.10). When correlation analyses were performed between aBSI and bone metabolic or tumor markers, alkaline phosphatase was significantly correlated with aBSI at the time of initial treatment (R = 0.69, P &lt; 0.05). In conclusion, aBSI is proposed as a useful and objective imaging biomarker in the detection of breast-cancer patients with bone metastasis at high risk of SRE.

Conventional imaging does not always accurately depict the pathological response to neoadjuvant chemotherapy (NAC). Diffusion-weighted imaging (DWI) may provide additional insight into the chemotherapeutic effect. This study assessed whether the apparent diffusion coefficient (ADC) correlated with pathological outcome and prognosis in breast cancer patients receiving NAC. Fifty-six patients with locally advanced breast cancer received surgery after NAC. Dynamic contrast-enhanced (DCE) and DWI were performed before and after NAC. The pathological response was classified into five categories from no response to complete response according to amount of residual cancer. The correlation between ADC and postoperative pathologic and prognostic outcome was assessed. The distribution of the pathological response classification was as follows: no response, 3 cases; mild response, 22 cases; moderate response, 12 cases; marked response, 11 cases; complete response, 8 cases. ADC after NAC correlated with pathological response, but ADC before NAC did not. The change in ADC after chemotherapy had better correlation coefficient (r = 0.67) than change in size (r = 0.58) and ADC after NAC (r = 0.64). Although the group with larger change of tumor size showed only marginal significance compared with the smaller change group (p = 0.089), the group with higher change of ADC showed significantly better prognosis than the lower one (p = 0.038). Change in ADC after chemotherapy better correlated with pathological outcome and prognosis than change in tumor size. DWI has potential in evaluating the pathological outcome of NAC in breast cancer patients.

BACKGROUND: We designed MRI-guided quadrantectomy using 2-dimensional images reconstructed from MRI to enable virtual simulation of breast-conserving surgery. This study evaluated the efficacy of our approach, which involved projection of the 2-dimensional reconstruction images directly onto the breast to guide planned resection compared with the conventional approach with preoperative localization with hooked wires, for patients with ductal carcinoma in situ (DCIS) detected by mammographic calcifications. STUDY DESIGN: Eighty-six patients with calcifications &gt;= 2 cm in diameter on mammogram who were diagnosed with DCIS on preoperative percutaneous biopsy underwent breast-conserving surgery. In 32 patients, lesion localization was done using the conventional technique of hooked wires. In 54 patients, preoperative planning was performed using supine MRI and projection of reconstructed 2-dimensional images directly onto the breast surface. Surgical outcomes in the 2 groups were compared. In the latter group, we also compared accuracy of DCIS detection between supine MRI and specimen mammography. RESULTS: Final pathologic assessment of the 86 patients was DCIS in 67 and DCIS with microinvasion (T1mic) in 19 patients. The rate of additional intraoperative margin resection and presence of DCIS at the surgical margin were significantly lower with our MRI-guided technique vs the hooked-wire approach. Supine MRI detected a considerably larger area of DCIS than did specimen mammography. CONCLUSIONS: Compared with a conventional approach using hooked wires, our MRI-guided quadrantectomy might be useful for patients with DCIS and DCIS with T1mic detected by mammographic calcifications, due to the superior ability to detect DCIS on MRI compared with mammography. (C) 2014 by the American College of Surgeons.

PURPOSE: To compare two fat suppression methods in contrast-enhanced MR imaging of breast cancer at 3.0 T: the two-point Dixon method and the frequency selective inversion method. MATERIALS AND METHODS: Forty female patients with breast cancer underwent contrast-enhanced three-dimensional T1-weighted MR imaging at 3.0 T. Both the two-point Dixon method and the frequency selective inversion method were applied. Quantitative analyses of the residual fat signal-to-noise ratio and the contrast noise ratio (CNR) of lesion-to-breast parenchyma, lesion-to-fat, and parenchyma-to-fat were performed. Qualitative analyses of the uniformity of fat suppression, image contrast, and the visibility of breast lesions and axillary metastatic adenopathy were performed. RESULTS: The signal-to-noise ratio was significantly lower in the two-point Dixon method (P < 0.001). All CNR values were significantly higher in the two-point Dixon method (P < 0.001 and P = 0.001, respectively). According to qualitative analysis, both the uniformity of fat suppression and image contrast with the two-point Dixon method were significantly higher (P < 0.001 and P = 0.002, respectively). Visibility of breast lesions and metastatic adenopathy was significantly better in the two-point Dixon method (P < 0.001 and P = 0.03, respectively). CONCLUSION: The two-point Dixon method suppressed the fat signal more potently and improved contrast and visibility of the breast lesions and axillary adenopathy.