Regional recurrence after sentinel lymph node biopsy for breast cancer is rare, with an incidence rate of less than 1%. The rate of axillary lymph node metastasis is similar in T1a breast cancer and Tis breast cancer. In this report, we present 2 cases of axillary recurrence after sentinel lymph node biopsy for T1a breast cancer. None of the patients experienced distant recurrence, and both patients underwent axillary dissection, chemotherapy, endocrine therapy, and radiation therapy. A notable commonality between these cases was the presence of multiple invasive lesions at the time of the initial diagnosis. Currently, the extent of invasion is assessed by its maximum diameter, and the presence of multiple lesions does not influence staging. However, multiple lesions may serve as a poor prognostic marker, necessitating a judicious approach to the initial treatment. Following resection for regional recurrence, it is crucial to pursue a multidisciplinary curative approach similar to the initial management of early breast cancer with lymph node metastasis.

BACKGROUND:Trastuzumab (Tz) is assumed to prime antibody-dependent cellular cytotoxicity (ADCC); however, it remains unclear whether Tz therapy can clinically induce adaptive cellular immunity.OBJECTIVE:Adaptive Cellular Immune Effect of Tz Therapy.METHODS:This study included 29 surgical invasive breast carcinomas administered neoadjuvant chemotherapy with Tz (15 cases) or without Tz (14 cases). The numbers of immunoreactive cells (CD4, CD8, CD56, and Fox-P3) in three different compartments (intratumoral, adjacent stromal, and distant stromal) were determined.RESULTS:The average number of adjacent stromal CD4-positive, CD8-positive, and Fox-P3-positive cells in the Tz+ group was significantly greater than that in the Tz- group (p = 0.036, 0.0049, and 0.043, respectively). However, the number of Fox-P3-positive cells was much less than that of CD4-positive cells. Moreover, distant stromal CD4-positive and CD8-positive cells in the Tz+ group was also significantly greater than that of the Tz- group (p = 0.029 and 0.032, respectively). Only a small number of CD56-positive natural killer cells, playing a main role in ADCC, accumulated at the tumor site after Tz therapy.CONCLUSIONS:The results suggest that Tz therapy induces adaptive cellular immunity, including infiltration of both CD4-positive helper T cells and CD8-positive cytotoxic T cells into the breast carcinoma lesion.

BACKGROUND:Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors.METHODS:We used surgically resected, formalin-fixed, paraffin-embedded tissues of 22 DCIS and 30 IDC lesions. We performed immunohistochemical intrinsic subtyping, array-based comparative genomic hybridization, and unsupervised clustering.RESULTS:The samples were divided into 2 major clusters, A and B. Cluster A showed a greater number of gene and chromosome copy number alterations, a larger IDC/DCIS ratio, a higher frequency of nonluminal subtype, a lower frequency of luminal subtype, and a higher nuclear grade, when compared with cluster B. However, there was no difference in the frequencies of lymph node metastasis between clusters A and B. We identified 9 breast-cancer-related genes, including TP53 and GATA3, that highly contributed to the discrimination of A and B clusters.CONCLUSION:Classification of breast tumors into rapidly progressive cluster A and the other (cluster B) may contribute to select the treatment appropriate for their progression risk.

Combination chemotherapy with pertuzumab, trastuzumab, and docetaxel is recommended as the first-line treatment for patients with HER2-positive unresectable or metastatic breast cancer. We report 2 cases of unresectable breast cancer for which pertuzumab, trastuzumab, and docetaxel therapy was effective. Case 1: A woman in her 40s was diagnosed with TxN3aM0, Stage ⅢC, HER2-positive, hormone receptor-positive advanced breast cancer. After administration of 6 courses of pertuzumab, trastuzumab, and docetaxel therapy, she underwent surgery(Bt+Ax[Ⅱ]). Histopathological examination revealed that chemotherapy effect was Grade 3. Case 2: A woman in her 60s was diagnosed with de novo Stage Ⅳ, HER2- positive, hormone receptor-negative breast cancer. She was administered 8 courses of pertuzumab, trastuzumab, and docetaxel therapy as the third-line treatment, because she initially refused treatment. Thereafter, she underwent surgery(Bt+Ax [Ⅰ]). In both cases, histopathological examination revealed complete response after chemotherapy. Thus, combination therapy of pertuzumab and trastuzumab may improve the prognosis in patients with HER2-positive breast cancer.

Objective: The clinicopathological features of apocrine carcinoma (AC) have not been fully characterized till date owing to its rare occurrence. We retrospectively reviewed data from 15 AC cases. Materials: Of 817 patients treated for primary breast carcinoma, we reviewed the data of 15 patients, who had been histologically diagnosed as AC. The expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) as well as Ki67 index were immunohistochemically evaluated. Fluorescence in situ hybridization was conducted for cases with equivocal immunohistochemical findings. Results: Of the 15 AC patients, 13 were menopausal, and the average age of the patients was 63.7 years. Two cases involved sequential or simultaneous bilateral development of breast cancer. Review of staging data revealed that stage 0 was 2 cases, I was seven and II was six, respectively. According to intrinsic subtype classification, one lesion was classified as luminal A, one as HER2-positive, and 13 as triple-negative lesions. Lymphatic and venous invasion were observed in eight and five cases, respectively. Among 7 patients who measured Ki67 labeling index, one case was strongly positive. As for adjuvant postoperative treatment, hormone therapy was administered in one case, anti-HER2 therapy in one case, and chemotherapy in 11 cases. No case received neo-adjuvant chemotherapy. Radiation therapy was performed in all cases after partial mastectomy. No recurrence was observed in any case with a mean follow-up period of 67.4 months. Conclusions: AC is a rare primary breast cancer characterized by an ERand PgR-negative profile, with infrequent overexpression of HER2 protein. Although associated with a good prognosis in the present series, AC appears to be overtreated. Because AC may develop bilaterally more frequently than general invasive ductal carcinomas, particular care needs to be taken in continued monitoring of AC and other malignant lesions.. Keyword breast cancer, apocrine carcinoma Received: January 12, 2017. Accepted: March 10, 2017. Correspondence: 滋賀医科大学外科学講座 北村 美奈 〒520-2192大津市瀬田月輪町 kmina@belle.shiga-med.ac.jp

Identifying an additional MRI-detected breast lesion on second-look ultrasonography (US) is technically challenging because of lesion displacement with the patient’s position change. The aim of this study is to help identify MRI-detected lesions on second-look US by developing a probing area, called “the predictive detection area” (PDA), and by assessing the PDA.

Abstract Background: Neoadjuvant chemotherapy (NAC) is widely performed for patients with locally advanced breast carcinomas. It is important to obtain precise information using imaging modalities about the distribution of residual carcinomas after NAC to predict the success of breast conserving surgery. However, the relationship between magnetic resonance imaging (MRI) shrinkage patterns and molecular subtypes of breast carcinomas has not yet been investigated. Methods: We analyzed the MRI shrinkage and pathological patterns of residual carcinomas after NAC in 54 consecutive breast carcinomas. The shrinkage patterns were classified into five categories: Type I and II (concentric shrinkage with or without any surrounding lesion), type III (shrinkage with residual multinodular lesions), type IV (diffuse contrast enhancement in the entire quadrant), and non-visualization. Results: The most common MRI shrinkage pattern was type I (39%) followed by non-visualization (26%). The most common pathological shrinkage pattern was type III (33%), followed by type II (28%) and non-visualization (22%). The concordance rates of the MRI patterns of non-visualization and type I were significantly lower than those of the MRI patterns of type II, III, and IV (p = 0.018). Moreover, in the luminal subtypes, the concordance rates of the MRI patterns of non-visualization and type I were significantly lower than those of the MRI patterns of type II, III, and IV (p = 0.026); however, in the non-luminal subtypes, this correlation was not significant. Conclusions: The results of the present study suggest that the cases with MRI shrinkage patterns of non-visualization and type I require caution regarding the surgical margins compared with the other types, especially the luminal subtypes. Citation Format: Tsuyoshi Mori, Kaori Tomida, Mina Kitamura, Sachiko Sakai, Yuki Kawai, Tomoharu Shimizu, Tomoko Umeda, Tomoyuki Ueki, Sachiko Kaida, Toru Miyake, Hiroya Iida, Hiroya Akabori, Naomi Kitamura, Tsuyoshi Yamaguchi, Hiromichi Sonoda, Shigeyuki Naka, Masaji Tani. Magnetic resonance imaging shrinkage patterns after neoadjuvant chemotherapy for breast carcinomas: Correlation with molecular subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3743. doi:10.1158/1538-7445.AM2017-3743

Invasive micropapillary carcinoma (IMPC) is a distinct histopathological variant of breast carcinoma and frequently develops lymph node metastases. CD44 is a family of transmembrane glycoprotein receptors with multiple variant isoforms (CD44v), which have tissue-specific expression. Previous studies have demonstrated a loss or gain of CD44v and CD44 standard form (CD44s) expression in breast carcinomas. In this study, we analyzed the immunoprofiles of CD44s, CD44v6, and CD44v9 in IMPC and compared them with those in a concurrent invasive carcinoma of no special type (ICNST) component, thus clarifying the significance of CD44 expression in IMPC.

e12530 Background: Sentinel lymph node (SLN) biopsy has been established as a method of predicting axillary nodal status in early-stage breast cancer. High body mass index (BMI) has been shown to correlate with a high incidence of failure in identifying SLNs. The indocyanine green (ICG) fluorescence imaging method has been reported to be useful for SLN detection in early-stage breast cancer. In this study, we investigated the usefulness of the ICG fluorescence imaging method in patients with high body mass index and early-stage breast cancer. Methods: We evaluated 484 patients with clinically node-negative breast cancer by using the ICG fluorescence imaging method from January 2006 to December 2014. A 0.3-mL 0.5% ICG solution was intradermally injected in the areola closest to a tumor. Fluorescence images were obtained by using the fluorescence imaging system PDE-Neo (Hamamatsu Photonics Co., Japan). SLNs were then dissected by fluorescence navigation. SLN biopsy was performed by referring to the axillary compression technique using a plastic device. Results: The patients’ mean age was 57.8 years (range, 26–86 years). The high BMI group ( > 25 kg/m2) included 107 patients, and the normal BMI group ( < 25 kg/m2) included 377 patients. The Japan Society for the Study of Obesity defined obesity as a BMI of > 25 kg/m2 for Japanese. Subcutaneous lymphatic channels were successfully visualized in all the patients. The detection rate of SLN was 99.1% (106/107) in the high BMI group and 99.7% (376/377) in the normal BMI group. The number of detected SLNs ranged from 0 to 7 (mean, 2.4) in the high BMI group and from 0 to 8 (mean, 2.4) in the normal BMI group. On pathological examination, 6 patients (5.6%) in the high BMI group and 25 patients (6.6%) in the normal BMI group were found to have lymph node metastases. However, this difference between the 2 groups was not significant. Conclusions: The ICG fluorescence imaging method allowed highly sensitive and real-time imaging and enabled the detection of SLNs regardless of BMI in all the patients with early-stage breast cancer in this study.

Umbilical metastases mainly arise from malignancies of the digestive and gynecological systems, but rarely from breast cancer. A 64-year-old woman with a history of breast cancer was referred to us for investigation of a painful lesion in the umbilicus. Immunohistochemical staining of a specimen obtained by biopsy from the nodule showed umbilical metastasis of breast cancer. After a work up, she was successfully treated with a combination of surgery and endocrine therapy. We report this case to reinforce that not all periumbilical tumoral deposits are consistent.

Early diagnosis and treatment for breast cancers has greatly improved in recent years, however, subset of this disease with early recurrence have remained to be unpredictable. Several studies has addressed that strong CD10 expression in tumor stroma is associated with poor survival rate of breast cancers, but no correlation between CD10 expression and disease-free survival has been elucidated yet. For these reasons, this study with modified immunohistochemical (IHC) staining evaluated the expression of CD10 in invasive breast carcinomas (IBCs) and analyzed correlations between CD10 expression on tumor cells, stromal cells and myeloid-like cells with clinicopathological parameters and recurrence status.

e15063 Background: We have recently shown that viable cancer cells spilled into peritoneal cavity during curative gastric cancer (GC) surgery more frequently in cases with advanced tumor invasion and lymph node metastasis. In addition, 2.8% of early GC without any vessel invasions showed viable cancer cells in the peritoneal cavity during surgery, suggesting the presence of other channels for the spilling of cancer cells. Laparoscopic distal gastrectomy (LDG) with intracorporeal reconstruction has been applied according to advances in surgical techniques. However, oncological evaluation of LDG may not be fully performed. In this study, we examined the possibility of spilling cancer cells into the peritoneal cavity during the surgery for alimentary reconstruction in GC. Methods: Patients with open distal gastrectomy (n=37) or laparoscopic assisted distal gastrectomy (n=73) for GC were prospectively evaluated cytological examination of remnant stomach just before alimentally tract reconstruction. Ki67 staining was examined for the proliferative activity of detected cells. Results: Cancer cells were detected in 25 (22.7%) of 110 remnant stomachs of the patients received gastrectomy just before reconstruction. According to the depth of tumor invasion, incidence of cancer cell detection in patients with mucosal (m), submucosal (sm), proper muscle (mp), subserosal (ss), or serosal (se) tumor invasion was 1/28 (3.6%), 4/23 (17.4%), 4/15 (26.7%), 8/17 (47.1%), or 8/27, (29.6%), respectively. Cancer cells detected formed clustering. All of cases with cancer cells showed positive for Ki67 staining, indicating having proliferative ability. Incidence of cancer cell detection in the remnant stomach was significantly more in differentiated type than in undifferentiated type (p < 0.05). Conclusions: Viable and proliferative cancer cells present in the remnant stomach at the reconstruction of alimentary tracts after gastrectomy for GC. The prevention from spilling out cancer cells into peritoneal cavity should be seriously considered. Complete laparoscopic intracorporeal reconstruction should be accessed carefully from the oncological points of view as well as minimally invasive view.

Preoperative neoadjuvant chemotherapy (NAC) is considered to be the standard treatment for locally-advanced breast carcinomas. Obtaining precise information regarding the tumor extent and distribution by imaging modalities to assess the success of breast-conserving surgery following NAC is extremely important. Analysis of the detailed radiopathological correlation of magnetic resonance imaging (MRI) following NAC has not been reported previously. The MRI and histopathological shrinkage patterns of residual breast carcinomas in 27 consecutive cases were analyzed following NAC and classified into five categories: Types I and II (concentric shrinkage with and without surrounding lesions, respectively); type III (shrinkage with residual multinodular lesions); type IV (diffuse contrast enhancement in whole quadrant); and non-visualization. The present study clearly demonstrated that the most common MRI shrinkage pattern was type I (11 cases), followed by type II and non-visuali-zation, and the most common histopathological shrinkage pattern was type II (11 cases), followed by type III (8 cases). The concordance rate between MRI and pathological patterns was 48% and the worst concordance MRI pattern was type I. MRI is considered to be a useful method for evaluation of the residual carcinoma following NAC. However, the concordance rate was low in the MRI pattern I cases and tiny foci of residual carcinoma were present in half of the non-visualization cases, as shown by MRI. Therefore, the tumor extent must be completely resected for patients who undergo NAC, and postoperative radiation may be important for preventing local recurrence of breast carcinoma.

Male breast carcinoma is an uncommon neoplasm, accounting for 0.6% of all breast carcinomas. Invasive ductal carcinoma of no special type is the most common type of male breast carcinoma, and mucinous carcinoma occurring in the male breast is extremely rare. In the present study, we report a case of mucinous carcinoma of the male breast and discuss the clinicopathological features of this type of tumor. A 63-year-old Japanese male presented with a gradually enlarged nodule in the right breast. The resected breast specimen revealed pure mucinous carcinoma and immunohistochemical analyses demonstrated that tumor cells were positive for estrogen receptor (ER), but negative for progesterone receptor (PgR). In addition, HER2 expression was not amplified. Pure mucinous carcinoma is generally associated with a low incidence of lymph node or distant metastases, and excellent disease-free survival in females. However, certain cases of this type of tumor with axillary lymph node metastasis in the male breast have been reported. In addition, the immunoprofiles of mucinous carcinoma in males are fundamentally the same as those in females. More than 90% of cases show positive immunoreactivity for ER and/or PgR, and HER2 expression is not amplified. However, it has been reported that breast cancer in males is more frequently positive for ER than in females, and has less HER2 overexpression. The high rate of hormone receptor-positive breast cancer in males is considered to be due to similar conditions as those in breast cancer in postmenopausal women. The pathogenesis of male breast carcinoma, including mucinous carcinoma, remains unclear; therefore, additional clinicopathological studies are required.

In the present study, we measured breath alcohol concentration(BAC)after the administration of alcohol-containing docetaxel(OTX)in breast cancer patients, and examined the safety of OTX outpatient administration. Twenty breast cancer patients who received OTX chemotherapy at our outpatient facility were included. The administered doses were 100mg/m2 in 5 cases, 75mg/m / 2 in 13 cases, and 60 mg/m2 in 2 cases. BAC was measured 3 times: immediately after infusion, 30 minutes after infusion, and 60 minutes after infusion. No symptoms of hot flash or drunkenness due to alcohol were observed. BAC was detected in 10 cases(50%)immediately after infusion, in 7 cases(35%)at 30 minutes after infusion, and in 1 case(5%) at 60 minutes after infusion. BAC was more than 0.15mg/L in only 1 case(5%)and reduced to less than 0.15mg/L in all cases after 30 minutes. Our results suggest that the effects of alcohol are alleviated 60 minutes after infusion and that patients receiving OTX could return home safely.

Here we present a case of breast cancer in which cardiac dysfunction had previously been observed on trastuzumab(TRS) administration; the condition then improved but reoccurred on readministration of TRS. A 52-year-old woman received preoperative chemotherapy for StageIIIC left breast cancer(fluorouracil, epirubicin and cyclophosphamide followed by docetaxel and TRS), and then underwent partial mastectomy and axillary lymph node dissection. For adjuvant therapy, she received endocrine therapy and TRS. Radiation therapy was administered to the left residual breast. The patient complained about palpitation in the 5th cycle of TRS, and left ventricle ejection fraction(LVEF)decreased to 45.3% from 64%. Therefore, we stopped TRS administration. Palpitation improved, and LVEF increased to 53% after 2 months. TRS was administered again; however, palpitation reoccurred and LVEF decreased to 44%. TRS administration was once again discontinued. However, according to the HERA trial report regarding patients with a history of anthracycline and radiation therapy, TRS administration could be resumed when LVEF is greater than 50%, but we should be more careful during readministration of TRS.