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In this article, we report the case of a 78-year-old woman who consulted our hospital for a right breast mass detected on mammography during her cancer screening. Biopsy specimens showed atypical lymphocytic infiltration with a follicle-like growth pattern, suggesting a follicular lymphoma (FL). Immunohistochemically, the atypical lymphoid cells were diffusely and strongly positive for CD20, BCL2, and BCL6, but negative for CD10. IGH- BCL2 translocation was confirmed by fluorescence in situ hybridization analysis, leading to the diagnosis of primary breast FL. The most important differential diagnosis of this case was marginal zone lymphoma (MZL), which usually shows a CD10−/BCL2+ immunophenotype and is one of the common histological types in primary breast lymphomas. FLs with an atypical immunophenotype exist in a certain percentage of patients. Therefore, FL is considered to be a heterogeneous entity. It is important to distinguish FL from MZL in primary breast lymphomas because FLs may have a worse prognosis than MZLs.

BRCAness is defined as a phenotypic copy of germline BRCA mutations, which describes presence of homologous recombination defects in sporadic cancers. We detected BRCAness by multiplex ligation-dependent probe amplification (MLPA) and explored whether BRCAness can be used as a predictor of prognosis. BRCAness status was classified for total 121 breast cancer patients. Forty-eight patients (39.7%) were identified as BRCAness positive. Tumors of BRCAness were more likely to be hormone receptors negative (95.8% vs. 50.7%, P P = 0.001) and triple-negative breast cancer subtype (91.6% vs. 42.5%, P P P = 0.002) were significantly lower in BRCAness patients. In neoadjuvant chemotherapy subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, P = 0.041). Cox regression multivariate analysis showed that BRCAness was the independent prognostic factor for DFS (HR 2.962, 95%CI 1.184–7.412, P = 0.020), but not for OS (HR 2.681, 95%CI 0.618–11.630, P = 0.188). BRCAness is associated with specific characteristics and may suggest resistance to taxane-based chemotherapy. BRCAness can be used as a negative prognostic indicator for breast cancer.

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

Objective A previous randomized phase II study showed that neoadjuvant nab-paclitaxel (nab-PTX) 100 mg/m2) was effective and well-tolerated in patients with HER2-negative early-stage breast cancer, compared with docetaxel (DTX). We evaluated patient outcomes in terms of the Functional Assessment of Cancer Therapy-Breast (FACT-B), as a measure of health-related quality of life (HRQoL). Materials and methods Stage I-III HER2-negative breast cancer patients from the previous study were included. They received either four cycles of nab-PTX (100 mg/m2 days 1/8/15) every 4 weeks, or DTX (75 mg/m2 day 1) every 3 weeks, both followed by four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC). Patients completed a health-related quality-of-life questionnaire at baseline, after one and four cycles of taxanes, before administration of FEC, and after administration of one and four cycles of FEC. Results Thirty-six eligible patients were enrolled. The baseline characteristics of the two groups were well balanced. FACT-B scores at baseline and after four cycles of taxanes were 115/108 (DTX/nab-PTX) and 99/92, respectively. There were no significant differences between DTX and nab-PTX for FACT-B, FACT-B-Trial Outcome Index (FACT-B-TOI) and FACT-General. FACT-B and FACT-B TOI scores tended to decrease after one cycle and after four cycles of chemotherapy which did not recover to the baseline scores through the end of chemotherapy in each group. Conclusion There were no significant safety differences between nab-PTX and DTX. HRQoL tended to decrease during taxane-based anticancer treatment, with no significant differences between the treatments. We suggest that the HRQoL questionnaire has limited ability to evaluate different chemotherapy schedules. Trial registration UMIN000009855. Nov 20, 2012 registered.

The use of color Doppler ultrasound (CD) for distinguishing between benign and malignant breast lesions remains controversial. This study (JABTS BC-04 study) was aimed at confirming the usefulness of our CD diagnostic criteria. We evaluated ultrasound images of 1408 solid breast masses from 16 institutions in Japan (malignant: 839, benign: 569). Multivariate analysis indicated that vascularity (amount of blood flow), vascular flow pattern ("surrounding marginal flow" or "penetrating flow") and the incident angle of penetrating flow were significant findings for distinguishing between benign and malignant lesions. However, the sensitivity and specificity of B-mode alone did not improve significantly with CD addition (97.6% → 97.9%, 38.3% → 41.5%, respectively). We explored the causes of these negative results and found that age should have been considered when evaluating vascularity. Simulation experiments suggested that specificity is significantly improved when age is taken into consideration (38.3% → 46.0%, p0.001) and we thereby improved our diagnostic criteria.

Background Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with BRCA1/2 mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with BRCA1/2 mutations. Methods A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the BRCA1 and BRCA2 genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR). Results (a) Of 325 patients (with or without invasive cancer), 19.1% (62/325) tested positive for BRCA1/BRCA2 mutations. And 18.4% (9/49) was positive for BRCA1/BRCA2 mutations in DCIS, compared with 19.2% (53/276) in IDC (p = 1.000). Among BRCA mutations, 14.5% (9/62) had DCIS compared with nonmutations (15.2%, 40/263). Incidence of DCIS was 3.0% (1/33) of BRCA1 mutations and 27.5% (8/29) of BRCA2 mutation (p = 0.009). (b) Median age of diagnosis in BRCA mutation carriers was 39 years, compared with 46 years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between BRCA mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX ≥ 2 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266–20.763; p = 0.022), age at diagnosis ≤35 years (OR 0.149, 95% CI 0.023–0.954, p = 0.045) and ER+/HER2+ status (OR 5.034, 95% CI 1.092–23.210, p = 0.038) remained as independent significant predictors for BRCA mutation. Ki67 index (cut off by 14% or 30%) did not differ between BRCA mutation carriers and noncarriers (p = 0.459 and p = 0.651). (c) There was a significant difference in ER‐positive tumors among BRCA2 carriers and noncarriers (p = 0.042). Subgroup analysis showed BRCA2 carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+/PR+ (p = 0.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) BRCA mutation was not associated with an increased risk of IBTR and CBTR. Conclusion DCIS is equally as prevalent in patients who were BRCA mutation carriers as in high familial‐risk women who were noncarriers, but occurs at earlier age. BRCA2 carriers have higher incidence in DCIS than that of BRCA1 carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX ≥2, age at diagnosis ≤35 years and ER+/HER2+ might be independent predictors for BRCA mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and BRCA testing.

β-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin (CAβ-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAβ-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAβ-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAβ-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of β-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear β-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear β-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that β-catenin expression enhances tumor progression via chemokine production in breast cancers and that β-catenin signaling is a critical regulator of the aggressive traits of breast cancers.

This study compared the clinical utility of indocyanine green (ICG) fluorescence and radioisotope (RI) for sentinel lymph node (SLN) detection in breast cancer.Women with node-negative breast cancer underwent SLN biopsy using ICG fluorescence and RI. The primary end point was the sensitivity of ICG fluorescence compared with RI in the patients with tumor-positive SLNs. Secondary end points included detection rates for SLN, the additive effect of ICG fluorescence to RI, signature of positive SLNs according to tier, and adverse events related to ICG administration.A total of 847 women with clinical node-negative breast cancer underwent SLN biopsy, and 821 patients were included in the per-protocol analysis. SLN mapping was performed using ICG fluorescence and RI. The overall detection of SLNs using ICG fluorescence was identical to RI (97.2 vs. 97.0 %, P = 0.88), and the combination of both methods achieved a significant improvement compared with RI alone (99.8 vs. 97.0 %, P0.001). The detection rate for tumor-positive SLN was 93.3 % for ICG fluorescence and 90.0 % for RI, and the sensitivity of the ICG fluorescence method was 95.7 % (95 % CI 91.3-98.3, P = 0.11). The additional use of ICG significantly improved positive SLN detection for RI (97.2 vs. 90.0 %, P0.001). There were no serious adverse events related to hypersensitivity to ICG.The ICG fluorescence method may be an acceptable alternative to SLN detection using RI in breast cancer.

Because nipple discharge is caused by carcinoma as well as benign disease, identification of intraductal abnormalities with ductography is important. Ductography is an invasive mammographic examination in which contrast material is injected directly into the duct. Failure to cannulate or extravasation may occur. Ductography shows evidence of lesions, such as filling defects, duct obstruction, or wall irregularity, but it does not reveal the lesion itself. Furthermore, ductography produces a two-dimensional image, so it does not show the shape of the dilated duct or the precise location of the intraductal lesion in the breast. We applied three-dimensional (3D) heavily T2-weighted imaging with fat suppression of the breast to produce MR ductography. The dilated ducts are seen in 3D as tubular structures with high signal, and intraductal abnormalities are seen as signal defects. Furthermore, MR ductography can show an obstructed duct that cannot be seen on ductography. We also performed 3D breast MRI with the intravenous infusion of contrast material to show the lesion itself. Finally, we fused these 2 volume images into a single 3D fused image that not only shows the existence of intraductal abnormality, but reveals the shape, size, and extent of lesion, allowing us to understand easily the relationship between the ducts with dilation and any intraductal lesions in the breast. We herein introduce and describe this noninvasive method and discuss various factors related to its diagnostic use.

【Background and Aim】 To date, fluorescence imaging has been used gradually for real time diagnosis in various clinical situations. Evaluation of margin on surgical specimens is essential to decide whether additional resection should be performed for breast cancer surgery. In the same context, rapid assessment of biopsy specimen is crucial because when they do not contain any part of the lesions, re-examination should be need. A fluorescence probe named γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) was rapidly activated by an enzyme, γ-glutamyltransferase (GGT). It was overexpressed in variety of cancers so promising for clinical use. The aim of this study is to examine the usefulness of the probe for breast cancer detection. 【Material and Methods】 We investigated the patients of breast cancer or benign disease who received examination consecutively from March 2015 to February 2016 in our hospital. The samples were obtained by core needle biopsy (CNB) or vacuum-assisted breast biopsy (VAB).We sprayed the probe on these samples immediately after examination and shoot images by CCD camera. To evaluate the fluorescence intensity along the time, we used a filtered CCD camera that could detect specifically gGlu-HMRG color (Discovery® INDEC Medical Systems Inc.). The images were automatically obtained every 30 seconds for 10 minutes after adding the probe on the specimens. The average value of the image in each region of interest (ROI) was analyzed using image analysis program Image J (https://imagej.nih.gov/ij/). We investigated the change of fluorescence intensity with the passage of time. We also compared the fluorescence intensity of malignant lesions with benign ones, and analyzed whether the fluorescence intensity could distinguish the malignant lesions from benign ones. 【Result】 We obtained 362 samples from96 tumors. Fifty-six tumors with 215 samples were benign, while 40 tumors with 147samples are malignant histologically. The fluorescence was immediately observed after sprayed the probe. The intensity had been increasing in proportion to time. The malignant specimens were rapidly increasing; in contrast, the benign ones were slowly. For example, when it took 60 seconds after spraying the probe that the intensity increase up to some level in malignant specimens, while benign one took 240 seconds up to the same level on average. Comparing the malignant lesions with benign ones after sprayed 120 seconds, the fluorescence intensity was higher in malignant specimens than benign ones (average fluorescence intensity; benign 0.9, malignant 2.3 p=0.0138). By ROC analysis whether the fluorescence intensity could distinguish the malignant lesions from benign, AUC, sensitivity and specificity was 0.63, 70% and 57%, respectively (cut off 0.2). 【Conclusion】 The probe was contributory to distinguish malignant and benign lesions and may be useful for the rapid diagnosis of CNB in practice. We are now trying to seek a more accurate probe to differentiate benign and malignant lesion as a next step. Citation Format: Takamaru T, Akashi ST, Kuwayama T, Sawada T, Hirota Y, Urano Y, Nakamura S. γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is promising fluorescence probe for rapid diagnosis of breast cancer; - The feasibility study of real time imaging for breast cancer examination - [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-01-09.

In 60 parients with primary breast cancer, immunohistochemical staining of the tumor cells was conducted using a monoclonal antibody Ki-67, and their Ki-67 scores (positive cells/total tumor cells) were determined to clarify relationships between clinicopathological factors, recurrence, p53 (mutant type), estrogen receptor level and prognosis. Ki-67 recognizes a nuclear antigen expressed by cells in G1, S, G2 and M phases of the cess cycle but not G0. Ki-67 scores of the breast carcinomas distibuted from 3% to 62%, with an average of 26.6%. There were strong correlations between the Ki-67 score and recurrence (p

Third-generation aromatase inhibitors(AIs)are now common in adjuvant hormone therapy for breast cancer in postmenopausal women. However, a suitable treatment has yet to be established for patients who develop cancer recurrence during or after adjuvant AI therapy.This prospective study evaluated the efficacy and safety of 120mg/day toremifene citrate(TOR-120)administered orally to 23 patients with recurrent breast cancer who were receiving or had received adjuvant AI therapy. Primary therapy for recurrence was TOR-120 monotherapy.The response rate was 13. 0%(partial response: three patients), the clinical benefit rate was 78. 3%(partial response: three patients; long-term stable disease: 15 patients), and median time to progression was 8. 1 months. Grade 1 adverse events such as loss of appetite, sweating, flushing and edema face were observed.TOR-120 monotherapy was effective and safe as a primary hormone therapy for recurrent breast cancer unresponsive to AIs.

Introduction: mammographic density is a strong risk factor for breast cancer and an essential determinant of screening sensitivity, but the breast density of Japanese women has yet to be objectively examined. Single mammographic examination fails to detect approximately half of breast cancers in women with dense breasts. We objectively evaluated mammographic density to clarify the relation between breast density and incidence of breast cancer in Japanese women. Method: We enrolled 269 patients diagnosed with breast cancer and 397 healthy controls, who participated in screening mammography at Showa University Hospital. Breast density was measured using Volpara (a software application which analyses breast composition volumetrically). Results: The average age of both control and breast cancer groups was 55. Of the control group, 308 (78%) were characterized as having dense breasts, being defined as volumetric density grade (VDG) 3 or 4. More than 50% of the total population (all ages) had dense breasts (VDG 3 or 4) and more than 20% were extremely dense (VDG:4). Of the breast cancer patients, 232 (87%) were VDG 3 or 4. 52 (23%) of those with dense breasts showed negative results in single mammography examination. In primary breast cancer patients with dense breasts, 30% of those under age 70, but only 13% of those over age 70, showed no abnormal findings from mammographic examination. Conclusion and Discussion: In comparison of our present results and other papers, In the Japanese control group, 72% of patients had dense breasts (VDG 3 or 4) at age 50 or greater, but in Holland, for example, only 36% of women had breasts classed as dense. 87% of Japanese women with breast cancer had dense breasts, approximately the same ratio (88%) as found in Korea. For Japanese and other Asians, women under 70 years old with dense breasts may warrant additional screening. Citation Format: Sawada T, Ikeda M, Kuwayama T, Akashi ST, Nakamura S. Digital measurement of mammographic density and the risk of overlooking cancer in Japanese women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-03.

To assess the diagnostic performance of sentinel lymph node (SLN) biopsy using the indocyanine green (ICG) fluorescence method compared with that using the blue dye method, a prospective multicenter study was performed.Patients with T1-3 primary breast cancer without clinical lymph node involvement were included in this study. ICG as a fluorescence-emitting source and indigo carmine as blue dye were injected into the subareolar area. Extracted lymph nodes were examined to identify the first, second, and other SLNs. The identified nodes were classified according to the ICG fluorescence signal and blue dye uptake.Ninety-nine eligible patients were included in this study. The ICG fluorescence method identified an average of 3.4 SLNs (range, 1-8) in 98 of 99 patients (detection rate, 99 %). The number of lymph nodes identified by the fluorescence method was significantly higher than that identified by the blue dye method (p0.001). SLN involvement was identified in 20 % (20 of 99) of patients, all of whom tested positive for the first SLN. In 16 patients, complete axillary lymph node dissection (ALND) was performed. In 25 % (4 of 16) of these patients, axillary metastases were identified; however, no axillary involvement was found in 8 patients with only one involved node, which was isolated as the first SLN.High rate of SLN detection was achieved using the ICG fluorescence method. The first SLN identified by fluorescence imaging provides an exact indication of the axillary status. Therefore, the ICG fluorescence method provides precise information required to avoid unnecessary ALND.

Objective: Breast cancer cells with CD44+CD24–/low gene expression signature have been suggested to have stem cell-like tumor-initiating properties. The purpose of this study is to clarify the gene expression profiling of cells with CD44+CD24–/low gene expression signature in the luminal subtype. Methods: Laser capture microdissection was used to select the isolation of cancer cells in 35 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT2 Profiler PCR Array was used for gene expression analysis in the groups of CD44+CD24–/low and CD44+CD24+ gene expression signature. Results: Thirty-five tumors were divided into 3 groups. Group A was composed of the CD44+CD24–/low type, in which the ratio of CD44/CD24 was >10.0. Group B was composed of the CD44+CD24+ type, in which the ratio was >0.1 and ≤10.0. In group C, composed of the CD44–/lowCD24+ type, the ratio was Conclusion: This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44+CD24–/low gene expression signature. In addition, either ALDH1 or SOX2 may be a candidate marker for cancer stem cells in luminal subtype breast cancer.

The correlations between mRNA expressions of 5-fluorouracil(5-FU)-related enzymes; thymidylate synthase(TS), dihydropyrimidine dehydrogenase(DPD), thymidine phosphorylase(TP), and orotate phosphoribosyltransferase (OPRT)in breast cancers, along with disease-free survival(DFS), were investigated in 35 patients treated with postoperative adjuvant chemotherapy using cyclophosphamide, methotrexate and 5-fluorouracil(CMF). The patients treated with CMF were divided into two groups, a lower group(L group)and a higher group(H group), according to the median value of the mRNA expression for each enzyme in 220 breast cancer specimens, which were resected between 1996 and 1998 in our institute. 5-year DFS was not significantly different between TS-L and H group(60% and 80%, p=0.38), DPD-L and H group(57.9% and 86.7%, p=0.088), and TP-L and H group(70% and 73.3%, p=0.89), respectively. 5-year DFS in the OPRT-H group(88.9%)was significantly better than that in the OPRT-L group(50%) (p=0.024). In the OPRT-H group, despite the fact that the proportion of patients with lymph node involvement in the CMF group was significantly higher than that in the postoperative adjuvant hormone therapy group, 5-year DFS was not significantly different between the two groups(p=0.10). Our results suggest that OPRT level was the significant predictive marker for DFS in the breast cancer patients treated with postoperative adjuvant chemotherapy using CMF.

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.

To evaluate the feasibility and efficacy of weekly paclitaxel and 5'-DFUR combination therapy in advanced or recurrent breast cancer, 13 patients were enrolled in this pilot study. 5'-DFUR was administered orally at a dose of 800 mg/day for 14 consecutive days, and paclitaxel was administered by 1 hour infusion at a dose of 80 mg/m2 after short premedication on day 1 and 8. This was repeated every 3 weeks, until disease progression or severe side effects precluded further treatment. Antiemetic agents and G-CSF were also administered, as needed. Nine patients had not received prior therapy, and four patients had received prior anthracycline containing therapy, two of whom were concomitantly receiving docetaxel treatment. Median administration time was 14 weeks, and median time to progression was 16.6 weeks. The overall response rate was 46.2% with 7.7% complete response and 38.5% partial response, and the response rate was consistent regardless of metastatic sites. Two patients achieved stable disease for at least 6 months and the clinical benefit was 61.5%. Responses were observed in 25% of the patients with prior anthracycline therapy. Grade 3/4 side effects involved leukopenia in 15.4%, peripheral neuropathy in 7.7%, malaise in 23.1% and nausea in 7.7%. There were no complaints of severe diarrhea. Although one patient withdrew from this study because of a hypersensitive reaction, this regimen was generally well tolerated and QOL was high enough so that it was possible to continue the regimen. Weekly paclitaxel and 5'-DFUR combination therapy seems to be feasible and effective in patients with advanced or recurrent breast cancer.

1091 Background: Near-infrared fluorescence signal of indocyanien green (ICG) can visualize subcutaneous lymphatic flows and draining (sentinel) lymph nodes (SLNs). In fluorescence ICG Breast Study...

Background: Sentinel lymph node (SLN) biopsy guided by radioisotope (RI), blue dye or in combination methods is common. A high identification rate is reported for the RI-guided method. On the other hand, it has the demerits of radiation exposure, being expense, and it can only be used in a radiation-controlled area. The blue dye method, however, is safe and inexpensive, but the identification rate is lower compared with the RI method and requires training. The indocyanine green (ICG) fluorescent method involves the application of the fluorescing property. Lymph flow can be traced from outside the body with a photodynamic eye (PDE) camera simultaneously with an operation procedure. The ICG method is safe, inexpensive and requires little training, therefore its use will be widely permitted in any general hospitals. Recently, based on several retrospective clinical trials, the identification rate with the ICG fluorescent method has been reported to be equal to or greater than the RI method. The purpose of this multicenter study is to prospectively assess the diagnostic performance of SLN biopsy using the ICG fluorescence technique compared with RI. Materials and methods: In this validation study, the patients aged from 20 to 75 years-old with operable primary invasive breast cancer (cT1c-2N0M0) have been nominated and required the written informed consent. All candidates underwent SLN biopsy using the combined methods with RI and ICG fluorescence. The target sample size was 840 patients to evaluate the sensitivity of ICG method as a primary endpoint, and after 200 patients were enrolled we analyzed the identification rate and the SLN-positive rate of the RI and ICG methods respectively as the interim analysis planned beforehand. Results: Two hundred eligible patients were enrolled in this study from May 2011 to February 2012. Their median age was 53.0 years (range: 27-74 years). The number of patients with cT1c was 106 and that with cT2 was 94. The identification rate of the RI and the ICG method was 97% (194/200) and 96% (192/200) respectively. Of the 194 patients that were identified with the RI method, 186 (95.9%) were also identified with the ICG method. ICG identified 6 patients that were not identified by RI. On the other hand, RI identified 8 patients that were not identified by ICG. The SLN-positive rate was 25.5% (51/200). This rate was higher than we expected. Of the 51 patients with positive metastatic lymph nodes, 23 patients (21.7%) had cT1c breast cancer and 28 (29.8%) had cT2 breast cancer. The positive rate of the first SLN was 23.5% (47/200) and tumor cells skipped to the second or further tier in four cases (2%). Conclusions: The ICG-guided SLN biopsy procedure achieved a high identification rate almost equal to that with the RI method. Using this combination method, the identification rate was 100%. We will assess the sensitivity and the additive effect of combining the ICG fluorescence method with the RI method, etc., when all 840 patients have been enrolled (UMIN000005167). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-03.

Objective Breast cancer cells with CD44 + CD24-/low gene expression signature have been suggested to have stem cell-like tumor-initiating properties. The purpose of this study is to clarify the gene expression profiling of cells with CD44 + CD24-/low gene expression signature in the estrogen receptor (ER) positive tumors. Methods Laser-captured microdissection was used to select the isolation of cancer cells in 32 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT2 Profiler PCR Array was used for gene expression analysis in the groups of CD44 + CD24-/low and CD44 + CD24+ gene expression signature. Results Thirty-two tumors were divided into 2 groups. Group A was composed of the CD44 + CD24-/low type, in which the ratio of CD44/CD24 was >10.0. Group B was composed of the CD44 + CD24+ type, in which the ratio was >0.1 and ≦ 10.0. The number of tumors in group A and B were 4 and28, respectively. Regarding the correlation of CD44/CD24 status with tumor characteristics, the tumors of group A were significantly associated with axillary lymph node metastasis compared with those of group B (P = 0.009). There were no significant differences in tumor size, nuclear grade between the two groups. HER2 status in the tumors of group B was significantly higher than group A (P = 0.028). According to signaling pathways, the number of expression genes for the Notch pathway in group A was significantly greater than in group B (P = 0.028). Overexpressed genes for ALDH1 (P = 0.021) and SOX2 (P = 0.018) were noted in group A compared to group B. Conclusion This study suggests that the Notch pathway may be an important signaling pathway in luminal subtype with CD44 + CD24-/low gene expression signature. In addition, either ALDH1or SOX2 may be a candidate marker for cancer stem cells in the ER positive breast cancer. Disclosure All authors have declared no conflicts of interest.

1122 Background: Sentinel lymph node (SLN) biopsy using indocyanine green (ICG) fluorescence method is a technique that utilizes the fluorescing property of ICG reagent that is used in the dye meth...

Purpose: Breast cancer cells with a CD44+CD24-/low phenotype have been suggested to have tumor-initiating properties with stem cell-like. The purpose of this study is to clarify the gene expression profiling of cells with different CD44/CD24 genotypes within breast cancer. Methods: Laser-captured microdissection was used to select the isolation of cancer cells in 36 frozen tissues of breast cancer, and RNA extracted from these cells was examined by real-time RT-PCR to quantify CD44 and CD24 expressions. Human stem cell RT2 profiler PCR array was used for gene expression analysis in the groups of different CD44/CD24 genotype. Associations between different CD44/CD24 genotypes and clinical variables were assessed by Fisher's exact test, and the Mann-Whitney U test was used for gene expression profiling. P Results: Thirty-six tumors were divided into 3 groups. Group A was composed of CD44+CD24-/low genotype, in which the ratio of CD44/CD24 was >1.0. Group B was composed of CD44+CD24+ genotype, in which that was 0.1 < ratio ≤ 1.0. In group C of CD44-/lowCD24+ genotype, that was < 0.1. The number of tumors in group A, B and C was 5, 29 and 2, respectively. Regarding the correlation of CD44/CD24 status with tumor characteristics, tumors of group A were significantly associated with lymph node metastasis compared with those of group B (P=0.029). The number of tumor with HER 2 score 3 within group A and B was 0 and 11, respectively. There was no significantly difference in ER status and tumor size. As far as the signaling pathways, the number of expression genes for Notch pathway in group A was significantly greater than in group B (P=0.028), and that for Wnt pathway was not significantly different between group A and B. Overexpressed gene in group A was NUMB, which is related to the programmed cell death. MYST1 and SOX2 tended to show higher levels of group A than of group B. Conclusion: This study suggests that Notch pathway may be more important than Wnt pathway on breast cancer with CD44+CD24-/low genotype, and the CD44+CD24-/low status would be associated with low/negative HER2 expression. Moreover, the gene of self-renewal markers, such as MYST1, SOX2 and NUMB might be a target for therapy against breast cancer with low/negative HER2 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4687.