Yuki Kawai

Indocyanine green fluorescence imaging system for sentinel lymph node biopsies in early breast cancer patients.

PurposeThis study presents a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using indocyanine green (ICG) fluorescence imaging.MethodsThis study enrolled 128 patients with clinically node-negative breast cancer. Fluorescence imaging was obtained after ICG was injected into the areola. Subcutaneous lymphatic channels were immediately visible.ResultsLymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel was 60%, two channels were 24%, and three channels were 16%. The number of fluorescence SLN ranged from 1 to 6, and blue-dyed SLN ranged from 0 to 3. In the latter, SLN were not identified in 44 patients. Nineteen patients had pathologically identified lymph node metastases. All of them were recognized by fluorescence imaging, but 8 patients had lymph nodes with metastases were not identified by dye method.ConclusionThis ICG fluorescence imaging technique is feasible and safe for detecting SLN in a less invasive manner than conventional mapping, with real-time observations.

The Kampo Medicine Goshajinkigan Prevents Neuropathy in Breast Cancer Patients Treated with Docetaxel

BACKGROUND Goshajinkigan (GJG) is used for the treatment of several neurological symptoms. We investigated the efficacy of GJG and mecobalamin (B12) against neurotoxicity associated with docetaxel (DOC) in breast cancer patients. MATERIALS AND METHODS Sixty breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. Neuropathy was evaluated according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver. 3.0, and a visual analogue scale (VAS). This study employed a randomized open design. RESULTS The incidence of neuropathy was 39.3% in the GJG group, and 88.9% in the B12 group (p<0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases, and VAS was 2.7 ± 2.2. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case, and VAS was 4.9 ± 2.4. CONCLUSIONS Concomitant administration of GJG is useful in preventing neuropathy in breast cancer patients treated with a DOC regimen.

Breath Alcohol Concentration in Japanese Breast Cancer Patients Following Alcohol-Containing Chemotherapeutic Agent Infusion

Background: Preparations containing dehydrated ethanol as an additive, due to its water-insoluble properties, have been frequently used for chemotherapeutic agents, such as paclitaxel (PTX), docetaxel (DOC) and eribulin. When selecting these drugs, the influence of alcohol on the central nervous system (CNS) must be considered. In this study, we measured the breath alcohol concentration (BAC) in Japanese breast cancer patients treated with these agents. Method: Japanese patients with breast cancer receiving outpatient chemotherapy with alcohol-containing agents were registered. The BAC was measured immediately after drip infusion and 30 and 60 minutes later. Result: Thirty-one female patients were enrolled in this study. Breath alcohol was detected in 18 patients (58%) immediately after administration: 6 patients (75%) with PTX, 10 (50%) with DOC and 2 (67%) with eribulin. After 30 minutes, no patient had BAC over 0.15 mg/L, but breath alcohol under 0.1 mg/L was detected in 1 patient with PTX and 1 with DOC after 60 minutes. Conclusion: The influence of alcohol may disappear 60 minutes or more after administration, making it possible to travel home safely at this time.

Mucinous carcinoma occurring in the male breast

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.

Feasibility Study of Docetaxel and Cyclophosphamide Six- Cycle Therapy as Adjuvant Chemotherapy for Japanese Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients

BACKGROUND We compared treatment completion rates and safety of docetaxel and cyclophosphamide six- cycle therapy (TC6) with docetaxel followed by 5FU, epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. MATERIALS AND METHODS We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer patients. The primary endpoint of this trial was toxicity. As second endpoints, the treatment completion rate and relative dose intensity were evaluated. RESULTS The TC6 and T-FEC group consisted of 22 and 21 patients, respectively. Concerning hematological toxicity, grade 3 or higher adverse reactions included neutropenia and febrile neutropenia. As non-hematological adverse events, exanthema and peripheral neuropathy were frequently reported in the TC6 group, whereas more patients of the T-FEC group reported nausea and vomiting. In TC6, the treatment completion rate was 86.4% and the relative dose intensity of docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively. CONCLUSIONS These results suggest that TC6 is tolerable in Japanese, and that this regimen can also be performed in outpatient clinics. However, with the TC6 regimen, the compliance was slightly lower than with the T-FEC regimen, and supportive therapy needs to be managed appropriately.

Abstract P1-15-11: The Kampo medicine Goshajinkigan prevents docetaxel-related peripheral neuropathy in breast cancer patients

Background: Although taxanes have become a key chemotherapeutic drug in breast cancer treatment. Taxanes inhibit the growth of cancer cells by disrupting the functioning of their microtubules; however, the microtubules of nerve cells are also affected by this process, which can cause neurological disorders. The Kampo medicine Goshajinkigan (GJG) is a traditional Japanese medicine that is used for the treatment of several neurological symptoms including pain and numbness, GJG is comprised of 10 herbs, each of which contains numerous active ingredients. Recently, GJG has been reported to prevent anticancer drug-induced peripheral neuropathy in colorectal cancer. We performed the present prospective randomized study to confirm the effects of GJG and mecobalamin (B12) against docetaxel (DOC)-associated peripheral neurotoxicity in breast cancer patients. Patients and method: Between May 2007 and April 2011, 60 breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. The patients were treated with TC (75mg/m 2 docetaxel and 600 mg/m 2 cyclophosphamide) every 3 weeks for 4 cycles, docetaxel alone (100mg/m 2 ) every 3 weeks for 4 cycles, and XT (900mg/m 2 capecitabine administered orally twice a day on days 1–14 plus 60 mg/m 2 docetaxel) every 3 weeks for 6 cycles. Peripheral neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver.3.0, and a visual analogue scale (VAS). Results: The median age of the GJG group was 58 years old (35 to 70 years old), the B12 group was 55 years old (33 to 69 years old), and they were all females. For the regimens, in the GJG group, TC, DOC only, and XT were administered in 19 cases, 13 cases and 1 case, respectively. In the B12 group, they were 15 cases, 11 cases and 12 cases, respectively. The cumulative dose of DOC was 338.5 mg/m2 in the GJG group, and 340 mg/m2 in the B12 group. Peripheral neuropathy occurred significantly less frequently in the GJG group (39.3%) than the B12 group (88.9%) (p Conclusion: The present study is the first prospective control study to prove the efficacy of GJG against docetaxel-induced peripheral neuropathy in breast cancer patients. Our findings suggest that DOC-associated peripheral neurotoxicity can be suppressed by the administration of GJG. It will be necessary to confirm the usefulness of GJG in larger prospective studies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-11.

Cetuximab as salvage monotherapy in chemotherapy‑refractory metastatic colorectal cancer: A single‑center report

In July 2008, cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), was approved in Japan for clinical use against chemotherapy-refractory metastatic colorectal cancer (mCRC). At Shiga University of Medical Science, between December 2007 and April 2012, a total of 24 EGFR-positive mCRC cases were administered immunohistochemistry with cetuximab as salvage monotherapy. The safety, side-effects and clinical efficacy of the treatment, including response rate, time to treatment failure, progression-free and overall survival, K-ras mutation status and impact on outcome, were investigated. The patient tumor growth control rate (TCR) was 38%, the mean time to progression (TTP) was 9.8 weeks [95% confidence interval (CI), 7.2–12.4] and the mean overall survival (OS) was 49.4 weeks (95% CI, 30.1–68.8). The most common adverse reactions reported were skin reactions, including acne (67%), hand-foot syndrome (16.7%) and paronychia (16.7%), followed by hypocalcemia (50%), hypomagnesemia (16%), stomatitis (20%) and gastrointestinal disorders (12%). The results of the present single-center study demonstrated that cetuximab monotherapy is beneficial for the treatment of chemotherapy-refractory patients with mCRC and that it has an acceptable level of safety and manageable side-effects.

Safety Assessment of Intravenous Administration of Trastuzumab in 100ml Saline for the Treatment of HER2-Positive Breast Cancer Patients

BACKGROUND The infusion rate is considered to affect incidence and severity of infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is approved for 90-minute infusion as the initial dose followed by 30-minute infusion with 250 ml saline. In the study, we evaluated the safety of TRS intravenously administered over 30 minutes with 100 ml saline to reduce burden of patients, safety of infusion with 250 ml saline already being established. MATERIALS AND METHODS Women with HER2 positive breast cancer, ≥18 years and ≥55% left ventricular ejection fraction (LVEF), were registered in the study. Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS 100ml over 30 minutes in a three-week cycle. RESULTS A total of 31 patients were recruited, 24 for adjuvant therapy and seven with metastases. The median age was 59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with the median of 15. Mild IR occurred in two patients at the first dose. However, no IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of serum brain natriuretic peptide or any other adverse events were reported. CONCLUSIONS Intravenous infusion of TRS with 100 ml saline over 30 minutes in breast cancer patients can be considered safe based on results from the study. It can be given on an outpatient basis as with the currently recommended dilution in 250 ml saline.

Umbilical metastasis derived from breast cancer: report of a case.

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.

New fluorescence imaging method for sentinel lymph node biopsy in patients with early breast cancer.

e11578 Background: Indocyanine green (ICG) is a popular diagnostic reagent for the examination of hepatic function and cardiac output. In this study, based on the fluorescence characteristics of ICG, we present a new method that enables the detection of sentinel lymph nodes (SLN) with high sensitivity using ICG fluorescence imaging. METHODS Fluorescence images were obtained using the fluorescence imaging system, the Photodynamic Eye (Hamamatsu Photonics Co., Japan). A 0.5% ICG solution combined with Indigocarmine was intradermally injected for 0.3 ml in the areola closest to a tumor. Subcutaneous lymphatic channels draining from the areola to the axilla or other directions were visible by fluorescence imagings immediately. The point where the fluorescence disappeared was identified on the skin, and the skin has been pressed with the capsule. The point of fluorescence seemed was then incised, and the SLN were then dissected by fluorescence navigation. RESULTS This study enrolled 202 patients with clinically node-negative breast cancer. Their average age was 53.9 years (ranged from 29 to 82 years). Sixty five patients were premenopausal, and 137 patients were postmenopausal. There were five cases of Tis lesions and 117 cases with T1 lesions and 80 cases with T2 lesions. Subcutaneous lymphatic channels and SLN were successfully visualized in all patients. One lymphatic channel to the axilla was 53%, two channels were 32%, and three channels were 16%. The channels to other directions were not seen. The number of fluorescent SLN ranged from 1 to 6 (mean: 3.1), and blue dyed SLN ranged from 0 to 3 (mean: 1.2). In the latter, SLN were not identified in 76 patients (identification rate: 62.4%). Twenty three patients had lymph node metastases pathologically. All of them were recognized by fluorescence imagings, but, in 10 patients, lymph nodes with metastases were not identified by a blue dye. CONCLUSIONS The fluorescence imaging method is therefore considered to be a new and effective method for SLN mapping, which allows easy, highly sensitive and real-time imaging-guided SLN mapping in patients with early breast cancer. The current results show that SLN mapping guided by ICG fluorescence imaging could therefore be a promising tool.