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Invasive lobular carcinoma (ILC) has a different treatment response from invasive ductal carcinoma (IDC). We assessed whether perioperative chemotherapy was associated with improved prognosis in patients with ILC. Retrospective data of women who underwent surgery for ILC were extracted from the SEER database. Subjects were divided into non-chemotherapy and chemotherapy groups. Overall, 10 537 patients were included, and 2107 patients were stratified into each group after propensity score matching. Perioperative chemotherapy significantly improved 10-year survival rates for ILC, particularly in patients with large tumor size and lymph node metastases. Perioperative chemotherapy is effective for ILC patients with proper selection.

Hormone receptor and human epidermal growth factor receptor 2 (HER2) protein tests in metastatic breast cancer tissue are recommended in the guidelines of the American Society of Clinical Oncology/American Pathology Association. As part of a multi-institutional study by the National Hospital Organization, we conducted an investigation to examine these molecular markers, using cytological specimens as a substitute for tissue specimens from breast cancer metastasis. To confirm the usefulness of receptors tested in metastatic lesions, the treatment course of registered metastatic breast cancer patients was analyzed. During the April 2015 to March 2016 registration period, there were 62 registrations. Types of metastatic lesions include pleural fluid (44 samples), ascites (14 samples), lymph nodes (2 samples), pericardial fluid (1 sample), and dorsal subcutaneous mass (1 sample). A stable test result was obtained by adopting the receptor examination method, using cell block for immunostaining cytological specimens. The discordance rates of estrogen receptor (ER), progesterone receptor (PR), and HER2 protein expression were 18.2% (95% confidence interval (CI): 7.9-28.8%), 36.4% (95% CI: 23.7-49.1%), and 8.2% (95% CI: 0.1-16.3%), respectively, between the primary tumor and metastatic lesion. Patients who changed from primary negative to metastatic positive ER status had taken a significantly longer time for metastatic foci to appear. Patients with positive ER status in metastatic lesions had significantly better prognosis than ER-negative cases (P = 0.030) by the Log-Rank test. The ER status of the metastatic lesion and the metastatic site were independent prognostic factors by Cox multivariate analysis. Receptor examination with cytological specimens in metastatic lesions has been useful as it provides guidance for the treatment of metastatic breast cancer.

Background: Triple-negative breast cancer (TNBC) is a biologically heterogeneous disease that is often associated with worse outcomes compared with other subtypes such as hormone receptor-positive tumors and HER2-positive tumors. While chemotherapy remains the mainstay of standard therapy for metastatic TNBC (mTNBC), several novel treatments have been developed over the past few years. In this review article, we review the major developments in the management of patients with mTNBC. Summary: The combination of chemotherapy and immunotherapy is a potential therapeutic option for PD-L1-positive mTNBC, as the FDA recently approved atezolizumab (Tecentriq) and pembrolizumab (Keytruda) in combination with chemotherapy. Also, 2 targeted therapies-olaparib (Lynparza) and talazoparib (Talzenna)-are FDA approved for the management of mTNBC with germline BRCA mutations, and sacituzumab govitecan, an anti-Trop2 antibody-drug conjugate (ADC), was recently approved for previously treated mTNBC. A number of promising therapies are on the horizon, including AKT inhibitors for PI3K-altered TNBC as well as other ADCs. Key Message: The successful clinical development of immunotherapies, PARP inhibitors, and ADCs for the management of mTNBC has improved the survival outcome of patients. Over the coming years, the therapeutic developments in precision medicine will likely change the mTNBC landscape, and might make the current definition of TNBC as breast cancer that is estrogen receptor negative, progesterone receptor negative, and HER2 negative obsolete.

Cancer chemoprevention is defined as the use of natural, synthetic, or biochemical agents to reverse, suppress, or prevent carcinogenic processes in neoplastic diseases. Although the precise mechanisms that promote breast cancer are not fully understood, several recent clinical trials suggest that chemoprevention is a rational and attractive strategy for selected high-risk populations in a prophylactic setting. Conventionally, endocrine interventions using selective estrogen receptor modulators and aromatase inhibitors have already been applied clinically in high-risk populations. In particular, the chemoprevention approach for BRCA germline mutation carriers is drawing attention as an alternative option to invasive prophylactic mastectomy. Although the evidence from prospective clinical studies was limited, this review aims to provide an up-to-date overview of the biological mechanisms and the efficacy of various chemopreventive agents, including new promising candidates that target BRCA deficiency, and discuss future challenges and prospects for breast cancer chemoprevention.

Eribulin mesylate (eribulin) is an efficient microtubule inhibitor that is used for metastatic breast cancer. However, breast cancer can develop resistance to eribulin. This resistance mechanism needs to be elucidated. A transposon mutagenesis screen was conducted using a pPB-SB-CMV-puro-SD plasmid and pCMV-PBase transposase. Viability and cytotoxicity were analyzed by MTT assay and flow cytometry, respectively. Real-time PCR and western blot were used for gene expression analysis. In addition, vivo study was also designed to analyze therapy efficiency. TAB2, which is part of the nuclear factor-kappa B (NF-κB) pathway, was identified as a candidate eribulin-resistant gene. TAB2 down-regulation resulted in significantly lower cell viability and higher cytotoxicity of cells treated with eribulin, while TAB2 up-regulation showed opposite results. Similarly, combination of NF-κB inhibitors [Bay-117082 and QNZ (quinazoline derivative)] with eribulin showed significantly lower cell viability and higher drug cytotoxicity than single agent treatment with eribulin in MDA-MB-231 cells. However, QNZ increased NF-κB activity in MCF7 cells by up-regulating TAB2, which reduced the sensitivity to eribulin. Furthermore, combination of Bay-117082 with eribulin induced greater regression of MDA-MB-231 tumors compared to eribulin monotherapy in vivo. These results consistently illustrated that TAB2-NF-κB pathway may increases resistance to eribulin in breast cancer models. Moreover, these results support the use of a combination strategy of eribulin with NF-κB inhibitors, and provide evidence that transposon mutagenesis screens are capable of identifying drug-resistant genes.

Background Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. Methods The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. Results Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5–61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0–73.5) and 78.1% (95% CI 63.8–92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1–9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. Conclusions Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer. Trial registrations This trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334). Date of trial registration: April 1st, 2013.

Background The optimal choice of antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) needs to be clarified. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy (HEC). Methods Randomized trials that compared different antiemetic regimens were included from MEDLINE. Quality was assessed using the Cochrane risk-of-bias tool. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Data were pooled using random-effects models. We conducted indirect comparisons using network meta-analysis of a Bayesian model. The main outcomes were the odds ratio (OR) for overall complete response (CR [i.e., no emesis and no rescue]). Safety was assessed from the trial description. All statistical tests were two-sided. Findings We systematically reviewed 24 randomized control trials (12,104 participants), which compared 12 different antiemetic regimens. Palonosetron (PAL) 0·75 mg (PAL0·75) + dexamethasone (Dex); aprepitant (APR) + a serotonin-3 receptor antagonist (5HT3) + Dex; and APR + PAL (0·25 mg or 0·50 mg) + Dex were more favorable than the reference regimen (OR, 1·51; 95% credibility interval [95%CrI], 1·18-1·91; OR, 1·78; 95%CrI, 1·58-2·05; and OR, 2·28; 95%CrI, 1·66-3·18, respectively). The oral combination of netupitant and palonosetron (NEPA) was more effective than conventional regimens (OR, 2·39; CrI, 1·73-3·30). Olanzapine (OLZ)-containing regimens were apparently the most effective: the ORs of OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + APR + 5HT3 + Dex were 2·78, 2·58, and 4·98, respectively. Interpretation The regimens of PAL0·75 + Dex, APR + 5HT3 + Dex, and APR + PAL + Dex were more favorable in conventional regimens (i.e., regimens without NEPA or OLZ), which support the NCCN guideline strategy. NEPA could be a better choice than conventional regimens. OLZ-containing regimens could be an optimal choice; thus, more trials need to be accumulated. Citation Format: Yokoe T, Hayashida T, Nagayama A, Seki T, Takahashi M, Takano T, Abe T, Kitagawa Y. Comparative effectiveness of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-11.

The response of triple-negative breast cancer (TNBC) to chemotherapy is heterogeneous; particular subtype classifications based on mRNA gene expression analysis have been demonstrated to be associated with a pathological complete response (pCR). The aim of the present study was to investigate additional clinical and pathological characteristics associated with pCR status. The pathological and clinical characteristics of 40 TNBC patients who underwent neoadjuvant chemotherapy followed by surgery were retrospectively analyzed by dividing the cases into two groups according to the response to treatment: pCR (n=12) and non-pCR (n=28). Clinically, patients in the pCR group presented tumors with a significantly less advanced Tumor-Node-Metastasis stage (P=0.030) and mammographic calcification was less common (17 vs. 58%; P=0.034). Pathologically, whereas all cases in the pCR group (12/12, 100%) were of the histological type ‘invasive ductal carcinoma, not otherwise specified’ (IDC-NOS), the non-pCR group consisted of a lower proportion of IDC-NOS cases (20/28, 71%) and more cases of special histological types, including mucinous, metaplastic, medullary and apocrine carcinomas (P=0.079). The positive rates of androgen receptor (AR) and forkhead-box A1 (FOXA1) tended to be lower in the pCR group (AR, 0 vs. 29%, P=0.079; FOXA1, 8 vs. 29%, P=0.233). The Ki-67 score was significantly higher in the pCR group than in the non-pCR group (P=0.041). The results suggest that patients with TNBC who present with clinically less advanced tumors and less frequent mammographic calcification are more likely to respond to chemotherapy. From a pathological standpoint, IDC-NOS type, negative AR status and higher Ki-67 scores may be associated with chemotherapy sensitivity.

Mammography and ultrasound are widely used for breast cancer diagnosis. In 2003, the American Society of Radiological Surgery created “Breast Imaging Reporting and Data System (BI-RADS)” to standardize the terms in breast ultrasonic diagnosis. Although BI-RADS categorization of ultrasound is globally used, quality consistency remains an urgent task in breast ultrasound diagnosis. Although there are such quality control problems, the importance of ultrasonic examination in breast cancer diagnosis is increasing. "Comparative Exam for Verifying the Effectiveness of Ultrasound in Breast Cancer Screening (Japan Strategic Anti-cancer Randomized Trial: J-START )”, a randomized controlled trial, showed that breast screening by combined application of mammography and ultrasound was significantly better in detecting early breast cancer compared to mammography alone among women in their 40s. Despite some argument about the increase of false positive cases, breast screening is becoming more important and popular in the countermeasure-type screening settings in Japan. Moreover, the education of doctors and technicians responsible for ultrasonographic screening and improvement of examination accuracy is an urgent matter. Since the accuracy of the breast ultrasound examination depends on the equipment, environment, technicians and doctors, it is necessary to solve the problem in quality control. Therefore, we are collaborating with a company which specializes in Artificial Intelligence (AI) to develop a “quality-controlled” breast ultrasonographic diagnosis system by using AI technology. The system can detect the presence of a lesion and make diagnosis real-time during the ultrasonic examination. This system uses a technology called Convolutional Neural Network, which is frequently used in image analysis by AI. We selected ultrasonographic images for machine learning from patients who underwent ultrasonographic screening between January 2016 and December 2018 in Keio University Hospital, Japan. All patients who were diagnosed as malignant underwent biopsy and were diagnosed histologically. The patients who were diagnosed as benign either underwent biopsy or a half-year or more observation. Trained physicians added annotations to each selected image. Annotation was added on 901 images, of which 630 images (138 images of normal mammary gland, 242 images of benign tumor, 250 images of malignant tumor) were used as training data. We tested the system by using 271 images(70 images of normal mammary gland, 97 images of benign tumors, 104 images of malignant tumors) as test data. As a result, sensitivity of mass (benign or malignant) detection among normal breast was 91.8%, and specificity was 91.4%. The sensitivity in the detection of malignant lesion among masses was 86.2%, and the specificity was 88.4%. In conclusion, we succeeded to develop a real time working, quality-controlled, breast ultrasonographic diagnosis system using artificial intelligence. We plan to improve both sensitivity and specificity by adding more learning data for clinical application in near future. Citation Format: Masayuki Kikuchi, Tetsu Hayashida, Rurina Watanuki, Ayako Nakashoji, Yuko Kawai, Aiko Nagayama, Tomoko Seki, Maiko Takahashi, Yuko Kitagawa. Diagnostic system of breast ultrasound images using Convolutional Neural Network [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-09.

Triple negative breast cancer (TNBC) is a heterogenous subtype of breast cancer often associated with an aggressive phenotype and poor prognosis. Antibody–drug conjugate (ADC), comprising of a monoclonal antibody linked to a cytotoxic payload by a linker, is gaining increasing traction as an anti-cancer therapeutic. Emerging ADC drugs such as sacituzumab govitecan (IMMU-132) and trastuzumab deruxtecan (DS-8201a) are in late stages of clinical development for patients with metastatic breast cancer, including TNBC. In this article, we review and discuss the development and clinical application of ADCs in patients with advanced TNBC.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately impacts younger women and is associated with a poor prognosis. Systemic treatment options for metastatic TNBC (mTNBC) are limited to cytotoxic chemotherapy agents with low response rates. This encouraged the clinical development of sacituzumab govitecan (IMMU-132), an antibody-drug conjugate targeting Trop-2, a potential target in epithelial cancer such as TNBC. Areas covered: We summarize the key features, pharmacokinetics, and the safety and efficacy data of sacituzumab govitecan. We also discuss the future directions of this novel therapeutic agent for mTNBC. Expert opinion: Based on the efficacy and tolerability observed in the phase 1/2 clinical trial, sacituzumab govitecan was granted breakthrough therapy designation by the Food and Drug Administration as ≥3

Background It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. Methods Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. Results We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. Conclusion Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. Implications for practice Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Background: Hormone receptor (Estrogen receptor (ER), Progesterone receptor (PgR)) is an important biological marker for predicting prognosis and making effective treatment decisions. Discordance in these biomarkers between the primary tumor and recurrent lesions is reported frequently. However, it is not well known whether these biomarkers are affected by neoadjuvant chemotherapy and their impacts on outcomes still remain to be elucidated. The aim of the present study is to evaluate the changes in HR status after neoadjuvant chemotherapy in patients with operable breast cancer and their relationship with response to treatment and prognosis. Patients and Methods: Of 162 patients with stage II/III breast cancer patients receiving neoadjuvant chemotherapy from January 2005 to September 2012 at Keio University Hospital, 140 patients with non-pCR were analyzed. Patients were treated with sequential anthracycline and taxane. ER and PgR were assessed in both CNB performed prior to neoadjuvant chemotherapy and surgical samples. HR status was assessed by immunohistochemistry (IHC). ER/PgR status was determined using the Allred score and defined as positive when score was 3 and more. HR status was considered positive in cases of ER and/or PgR positivity. Pathological response criteria were classified as grade 0, 1, 2, or 3: grade 0 includes almost no change in cancer cells; grade 1 includes slight or marked changes in less than two thirds of area; grade 2 includes marked changes in more than two thirds of area; grade3 includes necrosis or disappearance of all tumor cells. Results: ER, PgR and HR positive rates before neoadjuvant chemotherapy were 72.9%, 67.1% and 76.4%, respectively. Changes in ER, PgR and HR status between CNB and surgical samples were 12.1% (4.3% gain; 7.8% loss), 17.1% (2.1% gain; 15.0% loss) and 9.3% (2.9% gain; 6.4% loss), respectively. In ER-discordant group, grade 2 rate of pathological response was significantly higher than ER- concordant group (61.1% vs. 30%, p=0.033), whereas there were no significant differences of pathological response between discordant and concordant group in PgR status. In the disease free survival (DFS), there were no significant difference between concordance and discordance group for ER, PgR and HR (p=0.216, 0.859, 0.233) after a median follow-up of 40.4 months. But patients with a loss in ER and/or HR status had a trend to a shorter DFS compared with the concordant ER and/or HR-positive group (p=0.169 and 0.154) Conclusions: After neoadjuvant chemotherapy, discordance of biomarkers was seen in 5-20%. The pathological response was significantly associated with the change in ER status. A loss in ER and/or HR status may affect a prognosis of breast cancer after neoadjuvant chemotherapy, but still need further investigation. Citation Format: Toshiaki Kurihara, Hanako Ueno, Masaru Takemae, Aiko Nagayama, Maiko Takahashi, Tetsu Hayashida, Hiromitsu Jinno, Yuko Kitagawa. Prognostic impact of discordance in hormone receptor status after the neoadjuvant chemotherapy in primary breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-06-49.

Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. ADCs that have gained regulatory approval from the US Food and Drug Administration (FDA) include brentuximab vedotin for CD30-positive Hodgkin's lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Several other agents are in advanced stages of clinical development, including sacituzumab govitecan for breast cancer, mirvetuximab soravtansine for ovarian cancer, rovalpituzumab tesirine for lung cancer, depatuxizumab mafodotin for glioblastoma, and oportuzumab monatox for bladder cancer. This review provides an overview of the recent clinical experience with the approved, most advanced, and other promising candidates of ADCs for solid tumors, including a description of biology and chemistry of ADCs, drug resistance and biomarkers, and the future perspective on combination strategies with these new immunoconjugates.

BACKGROUND Taxanes are among the key drugs for breast cancer treatment. This study aimed to evaluate the efficacy of upfront weekly nanoparticle albumin-bound paclitaxel (Nab-PTX; 100 mg/m2) for human epidermal growth factor 2 (HER2)-negative breast cancer. PATIENTS AND METHODS Patients with stage II to IV breast cancer received 12 cycles of weekly 100 mg/m2 Nab-PTX as first-line treatment. Preoperative chemotherapy with anthracyclines after Nab-PTX was recommended. RESULTS From 2012 to 2014, we enrolled 66 patients. The overall response rate after Nab-PTX was 59.1% [95% confidence interval(CI)=47.2% to 71.0%), 63.6% in those with hormone receptor-positive tumors, and 36.4% in those with triple-negative tumors. The pathological complete response rate at surgery was 15% (95% CI=6.1% to 24.4%). Toxicity analysis showed grade 2 peripheral neuropathy in 38 patients (57.6%), grade 2/3 leukocytopenia in 29 (43.9%) and grade 2/3 liver dysfunction in five (7.5%). CONCLUSION Weekly neoadjuvant Nab-PTX at 100 mg/m2 led to good response rates (59.1%) and was well tolerated.

Background We previously described a systematic assessment of the neoadjuvant therapies for human epidermal growth factor receptor-2 (HER2) positive breast cancer, using network meta-analysis. Accumulation of new clinical data has compelled us to update the analysis. Methods Randomized trials comparing different anti-HER2 regimens in the neoadjuvant setting were included, and odds ratio for pathologic complete response (pCR) in seven treatment arms were assessed by pooling effect sizes. Direct and indirect comparisons using a Bayesian statistical model were performed. All statistical tests were two-sided. Results A database search identified 993 articles with 13 studies meeting the eligibility criteria, including three new studies with lapatinib (lpnb). In an indirect comparison, dual anti-HER2 agents with CT achieved a better pCR rate than other arms. The credibility intervals of CT + tzmb + lpnb arm were largely reduced compared to our former report, which we added sufficient clinical evidence by this update. Values of surface under the cumulative ranking (SUCRA) suggested that CT + tzmb + pzmb had the highest probability of being the best treatment arm for pCR, widening the difference between the top two dual-HER2 blockade arms compared to our former report. The overall consistency with our first report enhanced the credibility of the results. Conclusion Network meta-analysis using new clinical data firmly establish that combining two anti-HER2 agents with CT is most effective against HER2-positive breast cancer in the neoadjuvant setting. New pzmb related trials are required to fully determine the best neoadjuvant dual-HER2 blockade regimen.

Background: Analysis of gene expression arrays has resulted in the recognition of several fundamentally different subtypes of breast cancer. These subtypes have different natural histories and different responses to systemic and local therapies. However, widespread use of gene expression profiling is limited because of its expense and of technical difficulty. Alternatively, this classification has also been reproduced in immunohistochemical studies. The objective of this study was to evaluate the clinical utility of immunohistochemical classification of breast cancer intrinsic subtypes in the prediction of pathological compelete response (pCR) in a cohort of breast cancer patients receiving the sequential combination of taxane followed by anthracycline as preoperative chemotherapy. Materials and methods: A prospective database of 150 women with stage II/ III breast cancer, who received neoadjuvant chemotherapy, was analyzed. The regimens were either four cycles of docetaxel (40 mg/m2 on day 1 every 3 weeks) with S-1 (80 mg/m2 on days 1–14 every 3 weeks) followed by four cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2) and cyclophosphamide (500 mg/m2) (FEC) or four cycles of docetaxel (60 mg/m2 on day 8 every 3 weeks) with capecitabine (1650 mg/m2 on days 1–14 every 3 weeks) followed by four cycles of FEC. Subtypes were classified into luminal A (lumA) (ER+ and/or PgR+, HER2−, Ki6714%), triple-positive (TP) (ER+ and/or PgR+, HER2+), HER2 (ER−, PgR−, HER2+), and triple-negative (TN) (ER−, PgR−, HER2−) by using immunohistochemically stained specimen obtained by core needle biopsy. Absence of invasive tumor cells in the breast at the time of surgery was defined as pCR. Results: We found 34 women in lumA, 54 in lumB, 15 in TP, 8 in HER2, 33 in TN. The median age in each group was 53, 51, 50, 57 and 53 respectively (p = .397). The mean tumor size was 3.2cm, 3.5cm, 4.4cm, 3.9cm and 3.6cm respectively (p = .158). The clinical response rate measured by physical examination (calliper) was 80.6%, 93.9%, 86.7%, 100% and 82.4% (p = .378). pCR rate was 5.9%, 14.8%. 13.3%, 50%, 21.2% respectively (p = .031). The multivariate analysis showed ER negative, PgR negative and intrinsic subtype (TN) were the significant predictive factors of pCR (p = .027, p = .003, p = .004). Conclusion: This study indicated that immunohistochemical classification of intrinsic subtype might be a useful predictive biomarker of pCR in breast cancer patients treated with preoperative chemotherapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-09.

Primary malignant lymphoma of the small intestine is uncommon. We herein present a case of malignant lymphoma of the ileum, which was treated by laparoscopically assisted surgery. A 60-year-old male with lower abdominal pain and vomiting was admitted to our hospital. A standing abdominal X-ray showed niveau formation. Computed tomography demonstrated circumferential wall thickening in the terminal ileum. Laparoscopically assisted surgery was performed under a diagnosis of tumor of the ileum. Under laparoscopic exploration, tumor of the ileum was detected. Partial resection of the ileum and dissection of lymph nodes were performed extracorporeally. Histological findings demonstrated diffuse large atypical lymphocytes with vesicle-like chromatin and clear nucleolus. Immunologically, CD20 and CD79a were positive. These findings were compatible with those of diffuse large B-cell lymphoma. Paraintestinal lymph nodes were also involved. The postoperative course was uneventful. Neither gallium scintigraphy nor FDG-PET showed any scintillation. The patient was given R-CHOP therapy and is currently doing well with no sign of recurrence. In conclusion, we propose that laparoscopic surgery for malignant lymphoma of the small intestine is a feasible and promising therapeutic option, especially in a case demonstrating bowel obstruction, because this procedure is thought to be minimally invasive, allows quick postoperative recovery and shortened hospital stay could be expected.

Background The growing number of antihuman epidermal growth factor receptor-2 (HER2) agents suggests the need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. This study aims to assess the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer. Methods Randomized trials that compared different anti-HER2 regimens in the neoadjuvant setting were included. The odds ratio (OR) for pathological complete response (pCR), treatment completion, and safety was utilized for pooling effect sizes. Network meta-analysis using a Bayesian statistical model was performed to combine the direct and indirect evidence of neoadjuvant therapy for HER2-positive breast cancer. All statistical tests were two-sided. Results A database search identified 1047 articles, with 10 studies meeting the eligibility criteria. A total of 2247 patients in seven different treatment arms were assessed. Anti-HER2 agents evaluated included trastuzumab (tzmb), lapatinib (lpnb), and pertuzumab (pzmb). Network meta-analysis showed no statistically significant difference between dual targeting treatment arms; however, lpnb reduced treatment completion due to adverse events. Patients in dual targeting arms had statistically significantly more pCR than those in other treatment arms (chemotherapy [CT] + tzmb + pzmb vs CT + tzmb, OR = 2.29, 95% credibility interval = 1.02 to 5.02, P = .02). The surface under the cumulative ranking probability curve indicated that CT + tzmb + pzmb had the highest probability of being the best treatment arm in terms of pCR. Conclusions This study indicates that combining two anti-HER2 agents with CT is the most effective treatment modality in the neoadjuvant setting for HER2-positive breast cancer.

e11598 Background: The growing number of anti-HER2 agents suggests the eventual need for defining the optimal choice of neoadjuvant therapy for HER2-positive breast cancer. Multiple-treatments meta-analysis synthesizes information from a network of trials and combines direct and indirect evidence on the relative effectiveness. An indirect estimate of the benefit of A over B can be obtained by comparing trials of A v C with trials of B v C. In this study, we assessed the efficacy and safety of neoadjuvant therapy for HER2-positive breast cancer by conducting the direct and indirect comparisons from multiple RCTs. Methods: The primary outcome of the study was the number of the patients who achieved pathological complete response (pCR) defined as no invasive residual in breast or node. Secondary objectives were the number of patients who completed the treatment as planned and adverse events including diarrhea, neutropenia, cardiac events and skin disorder. Results: We identified 1047 articles by database search and 10 studies met our criteria. A total of 2247 patients in 7 different treatment arms were assessed; chemotherapy (CT) alone, CT with single or dual anti-HER2 agents and dual anti-HER2 agents without CT. Anti-HER2 agents evaluated were trastuzumab (T-mab), lapatinib, pertuzumab (P-mab). There was no significant difference between dual targeting treatment arms (CT + T-mab + lapatinib v CT + T-mab + P-mab, OR; 1.11, [0.42-2.86], p=0.41), however, lapatinib reduced the treatment completion mainly due to adverse events. Patients in dual targeting arms had significantly higher incidence of pCR than in other treatment arms. (CT + T-mab + P-mab v CT + T-mab, OR; 2.29, [1.02-5.02], p=0.02) Surface under the cumulative ranking probability curve (SUCRA) also indicated that CT + T-mab + P-mab had the highest probability of being the best treatment arm for pCR followed by CT + T-mab + lapatinib and CT + T-mab. Conclusions: This study provides evidence that combining two anti-HER2 agents with chemotherapy are the most effective treatment arms. Considering the cost and limited medical resources, CT + T-mab showed a well-balanced profile for efficacy, completion and safety.

with an appropriate diagnostic tool is a clinical concerning matter. Different modalities have been proposed with different efficacy such as breast duct endoscopy, Breast CT scan and various biopsy techniques. In this study we tried to investigate the role of core needle biopsy (CNB) as a fast and easy diagnostic procedure in plasma cell mastitis, considering open biopsy as gold standard. Material and methods: To evaluate the efficacy of CNB in diagnosis of plasma cell mastitis and differentiate it from a malignant lesion certainly, we analyzed the clinical and histopathological data of 76 patients with primary diagnosis of plasma cell mastitis from January 2001 to December 2008. All of them had a palpable mass in breast and their primary diagnosis was obtained by means of CNB. 48 out of these 76 patients (63.15%) who had undergone incisional or excisional biopsy as diagnostic or therapeutic option afterwards were included in the study. Results of definitive pathologic examination were compared with CNB results. Results: Of 48 patients with median age of 34 years (range 22-48), 27 (56.25%) underwent excisional biopsy and 21 (43.75%) underwent incisional biopsy. Tuberculosis in 3 patients (6.25%) and Breast cancer in 8 patients (16.66%) were confirmed after pathologic examination of the surgical specimen. The average follow-up period was 54 months. There were 9 chronic wound with delayed healing and 10 chronic fistulae during postoperative period. The rate of chronic wound in excisional and incisional biopsy group were 7.4% and 33.33% and rate of fistulae formation for them were 7.4% and 38.09% respectively. Conclusions: The results show that diagnosis of plasma cell mastitis which is obtained from CNB of a breast mass is not reliable. We suggest performing surgical biopsy in all above-mentioned patients. Excisional biopsy prevents delayed treatment in malignant lesions or inappropriate treatment in tuberculosis. Besides it usually is the only therapeutic procedure required for plasma cell mastitis.