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The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 remains a major global crisis and continues to spread relentlessly around the world. In Japan, the number of infected people has incrementally increased since April 2020. The COVID-19 pandemic has exerted a major impact not only on our daily lives but also on healthcare. As the infection continues to spread, many medical institutions have devoted all efforts to minimize the risk of infection not only for patients but also for medical personnel by prioritizing medical care, reserving treatment, and extending consultation intervals. Cancer treatment is one of the priorities for medical care even during an epidemic infection as there is a concern of decreasing curability or therapeutic effect from postponement. As the COVID-19 situation evolves rapidly, we created an informative triage to provide appropriate medical treatment to breast cancer patients. In this triage, we offer guidance on preparing for the impact of the COVID-19 pandemic in breast cancer patients, prioritizing triage and diagnostic procedures, and providing advice on surgical, radiation, and oncological treatments.

Background With the introduction of dose-dense therapy, the use of primary pegfilgrastim (PEG-G) has been increasing in breast cancer treatment. A rare side effect of PEG-G is aortitis. We describe a case of PEG-G-induced aortitis. Case presentation The patient was a 43-year-old woman with stage IIA breast cancer. Due to the subtype of triple-negative breast cancer, preoperative dose-dense epirubicin–cyclophosphamide chemotherapy was started. PEG-G was administered on day 3 after the first cycle of epirubicin–cyclophosphamide chemotherapy. On day 11, she had a fever (39.4 °C) and an elevated C-reactive protein level (27.1 mg/dL). Emergency computed tomography revealed diffused wall thickening of the aortic arch without any other signs of infection. Despite administering antibiotics, her general condition and laboratory findings deteriorated until day 18. Based on these observations, she was diagnosed with PEG-G-induced aortitis. Antibiotics were discontinued, and she was treated with prednisolone thereafter. Subsequently, her clinical symptoms and laboratory findings improved around day 39. A second computed tomography scan revealed a decrease in the aortic arch wall thickening, and she was discharged on day 43. Conclusions We successfully treated PEG-G-induced aortitis using prednisolone. Although this side effect is rare, cancer patients receiving PEG-G for chemotherapy should be monitored for aortic inflammation.

Background: Febrile neutropenia (FN) is one of the greatest concerns when maintaining chemotherapy dosage for early breast cancer patients. However, the incidence proportion of FN remains unclear because of the empirical prescription of oral antibiotics, the use of G-CSF, and the absence of body temperature examination and hematology test. Therefore, we performed a prospective cohort study of FN in breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. Methods: Breast cancer patients were prospectively enrolled from August 2015 to July 2017. The regimens included 4 cycles of FEC (epirubicin 100 mg/m²), E(A)C (epirubicin 90 mg/m² or doxorubicin 60 mg/m²), and TC (docetaxel 75 mg/m²). Considering the current practice of empirically prescribing oral antibiotics without hematology tests, we followed 2 groups and surveyed FN using 2 different definitions: true FN (T-FN): ≥ 37.5°C and grade 4 neutropenia by a hematologic test with a visit to the hospital (visiting group), and surrogate FN (S-FN): ≥ 37.5°C and oral antibiotic intake without a mandatory visit to the hospital (non-visiting group). The primary objective was to investigate the FN incidence of each regimen during the first 4 cycles. The overall incidence proportion of FN was calculated as (patients with T-FN or S-FN) / (total patients). The proportion of T-FN or S-FN in each group was also examined. In the secondary analysis, the risk factors of FN and the safety of FN management in the non-visiting group were investigated. Multiple logistic regression analysis was performed to assess the risk factors. As we assumed that FN occurs in 20% of the patients by these regimens, the planned sample size based on the confidence intervals was 1000. This trial was registered as UMIN 000017857. Results: A total of 1005 female patients with Stage I to III breast cancer were enrolled. Of these patients, 25 were excluded because of incomplete treatments or other regimens administered. There were 477 patients in the visiting group and 503 patients in the non-visiting group. The numbers of patients in each regimen were 338 in FEC, 335 in E(A)C, and 307 in TC. The overall incidence proportions of FN were 22.5%, 27.5%, and 33.9% in FEC, E(A)C, and TC, respectively. The incidence proportions of T-FN were 27.7%, 22.4%, and 36.6%; those of S-FN were 17.3%, 32.4%, and 31.5%. Pegfilgrastim (PEG-G) was used in the 1st cycle more frequently in the non-visiting group than in the visiting group: in FEC, E(A)C, and TC, 39.0%, 11.8%, and 52.1% in the non-visiting group; 4.71%, 1.82%, and 14.1% in the visiting group, respectively. The risk factors of FN were regimen (TC: OR: 2.67, 95%CI: 1.36-5.26), age (> 65 OR: 2.24, 95%CI: 1.34-3.75), neutrophil count at registration (/1000/μl: OR: 0.8, 95%CI: 0.67-0.95), pre-/post-operation (pre-: OR: 0.51, 95%CI: 0.29-0.88), and PEG-G (OR: 0.04, 95%CI: 0.01-0.34). There were no significant differences in the frequency of grade 3 adverse events, hospitalization, intake of oral antibiotics, and relative dose intensity between the visiting group and the non-visiting group. Therapeutic daily G-CSF was more frequently used in the visiting group than in the non-visiting group. Conclusions: FN occurred at a rate higher than 20% in these 3 regimens, most frequently in TC. Neutrophil count at registration was found to be one of the risk factors of FN. The current practice of prescribing antibiotics without hematologic tests is acceptable for FN management because the outcomes were not significantly different between the visiting group and the non-visiting group. Citation Format: Takashi Ishikawa, Kentaro Sakamaki, Kazutaka Narui, Hideki Nishimura, Takafumi Sangai, Kentaro Tamaki, Yoshie Hasegawa, Ken-ichi Watanabe, Nobuyasu Suganuma, Shintaro Michishita, Sadatoshi Sugae, Tomohiko Aiharya, Koichiro Tsugawa, Hiroshi Kaise, Hirofumi Mukai. Prospective cohort study of febrile neutropenia in breast cancer patients with neoadjuvant and adjuvant chemotherapy: CSPOR-BC FN Study [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 P5-14-09.

β-ray strontium-89 (Sr-89) intra-irradiation therapy has been approved and clinically used to reduce bone metastasis pain not alleviated by bone-modifying agents, external radiation, and analgesic agents. We examined the efficacy of zoledronic acid (ZOL) and Sr-89 combination therapy compared with ZOL alone in breast cancer patients with bone metastases.A randomized controlled trial was conducted on breast cancer patients with bone metastasis to compare the efficacy between ZOL monotherapy and ZOL plus Sr-89 combination therapy. The primary endpoints were changes in urinary NTX levels at 13 weeks and brief pain inventory scores. The secondary endpoints were analgesic drug usages, response rates, changes in bone metabolism markers, quality of life, and adverse event rates.Thirty of the planned 60 cases were randomly assigned to ZOL alone or ZOL + Sr-89. There were no significant differences in the changes in urinary NTX levels between the 2 groups (P = 0.365). There was no consistent difference in the pain score changes between the 2 groups. Sr-89 addition to ZOL slightly reduced the white blood cell and platelet counts. However, all adverse events were Grade 1. Safety and analgesic drug dose reduction were more evident in ZOL + Sr-89.This trial showed the lack of benefits from Sr-89 addition to ZOL for breast cancer patients with painful bone metastases. However, safety and analgesic drug dose reduction were more evident in ZOL + Sr-89, indicating its potential for pain control. Sr-89 therapy is safe, thus more effective radiopharmaceuticals are anticipated.

Background/Aim: To investigate the utility of peripheral blood biomarkers – absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) – for predicting outcomes in eribulin-treated patients with metastatic human epidermal growth factor receptor type 2 (HER2)-negative breast cancer. Patients and Methods: ALC, NLR, and PLR were retrospectively obtained from pre-treatment blood sampling results of 120 patients and stratified according to means. Univariate and multivariate analyses were performed to investigate the association of clinicopathological factors, including these values, with overall survival (OS) and progression-free survival (PFS). Results: The ALC, NLR, and PLR cut-off points were 1,285/μl, 3.3, and 235, respectively. No biomarkers were associated with PFS. However, univariate analysis showed ALC (p=0.044) and PLR (p=0.044) to be significantly associated with OS. Conclusion: ALC and PLR can predict eribulin efficacy in terms of OS, reflecting the antitumour immune response in the microenvironment and indicating eribulin’s effectiveness.

Background: It is well known that the prognosis of non pCR TNBC patients was poor after anthracycline and taxan treatment. For such patients, capecitabine seems to be effective to reduce recurrence based on the HR 0.58 of the CREATE X trial (Masuda, N. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 376, 2147. 2017) . However, the target of capecitabine is still unclear for TNBC. We classified non pCR tumors as BRCAness and Sporadic using BRCAness test(MRC-Holland, Amsterdam, the Netherlands). The recurrence rate of the BRCAness group was about 70%. Carboplatine is expected to be effective against BRCAness tumors, as it is a DNA damaging agent. In this study BRCAness can be checked just before carboplatin treatment using surgical specimens. Then the efficacy of carboplatin will be directly known to make comparison between DFS in the carboplatin group and that of the observation group. Trial design: This is anopen label, randomized phase III study that will enroll TNBC with residual invasive cancer after surgery with preoperative chemotherapy including both anthracycrine and taxan. Patients are randomly assigned to either the carboplatin group or observation group. The patients in the carboplatin group are treated with carboplatin at AUC 6 and those in the observation group are observed at only 3 years. Eligibility criteria: 1) ER and PgR 2) Preoperative chemotherapy including both anthracycrine and taxan. 3) Residual invasive cancer on breast tumors or lymph node metastasis in surgical specimens. 4) 20-79 year old women. 5) No chemotherapy within 5 years. 6) Not bilateral breast cancer, without metastasis, no prior breast cancer. 7) No severe bone marrow suppression. Specific aims:Primary objective is DFS (Disease Free Survival). Secondary objectives are overall survival and safety. STATISTICAL METHODS: The 3 years recurrence rate of the observation group was estimated as 40% and hazard ratio at 0.58 based on the CREATE X trial. For both groups, 135 patients are necessary. This study is powered to approximately 80% to test the superiority of carboplatin group at a 2-sided α=0.05 using a stratified log-rank test. Activation Date:22ndMarch 2018. No patients had been enrolled till 3rd July. Citation Format: Tanino H, Suzuki M, Kaise H, Miyashita M, Chishima T, Hayashi M, Miyoshi Y, Futamura M, Ohtani S, Nagahashi M, Ohta T, Kosaka Y, Ishikawa T, Hasegawa Y, Kubota T, Sangai T, Iwatani T, Yamada A, Akazawa K, Kohno N. Phase 3 trial of carboplatin in triple negative breast cancer (TNBC) patients with residual invasive carcinoma after neoadjuvant chemotherapy (JONIE4:J-CAT trial) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-04.

A 52-year-old woman with a strong family history of breast cancer was diagnosed as having triple-negative breast cancer (TNBC) in her right breast. Neoadjuvant chemotherapy (NAC; four cycles of epirubicin/cyclophosphamide/5-fluorouracil) was performed, followed by breast-conserving surgery and axillary lymph node dissection. Histopathological analysis of the surgical specimens demonstrated a few focal tumor cells remaining in the stroma, but not a pathological complete response (pCR). Weekly paclitaxel was subsequently added to the treatment regimen. A total of 17 months after the adjuvant treatments, TNBC recurred in her left breast with massive lymph node metastasis. Because of the early recurrence after standard treatment, NAC was administered together with carboplatin and paclitaxel. Histopathological analysis of the partially resected breast and axillary lymph nodes demonstrated a pCR. No recurrent disease was found 2 years after the second TNBC treatment. This case underlines the importance of platinum-based chemotherapy and prophylactic mastectomy for patients with BRCA dysfunction.

Background Pathological complete response (pCR) is often achieved by neoadjuvant chemotherapy (NAC), particularly in hormone receptor-negative breast cancer. Contrast-enhanced magnetic resonance imaging (cMRI) is the most reliable imaging modality to evaluate the pathological effect of NAC. Ultrasonography is indispensable to collect representative specimens from the target lesion by core needle biopsy (CNB). This study aimed to evaluate the accuracy of predicting pCR by adding CNB after NAC, in cases with complete clinical response (cCR) diagnosed by cMRI. Methods In this prospective multicentre study, we evaluated patients diagnosed with cCR by cMRI after NAC. Ultrasound-guided CNB (uCNB) using a 14G needle was performed without clip markers under general anaesthesia as planned surgery. Specimens collected by uCNB were compared to those resected surgically and were categorized as (i) no carcinoma (ypT0), (ii) no invasive carcinoma and only residual carcinoma in situ (ypTis) and (iii) residual invasive carcinoma. The concordance of pathological results between the uCNB and surgical specimens was evaluated. Results Of the 83 patients evaluated, 41 (49.4%) and 17 (20.5%) of them had ypT0 and ypTis, respectively. The false negative rates (FNR), sensitivity and specificity for predicting ypT0 by uCNB were 50.0%, 50.0%, 100%, respectively, and those for predicting ypT0+ypTis were 28.0%, 72.0% and 98.3%, respectively. The concordance rates were 74.7% (62/83) for ypT0 and 90.4% (75/83) for ypT0+ypTis. Conclusion In cCR cases diagnosed by cMRI, uCNB was not accurate enough to predict pCR. Additional modalities like clip placements and/or thicker core needles may be required for better prediction.

Background: Neoadjuvant chemotherapy (NAC) for breast cancer has been improved and pathological complete response (pCR) achieved in about 50% of Her2 positive tumor and over 30% of triple negative tumor. It is possible that not to perform surgery if pCR is diagnosed accurately. This study was performed to examine diagnostic ability of core needle biopsy (CNB) to detect pCR by NAC. (Study registry number: UMIN000012035) Methods: In this multicenter study, we registered histologically proved breast cancer patients who were diagnosed as clinical complete response (cCR) after NAC. The cCR was diagnosed by contrast-enhanced magnetic resonance imaging (MRI) after NAC by radiologists in each facility. Regimens of NAC were not specified by study protocol. A clip marker was not placed in the tumor before NAC. At the operating table, ultrasound-guided CNB is performed before starting the surgery. The CNB was performed with 14 gauge needle without vacuum assistance and requiring three biopsy specimens. The concordance of pathological results between a core needle biopsy and a surgical specimen is examined by pathologists at each facility. The pathological diagnosis was categorized as i) no carcinoma (pCR), ii) carcinoma in situ (CIS) and iii) invasive carcinoma. Results: The study included 86 women from 10 facilities, accrued from December 2013 to March 2017. Median age was 53.5 (31-75) years and median tumor size before NAC was 2.3 (0.9-7.3) cm. Estrogen receptor was positive in 32 (37%). HER2 was positive in 40 (47%). The clinical stage before NAC was stage I 19 (22%), II 48 (56%), III 16 (19%) and IV 3 (3%). All cases were administered cytotoxic agents. Both anthracycline and taxane were given in 70 cases (81%), and trastuzumab was administered in 35 (41%) cases. As for breast surgery, partial resection was performed in 53 cases (62%), whereas 33 cases (38%) underwent mastectomy. Pathological examination on surgical specimen revealed pCR (i) in 41 cases (48%), CIS (ii) in 17 cases (20%) and invasive carcinoma (iii) in 28 cases (32%). Results of pathology of CNB and surgical specimens are shown in table 1. Table 1. Pathological diagnosis of CNB and surgical specimens Surgical specimen No carcinoma (pCR)Residual carcinomaTotalCNBNo carcinoma (pCR)41 (NPV=63%, spec.=100%)24 (FNR=53%, 14 were CIS)65 (76%) Residual carcinoma021 (PPV=100%, sens.=47%)21 (24%)Total41 (48%)45 (52%)86 (100%)CNB: core needle biopsy, FNR: false-negative rate, CIS: carcinoma in situ, NPV: negative predictive value, PPV: positive predictive value, sens.: sensitivity, spec.: specificity. The kappa value was 0.455 which was not enough for accurate diagnosis. In 24 discordant cases, residual tumor was found in surgical specimen but not in CNB, residual disease was CIS in 14 cases. Conclusions: Up to 10% false negative rate of pCR may allow us to proceed to an observational study without performing surgery.This study revealed that the ultrasound-guided CNB for cCR cases by MRI was not accurate enough to omit surgery. Thus, imaging diagnosis and biopsy methods need to be improved. However, it is still possible to consider because the post-operative radiotherapy may compensate for surgery in cases with CIS after NAC. Citation Format: Narui K, Ishikawa T, Hasegawa Y, Kaise H, Kawate T, Yamada K, Suzuki Y, Niikura N, Kohno N, Kimoto T, Sugae S, Yamada A, Kosaka Y, Miyashita M, Okamura T, Shimizu D, Tanino H, Sakamaki K, Tokuda Y. Feasibility study to diagnose pathological complete response by neoadjuvant chemotherapy in breast cancer adding core needle biopsy (KBOG1301 supported by JONIE) [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 P5-22-09.

Background Cowden syndrome is characterized by multiple hamartomas in various tissues, including the skin, brain, breast, thyroid, mucous membrane, and gastrointestinal tract, and is reported to increase the risk of malignant disease. Case presentation We describe the case of a 52-year-old woman in whom a tumor was diagnosed in the left cerebellar hemisphere and treated by surgical resection. Phosphatase and tensin homolog (PTEN) mutation in exon 8 insertion was found in the brain tumor tissue and leukocytes. This finding supported the diagnosis of Cowden syndrome. She consequently developed endometrial cancer and underwent abdominal total hysterectomy with bilateral salpingo-oophorectomy. Four years later, hormone receptor-positive breast cancer was found in the right breast, and breast-conserving surgery with radiation therapy and sentinel lymph node biopsy was performed. Conclusions Herein, we describe a patient who was diagnosed as having familial breast cancer associated with PTEN mutation-related Cowden syndrome. We also reviewed reports of this syndrome in the literature for disease appraisal.

My arguments regarding postmastectomy radiotherapy (PMRT) for this case are based on the following 4 reasons: (1) high rate of local recurrence in the no PMRT group in the Early Breast Cancer Trialists' Collaborative Group meta-analysis on which the present guideline is based, (2) stage migration by sentinel node biopsy, (3) possible adverse events of radiotherapy, and (4) problems on extrapolation of data from western countries.

Background Many triple-negative breast cancers (TNBCs) show impaired breast cancer susceptibility gene I (BRCA1) function, called BRCAness. BRCAness tumors may show similar sensitivities to anticancer drugs as tumors with BRCA1 mutations. In this study, we investigated the association of BRCA mutations or BRCAness with drug sensitivities in TNBC. Methods BRCAness was evaluated as BRCA1-like scores, using multiplex ligation-dependent probe amplification in 12 TNBC cell lines, including four with mutations. Sensitivities to docetaxel, cisplatin, and epirubicin were compared with BRCA mutations and BRCA1-like scores. Cisplatin sensitivity was examined in BRCA1 knockdown Michigan Cancer Foundation-7 cell lines. Results Eight and four cell lines had characteristics of BRCAness and non-BRCAness, respectively. The 50% inhibitory concentration of docetaxel was higher in BRCA mutant and BRCAness cell lines than their counterparts. BRCA1-like scores showed a weak positive correlation with docetaxel sensitivity (r = 0.377; P = 0.039). Regarding cisplatin, scores were lower in BRCA mutants and BRCAness tumors than their counterparts. A negative correlation was found between BRCA1-like scores and cisplatin sensitivity (r = −0.407; P = 0.013). No differences were found for epirubicin. BRCA1 gene knockdown increased the cisplatin sensitivity of Michigan Cancer Foundation-7 cells. Conclusions BRCA1-like scores were associated with cisplatin sensitivity and docetaxel resistance. BRCA1-like score is hence a promising indicator for estimating drug sensitivities in TNBC.

With the increasing use of adjuvant chemotherapy for treating early breast cancer, febrile neutropenia management has become crucial. Guidelines for febrile neutropenia management are mostly based on a Caucasian population survey although ethnic differences are reported in terms of adverse events. We survey the current status of febrile neutropenia and risk factors in Japanese female breast cancer patients receiving neoadjuvant and adjuvant chemotherapy regimens potential for febrile neutropenia. Subsequently, we plan to conduct a multicenter prospective cohort study involving 1000 patients with operable breast cancer. With the current state of oral antibiotics being routinely prescribed without hematology tests, we survey febrile neutropenia based on two different definitions, namely, true febrile neutropenia: ≥37.5°C and Grade 4 neutropenia, and surrogate febrile neutropenia: ≥37.5°C and oral antibiotic and antipyretic intake. The comparison of true febrile neutropenia and surrogate febrile neutropenia incidences is anticipated to provide information on the safety and feasibility of chemotherapy management without performing blood tests.

Background: Neoadjuvant chemotherapy (NAC) reduces tumor size, and increases the frequency of breast-conserving surgery in operable breast cancers. Response predictions to NAC are made based on diagnostic imaging. Although various studies have reported the optimal timing for diagnostic imaging, this still remains unclear. Purpose: To identify the optimal timing of diagnostic imaging for the response prediction to NAC, and to evaluate the accuracy of response prediction. Methods: We evaluated 146 cases enrolled in the JONIE-1 study (a randomized controlled trial comparing zoledronic acid plus chemotherapy with chemotherapy alone as a NAC in patients with HER2-negative primary breast cancer). The chemotherapy regimen was FEC100×4 courses followed by weekly paclitaxel 80×12 courses (± zoledronic acid). Statistical analysis of the association between the tumor reduction ratio and the histopathological response and the prediction of pathological complete response (pCR) was performed using JMP software. The maximum tumor diameter was evaluated using magnetic resonance imaging and ultrasound on each patient 3 times (before NAC, after FEC treatment, after NAC) and tumor reduction ratios were calculated. Results: The average age of the patients was 49.8 years old. The menopause status was pre-menopause in 84 patients, and post-menopause in 58 patients. Regarding the subtype classification, 116 patients were of the luminal type (Lum) and 26 patients were triple negative (TN), and the Ki-67 labeling index had a median of 25% (1%-93%). Pathological examination demonstrated that 16 patients had pCR(11.3%, Lum, 9;TN: 7), and 126 patients had non-pCR (88.7%, Lum:107; TN:19). Seven patients had clinical-CR (4.8%, Lum: 4; TN: 3) at post-FEC, and 26 patients (17.8%, Lum: 20; TN: 6) at post-NAC. The prediction of pCR at post-FEC and post-NAC was evaluated by single variable analysis, resulting in an AUC (0.75645) p=0.0017 at post-FEC, and AUC (0.76563) p=0.0001 at post-NAC. The sensitivity / specificity / positive predictive value / negative predictive value were 0.625 / 0.873 / 0.385 / 0.948 at post-FEC, 0.250 / 0.976 / 0.571 / 0.911 at post-NAC, respectively. In TN cases, the values were 0.714 / 0.947 / 0.833 / 0.900 in post-FEC, and 0.429 / 1.000 / 1.000 / 0.826 in post-NAC. Conclusions: Diagnostic imaging evaluation performed after FEC treatment was useful for the prediction of pCR. Furthermore, the reliability was high in Triple Negative Sub type, but is affected by the existence of residual tumors in Luminal type. Citation Format: Kaise H, Ishikawa T, Miura D, Hasegawa Y, Horiguchi J, Hayashi M, Takao S, Kim SJ, Tanino H, Miyashita M, Konishi M, Shigeoka Y, Yamagami K, Suzuki M, Taguchi T, Akazawa K, Kohno N. Early and accurate prediction of pathological response by magnetic resonance imaging and ultrasonography in patients undergoing neoadjuvant chemotherapy for operable breast cancer. [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 P3-07-50.

It remains unclear whether dental implants are a risk factor for the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We retrospectively evaluated the status of dental implants in patients given intravenous bisphosphonates (BPs) in a breast cancer cohort to elucidate the risk for BRONJ at the implant site. We established a BRONJ oral monitoring program for 247 breast cancer patients given intravenous BP in our institution. The 3-year cumulative incidence rate was determined. The systemic and local risk factors of 44 patients who completed comprehensive oral examinations were evaluated by logistic regression analysis. The 3-year cumulative incidence rate of the 247 patients was 0.074 % (8/247, 95 % CI 0.0081-0.014). In the 44 orally examined patients, 6 (13.6 %: 6/44) had dental implants. Of these 6 patients, 1 developed BRONJ at the implant site. There were no significant differences in the age, total BP treatment period, number of residual teeth, time of regular oral monitoring, oral hygiene level, or dental implant insertion. Although a case of ONJ was identified, dental implants which were inserted before intravenous BP administration were not a risk factor for the development of ONJ in breast cancer patients.

In patients with cancer and Parkinson's disease, the DJ-1 protein may be secreted into the serum during the impaired response of the underlying cell-protective mechanisms. In order to determine the clinical significance of DJ-1 protein in the sera of breast cancer patients, we examined blood samples from a breast cancer group (n = 180) and a non-cancerous control group (n = 300). Higher levels of DJ-1 were detected in the breast cancer group (mean level, 42.7 ng/mL) than the control group (28.3 ng/mL) by ELISA (P = 0.019). Higher DJ-1 levels were significantly associated with advanced clinical grade, according to the TNM classification, negative hormone receptor status, and high Ki-67 labeling index, of biopsied materials; samples showed low DJ-1 protein expression despite upregulated DJ-1 mRNA. DJ-1 isoforms could be detected clearly in 17 blood samples (from 11 breast cancer patients, and 6 non-cancerous controls) by 2-D gel electrophoresis and immunoblot analysis. The isoform at the pI of 6.3 showed the highest intensity in all 11 cancer cases. Conversely, in the 6 non-cancerous cases, isoforms other than the pI 6.3 isoform were highly expressed, and there was a significant difference in the isoform pattern between breast cancer cases and controls (P = 0.00025). These data indicate that high levels of DJ-1, probably of isoform at pI 6.3, is a candidate serum marker of breast cancer.

The clinical features of the early stages of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients with breast cancer remain unclear. A retrospective cohort study was conducted of patients with breast cancer who received intravenous bisphosphonate (BP) treatment in a single center in order to clarify the status of the early stages of BRONJ.A BRONJ oral monitoring program was established in 247 breast cancer patients given intravenous BP treatment at the institution. The differences in age, BP treatment period, number of remaining teeth, oral hygiene status, presence of regular oral monitoring and the existence of suspected BRONJ (stage 0) among eight BRONJ and 36 non-BRONJ subjects who completed oral examinations were then compared.BRONJ was observed in 0.4% of subjects on the first visit to the oral surgery clinic and in 3.2% of subjects during the follow-up period. Logistic regression analysis revealed that the odds ratio for identifying patients with BRONJ during follow-up by the presence of stage 0 at first visit was 24.0 (95% confidence interval [CI] = 3.6-161.7). The area under the receiver operating characteristic curve for identifying subjects with BRONJ by the presence of stage 0 was 0.82 (95% CI = 0.63-1.00).The results suggest that patients with stage 0 BRONJ on the first visit may progress to advanced BRONJ during the follow-up period. The oral monitoring program may contribute to the early detection of BRONJ.

Background: Zoledronic acid (ZOL) has been found to have a synergistic anti-proliferative effect when used in combination with antitumor drugs. We suggested that the addition of ZOL to neoadjuvant chemotherapy (CT) has potential anti-cancer benefit in postmenopausal patients with triple-negative breast cancer in JONIE-1 Trial (50% pCR rate in ZOL+CT: CTZ versus 0% in CT, p = 0.029). We analyzed the disease-free survival (DFS) as a secondary endpoint and baseline Ki67 levels between two groups. Methods: Women with Stage IIA-IIIB HER-2-negative breast cancer were randomly assigned 1:1 to CTZ group or CT group, CT was FEC100 q3w × 4 cycles followed by weekly paclitaxel for 12 cycles and ZOL 4mg was administered every 3-4 weeks. Among 188 patients recruited between March 2010 and April 2012 excluding 10 from the primary assessment, 178 patients were assessed. The aims of this study were to compare the relative efficacy or CTZ with the efficacy of CT in prolonging DFS in all patients and also to compare the pCR rates between baseline Ki67 high (20% and >20%) with Ki67 low ( Results: During a mean follow-up period of 34.4 months, breast cancer specific events (recurrence and death) occurred 17 participants, 7 in CTZ group and 10 in CT group. The 1-year, 2-year, and 3-year DFS rates were 97.7%, 88.4%, and 88.4% in CTZ versus 100%, 84.8%, and 81.1% in CT, respectively. In the ER positive cohort studied for Ki67 consist of 109 patients, 40 were in Ki67 low group and 69 were in Ki67 high group. Among Ki67 low group, number of pCR was none out of 18 in CTZ and 1 out of 22 in CT (p = .550). Among Ki high group, that was 6 out of 38 in CTZ and 3 out of 31 (p = .352). Conclusion: We could not find a modest improvement in disease-free survival compared the addition of ZOL to neoadjuvant CT with CT alone. Ki67 study for central analysis has been under investigation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD3-7.

The radionuclide (RN) method employed for sentinel lymph node biopsy is generally safe for adult medical care workers. However, the number of pregnant medical care workers who attend surgery has recently been increasing, along with the increasing number of female surgeons. In particular, female surgeons are concerned about the position of a surgeon's lower abdominal region being close to the RN injection site. We measured the exposure dose of the lower abdominal region in medical care workers and investigated the possible exposure effect on fetuses.A dose of (99m)Tc-phytic acid (37 MBq) was subcutaneously injected into the areola of the nipple of patients. Scintigraphy and surgery were performed after 1 and 4 h, respectively. At the time of the local injection, a personal dosimeter measured the exposure dose in the surgeon, first and second assistants, anesthesiologist, and scrub nurse.The median exposure doses were 3, 1, 1, 0, and 0 μSv in the surgeon, first and second assistants, anesthesiologist, and scrub nurse, respectively. Protective clothing reduced the mean exposure dose by 66 %.In surgeons, the exposure dose from daily life activities (1 mSv/year) corresponds to the dose received after performing 333 surgeries (using 3 μSv as the median). However, the maximum value measured was 24 μSv; at this value, the total exposure dose exceeds 1 mSV in the 42nd surgery. Medical care workers can further reduce their exposure dose by paying attention to the surgical procedure and to their posture and position.

Background and Objective We evaluated an alternative procedure for sentinel lymph node biopsy (SLNB) for breast cancer after approval of the study by the Ethics Committee of Tokyo Medical University Hospital in 2004. We examined the efficacy and safety of SLNB using the photosensitizer talaporfin sodium (Laserphyrin®, Meiji Seika Pharma, Tokoyo, Japan), compared with current methods. Study Design/Patients and Methods The study included 21 breast cancer patients (Japanese women; median age, 54 years; range, 35–75). All patients received a breast cancer operation combined with SLNB between June 2004 and May 2005. Three milliliters of talaporfin solution was locally injected into the subareolar region just before the operation. We attempted to identify a sentinel lymph node (SLN) that exhibited fluorescence and was consistent with a radioisotope (RI) localization technique. Our purpose was to verify the accuracy and validity of the talaporfin fluorescence imaging method after 8 years of application. Results There was no consistent correlation between fluorescence and pathological SLN metastasis, although all four cases of pathological SLN metastasis revealed positive fluorescence. In some cases in which we could not identify SLNs by the RI technique, we could identify SLNs using talaporfin. The method using talaporfin did not adversely affect the patients after the operation, even the chronic renal failure patient. After 8 years, all patients are alive, and none had lymph node recurrence. Side effects were not observed. Conclusion SLNB using the photosensitizer talaporfin sodium in breast cancer patients is considered to be useful as complementary to other current methods. We could evaluate the accuracy and validity of this method 8 years after all of the procedures were performed. In the future, a large-scale clinical study with statistical analyses should be conducted. Lasers Surg. Med. 45:558–563, 2013. © 2013 Wiley Periodicals, Inc.

Parkinson's disease is associated with DJ-1/Parkinson protein 7 dysfunction. In contrast, hyperactivity of DJ-1 increases the resistance of cancer cells to apoptosis. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. However, we previously found that there were approximately 50 % patients with breast cancers that expressed low levels of DJ-1 protein, despite mRNA upregulation. Furthermore, low DJ-1 expression was a significant predictor of poor clinical outcome in these patients. This study aimed to determine the association between low DJ-1 protein expression and pathological complete remission (pCR) after neoadjuvant chemotherapy in breast cancer patients. Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 205 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization. Chemotherapy comprised epirubicin/cyclophosphamide taxane-based regimens with or without the inclusion of trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR. Low DJ-1 protein expression was detected in 45.3 % (93/205) of all breast cancer cases and in 79.6 % (39/49) of pCR cases, irrespective of maintained mRNA levels. DJ-1 expression [hazard ratio (HR): 1.36; 95 % confidence interval (CI): 1.01-1.84] and HER2 status (HR: 0.84; 95 % CI: 0.62-1.14), in contrast to histological grade, hormone receptors status, Ki-67 labeling index, and intrinsic subtype, were significant predictors of pCR. Low DJ-1 expression predicted pCR in luminal A (P = 0.0004), luminal B (P = 0.0194), and triple negative (P = 0.0143) subtypes breast cancer patients and in patients receiving additional trastuzumab treatment (P = 0.008). In conclusion, low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy in breast cancer patients.

Background: Zoledronic acid (Zol) is the most potent inhibitor of bone resorption in bisphosphonates. In order to examine whether the inhibitory effect is involved in the mechanism of bone metastasis in breast cancer, a bone-seeking clone was examined. It was established by repeated sequential passages of metastatic cells from bone in nude mice and in vitro, and it exclusively metastasizes to bone with larger osteolytic lesions than MDA-MB-231 parental cells. Recent findings indicate that epidermal growth factor (EGF) signaling is also an important mediator of bone metastasis. We examined the synergistic effects of gefitinib on the proliferation and invasion of a bone-seeking clone compared with MDA-MB-231. Materials and Methods: The cellular proliferation was estimated using WST-1. Migration in the matrigel in a Boyden chamber was applied to the invasion assay. Results: Treatment with 1 µM of Zol reduced 51% of cell proliferation in the bone-seeking clone; however, the inhibited rate was 37% in MDA-MB-231. The migration was also inhibited with 10 µM of Zol (bone-seeking clone: 69% reduction, MDA-MB-231: 54% reduction). The reduction rates of both assays by Zol treatment were significantly higher in the bone-seeking clone than in MDA-MB-231. Treatment with 10 µM of Zol plus 1 µM of gefitinib resulted in a proliferation reduction rate of 27% compared to that with 10 µM Zol treatment in the bone-seeking clone and no reduction in MDA-MB-231. The migration reduction rate was 88% in the bone-seeking clone and no reduction in MDA-MB-231. There was a significant difference between the bone-seeking clone and MDA-MB-231 in the reduction rates of both cellular proliferation and migration. Although the effect of gefitinib was synergistic with that of Zol in the bone-seeking clone, it was not clear in MDA-MB-231. Conclusion: There appear to be at least two independent signaling pathways that occur in osteolytic bone metastasis. One is involved in the bone resorption of bisphosphonates, and the other is an EGFR signaling pathway. Clinically, the combination of Zol and gefitinib is suggested to be a strong therapy specific to bone metastasis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-09.

61歳, 女性. 1993年に左乳癌にて胸筋温存乳房切除術, 腋窩リンパ節郭清施行. 病理組織学的診断は浸潤性小葉癌n=8/12, Estrogen receptor (ER) (+), Progesterone receptor (PR) (+). 術後放射線療法 (左鎖骨上, 左腋窩, 傍胸骨) 50Gy施行. 術後薬物療法はクエン酸タモキシフェン (20mg/day) とフルオロウラシル (200mg/day) を3年間投薬. 術後10年無再発にて経過. 2003年8月より下腹部痛出現. 経過観察していたが症状増強するため, 2004年7月に下部消化管内視鏡検査を施行. 直腸に全周性の発赤と狭窄を認め, 同部位の生検結果は低分化腺癌であった. 腫瘤を形成しないびまん性病変で, 直腸癌としては非典型的のため乳癌転移も疑い免疫染色を施行した所, 乳腺原発巣と同様にER (+), PR (+) であった. 以上より乳癌直腸転移と診断し, エキセメスタン (25mg/day) の内服を開始した. 内服2カ月後より腹部症状は軽快し, 22カ月経過し現在も外来通院している.

My arguments regarding postmastectomy radiotherapy (PMRT) for this case are based on the following 4 reasons: (1) high rate of local recurrence in the no PMRT group in the Early Breast Cancer Trialists’ Collaborative Group meta-analysis on which the present guideline is based, (2) stage migration by sentinel node biopsy, (3) possible adverse events of radiotherapy, and (4) problems on extrapolation of data from western countries.

Mammary ductoscopy (mammoscopy) is an ideal diagnostic method for intraductal lesions. The usefulness of mammoscopy for intraductal lesions was evaluated. Mammoscopy was performed in 315 cases with nipple discharge. The mammoscopic findings of 46 breast cancer cases (47 lesions) and 109 intraductal papilloma cases (119 lesions) were compared with pathological findings. Carcinoma was recognized by mammoscopy in 38 of 47 lesions (80.9%). Intraductal masses were detected by mammoscopy in 115 of 119 intraductal papilloma lesions. The shape of the mass was classified as hemispheric, papillary, or flat protrusion. The hemispheric and papillary shapes were most common in cases of intraductal papilloma and the flat protrusion type was most common in cases of carcinoma. The amount of material collected by intraductal biopsy under mammoscopic observation was smaller in carcinoma than in intraductal papilloma because the carcinoma lesions were usually located in peripheral ductlobular units and had weak tissue cohesion compared with that of intraductal papilloma. Of 133 intraductal biopsies performed for 69 intraductal papillomas, 17 biopsies yielded material insufficient for diagnosis in. The effectiveness of treatment by intraductal biopsy was recognized in 38 of 46 intraductal papillomas in which clinical follow-up continued for more than two years (82.6%). The therapeutic results of biopsy were poor in cases of multiple intraductal masses in multiple duct-lobular units. Mammoscopy contributes not only the diagnosis in cases of nipple discharge, but is also of benefit in the treatment of intraductal papilloma.

症例は70歳女性.平成8年8月,右C領域の腫瘤を主訴として来院.同年12月にT2a, N0, M0, Stage II乳癌の診断で当科にて乳房円状部分切除術およびLevel II郭清を施行した.切除断端は陰性で,組織型は充実腺管癌, n0, f (+), ly (-), v (-)であった.放射線療法は本人の希望にて施行せず,遠方のため近医での外来通院となった.その間補助療法は施行されず,平成10年10月創部の硬結を主訴に再来した.マンモグラフィにて,同部位に一致した集簇型微細石灰化像と,超音波上の腫瘤像を認めたため,残存乳房内の局所再発と診断し,外来にて局麻下に乳腺部分切除術を施行した.術後の病理組織検索においては約1.5cmの腫瘤を認めるも,癌細胞は認められず,間質組織に瀰漫性に広がる微細石灰沈着が著明な巨細胞肉芽腫であり,ヘモジデリン貪食細胞の集団も認められた.現在再発の徴候は認められていない.

Antioxidants have been proposed to have antiatherogenic potential by their inhibition of low density lipoprotein (LDL) oxidation. Here, we report an antioxidant, BO-653 (2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di- tert- butylbenzofuran), designed to exhibit antioxidative potency comparable to that of α-tocopherol, but yet possess a high degree of lipophilicity comparable to that of probucol. BO-653 exhibits a high affinity for LDL and is well distributed in aortic vessels in vivo . In atherosclerosis models of rabbits and mice, BO-653 has been shown to be able to suppress the formation of atherosclerotic lesions without untoward side effects. Specifically, there was no reduction of high density lipoprotein levels. This antioxidant provides additional evidence in support of the oxidized-LDL hypothesis, and itself is a promising candidate antioxidant for clinical use.

BACKGROUND: Clustered microcalcifications are important for the detection of breast carcinomas, but few reports have described chronological changes of the microcalcifications. METHODS: The mammographic features of 18 breast cancer cases for which previous survey films were available and in which clustered microcalcifications with no tumor shadows were recognized at diagnosis were studied. Chronological changeswere analyzed by measuring the increase in the length of areas containing calcifications and the diameters of microcalcifications on mammograms using computerized image analysis. RESULTS: Chronological changes in the length of areas of microcalcifications were classified into two types by simple linear regression. Fast increase was common in the comedo type of carcinoma and slow increase was common in the non-comedo type. Three of nine cases that received follow-up examinations on two or more occasions eventually changed from slow type to fast type, and the distributionpattern of diameters of microcalcifications also changed from non-comedo type to comedo type. A follow-up study of 48 cases with a cluster of fewer than five extremely fine calcifications revealed breast carcinoma in 7 patients within 5 years. CONCLUSION: The increase of microcalcifications was generally fast in comedotype and slow in non-comedo type lesions. An increase in the extent of microcalcification was seen occasionally during the last period between follow-up examinations in mixed type tumors, indicating a conversion of the intraductal component to a more malignant grade.

A case of simultaneous double cancer of the breast and malignant melanoma is reported. A 33-year-old single woman with a lentigo on left sole was admitted to the department of dermatology for further examination. In the same time, she moticed her left mastalgia and bloody nipple discharge. But no lump was palpated in the breast. She was performed a wide tumor excision of the left sole, and histological diagnosis was malignant melanoma. Initially, it was diagnosed that the complaints night depend on mastopathy, but cytological findings of the specimen indicated an existance of breast cancer. Mammography showed scattered malignant calcification and ultrasonography showed intraductal spreading. From these findings, a non-invasive ductal carcinoma on the left breast was suspected. Wide exsicion with out axillary dissection and radiation therapy were performed by histological findings. The postoperative course was uneventful and no tumor has recurred for about one year after the operation. There are a few reports of double cancer of the breast and malignant melanoma. The cancer patients must be followed up with attention to probable second malignancy.

A 44-year-old man with was seen at the hospital because of a tumor in the left lateral chest wall. The tumor was located in the 8th rib of left lateal chest to scapla. Intraoperative exsicional biopsy was conduted, which ruled out any malignant neoplasmas. Complete radical tumorectomy was carried out. Histologically, no atypical spindle-shapd fibroblasts with abundant collagen had grown, and the tumor infiltrated into the muscle and scapla on a permanent paraffin block. The definite diagnosis of extraabdominal desmoid tumor was made. There has been no evidence of recurrence, as of 6 months after the surgery. Extra-abdominal desmoid tumors of the chest wall are rare an only 17 cases have been reported in Japan. In a review of the literature, local recurrence occurs so frequently that the complete surgery should be the treatment of this tumor. We presented a case of extra-abdominal desmoid tumor with a review of the literature in Japan. The tumor including the first and second ris which was 8.0×6.0×2.5cm in size was resected en bloc.

1992年8月より1996年2月までに乳房温存療法を施行した微細石灰化像を示す乳癌は37例であり, これらをマンモグラフィ上の石灰化形態により線状型と顆粒型に分類し, 組織学的検索, EIC, 断端陽性率, 健存率について検討を加えた。線状型はnon-comedo typeに比べ, 有意にcomedo typeに多く認められた (p

Tumor lysis syndrome(TLS)induced by chemotherapy for solid tumors is rare. We report a case of a 59-year-old woman with breast cancer who developed TLS. She underwent surgery to treat breast cancer in 1992. 19 years after surgery, however, she was diagnosed with multiple bone metastases(disease free interval, 13 years and 3 months). In March 2011, gemcitabine regimen was initiated(1,250mg/m2, 14 days followed by a 7-day rest period)because of worsening of multiple bone metastases. The patient was immediately admitted and treated for suspected TLS when she presented at our hospital with symptoms such as depressed level of consciousness, serious anemia, hypercalcemia, hyperuricemia, and liver/renal dysfunction on day 16 of the first line of regimen. Rasburicase was found to be effective for hyperuricemia.

We evaluated an alternative procedure for sentinel lymph node biopsy (SLNB) for breast cancer after approval of the study by the Ethics Committee of Tokyo Medical University Hospital in 2004. We examined the efficacy and safety of SLNB using the photosensitizer talaporfin sodium (Laserphyrin®, Meiji Seika Pharma, Tokoyo, Japan), compared with current methods.The study included 21 breast cancer patients (Japanese women; median age, 54 years; range, 35-75). All patients received a breast cancer operation combined with SLNB between June 2004 and May 2005. Three milliliters of talaporfin solution was locally injected into the subareolar region just before the operation. We attempted to identify a sentinel lymph node (SLN) that exhibited fluorescence and was consistent with a radioisotope (RI) localization technique. Our purpose was to verify the accuracy and validity of the talaporfin fluorescence imaging method after 8 years of application.There was no consistent correlation between fluorescence and pathological SLN metastasis, although all four cases of pathological SLN metastasis revealed positive fluorescence. In some cases in which we could not identify SLNs by the RI technique, we could identify SLNs using talaporfin. The method using talaporfin did not adversely affect the patients after the operation, even the chronic renal failure patient. After 8 years, all patients are alive, and none had lymph node recurrence. Side effects were not observed.SLNB using the photosensitizer talaporfin sodium in breast cancer patients is considered to be useful as complementary to other current methods. We could evaluate the accuracy and validity of this method 8 years after all of the procedures were performed. In the future, a large-scale clinical study with statistical analyses should be conducted.

A case of squamous cell carcinoma with non-invasive ductal carcinoma in the hemilateral breast is reported with some discussion from a review of the literature. A 44-year-old woman was admitted to the hospital because of a lump of the left breast. The lump which was located in the lower-outer quadrant, was diagnosed as breast cancer by ultrasonography. And a mammogram pointed out a localized malignant calcification in the middle-outer area which suggested coexisting another carcinoma. The patient received a left modified radical mastectomy without both muscle resection. The tumor was 2.0cm in size and squamous cell carcinoma which was regarded as pure squamous carcinoma histologically. And there was a non-invasive ductal carcinoma separately. The postoperative course was uneventful and no tumor has recurred for 16 months after the operation. There are 93 case reports of squamous cell carcinoma of the breast in Japan, but we could not find any case of hemilateral mutiple cancer.

We encountered a patient who suddenly developed a high fever on the 7th day after an operation for a breast cancer and showed symptoms of shokc on the following day. This patient had undergone a modified radical mastectomy and had not received any drugs such as anticancer agents. She was examined for infection foci, but no infection was found at any of the sites investigated. Her condition improved by the administration of steroids and pressor agents as well as bu sorbent system dialysis, but symptoms and adnormal laboratory findings persisted for about 2 weeks. Her symptoms appeared to be caused by endotoxic shock due to bacteria of low pathogenicity such as indigenous flora. However, the extent of surgical invasion was mild in this case because meatectomy is a surface operation. The occurrence of such complication is considered to be extremely rare.

BACKGROUND: BRCA1 impaired cancers are sensitive to DNA damage. This is associated with the defective homologous recombination (HR) pathway in these tumors. In contrast, these tumors are resistant to mitotic poisons, because BRCA1 protein activates the mitotic spindle checkpoint and triggers apoptosis in microtubule damage. Both preclinical evidence and clinical evidence have shown that the single-agent taxane is not active for BRCA1 mutated breast cancers. It is reported that BRCA1 function may be impaired in approximately 60% of triple negative breast cancer (TNBC) without mutation. This is called ‘BRCAness’. Previous studies have demonstrated that BRCAness identified tumors with HR deficiency. Thus, taxane may not be necessary for all TNBC cases, although combined treatments of anthracycline and taxane are standard at present. STUDY PROTOCOL: We have launched a single arm study of neoadjuvant chemotherapy (NAC) for TNBC to confirm that taxane is unnecessary in BRCAness cases. For the study protocol, TNBC cases requiring NAC are enrolled. Four cycles of an anthracycline-based regimen (FEC 100 or dose-dense EC) are started and BRCAness is examined simultaneously in core-needle specimens. BRCAness is determined by Multiple Ligation-dependent Probe Amplification (MLPA) methods (FALCO Biosystems), which consist of 2 steps. These include copy number analysis in 34 loci specific to BRCA1 mutant and scoring with prediction analysis for microarray. If BRCAness is determined by MLPA, surgery is performed without proceeding to taxane. The primary endpoint is a pathological complete response (pCR) in surgical specimens. The expected pCR and threshold pCR are estimated at 55% and 40%, respectively, based on our previous randomized phase II trial comparing docetaxel plus cyclophosphamide with epirubicin plus cyclophosphamide followed by docetaxel for hormone receptor-negative breast cancer (Ishikawa T. ASCO 2013). With a one-sided significance of 5%, 70 BRCA cases are required. This study was approved in September 2015 and has been started. Interim analysis is planned when 30 cases are completed. Citation Format: Takashi Ishikawa, Saeko Teraoka, Hiroshi Kaise, Kimito Yamada, Mari Hosonaga, Ai Ueda, Yoko Kawai, Miki Okazaki, Mari S. Oba, Eiichi Sato. Single arm study of neoadjuvant chemotherapy without taxane for BRCAness cases in triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT126.

e12520Background: It is not clear which anthracycline regimen for breast cancer is most effective in the neoadjuvant chemotherapy. We compared CEF therapy with EC therapy in neoadjuvant setting for axillary lymph nodes metastasis-positive breast cancer in our hospital in order to examine which anthracycline regimen is more effective. Methods: We treated 221 cases (cT1-4 N1-3 M0) of breast cancers, performed operation after neoadjuvant chemotherapy (anthracycline and taxanes) in May 2003 to July 2014. The average observation period was 5.5 years. We separated 2 groups, CEF and EC. CEF group were patients performed CEF therapy (C: 500mg/m², E: 100mg/m², 5FU: 500mg/m² every 3 weeks intravenous drip) followed by taxanes. EC group were patients performed EC therapy (E: epirubicin 90mg/m², C: cyclophosphamide 600mg/m² every 3 weeks intravenous drip) followed by taxanes. Some patients received zoledronic acid or denosumab in clinical trials. We examined the percentage of pCR (pathological complete response), the...

Our aim in this study was to examine the safety and efficacy of the concurrent use of the radiopharmaceutical strontium-89 (Sr-89) chloride with zoledronic acid in standard anticancer therapy for breast cancer patients with painful multifocal bone metastases. The study comprised 16 breast cancer patients with painful multifocal bone metastases detected by bone scintigraphy, computed tomography or magnetic resonance imaging. All patients were treated with Sr-89 and zoledronic acid concurrently between March 2007 and February 2011 as part of a standard therapeutic regimen comprising chemotherapy, endocrine therapy, molecular targeting therapy and targeted radiotherapy. Sr-89 was administered intravenously at 2 MBq/kg to a maximum of 141 MBq per person. Safety was evaluated according to myelotoxicity as measured by the Common Terminology Criteria for Adverse Events (v3.0). To assess treatment efficacy, we monitored changes in analgesic drug dosages. Furthermore, bremsstrahlung imaging after the administration of Sr-89 was utilized to examine the relationship between the accumulation of Sr-89 in metastatic sites and treatment efficacy. Based on the results, a total of 14 out of 16 patients (88%) reported bone pain relief, indicating a high efficacy of Sr-89 combined with zoledronic acid. In responsive cases, a strong uptake of Sr-89 was observed on bremsstrahlung imaging at the same sites indicated by 99mTc bone scintigraphy. Moreover, severe myelosuppression (> grade 3) was not observed, and adverse events were tolerable. In conclusion, the use of Sr-89 with zoledronic acid in breast cancer patients with painful bone metastases was safe and effective when administered concurrently with other standard therapies. In the future, the treatment with Sr-89 at the early stage should be considered, and a large-scale clinical study should be conducted.