Masahiko Ikeda

Retrospective Analysis of Predictive Factors for Recurrence After Curatively Resected Papillary Thyroid Carcinoma

PurposeThis retrospective study analyzes the predictive factors after curative surgery for papillary thyroid carcinoma (PTC).MethodsWe analyzed 386 patients who underwent a curative operation for PTC in our hospital between 1977 and 1997, subject to the inclusion criteria.ResultsAccording to univariate analysis, pathological lateral cervical lymph node involvement (P < 0.0001), dedifferentiation of the tumor (P < 0.002), male sex (P < 0.0001), a large tumor (P < 0.005), and an age of over 50 years (P < 0.05) were significant factors. Cox’s proportional hazard model showed that a man (P < 0.05), aged over 50 years (P < 0.05), who had a large primary tumor (P < 0.05) with dedifferentiation (P < 0.05), and pathological lateral cervical lymph node metastasis (P < 0.005) was more likely to have recurrence of PTC.ConclusionsDetermining whether lymph node metastasis exists could be useful for predicting recurrence in patients who have undergone curative resection of PTC.

The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2015 edition.

• In the section entitled ‘‘Risk factors for breast cancer’’ in the 2013 edition, a decrease in breast cancer risk due to obesity in premenopausal women was determined to be probable. However, a large-scale pooled analysis in Japanese women reported in 2014 showed a significant increase in breast cancer risk in premenopausal women with a high body mass index. Due to this report, the description has been changed to ‘‘obesity may increase the risk of breast cancer in premenopausal women’’ in the 2015 edition. Body mass in Asian women might have opposite effects on breast cancer compared to that in Western women. • In the section entitled ‘‘Risk assessment and chemoprevention’’, 2 CQs have been added on risk assessment using information on single-nucleotide polymorphisms, and on breast density and the risk of breast cancer.

The Japanese Breast Cancer Society clinical practice guideline for epidemiology and prevention of breast cancer

The vital statistics of the Ministry of Health, Labour and Welfare show that the crude and age-adjusted death rates of patients with breast cancer increased consistently from the 1960s to 2011, but decreased in 2012. The number of deaths due to breast cancer in women was 12,529 in 2012. The crude death rate was 19.4 per 0.1 million population and ranked fifth highest, behind colon/rectum, lung, stomach, and pancreatic cancers in descending order. The age-adjusted death rate was 11.5 per 0.1 million population, which was second only to colon/rectum cancer and was followed by lung and stomach cancers. The age-specific death rate increased in a linear fashion under the age of 50 and slightly decreased until 80 years old. The ageadjusted death rate from breast cancer in Western countries is substantially greater than that in Japan, but has shown a tendency to decrease after reaching a peak around 1990, and thus the gap with Japan has been reduced [1].

The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese patients with breast cancer

BackgroundPerioperative dose-dense chemotherapy (DDCT) with granulocyte-colony stimulating factor (G-CSF) prophylaxis is a standard treatment for patients with high-risk breast cancer. The approval of this approach in Japan led to the widespread adoption of DDCT, despite limited efficacy and safety data among Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for Japanese patients with breast cancer.MethodsThis prospective, multicenter, phase II study evaluated 52 women with operable human epidermal growth factor receptor 2-negative breast cancer and axillary lymph node metastasis. Neoadjuvant DDCT (adriamycin plus cyclophosphamide or epirubicin plus cyclophosphamide followed by paclitaxel) was administrated every 2 weeks with G-CSF support. The study endpoints were the rates of pathological complete response (pCR), febrile neutropenia, treatment completion, toxicities, and the relative dose intensity (RDI).ResultsThe pCR rate was 21.9% (9/41) and the triple-negative (TN) subtype was significantly associated with a high pCR rate (triple-negative: 53.3% vs. luminal A: 7.7% and luminal B: 0%; p = 0.003). The treatment completion rate was 80.8% (42/52) and the average RDI was 98.9%. Most adverse events were manageable and tolerable. Six patients (11.5%) developed febrile neutropenia. Grade 3–4 adverse events were slightly more common among older patients (57%) with a low protocol completion rate (≥ 65 years: 42.9% vs. <65 years: 86.7%, p = 0.0062).ConclusionThe pCR rate for DDCT was similar to that of standard chemotherapy, although it was remarkably effective for the TN subtype. DDCT may be feasible for Japanese patients with breast cancer although caution is needed for older patients.

Safety and efficacy of gemcitabine and trastuzumab in HER2-directed therapy pretreated patients with HER2-positive metastatic breast cancer: SBP-01 study.

142 Background: Prognosis of HER2-positive metastatic breast cancer (MBC) has been dramatically improved by trastuzumab (Tmab). More recently, newer anti-HER2 agents such as lapatinib, pertuzumab and T-DM1 have prolonged survival. Despite the efficacy of these drugs, most patients develop progressive disease during or after treatment, and alternative anti-HER2 agents plus chemotherapies are required in subsequent lines of treatment. However, there are few evidence on efficacy of Tmab-containing regimens after disease progression. Gemcitabine (GEM) is non-cross resistant to anthracycline and taxane. Preclinical studies have shown that the combination of Tmab and GEM has synergistic effect against HER2-positive breast cancer cell lines. SBP-01 study assessed the efficacy and safety of the combination of Tamb and GEM in patients with HER2-positive MBC previously treated with anti-HER2 therapy. METHODS SBP-01 study included patients treated with one or more anti-HER2 directed regimens for MBC. Patients were administered with GEM 1250 mg/m2 on days 1 and 8 of each 21-day cycle and Tmab 4mg/kg loading dose and then 2mg/kg weekly. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival, and safety. RESULTS Between June 2011 and June 2014, 35 patients were enrolled. Patients had ER positive tumor (37.1%), a median of 2 metastatic organ sites, visceral metastasis (80.0%), prior (neo) adjuvant Tmab (22.9%) and a median of 2 prior chemotherapy regimens for MBC. Previous HER2-directed drugs included Tmab (94.3%), lapatinib (37.1%), T-DM1 (8.6%) and pertuzumab (2.9%). ORR was 22.9% (95% CI, 8.6%-36.8%). Median PFS was 146 days. Patients with stable disease response received a median of 7 cycles (6-28 cycles) of treatment. Grade3/4 leukopenia (20.0%) and neutropenia (48.6%) were observed. All non-hematological toxicities were less than grade3. CONCLUSIONS The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, and appears to make disease stable for long time period. CLINICAL TRIAL INFORMATION UMIN000005881.