Keisei Anan

Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study.

The purpose of this study is to evaluate how beverages containing Lactobacillus casei Shirota (BLS) and soy isoflavone consumption since adolescence affected the incidence of breast cancer. In a population-based case-control study, three hundred and six cases with breast cancer and 662 controls aged 40 to 55 were matched for age and residential area and included in the analyses. Diet, lifestyle and other breast cancer risk factors were investigated using the self-administered questionnaire and interview. Odds ratios (ORs) of BLS and soy isoflavone consumption for breast cancer incidence were independently and jointly estimated using a conditional logistic regression. The ORs of BLS consumption (≥ four times a week against < four times a week) was 0.65 and statistically significant (p = 0.048). The analysis of association between soy consumption and breast cancer incidence showed the more the isoflavone consumption is, the lower the odds of breast cancer becomes. Adjusted ORs for breast cancer in the second, the third and the fourth quartiles of soy consumption against the first quartile were 0.76, 0.53 and 0.48, respectively (trend test, p = 0.0002). The BLS-isoflavone interaction was not statistically significant; however, a biological interaction was suggested. Regular consumption of BLS and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women.

Axillary lymph node metastases in patients with small carcinomas of the breast: is accurate prediction possible?

OBJECTIVES To find out whether macroscopic classification of the tumour margin is predictive of axillary lymph node metastases and to identify a combination of clinical and pathological findings by which axillary node status can be predicted accurately in small carcinomas (T1) of the breast. DESIGN Retrospective study. SETTING Municipal referral centre, Japan. SUBJECTS All 1003 patients with T1 invasive carcinoma of the breast who had axillary lymph node dissection between January 1970 and December 1996 as part of their treatment. MAIN OUTCOME MEASURES The association between the incidence of axillary lymph node metastases and 10 clinical and pathological factors (age, palpability and size of tumour, macroscopic classification of tumour margin, clinical axillary status, radiating spiculation on a mammogram, histological type, lymphatic invasion, oestrogen and progesterone receptor status) were analysed. RESULTS Clinical axillary node status, macroscopic classification of tumour margin, lymphatic invasion, and age of the patient were significant predictors of axillary lymph node metastases (p < 0.01 in each case). Among 47 patients aged 65 or more whose tumours had well-defined margins and with a clinical N0 status in the axillae, the incidence of histological axillary lymph node metastasis was only 6% (n = 3) whereas it was 65% in 57 patients with tumours of ill-defined margins whose axillae were N1 or N2. CONCLUSIONS Macroscopic classification of tumour margins is an independent predictor of axillary lymph node metastases for patients with small carcinomas of the breast. However, even with combinations of the examined predictors of axillary node metastases, the subgroup of patients at minimal risk of metastasis was less than 5% in T1 breast cancer, whereas three-quarters of the patients had clear axillary lymph nodes. Most patients with T1 breast cancer will need surgical staging of the axillae by methods such as sentinel node biopsy.

Efficacy of goserelin plus anastrozole in premenopausal women with advanced or recurrent breast cancer refractory to an LH-RH analogue with tamoxifen: Results of the JMTO BC08-01 phase II trial

The aim of the present study was to assess the efficacy and tolerability of a luteinizing hormone-releasing hormone (LH-RH) analogue plus an aromatase inhibitor following failure to respond to standard LH-RH analogue plus tamoxifen (TAM) in premenopausal patients. Premenopausal women with estrogen receptor (ER)-positive and/or progesterone-receptor positive, advanced or recurrent breast cancer refractory to an LH-RH analogue plus TAM received goserelin (GOS) in conjunction with anastrozole (ANA). The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and safety. Between September 2008 and November 2010, 37 patients were enrolled. Thirty-five patients (94.6%) had ER-positive tumors, and 36 (97.3%) had human epidermal growth factor receptor (HER) 2-negative tumors. Thirty-six (97.3%) had measurable lesions and 1 (2.7%) had only bone metastasis. The ORR was 18.9% [95% confidence interval (CI), 8.0–35.2%], the CBR was 62.2% (95% CI, 44.8–77.5%) and the median PFS was 7.3 months. Eight patients had adverse drug reactions but none resulted in discontinuation of treatment. GOS plus ANA is a safe effective treatment for premenopausal women with hormone receptor-positive, recurrent or advanced breast cancer. The treatment may become viable treatment in the future, particularly when TAM is ineffective or contraindicated. Further studies and discussion are warranted.

Changes in Tumor Expression of HER2 and Hormone Receptors Status after Neoadjuvant Chemotherapy in 21,755 Patients from the Japanese Breast Cancer Registry

BACKGROUND We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. PATIENTS AND METHODS Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. RESULTS pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. CONCLUSION We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Breast Cancer in Japanese Men : Does Sex Affect Prognosis?

BackgroundBreast cancer has received much less investigative attention in Asian men than in Caucasian men. We examined whether the prognosis of Japanese men with breast cancer differs from that of Japanese women with the disease.MethodsThe clinicopathological features of 14 Japanese men with breast cancer were reviewed and age- and stage-matched case-control analysis of these men and 140 female patients was performed.ResultsDisease-free survival (p = 0.94) and overall survival (p = 0.62) did not differ significantly between the sexes. Five-year disease-free survival was 77% for the men and 75% for the women, and the 5-year overall survival was 92% for the men and 86% for the women. The disease recurred in 2 men but none died of breast cancer, although 3 died of other causes during the median follow-up period of 7 years. There were no significant differences in p53 mutation (p = 0.20) or erbB-2 oncoprotein overexpression (p = 0.33) between the men and women studied.ConclusionSurvival rates of Japanese male and female breast cancer patients are similar when age and stage of the disease are taken into consideration. However, comorbid disease mortality is likely the major contributor to clinical outcome in Japanese male breast cancer patients.

Oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: A phase II study

Capecitabine (Xeloda, X) and cyclophosphamide (C) can be given orally and they have synergistic effects with nonoverlapping toxicities in preclinical studies. A phase I study of the XC combination therapy was conducted in patients with metastatic breast cancer (MBC) and determined the recommended dose and schedule of 1657 mg/m2/day capecitabine and 65 mg/m2/day cyclophosphamide given orally for 2 weeks at a 3-week interval. A phase II study of the oral XC regimen was then conducted. This study enrolled patients with HER2-negative MBC who were earlier treated with anthracyclines. XC was given at the recommended doses on a 3-week schedule for at least six courses unless disease progression or unacceptable toxicities occurred. The primary endpoint was the response rate. Progression-free survival, overall survival, and adverse events were investigated as secondary endpoints. Forty-eight patients with the median age of 58 (range 32–72 years) years were registered. Three patients withdrew by choice before starting the treatment. A complete response was obtained in two of the 45 evaluable patients, and partial response in 14, resulting in an overall response rate of 35.6%. The median progression-free survival and overall survival were 199 (115–231) days and 677 (437∼) days, respectively. Grade 3 neutropenia and leukopenia developed in 11%, and that of anemia and thrombocytopenia in 2% patients. Nonhematological toxicities were mild. Hand--foot syndrome was observed in 14 patients but no one had grade 3–4 toxicity. Oral XC combination is effective with acceptable toxicities in patients with MBC.

Histopathological Predictors of Axillary Lymph Node Metastases in Patients with Breast Cancer.

BackgroundA tumor 30 mm or less in diameter is a standard candidate for breast conserving surgery (BCS) in Japan. Axillary lymph node metastases (ALNM) is the most important prognostic factor for survival in patients with breast cancer, but the role of axillary node dissection has been controversial. Histopathological predictive factors of axillary lymph node involvement have not been established. The purpose of this study was to determine the association between the incidence of ALNM and histopathological factors by univariate and multivariate analysis.MethodsSixty-five patients with noninvasive ductal carcinoma, and 993 patients with tumors 30 mm or less in diameter who underwent axillary dissection between 1988 and 1997 at our institute were reviewed. The association between ALNM and 13 histopathological factors (size, age, histological subtype, histological invasiveness, lymphatic invasion, vascular invasion, macroscopic classification, histological daughter mass, ductal spread, ER, PgR, p-53, and c-erbB-2) were analyzed by univariate and, when significant, by multivariate analysis.ResultsOnly one patient with noninvasive ductal carcinoma had ALNM, and 33.1% of 993 patients with a tumor 30 mm or less in size had ALNM.Multivariate analysis identified six factors as independent predictors for ALNM: lymphatic invasion, size, histological invasiveness, macroscopic classification, age and histological daughter mass.ConclusionsAxillary lymph node dissection can be omitted in patients with noninvasive ductal carcinoma. Histopathological features of tumors 30 mm or less in diameter can be used to estimate the risk of ALNM, and routine axillary node dissection might be spared in selected patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status, such as in elderly patients.

Tubular carcinoma of the breast: a histologic subtype indicative of breast-conserving therapy.

Abstract We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5–3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended.

Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database—Breast Cancer Registry

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed‐up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m2) categories; <18.5 (underweight), ≥18.5–<21.8 (reference), ≥21.8–<25, ≥25–<30 (overweight), and ≥30 (obese). We divided normal weight patients into two subgroups because this category includes many patients compared to others. The timing of BMI measurement was not specified. The Cox proportional hazards model and cubic spline regression were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking, alcohol, and physical activity were not controlled. A total of 1418 all‐cause, 937 breast cancer–specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all‐cause (HR: 1.46; 95% CI: 1.16–1.83) and breast cancer–specific death (HR: 1.47; 95% CI: 1.11–1.93) for all patients, and with all‐cause (HR: 1.47; 95% CI: 1.13–1.92) and breast cancer–specific death (HR: 1.58; 95% CI: 1.13–2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all‐cause death for all (HR: 1.41; 95% CI: 1.16–1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15–1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer–specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51–4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71–6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

Postoperative Follow-Up of Patients with Early Breast Cancer: Reappraisal of Serum Tumor Markers

Abstract The purpose of this study was to determine the most appropriate tests and procedures to detect disease progression effectively during the postoperative follow-up of patients with early breast cancer. We reevaluated our current surveillance protocol which involves the intensive follow-up of 643 patients with stage I disease. With the exception of one case of bone metastasis, all cases of recurrence (97%) were suspected from abnormal results detected during surveillance involving physical examination, serial determination of tumor markers, and chest roentgenography. Among 15 patients with asymptomatic distant metastasis, disease recurrence was suspected in 12 (80%) because of increased levels of serum tumor markers. No disease recurrence was detected by routine complete blood counts or automated chemistry studies alone. Our experience indicates that an effective follow-up regimen for patients with early breast cancer may include careful history-taking, physical examination, and the determination of serum tumor markers every 3–6 months for the first 3 years, then less frequently thereafter, and chest roentgenography every 6 months for 5 years, in addition to annual mammography. Serial determination of the tumor markers tumor polypeptide antigen, NCC-ST-439, and either carcinoembryonic antigen or carbohydrate antigen 15-3, seems to be of value for the selection of patients who should undergo radiologic exploration. The health benefits and cost-effectiveness of a follow-up focused on the measurement of serum tumor markers need to be evaluated in large prospective randomized trials.