Harms of screening mammography for breast cancer in Japanese women.

BACKGROUND: The US Preventative Services Task Force assesses the efficacy of breast cancer screening by the sum of its benefits and harms, and recommends against routine screening mammography because of its relatively great harms for women aged 40-49 years. Assessment of the efficacy of screening mammography should take into consideration not only its benefits but also its harms, but data regarding those harms are lacking for Japanese women. METHODS: In 2008 we collected screening mammography data from 144,848 participants from five Japanese prefectures by age bracket to assess the harms [false-positive results, performance of unnecessary additional imaging, fine-needle aspiration cytology (FNA), and biopsy and its procedures]. RESULTS: The rate of cancer detected in women aged 40-49 years was 0.28%. The false-positive rate (9.6%) and rates of additional imaging by mammography (5.8%) and ultrasound (7.3%) were higher in women aged 40-49 years than in the other age brackets. The rates of FNA (1.6%) and biopsy (0.7%) were also highest in women aged 40-49 years. However, they seemed to be lower than the rates reported by the Breast Cancer Surveillance Consortium (BCSC) and other studies in the US. CONCLUSIONS: The results, although preliminary, indicate the possibility that the harms of screening mammography for Japanese women are less than those for American women.

Neoadjuvant weekly paclitaxel with and without trastuzumab in locally advanced or metastatic breast cancer.

A phase II clinical trial was conducted to examine the clinical and pathologic efficacy and safety of neoadjuvant paclitaxel with or without trastuzumab in women with advanced or metastatic breast cancer. A total of 49 patients with advanced or metastatic breast cancer (clinical stage IIB -IV) were included. Patients with HER2-negative tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break for 4 cycles. Patients with HER2-positive tumors received weekly paclitaxel 80 mg/m2 (days 1, 8, 15) followed by a 1-week break and a trastuzumab 4 mg/kg loading dose, intravenously, followed by 2 mg/kg weekly for 4 cycles. The age of the patients was 51.6 +/- 1.6 years (mean +/- SE) and the size of their tumors was 5.8 +/- 0.4 cm (mean +/- SE). Thirty-two patients had HER2-negative tumors and 17 had HER2-positive tumors. Of 49 patients, 13 (26.5%) had a clinical complete response and 24 (49.0%) had a clinical partial response. Five (10.2%) patients had a pathological complete response (pCR) and three (6.1%) patients had a near pCR in the breast. A total of eight (16.3%) patients had a pCR or near pCR in the breast. The pCR or near pCR rate was 3.1% in the HER2-negative group and 41.2% in the HER2-positive group. With a median follow-up of 28 months (range, 1-45), the 3-year overall survival was 88%. Clinical responders showed a significantly better overall survival than non-responders (p < 0.01). Pathological responders showed a better overall survival than non-responders. There was no significant difference in overall survival between patients with HER2-positive and -negative tumors. In conclusion, combined neoadjuvant weekly paclitaxel and trastuzumab achieved high clinical and pathological response rates for HER2 -overexpressing breast cancers, despite the omission of an anthracycline.

Human leukocyte antigen as a predictive factor of developing bilateral breast cancer in Japanese women.

To investigate the relationship between human leukocyte antigen (HLA) type and bilateral breast cancer, a total of 213 female breast cancer patients were entered into this study. The lymphocyte cytotoxicity test was used for HLA typing. HLA frequency and haplotype antigen frequency were calculated with a microcomputer. A chi-squared test was used for comparing HLA frequency. At the start point of follow-up, 187 patients (87.8%) had unilateral and 26 patients (12.2%) had bilateral breast cancer. After a 10-year follow-up, 183 patients (85.9%) were unilateral and 30 patients (14.1%) were bilateral. Haplotype frequency of A24-Cw7 was significantly higher in bilateral breast cancer patients compared with unilateral breast cancer patients (p < 0.001). After the 10-year follow-up, 4 of 187 patients (2.1%) with unilateral breast cancer developed bilateral breast cancer. Two of 19 patients (10.5%) with haplotype A24-Cw7 developed bilateral breast cancer, whereas only 2 of 168 patients (1.2%) without haplotype A24-Cw7 developed bilateral breast cancer (p < 0.01). The true frequency of developing contralateral breast cancer in patients with haplotype A24-Cw7 was 93 per 100,000 per year. The risk of bilateral breast cancer in patients with haplotype A24 and Cw7 is 12 times higher compared with those without the haplotype. HLA typing is useful for selecting patients who are at high risk of contralateral breast cancer.

DPD activity and immunohistochemical DPD expression in human breast cancer.

We investigated dihydropyrimidine dehydrogenase (DPD) activity and its expression in breast cancer cases, and evaluated the prognostic significance of DPD expression in invasive breast cancer. A total of 49 paired of breast cancer tissues and the adjacent normal breast tissues were evaluated in this study. DPD expression of 191 patients with invasive breast cancer was also evaluated immunohistochemically. DPD activity in breast cancer ranged from 13.4-360.0 pmol/mg/min (mean, 162.9 pmol/mg/min). DPD activity in breast cancer tissues was significantly (p<0.001) higher than in adjacent normal breast tissue. DPD activity was significantly higher in DPD expression-positive tumors than DPD expression-negative tumors. The level of DPD activity was correlated with DPD expression. Patients with DPD expression-positive tumors had a significantly (p<0.05) poorer prognosis in disease-free survival compared to those with DPD-negative tumors. When evaluated in patients treated with 5-FU or 5-FU derivatives, DPD expression was a significantly (p<0.05) poorer prognostic factor in disease-free and overall survival. Using a Cox proportional hazards model, nodal status, ER status, and DPD expression were independent prognostic factors for both disease-free and overall survival. In conclusion, DPD expression may function as a marker of DPD activity and may be a prognostic indicator for patients with breast cancer.

Long-term suppression of lymphangitic lung metastasis from breast cancer using biweekly docetaxel: a case report.

A 45-year-old woman underwent a modified radical mastectomy for right breast cancer in July 1996. As lymph node metastases were quite advanced, chemotherapy was started with anthracyclines. Four years after surgery, cough and dyspnea appeared. Chest radiograph and CT showed reticular shadows bilaterally and slight pleural effusion, suggesting lymphangitic lung metastasis of breast cancer. Biweekly intravenous docetaxel (TXT,45 mg/m2) was initiated. Four courses of TXT ameliorated her complaints and radiographic findings. A total of 30 continuous courses of TXT suppressed disease exacerbation for 18 months until new lesions manifested in January 2002. The main side effects were grade 2 leukopenia and alopecia. This case report describes a patient with long-term suppression of lymphangitic lung metastasis of breast cancer using biweekly TXT without severe side effects or worsening quality of life.

Primary amenorrhea accompanied by adrenal adenoma: start of menarche soon after tumor resection.

We report a patient with primary amenorrhea accompanied by adrenal adenoma. A 21-year-old woman was admitted to our hospital because of primary amenorrhea and hyperprogesteronemia without virilization. Venous sampling showed progesterone overproduction at the left adrenal gland. Computed tomography revealed a 7 cm mass in left adrenal gland. Serum pregnenorone, 17-hydroxypregnenorone, dehydroepiandrosterone, 17-hydroxyprogesterone, deoxycorticosterone, and 11-deoxycortisol were elevated. The diagnosis of steroid hormone producing tumor was made. Following tumor resection, serum progesterone normalized 4 days later, and menarche occurred 51 days after operation. The present case indicated that adrenal functioning tumor should not be overlooked in patients with primary amenorrhea.

Effects of a bradykinin B(2) receptor antagonist, FR173657, on pulmonary ischemia-reperfusion injury in dogs.

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury. METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.

Breast-conserving surgery following radiation therapy of 50 Gy in stages I and II carcinoma of the breast: the experience at one institute in Japan.

This study evaluated the results of breast-conserving therapy experienced in one institute. A total of 217 breasts in 215 patients with clinical stages I and II breast cancer undergoing breast-conserving therapy between August 1991 and December 1999 were included. The actuarial 5-year local recurrence-free survival, disease-free survival and overall survival rates were 97.4%, 88.5% and 92.5%, respectively. Microscopic margins were negative in 176 (81.1%) of the total breasts and positive in 41 (18.9%). There were no differences in the age at operation, tumor size, clinical stage, lymph node status, estrogen receptor status, or distance from tumor to nipple between patients with positive surgical margins and with negative surgical margins. During the follow-up period, local recurrence occurred in seven patients. Local recurrence was significantly less frequent in patients with surgical margin-negative tumors than those with surgical margin-positive tumors, and also in ER-positive tumors than ER-negative or ER-unknown tumors. There was no difference in overall survival between patients with and without breast-recurrence. Using multivariate analysis, the surgical margin was determined to be an independent predictive factor for local recurrence in the conserved breast. Nodal status and ER status were independent prognostic factors, but local recurrence did not have an independent negative impact on survival. We conclude that microscopic surgical margin is the most important factor associated with local recurrence in the conserved breast among patients treated with breast-conserving surgery and radiation therapy of 50 Gy. Local recurrence however, has no adverse effect on survival of patients.

A hemophagocytic syndrome-like condition after emergency colectomy for perforated colon cancer: report of a case.

Hemophagocytic syndrome is a rare but often fatal condition, and little is known about why this disorder can occur following surgery. We report herein the case of a patient successfully treated for a hemophagocytic syndrome-like condition that developed after emergency right hemicolectomy for a retroperitoneal abscess secondary to perforated colon cancer. The 62-year-old man initially presented after the sudden development of severe right back pain, and computerized tomography scans revealed a retroperitoneal abscess continuous with a tumor in the ascending colon. An emergency right hemicolectomy was subsequently performed. On postoperative day (POD) 2, his blood platelet count suddenly dropped to 1 x 10(4)/microl and histological examination of a bone marrow specimen taken on POD 5 showed abnormal histiocytes that had phagocytosed not only megakaryocytes, but also erythrocytes and leukocytes, and a normocellular marrow with a normal number of megakaryocytes. Hemophagocytic syndrome was suspected, and predonine was administered. The patient's condition improved remarkably and he was discharged on POD 51.

Breast-conserving therapy versus modified radical mastectomy in the treatment of early breast cancer in Japan.

BACKGROUND: Breast-conserving therapy has been widely utilized as a treatment option for women with early breast cancer. However, no randomized study comparing modified radical mastectomy and breast-conserving therapy has been conducted in Japan. METHODS: Two hundred and twenty-eight Japanese women with early breast cancer enrolled in the Gunma Breast Conserving Therapy Study between 1991 and 1994 were examined to determine whether there is any difference in disease-free survival or overall survival between radical mastectomy and breast-conserving therapy. After informed consent was obtained, a total of 119 patients underwent breast-conserving therapy and 109 underwent mastectomy. RESULTS: Mastectomy was a more frequently utilized treatment than breast-conserving therapy in patients with clinical stage II lesions, older age, larger tumor size or shorter distance between tumor and nipple. The mean follow-up period for all patients was 81 months (median 86 months). There was no significant difference in overall survival or disease-free survival between breast-conserving therapy and mastectomy even after adjusting for the clinical stage of the disease. A multivariate analysis of tumor size, lymph node status, estrogen receptor status and operation method using the Cox proportion hazard model confirmed that only lymph node status was an independent prognostic factor. CONCLUSION: Breast-conserving therapy is comparable to modified radical mastectomy in overall survival and disease-free survival.