The effect of combined risk factors on breast cancer-related lymphedema: a study using decision trees.

BACKGROUND: The effect of combined risk factors on breast cancer-related lymphedema (BCRL) development has not yet been investigated. This study aimed to determine the combination of risk factors associated with BCRL development in patients who underwent breast cancer resection, including axillary lymph node dissection (ALND). METHODS: The participants included 129 women who were diagnosed with early-stage breast cancer and underwent breast cancer resection in this retrospective observational study. We performed a decision tree analysis to detect the combination of risk factors associated with BCRL development using age, body mass index (BMI), surgical side, mastectomy, the extent of ALND, and adjuvant therapy (chemotherapy, hormone therapy, and radiation therapy). RESULTS: Of the 129 participants, 11 (8.5%) developed BCRL. Postoperative chemotherapy was the optimal variable selected to classify patients who developed BCRL and those who did not. In participants with postoperative chemotherapy, the extent of ALND was selected as the second layer of the decision tree. When ALND was at level 3, BMI was selected as the third layer. We found that BCRL incidence was 44.4% in individuals with a BMI of 23.0 or higher. CONCLUSIONS: The combination of postoperative chemotherapy, level 3 ALND, and BMI of 23.0 or higher may further increase the risk of developing BCRL. The decision tree model will enable the identification of patients with a high risk of developing BCRL, and thus, preventive intervention, careful monitoring, and early treatment will be possible.

[A Case of Axillary Arterial Bleeding after Axillary Metastatic Lymph Node Necrosis during Treatment with Paclitaxel and Bevacizumabfor Breast Cancer].

A 44-year-old woman was diagnosed cT4bcN3cM1(LYM), Stage IV triple-negative breast cancer.Enhanced computed tomography revealed ipsilateral axillary lymph node metastasis, 10 cm in diameter.The supraclavicular and cervical lymph nodes also had metastases.She received paclitaxel(90mg/m2, on days 1, 8, and 15 every 4 weeks)in combination with bevacizumab(10mg/kg, on days 1 and 15 every 28 days).Her height was 165 cm, and her body weight was 100 kg.After 1 course of chemotherapy, a metastatic axillary lymph node with necrotic changes was removed spontaneously.A few days later, she experienced severe bleeding from her axillary artery, and she went into hypovolemic shock.Despite undergoing surgical hemostasis, the bleeding recurred twice, so we performed coil embolization of her subclavian artery.Thirty -five days after the first occurrence of bleeding, the patient died of sepsis and ARDS due to left arm necrosis.Bevacizumab is effective for the treatment of large tumors, but when the tumor is close to an artery, clinicians should be wary of fatal bleeding after necrosis.

Phase III randomized trial of toremifene versus tamoxifen for Japanese postmenopausal patients with early breast cancer.

BACKGROUND: Toremifene, a selective estrogen receptor modulator, is used as adjuvant therapy for postmenopausal patients with breast cancer in Japan. For Japanese patients, however, only limited data are available on the efficacy and safety profile of toremifene. To establish the long term efficacy and safety of toremifene for Japanese patients, we conducted a prospective, multicenter, randomized phase III trial comparing toremifene and tamoxifen. PATIENTS AND METHODS: The subjects were postmenopausal Japanese patients who had undergone surgery for node-negative breast cancer. Toremifene or tamoxifen was administered for 2 years. The primary endpoint was demonstration of the non-inferiority of toremifene compared with tamoxifen in respect of 5-year survival. Secondary endpoints were cumulative overall survival, cumulative disease-free survival, effects on lipid profiles, and adverse events. RESULTS: A total of 253 patients were enrolled. The baseline characteristics of the two treatment groups were well-balanced. Median follow-up was 66.5 months. Five-year survival was similar for toremifene and tamoxifen (97.0 vs. 96.9 %; 90 % confidence interval -3.9 to 4.1), indicating that toremifene is not inferior to tamoxifen for postmenopausal Japanese patients with early breast cancer. Cumulative overall survival and cumulative disease-free survival were also very similar for toremifene and tamoxifen (97.5 vs. 97.3 %, log-rank test P = 0.9458; 88.4 vs. 90.6 %, log-rank test P = 0.3359, respectively). Adverse events in both groups were similar and mostly mild or moderate. Thus, both are equally effective and well tolerated. CONCLUSION: Our results suggest that the efficacy and safety of toremifene and tamoxifen are equivalent for postmenopausal Japanese patients with early breast cancer.

Effectiveness of multi-detector row computed tomography in detection of the presence and extent of ductal carcinoma in situ.

BACKGROUND: As ductal carcinoma in situ (DCIS) lesions can spread widely in the ductal-lobular segment, often without palpable tumor, complete resection of the lesion in breast-conserving surgery requires establishment of the precise location and extent of the lesion during preoperative imaging studies. We investigated the potential of multi-detector row computed tomography (MDCT) in detecting and delineating DCIS lesions. METHODS: Overall, 74 patients with 75 DCIS lesions underwent breast MDCT. The size of the DCIS lesion in each patient was measured in the volume rendering images and compared to the size obtained by pathological mapping. The differences between the actual tumor size and that obtained from MDCT (L-Path and L-CT) were calculated, and the relationships between these differences and tumor characteristics were investigated. RESULTS: DCIS was detected fully or partially in 64 (84.9 %) of 75 lesions, whereas the detection rate of magnetic resonance imaging (MRI) was 90 %. The detection rate was not influenced by comedo/non-comedo status, but the detection rate of higher nuclear grade DCIS lesions tended to be higher than that of low grade lesions (p = 0.089), while the estimated size was also more accurate in the former (p = 0.046). Hormone receptor and Her2 status did not affect MDCT findings. CONCLUSION: MDCT is highly effective for detecting DCIS, especially the more aggressive types of DCIS. Moreover, the patient's position during MDCT imaging is more similar to that during surgery than that during MRI, making MDCT a highly useful presurgical imaging technique for the assessment of DCIS.

Evaluation of the usefulness of breast CT imaging in delineating tumor extent and guiding surgical management: a prospective multi-institutional study.

OBJECTIVE: The aim of the present study was to evaluate the usefulness of computed tomographic (CT) imaging in delineating tumor extent and guiding surgical management. BACKGROUND: The routine use of preoperative magnetic resonance imaging (MRI) is a controversial issue in breast cancer management. Negative studies with regard to the utility of MRI might be due to differences in positioning during imaging and subsequent surgery. METHODS: Candidates for breast-conserving surgery were eligible for the study. The surgeons marked the line of planned excision on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to help determine the extent of resection. The pathological findings were then compared with the CT-guided surgical plans. RESULTS: A total of 297 patients were involved. The surgeons widened the extent of resection in 42 (14.1%, 95% confidence interval 10.1%-18.1%) patients on the basis of the CT findings. Among the 6 patients whose procedures were changed to mastectomy, 4 had pathologically multicentric tumors and 2 had widely spread intraductal components. The remaining 36 patients underwent quadrantectomy instead of wide excision on the basis of the CT images. There were 3 patients in whom conversion from wide excision to quadrantectomy resulted in overexcision. Preoperative breast CT may have reduced the positive margin rate and also correctly changed the extent of surgery in 13.1% of patients. CONCLUSIONS: This prospective study suggests that breast CT, carried out in the supine position, is useful in the preoperative determination of the optimal surgical procedure.

Down-regulation of p73 correlates with high histological grade in Japanese with breast carcinomas.

BACKGROUND: p73, a homologue of p53, has been located at chromosome 1p36-33, a region of frequently observed loss of heterozygosity in breast cancers. The objective of the present study was to investigate the function of p73 in Japanese with breast cancers. METHODS: Sixty Japanese patients with breast cancer were assessed by polymerase chain reaction single strand confirmation polymorphism analysis and direct sequencing to detect the p73 allele. p73 mRNA levels were also determined in 40 out of 60 patients by reverse-transcriptional polymerase chain reaction. RESULTS: We analyzed the entire open reading frame of the p73 gene by polymerase chain reaction single strand confirmation polymorphism and sequencing, and failed to identify any mutations of p73 in the encoding regions detected. Loss of heterozygosity of p73 was infrequent and only found in 9% of breast carcinomas. We revealed a few polymorphisms with a frequency of 13% - 29%, which had been reported previously. Down-regulation of p73 mRNA expression was observed in tumor tissues in comparison to the normal breast tissues. A significant inverse correlation was found between p73 transcripts and high histological grade, suggesting that down-regulated p73 expression could be related to poor prognosis in those patients. CONCLUSION: Our results suggest that p73 may serve as a tumor suppressor gene and its expression plays a role in tumorigenesis in Japanese patients with breast cancer.

Radiologic-pathologic correlation of ductal carcinoma in situ.

Ductal carcinoma in situ (DCIS) accounts for 20%-25% of breast cancers detected at screening mammography. The lesions are diverse and commonly are classified on the basis of their mammographic features and histologic characteristics such as nuclear grade and presence or absence of necrosis. The most common mammographic finding in DCIS is microcalcifications, but a low-grade lesion without necrosis is less likely to manifest with calcifications than either an intermediate- or a high-grade lesion. Other mammographic findings might include a mass or architectural distortion. Magnetic resonance (MR) imaging has higher sensitivity than mammography for the detection of DCIS and greater accuracy for depicting the extent of disease. The MR imaging appearance of DCIS depends primarily on the presence and extent of abnormal periductal or stromal vascularity. Nonmasslike enhancement, the most common MR imaging finding, is often seen in association with clumped internal enhancement. The enhancement kinetics in dynamic MR studies vary, and no kinetic pattern is pathognomonic of a particular nuclear grade of DCIS. However, the kinetic pattern at delayed imaging does appear to be correlated with the mammographic findings: Mass lesions show strong washout; fine pleomorphic, fine linear, and fine linear-branching calcifications demonstrate a plateau enhancement pattern; and amorphous calcifications exhibit persistent enhancement. Multidetector computed tomography might be a useful adjunct to MR imaging for preoperative mapping.

Molecular morphological approach to the pathological study of development and advancement of human breast cancer.

Since the concept of gene profile-based intrinsic subtypes was proposed, various studies on pathological characteristics have been performed. Particularly, triplenegative (TN) breast cancer, which is negative for all hormone receptors [estrogen receptor (ER) and/or progesterone receptor (PgR) and human epidermal growth factor 2 (HER2)], has been attracting attention because effects of endocrine and targeting therapies cannot be anticipated and thus selecting a treatment method is difficult. TN cancer accounts for about 10%-15% of all invasive breast cancer cases in Japanese, which is significantly lower than the incidence reported in the United States. Cytokeratin (CK) 5/6 or epidermal growth factor receptor (EGFR) is positive in 80%, being classified as basal-like carcinoma, but it should be understood that TN breast cancer and basal-like carcinoma are not necessarily the same. Criteria for positivity judgment of ER, PgR, and HER2 were established to select treatment in cases positive for each marker, and greater importance is attached to strict accuracy control. Inversely, the level of negative findings to judge TN varies among the judgment criteria. In any case, the prognosis of TN breast cancer is poor. Pathologically, TN breast cancer shows certain morphological characteristics, such as high grade and a pushing margin, and abnormalities of BRCA1 and p53 are frequently noted. At present, as no effective therapeutic strategy has been established for TN breast cancer, further clarification of the molecular biological characteristics of such cancers is needed. In addition, the incidence of TN-type ductal carcinoma in situ (DCIS) is low, suggesting that TN does not remain preinvasive DCIS for a prolonged period and that it transforms to invasive cancer in an early stage. Because mammary gland basal cells have characters of progenitor or stem cells that differentiate into both luminal epithelium and myoepithelial cells, these cells may be utilized for the differential diagnosis of the benignity or malignancy of intraductal lesions in routine pathological practice. As proliferation markers, such as Ki-67, and multiple gene arrays for gene signature are also utilized to select adjuvant therapy, analysis may progress further in the future.

Effects of toremifene and tamoxifen on lipid profiles in post-menopausal patients with early breast cancer: interim results from a Japanese phase III trial.

OBJECTIVE: Toremifene and tamoxifen have been used for adjuvant therapy in post-menopausal patients with breast cancer in Japan. Dyslipidemias are common in post-menopausal women. However, limited data are available on the effects of these agents on lipid profiles in Japanese patients. The Japan Toremifene Cooperative Study Group has been conducting a Phase III randomized trial of post-menopausal patients with breast cancer. One of its secondary endpoints is to confirm the effects of these agents on serum lipid profiles. METHODS: The subjects were post-menopausal Japanese patients who had undergone surgery for early breast cancer. Toremifene or tamoxifen was administered for 2 years. Lipid levels were measured before and up to 24 months after initiation. RESULTS: Compared with baseline, at 24 months, the toremifene group (n = 123) showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001), and significantly increased high-density lipoprotein cholesterol levels (P < 0.001). Their triglyceride levels were not affected (P = 0.677). The tamoxifen group (n = 120) also showed significantly decreased total cholesterol (P < 0.001) and low-density lipoprotein cholesterol levels (P < 0.001); no significant changes occurred in high-density lipoprotein cholesterol (P = 0.297) or triglyceride levels (P = 0.120). CONCLUSIONS: Distinct differences between two selective estrogen receptor modulators on lipids were observed. Toremifene improved lipid profiles, particularly as an enhancer of high-density lipoprotein cholesterol. To a large extent, tamoxifen improved low-density lipoprotein cholesterol levels. The impact of these improved lipid profiles on the risk of cardiovascular diseases needs further confirmation.

Increased intratumoral androgens in human breast carcinoma following aromatase inhibitor exemestane treatment.

Sex steroids play important roles in the development of many human breast carcinomas, and aromatase inhibitors are used for the anti-estrogen therapy. Recent studies have demonstrated that aromatase suppressed 5alpha-dihydrotestosterone (DHT) synthesis in breast carcinoma cells, but intratumoral concentration of androgens and its significance have not been reported in the breast carcinoma patients treated with aromatase inhibitors. Therefore, we examined androgen concentrations in breast carcinoma tissues treated with exemestane, and further performed in vitro studies to characterize the significance of androgen actions. Intratumoral DHT concentration was significantly higher in breast carcinoma tissues following exemestane treatment (n=9) than those without the therapy (n=7), and 17beta-hydroxysteroid dehydrogenase type 2 (17betaHSD2) status was significantly altered to be positive after the treatment. Following in vitro studies showed that 17betaHSD2 expression was dose dependently induced by both DHT and exemestane in T-47D breast carcinoma cells, but these inductions were not additive. DHT-mediated induction of 17betaHSD2 expression was markedly suppressed by estradiol (E(2)) in T-47D cells. E(2)-mediated cell proliferation was significantly inhibited by DHT in T-47D cells, associated with an increment of 17betaHSD2 expression level. These findings suggest that intratumoral androgen actions are increased during exemestane treatment. 17betaHSD2 is a potent DHT-induced gene in human breast carcinoma, and may not only be involved in anti-proliferative effects of DHT on breast carcinoma cells but also serve as a potential marker for response to aromatase inhibitor in the breast carcinoma patients.

Randomized trial of cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil with node-positive breast cancer in Japan.

BACKGROUND: To compare the cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy and the anthracycline-containing regimen cyclophosphamide, epirubicin, and fluorouracil (CEF) to evaluate the efficacy and safety of the latter. METHODS: A total of 294 patients with axillary node-positive primary breast cancer of STAGE I-IIIa were randomly assigned to either CEF [cyclophosphamide (CPA) 500 mg/m(2) i.v. days 1 and 8; epirubicin (EPI) 60 mg/m(2) i.v. day 1; and 5-fluorouracil (5-FU) 500 mg/m(2) i.v. days 1 and 8] or CMF [CPA 500 mg/m(2) i.v. days 1 and 8; methotrexate (MTX) 40 mg/m(2) i.v. days 1 and 8; and 5-FU 500 mg/m(2) i.v. days 1 and 8]. Both treatment regimens were comprised of six cycles at 4-week intervals. Tamoxifen (TAM) 20 mg/day was concomitantly given to estrogen receptor (ER)-positive patients and those with undetermined ER status for 2 years. RESULTS: The overall 5-year survival was 77.1% for CEF and 71.4% for CMF [p = 0.24; hazard ratio 0.79 (95% CI 0.50-1.24)], and the 5-year disease-free survival was 55.7% for CEF and 48.9% for CMF [p = 0.15; hazard ratio 0.80 (95% CI 0.57-1.12)]. Although the log-rank test did not show a significant difference, both overall and disease-free survivals were higher for CEF according to the point estimates. Adverse drug reactions (ADRs) occurred more frequently in CEF. CONCLUSION: Whereas CEF had a good trend compare with CMF, it could not be proven statistically significant. The principal cause of the failure seems to be insufficient power, that is, the dose intensity (EPI: 60 mg/m(2)) set 10 years ago, when the trial began, was low, and the number of trial subjects was small because of the background of the times, which made the accumulation of cases extremely difficult. However, the trial should be considered to be meaningful, as it was the first, formally conducted controlled trial on chemotherapy in Japan.

Clinical usefulness of high-dose toremifene in patients relapsed on treatment with an aromatase inhibitor.

BACKGROUND: Aromatase inhibitors (AIs) have been employed as adjuvant therapy or as treatment for recurrent cases. However, when AI treatment fails, it is unclear which endocrine therapy is the most appropriate to introduce at this point and how effective it will be. In this study, we investigated the efficacy and safety of toremifene (TOR, Fareston(®)), a selective estrogen receptor modulator (SERM). METHODS: Patients with recurrent or advanced breast cancer who had measurable or evaluable lesions, and were diagnosed as having progressive disease during AI treatment and subsequently given TOR at 120 mg/day (TOR120) as endocrine therapy were selected and analyzed retrospectively in relation to their medical history. RESULTS: Of a total of 83 cases examined, 80 were evaluable. The objective response rate (ORR) was 15.0% (12/80), the clinical benefit (CB) rate was 45.0% (36/80), and median time to failure (TTF) was 7.8 months. TOR120 was also effective in the progressive disease cases relapsed on AI treatment. When TOR120 was used, as a first-, second- or third-line treatment, the CB rate was 57% (32/56); this fell to 17% (4/24) when TOR120 was used as a fourth-line or later treatment. There was no response in the five estrogen receptor (ER)-negative cases, compared with an ORR of 15% (10/67) in ER-positive cases. In cases with a human epidermal growth factor receptor 2 (HER2) score of 0, 1+, and 2+, the ORR was 11% (7/61), while there was no response in the five cases with scores of 3+. TOR120 was effective in cases previously treated with tamoxifen (TAM), with an ORR and CB rate of 12 and 29%, respectively. The last AI used was anastrozole in 30 cases and examestane in 46; the response rates to TOR120 were similar in both groups. With regard to adverse effects, hot flushes and/or night sweating was observed in 10 and 12 cases, respectively, but all of them were categorized as grade 1, and the treatment was rated excellent in acceptability. CONCLUSIONS: TOR120 was rated excellent in acceptability, and high efficacy was observed when it was used up to third-line treatment for AI-failure cases, although this study may show some selection bias because of the retrospective study. In addition, it was also considered effective for TAM-failure cases.

[Efficacy and safety of high-dose toremifene for hormone-responsive advanced or metastatic breast cancer patients with failed prior treatment by aromatase inhibitors].

BACKGROUND: Recently, aromatase inhibitors (AI) are widely used in postoperative adjuvant therapy for breast cancer. Nevertheless, studies of postoperative therapeutic strategies for recurrent breast cancer are insufficient. SUBJECTS AND METHOD: Data on 12 post-menopausal advanced/recurrent breast cancer patients in our department during June 2003- April 2007 were used for this study. No patient had responded to high-dose toremifene (TOR), a third-generation AI. Their therapeutic outcomes were analyzed retrospectively. The median observation period of the subjects was 16.1 months (4.0-40.9 months). Subjects were all hormone-sensitive. Overexpression of HER2 protein was found in only one case. During AI therapy immediately prior, exemestane (EXE) and anastrozole (ANA) had been given in nine and three cases, respectively. RESULTS: The complete response rate of AI therapy was 16.7% (2/12). The clinical benefit rate was 58.3% (7/12). The median of time to progression (TTP) was 33.8 weeks. Neither the presence nor absence of past history of treatment with tamoxifen (TAM) or other chemotherapies affected the anti-tumor effect. Analysis by the site of metastasis or recurrence revealed that the therapeutic effects were better for non-life-threatening cases in the lung, pleura, soft tissue, etc. The severities of adverse effects were all less than grade 2; the major ones were flushing and sweating. CONCLUSION: Results show that high-dose TOR given at an early stage can provide clinical benefits for post-menopausal advanced/recurrent breast cancer not responding to AI.

[Combination treatment with trastuzumab and Paclitaxel as primary therapy for advanced breast cancer].

PURPOSES: Despite many recent reports on the effects of trastuzumab for breast cancer, many problems remain regarding combination drug treatment and its significance. We report our experience with advanced breast cancer patients who received combination therapy with trastuzumab+paclitaxel. SUBJECTS AND METHOD: Three patients with human epidermal growth factor receptor 2(HER2)-positive advanced breast cancer were the subjects. Combination therapy with trastuzumab and paclitaxel was carried out as a primary therapy, and its therapeutic effects were evaluated based on image findings, tumor markers and observation of resected specimens. RESULTS: The primary tumors in the three patients were all clinically complete response (cCR). Those in two surgically treated patients were near pathologically complete response (pCR), ie, a small amount of cancer cells remained in the galactophore, whereas the histological therapeutic effect was Grade 2b. In two patients with liver metastases, the metastatic tumor disappeared on the image after the therapy. In two patients whose tumor marker was increased at the first examination, the level of increase was markedly lowered by the therapy. Neither infusion reaction nor heart functional impairment was found in any of the three patients. CONCLUSIONS: For patients with advanced breast cancer, a regimen containing trastuzumab would produce significant therapeutic effects if the cancer is HER2-positive. The regimen would also contribute to the prognosis of such patients since it might produce pCR. Since the risk of severe adverse effects is low and the treatment with trastuzumab can be conducted safely as an ambulatory treatment, high patient QOL seems possible. These findings suggest that combination therapy with trastuzumab+paclitaxel is effective as a primary therapy for HER2-positive advanced breast cancer.

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.

Treatment for the decline of ionized calcium levels during peripheral blood progenitor cell harvesting.

BACKGROUND: ACD-A solution containing sodium citrate and citric acid is used as an anticoagulant agent during peripheral blood progenitor cell (PBPC) harvesting, and in rare cases can cause fatal citrate intoxication. The aim of this study was to establish effective methods for stabilizing ionized calcium (ICa) levels during PBPC harvesting. STUDY DESIGN AND METHODS: ICa was measured during 46 apheresis procedures conducted in 26 patients. Four patients in four procedures were infused with calcium gluconate solution before PBPC harvesting; three patients in six procedures were infused with calcium gluconate when symptoms of citrate intoxication appeared; and four patients in five procedures received a continuous infusion. Five patients in five procedures took an isotonic sports drink containing calcium when hypocalcemic symptoms appeared. The ICa level, blood pressure, and pulse rate were measured. RESULTS: ICa declined rapidly from the preapheresis level of 1.081(+/-0.092) mM to 0.937(+/-0.081) mM (13.3%, p < 0.0001) 10 minutes after the start of apheresis and continued to decline until the completion of the procedure. When patients received a continuous infusion of calcium during apheresis, ICa was relatively stabilized. ICa significantly rose (6.1 +/- 3.6%, p < 0.02) within 2 to 5 minutes after oral intake of an isotonic sports drink containing calcium and was maintained within normal range for 31 to 55 minutes. CONCLUSION: An isotonic sports drink containing calcium has a quick stabilizing and a longer maintenance effect on ICa. Thus, we recommend the intake of an isotonic sports drink containing calcium as the easiest and best method for preventing hypocalcemia during apheresis.

[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study in postmenopausal women with advanced or recurrent breast cancer (no. 2)--evaluation of efficacy and safety at the recommended clinical dose CGS20267 Study Group].

In the first part of this late phase II study, we determined the recommended clinical dose of CGS20267 to be 1.0 mg once daily for the treatment of postmenopausal women with advanced or recurrent breast cancer. To further evaluate the efficacy and safety of CGS20267 at the derived or recommended clinical dose, 30 more patients were enrolled in the second part of the study, and were added to the patients treated at 1.0 mg in the first part. As a result of putting the first and second parts together, the objective response rate at 1.0 mg was found to be 38.3%, which was almost equal to that of the early phase II study (40.7%). Drug-related adverse events occurred in 35.4% of the patients at 1.0 mg, and all of the events were of grade 2 or lower. These results demonstrated that CGS20267 1.0 mg once daily is effective and well tolerated in the treatment of postmenopausal women with advanced or recurrent breast cancer.