[Follicle-Stimulating Hormone and Estradiol Levels in Japanese Women Treated with Toremifene and Anastrozole for Two Years - A Retrospective Analysis of Data from a Prospective Randomized Trial].

The criteria for biological postmenopause have not been clearly defined, although determining the menopausal status is crucial for selecting agents for adjuvant endocrine therapy for patients with breast cancer. The long-term effects of adjuvant toremifene(TOR)and anastrozole(ANA)on serum follicle-stimulating hormone(FSH)and estradiol(E2)levels in Japanese women were examined using data from a prospective randomized study that mainly studied serum lipids and bone metabolism for 2 years. The study medications were administered orally daily at 40 mg and 1 mg for TOR and ANA, respectively. Sixty-nine patients were randomly assigned to the TOR group(n=36)or ANA group(n=33). FSH and E2 levels were measured using chemiluminescent immunoassay. The mean ages of the patients in the TOR and ANA groups were 62.5 and 60.0 years, respectively. None of the patients experienced menstruation during the course of the study. The baseline serum FSH level in the TOR group(69.6mIU/mL)decreased to 59.2%, 54.6%, and 50.0% at 6, 12, and 24 months, respectively, after therapy commencement. The FSH levels ranged from 8.6 to 68.1mIU/mL and were<20mIU/mL in 2 patients(9.5%; 8.6 and 14.4mIU/mL). The serum FSH levels in the ANA group did not change markedly over 24months. The baseline serum E2 level in the ANA group(11.6 pg/mL)decreased to 72.4%, 70.7%, and 61.2%at 6, 12, and 24months, respectively, after therapy commencement. The serum E2 level in the TOR group did not change markedly over 24 months. When switching to other endocrine agents as adjuvant therapy for patients with breast cancer treated with TOR, the serum FSH level decreased to half of the preinitiation level, and one-tenth of the FSH levels was<20mIU/mL, while the postmenopausal serum E2 level was maintained.

[Doxifluridine, medroxyprogesterone acetate and cyclophosphamide(DMpC)combination therapy found effective for case of chest wall recurrent breast cancer with bone and pleural metastases].

A 67-year-old woman in poor general condition consulted my clinic with complaints of dyspnea and right chest wall pain. There was a huge and moist ulcer, caused by recurrence and post-radiation, on her right anterior to posterior chest wall. A chest X-ray demonstrated massive pleural effusion. Bone scinti gram showed multiple metastases in the spine, femur and pelvis. Her general condition was so poor that standard chemotherapy was unsuitable. Therefore, the patient was orally administered DMpC(doxifluridine, medroxyprogesterone acetate and cyclophosphamide)combination therapy. The pleural effusion had completely disappeared after 11 weeks, and the elevated serum CA15-3 and CEA value returned to a normal range 13 weeks later. No side effects were observed from this therapy. The patient clinically achieved good QOL in 6 months form this therapy with zoredronic acid administration. DMpC therapy appears to have few side effects and might be an effective treatment option for recurrent breast cancer patients with a poor general health condition.

Effects of toremifene and anastrozole on serum lipids and bone metabolism in postmenopausal females with estrogen receptor-positive breast cancer: the results of a 2-year multicenter open randomized study.

The potential long-term adverse effects on quality of life have to be considered when selecting agents for adjuvant hormonal treatment for postmenopausal patients with estrogen receptor-positive breast cancer. We performed a 2-year multicenter randomized study to assess the differences in the time course effects between toremifene (TOR) and anastrozole (ANA) on serum lipid profiles and bone metabolism. This study assessed the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A1), and apolipoprotein B (Apo B) as lipid profiles and bone-specific alkaline phosphatase (BAP) and the N-telopeptide of type-I collagen (NTX) as bone turnover markers in patients who received daily doses of 40 mg and 1 mg for TOR and ANA, respectively. A decreased serum level of TC, LDL-C, and Apo B was, respectively, observed at 6 months in 6.2, 12.9, and 13.8% of the patients who received TOR compared with the baseline. These decreases were maintained for at least 24 months. These lipid levels were not changed in those who received ANA. In the TOR patients, there was an increase in the serum level of HDL-C and Apo A1 at 6 months in 17.1 and 16.3%, respectively, which was maintained for at least 24 months, whereas these levels were almost stable in the patients who received ANA. Serum BAP decreased by 12.1% at 12 months and further decreased at 24 months and the serum NTX decreased by 22.0% at 6 months, which was maintained for at least 24 months in the patients who received TOR. In contrast, the serum BAP was increased by 26.0% at 6 months and by 29.2% at 12 months and the serum NTX increased by 21.3% at 24 months compared with baseline in those received ANA. However, the serum BAP increase was not significant at 24 months. TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer.

[A case of secondary inflammatory breast cancer with multiple metastases in which operation was possible through letrozole monotherapy].

A 55-year-old woman visited our clinic for rapid swelling of her left breast. The left breast was palpated, and a mass of about 10 cm with thick skin, and multiple lymph nodes in the supraclavicle and axilla were found. PET-CT images showed an increased uptake in her left breast, lymph nodes, spine of TH5, sternum, left lobe of liver, and both lungs. The serum tumor markers were also found to be elevated. A core needle biopsy was performed, and the tumor was diagnosed as secondary inflammatory carcinoma (invasive ductal carcinoma). Immunohistochemical staining showed negative for HER2 protein, but strongly positive for ER and PgR. Letrozole monotherapy administered her starting June, 2008. After 3 months, the metastases showed a notable response, which was subsequently maintained for 19 months. The tumor markers decreased to the normal range after 6 months, and the multiple metastases were not found by PET-CT after 1 year. A radiofrequency ablation operation was conducted on the remaining 3 cm breast cancer. Neoadjuvant endocrine therapy with letrozole was shown to be useful for post-menopausal breast cancer patients with strong hormone receptor expression.

Serum lipid and bone metabolism effects of Toremifene vs. Letrozole as adjuvant therapy for postmenopausal early breast cancer patients: results of a multicenter open randomized study.

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1-2, node metastases (n = 0-3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.

[Results of survey conducted on perioperative chemotherapy and supportive care in primary breast cancer (JBCRG01)].

We carried out a survey of supportive care at institutions that participated in the JBCRG01 study (FEC followed by docetaxel) as neoadjuvant therapy for operable breast cancer. The purpose was to share the information of supportive care for the treatment effect of perioperative intensive chemotherapy among institutions. Appropriate supportive care for nausea, vomiting, edema and febrile neutropenia (FN) is important with respect to the safety of chemotherapy. According to the results of the questionnaire, support from the family and the relationships with doctors, nurses and pharmacists familiar with the chemotherapy were important. The equipment and service for outpatients' cancer chemotherapy center are also important. This multicenter study enhances the exchange of information among institutes. The results of this survey suggest that adequate supportive care makes anthracycline and taxane chemotherapy manageable in the outpatient setting.

Prognostic predictors in breast cancer patients with postoperative 5-fluorouracil-based chemotherapy.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are enzymes involved in the metabolism of 5-fluorouracil (FU). To investigate the relationship of these activities with clinicopathological factors and survival, we measured TS (88 patients) and DPD (122 patients) activities in resected specimens of breast cancer by enzyme assay. Significant difference was found only in TS activity between tumors > or = 20 mm in diameter and those < 20 mm (p = 0.015). There were no significant differences in TS or DPD activity among any other factors. When patients were grouped based on the cut-off levels of TS and DPD activities, 5-year recurrence-free survival rate was 68.8% in the low TS group and 39.7% in the high TS group (p = 0.0081), and 50.8% in the low DPD group and 66.5% in the high DPD group (p = 0.1627). The Cox proportional hazard model demonstrated that in patients in whom we measured TS activity, significant prognostic factors were nodal status and estrogen receptor (ER) status by univariate analysis, and ER status was also significant by multivariate analysis. In patients in whom DPD activity was measured, the significant prognostic factor was ER status by univariate analysis, and ER and Progesterone receptor (PgR) status by multivariate analysis. These results suggested that TS activity, nodal status and hormone receptors may be possible predictors of clinical outcome in breast cancer, but further investigation on prognostic predictors in 5-FU-based chemotherapy is required.

Interim analysis of a phase II trial of cyclophosphamide, epirubicin and 5-fluorouracil (CEF) followed by docetaxel as preoperative chemotherapy for early stage breast carcinoma.

PURPOSE: A single-arm phase II multicenter trial of the combination of cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) followed by docetaxel as neoadjuvant chemotherapy is being conducted by the Japan Breast Cancer Research Group. This report describes an interim analysis of the clinical response and safety of 79 patients who finished preoperative chemotherapy and surgery. PATIENTS AND METHODS: Patients with operable breast cancer received C at 500 mg/m2, E at 100 mg/m2, and F at 500 mg/m2 every 21 days for 4 cycles followed by docetaxel at 75 mg/m2 every 21 days for 4 cycles. RESULTS: Of the 79 patients evaluable for analysis the median age was 46 years (28-59), and 61 patients (77.2%) had T2 tumors. A total of 312 of 316 (98.7%) cycles of CEF and 296 of 312 (94.9%) cycles of docetaxel were administered. Average total cumulative dose was 92% and 95% for CEF and docetaxel, respectively. The rate and grade of edema, neuropathy, arthralgia and myalgia were higher with docetaxel than with CEF. The overall clinical response rate was 70.9%. Breast conserving surgery was performed in 31 of 42 patients (73.8%) with a base-line tumor size of more than 3 cm. CONCLUSIONS: Interim data suggest that CEF followed by docetaxel is an active and tolerable neoadjuvant chemotherapy regimen. A final analysis is planned for 2005.

Analysis of ipsilateral breast tumor recurrences after breast-conserving treatment based on the classification of true recurrences and new primary tumors.

BACKGROUND: Ipsilateral breast tumor recurrences (IBTR) after breast-conserving treatment include two different entities: true recurrence (TR) thought to occur when residual cancer cells grow gradually to detectable size and new primary (NP) thought to be de novo cancer independently arising in the preserved breast. The patients with ipsilateral breast tumor recurrence (IBTR) are potentially at high risk for subsequent distant metastasis, but many studies do not distinguish between these types of recurrence. The aim of this study is to clarify the biological difference between TR and NP, and to show the clinical significance of classifying IBTR into these two types of recurrence. PATIENTS AND METHODS: A total of 172 patients with IBTR after breast-conserving therapy from the cohort of a long-term large scale study (Research of cancer treatment from the Ministry of Health, Labor and Welfare of Japan (no.13-9)) were analyzed. We classified IBTRs as TR or NP based on tumor location and pathological findings. The characteristics of the primary tumors of TR and NP were compared. Survival rates and risk factors of each type of IBTR were examined by the Kaplan-Meier method. The results of salvage surgery were also analyzed. RESULTS: Of the 172 patients, 135 patients were classified as TR and 26 as NP. Eleven cases could not be categorized. The primary tumor of TR was characterized by a high rate of lymph node metastasis (37.8%) and short disease-free interval (mean DFI; 46.6 months) while that of NP showed a rather low lymph node positivity (8.7%) and longer DFI (62.1 months). The risk factors for TR were young age, positive surgical margin, omission of irradiation and positive lymph node metastasis. Those for NP were young age, omission of irradiation and contralateral breast cancer after the primary operation. The 5-year survival rates after IBTR were 71.0% in TR and 94.7% in NP (p=0.022). Salvage operation was performed in 136 IBTRs. Eighty-one patients underwent salvage mastectomy and 55 patients underwent repeat lumpectomy. Five-year survival rates after salvage operation were 75.7% for mastectomy and 84.2% for lumpectomy (N.S.). Twenty percent of patients who underwent repeat lumpectomy developed secondary local relapse within 5 years after salvage treatment. The risk factors for secondary local relapse were analyzed. Limited to cases of IBTR which received radiation therapy after the primary operation, NP was the only factor influencing secondary local relapse by univariate analysis. CONCLUSIONS: TR and NP show clinically quite different features; time to occurrence, characteristics of the original tumor, prognosis and risk factor profile for IBTR were all different. Classifying IBTR as TR or NP can provide clinically significant data for the management of IBTR.

Clinical effects of combination therapy with mitoxantrone, vincristine, and prednisolone in breast cancer.

PURPOSE: We assessed the clinical efficacy and safety of mitoxantrone hydrochloride which has been used as an anticancer drug in our hospital to treat breast cancer patients since 1993. METHODS: A group of 23 patients with breast cancer were given one course of the following regimen every 3 weeks: mitoxantrone hydrochloride (8 mg/m(2) i.v. day 1), vincristine sulfate (1.2 mg/m(2) i.v. day 1), and prednisolone (30 mg orally days 1-7). RESULTS: The response rate was 52.2% including a complete response in four patients, and a partial response in eight patients. Adverse drug reactions included leukocytopenia (78.3%, 18/23 patients), alopecia (30.8%, 7/23), and peripheral neuropathy and generalized fatigue (26.1%, 6/23). In patients responding to the drug regimen, 50% survival was 29 months, and in those not responding it was 12 months. CONCLUSION: Combination treatment with mitoxantrone hydrochloride, vincristine sulfate and prednisolone is an effective treatment for breast cancer.

Evaluation of sensitivity to 5-FU on the basis of thymidylate synthase (TS)/dihydropyrimidine dehydrogenase (DPD) activity and chromosomal analysis in micro tissue specimens of breast cancer.

BACKGROUND: Preoperative assessment of the anticancer drug sensitivity of tumors plays an important role in the selection of therapy. If evaluation of the 5-FU sensitivity of microtissue specimens obtained by techniques such as core needle biopsy could be performed, the addition of fluorouracil to adriamycin and cyclophosphamide may further enhance response rates. In order to evaluate a simple sensitivity test for the anti-tumor agent 5-fluorouracil (5-FU), we examined whether an assay of a small sample could measure mRNA to predict the activities of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In addition, gene abnormalities on chromosomes 1 and 18 corresponding to DPD, TS and the relationships between the gene abnormalities and the amount of mRNA and activity were examined. METHOD: TS and DPD activity were measured using the fluorodeoxyuridine monophosphate ligand binding assay and radio enzymatic assay, respectively, while mRNA levels were assayed by real-time polymerase chain reaction. Chromosome 1 and 18 aberrations were investigated by fluorescence in situ hybridization (FISH) with centromere probes. RESULTS: TS mRNA and TS activity showed a positive correlation (r=0.518, p=0.0017). TS activity and TS mRNA were significantly higher in the nuclear grade 3 group than in the other groups (p=0.04, p=0.0072, respectively). TS activity and mRNA in tumor tissue tended to decrease in the progesterone receptor positive groups (p=0.059, p=0.066, respectively). There was no correlation between DPD mRNA and DPD activity in tumor tissue (r=0.139, p=0.4423). DPD mRNA was measured as 282.88+/-170.68 copies/cell in tumor tissue and 635.88+/-310.04 copies/cell in normal tissue, and was thus significantly higher in normal tissue (p<0.001). CONCLUSIONS: TS mRNA showed a positive correlation with TS activity, suggesting that this method of using small amounts of tissue can replace anti-cancer drug sensitivity tests.

3D imaging of intraductal spread of breast cancer and its clinical application for navigation surgery.

BACKGROUND: To perform optimal tumor resection of breast cancer, preoperative information concerning intraductal spread of cancer (ISC) is very important. METHODS: To detect ISC, three-dimensional (3D) imaging methods including helical CT, MRI, and ultrasound were examined in patients with primary breast cancer by comparison with multi-sliced pathological specimens. RESULTS: The sensitivity of each modality for detecting ISC was 64.7%, 90.2% and 78.6%, and the specificity was 97.1%, 62.9% and 100%, respectively. Subsequently, the potential of each modality for navigation in breast conserving surgery was assessed. Three-dimensional helical CT navigation could reduce the positive rate of the specimen margins, and 3D MRI navigation using a special mapping sheet enabled removal of non-palpable breast cancer without positive margins in 66.7% of patients preliminarily. Real-time 3D ultrasound images correlated with the resected tumor size, with the difference between the two less than 2 cm in 72.7 % of the patients with ISC. CONCLUSION: Three-dimensional images from each modality were reliable enough for diagnosis of tumor spread, and surgical navigation using these images seemed to have potential clinical application for breast conserving surgery. Prospective studies for navigation surgery with more patients are needed.

[A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy].

A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.

[A case of aged advanced breast cancer with multiple lung and pleural metastases responding to exemestane monotherapy].

A 76-year-old woman was diagnosed with advanced breast cancer with bilateral multiple lung and pleural metastases in March 2003. Her CEA and CA15-3 level were 7.6 ng/ml and 98.3 U/l, respectively. However, she refused intensive chemotherapy and chose a hormonal monotherapy with exemestane instead. The patient then did not return to our department for about one year, during which time she continued to take the same medications. When she visited again, CEA and CA15-3 level were reduced to within the normal range, and her multiple lung and pleural metastases were found to have almost completely disappeared upon computed tomography. Exemestane is expected to be an effective agent for the treatment of hormonal receptor-positive postmenopausal woman with life-threatening advanced breast cancer.

[Three-dimentional volumetric interpolated breath-hold magnetic resonance imaging for the diagnosis of breast tumors].

PURPOSE: Three dimensional volumetric interpolated breath-hold examination magnetic resonance imaging(3D-VIBE MRI) has the advantage of improving z-axis resolution, which makes it possible to obtain high quality multi-planar reconstruction (MPR) and 3-D reconstruction images. Using these capabilities of 3D-VIBE MRI, we have attempted to diagnose and evaluate breast tumors for preoperative planning. MATERIALS AND METHODS: One hundred patients with breast cancer and 5 patients with benign breast tumors were scanned by 1.5-T MR imaging, and the findings were compared with pathological findings. Triple-phase contrast-enhanced 3D-VIBE MRI was performed at 20 seconds (early arterial phase), 50 seconds (late arterial phase) and 180 seconds (equilibrium phase) after the beginning of injection of contrast material. Dynamic imaging was performed with 20 ml Gd-DOTA injected at a rate of 3.0 ml/sec. We also attempted to diagnose breast tumor for the detection of the primary lesion, estimation of histologic type, prediction of extensive intraductal components (EIC) and axillary lymph node metastases from breast cancer. RESULTS: (1) The diagnostic accuracy for breast cancer was 96.0% and it was 100.0% for benign disease. (2) The accuracy of the histologic estimation for breast cancer was 56.4%, and it was 83.3% for benign disease. (3) The accuracy of evaluation of ductal spread of breast cancer was 52.4%. (4) The accuracy was 72.4% for lymph node metastasis from breast cancer. CONCLUSION: This method provides useful information about the location of the primary tumor and lymph nodes. 3D-VIBE method is considered especially important for the preoperative evaluation of axillary lymph node status.

Phase II study of 4-weekly capecitabine monotherapy in advanced/metastatic breast cancer.

BACKGROUND: A multicenter, phase II study was conducted to evaluate the efficacy and safety of the Japanese intermittent 4-week regimen of capecitabine in patients with advanced/metastatic breast cancer. METHODS: Fifty patients who had received no more than one prior chemotherapy regimen for advanced/metastatic disease were enrolled from 23 centers and received at least two 4-weekly cycles of capecitabine (828 mg/m² orally twice daily for 3 weeks followed by a 1-week rest period). RESULTS: The overall response rate assessed by the Independent Review Committee (standard population, n = 46) was 28.3% (95% confidence interval 16.0-43.5%), including complete responses in 6.5%. Stable disease was observed in 20 patients and maintained for more than 6 months in 10 patients. The median duration of response in 13 evaluable responders was 5.3 months. Among evaluable patients (n = 47), median time to disease progression was 5.1 months. Median overall survival was 20.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (66%), nausea (26%), stomatitis (22%) and diarrhea (20%). Grade 3/4 treatment-related adverse events were seen in 23 patients (46%). The most common grade 3/4 adverse events were lymphocytopenia (22%), hand-foot syndrome (18%) and hyperbilirubinemia (10%). CONCLUSIONS: Although the target overall response rate was not reached, the Japanese intermittent 4-week regimen of capecitabine was shown to be an effective and well-tolerated first- or second-line therapy for advanced/metastatic breast cancer.

Phase II study of preoperative sequential FEC and docetaxel predicts of pathological response and disease free survival.

Purpose This multicenter phase II study examined the impact of pathological effect on survival after preoperative chemotherapy in Japanese women with early stage breast cancer. Patients and methods Prior to surgery, patients received four cycles of FEC (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2) q3w) followed by four cycles of docetaxel (75 mg/m(2) q3w). Primary endpoint was 3 year disease free survival (DFS) stratified by the absence or presence of Quasi-pCR (QpCR; absence of invasive tumor or only focal residual tumor cells). Secondary endpoints were predictors for QpCR, clinical response, breast conservation rate, and safety. Results Between June 2002 and June 2004, 202 women were enrolled. Among 191 assessable patients, 25% achieved QpCR. With 40 months median follow-up, 3 year DFS was estimated at 91% for all patients. 3 year DFS for patients with QpCR was 98% vs. 89% without QpCR (hazard ratio 0.38 [95% Confidence Interval 0.09-0.84], P = 0.0134). HER2 status and response to FEC were independent predictors of QpCR. The overall clinical response was 75%; 85% of patients achieved breast conservation. Grade 3/4 neutropenia was the most common adverse event, observed in 44% and 35% of patients during FEC and docetaxel, respectively. Treatment related side effects were manageable; there were no treatment related fatalities. Conclusion FEC followed by docetaxel is an active and manageable preoperative regimen for women with early stage breast cancer. QpCR following preoperative chemotherapy predicts favorable DFS. HER2 overexpression and clinical response to FEC predict QpCR.

Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases.

BACKGROUND: The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. METHODS: Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. RESULTS: At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. CONCLUSIONS: Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases.

Crossover trial for lipid abnormality in postmenopausal breast cancer patients during selective estrogen receptor modulators (SERMs) administrations.

The objective of this study was to evaluate the different profiles of serum lipids resulting from the administration of selective estrogen receptor modulators (SERMs). Postmenopausal primary breast cancer patients (n = 197) with node-negative, hormone receptor-positive who were treated at our department or in other related medical institutions from April 1997 through March 2001 were given adjuvant therapy. The adjuvant therapy included 1 year's administration of tamoxifen (TAM) 20 mg or toremifene (TOR) 40 mg. The profiles of serum lipids such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL) and triglyceride (TG) were observed. After 1 year administration TC had significantly decreased (p < 0.001) both in the TAM group and the TOR group, but no significant difference was found between these groups (p = 0.249). HDL had significantly decreased in the TAM group (p < 0.001), while it had significantly increased in the TOR group (p < 0.001), and a significant difference was found between the groups (p < 0.001). TG had significantly increased in the TAM group (p < 0.001) but significantly decreased in the TOR group (p < 0.001). The medication was switched in those who still had abnormal lipid metabolism and given to them for another year. After 1 year from the crossover TC and HDL had increased to the levels of before administration (p < 0.001) and TG had decreased in those (n = 57) whose medication was switched from TAM to TOR. While TC had decreased and TG had increased in those (n = 23) whose medication was switched from TOR to TAM (p < 0.001). The above findings have suggested that TOR provides better profiles of lipid metabolism than TAM.