Effect of adjuvant chemotherapy in patients with ER + /HER2- breast cancer, assessed by propensity score matching: significance of nuclear grade and nodal status.

BACKGROUND: Survival benefits of chemotherapy (CT) differ among patients with estrogen receptor-positive (ER +) breast cancer. This study investigated the survival benefits of CT for ER + and human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) patients by propensity score matching (PSM). METHODS: Patients with stages I-IIIER + /HER2- BC were enrolled in this study. The primary endpoints were 5-year recurrence-free survival (RFS) and overall survival (OS) in the non-CT and CT groups of the selected population matched by PS. The PS was analyzed by a logistic regression model with factors those influence provided indication of chemotherapy [tumor size, nuclear grade (NG), progesterone receptor, and nodal status]. RESULTS: This study enrolled 895 patients between 2000 and 2015. The median follow-up period was 5.7 years. Overall, the 5-year RFS was 94.3% and 90.1% in the non-CT and CT-treated groups, respectively (p = 0.106). The 5-year OS was 97.5% in the non-CT group and 95.6% in the CT group (p = 0.047). Using PSM, 236 patients were selected. After matching, both the 5-year RFS and the 5-year OS were higher in the CT group than in the non-CT group (96.8% vs. 82.7%, p = 0.003 and 100% vs. 91.9%, p < 0.001, respectively). Particularly in the case of the node negative/NG3 and 1-3 node positive/NG2 patients after PSM, the 5-year RFS was significantly higher in the CT group than in the non-CT group (p = 0.041 and p = 0.006, respectively). CONCLUSION: After PSM, CT significantly improved both the RFS and OS of ER + / HER2- BC patients, especially for node negative/NG3 and 1-3 node positive/NG2 patients.

Breast-conserving surgery without radiation in elderly women with early breast cancer.

BACKGROUND AND OBJECTIVES: Irradiation after breast-conserving surgery (BCS) decreases the incidence of ipsilateral breast tumor recurrence (IBTR) and breast cancer-related death. However, daily radiation treatments are burdensome to elderly patients, whose risk of IBTR is relatively low. Since 2001, we have offered BCS without radiation to patients meeting our selection criteria. This study assessed the prognosis of the patients who chose this option. METHODS: Between 2001 and 2014, 203 patients met the selection criteria: aged ≥60 years; pathologically node-negative, hormone-positive breast cancer; a negative surgical margin; and no lymphovascular invasion. Among these patients, 84 and 119 underwent BCS with or without radiation, respectively. IBTR, overall survival (OS), and breast cancer-specific survival (BCSS) were evaluated. RESULTS: The median follow-up duration was 6.2 years. There were no significant differences in tumor size or the number of patients with adjuvant therapy between the groups. The 5-year IBTR rates were 0.9% and 1.6% in the non-irradiated and irradiated groups, respectively (p = 0.308). The 5-year OS rates were 94.1% and 98.7% (p = 0.391). Similarly, the 5-year BCSS rates were 97.2% and 98.7% (p = 0.812). CONCLUSION: It is suggested that the omission of irradiation could be an option for elderly breast cancer patients who satisfy our criteria.

Long-term effect of exemestane therapy on bone mineral density supported by bisphosphonates: Results of 5-year adjuvant treatment in postmenopausal women with early-stage breast cancer.

PURPOSE: Unlike anastrozole, the effect of long-term exemestane (EXE) therapy on bone mineral density (BMD) is still unknown. We assessed changes in BMD from baseline to 5 years of EXE treatment. METHODS: Postmenopausal women with endocrine-responsive breast cancer receiving EXE as adjuvant therapy were enrolled in this study. EXE was administered for 5 years. The BMD of the lumbar spine (LS) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry at baseline and after 6 months and 1, 2, 3, 4, 5 and 6 years. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis with a T-score of -2.5 or lower. RESULTS: Eighty-one patients were enrolled in the study between 2005 and 2010. The median follow-up period was 54.9 months. Forty-two patients were administered Bis. Overall, the BMD of the LS increased by 7.3% from baseline and that of the FN increased by 3.4% with 5 years of EXE treatment. At the sixth year (i.e. 1 year after the treatment), BMD of the LS increased by 7.2% and that of the FN increased by 5.7%. Furthermore, the BMD of the FN increased by 12.0% in patients treated upfront with Bis and by 1.2% in those not treated with Bis (P = 0.0262). Fractures developed in nine patients (11.1%) and seven (8.6%) had fragility fractures. CONCLUSION: Oral Bis improves BMD of the FN in patients with osteoporosis. Five-year EXE treatment with proper addition of Bis helps maintain the BMD of the LS and FN at the sixth year.

[Ethinylestradiol Following Everolimus plus Exemestane Was Effective in Postmenopausal Endocrine-Responsive Metastatic Breast Cancer - A Case Report].

A 71-year-old woman diagnosed with left breast cancer underwent mastectomy and axillary dissection in 1987. Pathological findings showed invasive ductal carcinoma that was ER and PgR positive and HER2 negative.5 -FU and tamoxifen were administered for 2 years as adjuvant therapy.Bone metastasis was found in 2002, and endocrine therapy was started, using anastrozole, exemestane, letrozole, medroxyprogesterone acetate, and fulvestrant.However, liver, lung, pleural, penetiral, and lymph-node metastases were observed, and the following chemotherapy regimen was administered: CAF, capecitabine, paclitaxel, vinorelbine, gemcitabine, methotrexate plus mitomycin C, and eribulin.Then, estrogen therapy with ethinylestradiol( EE2)was started in December 2013.T he pleural effusion disappeared and the liver metastases were reduced.After 11 months of progression-free survival(PFS), regrowth of the liver metastases was seen.Thus, everolimus plus exemestane was administered, and approximately 8 months of PFS was obtained.Therefore, both EE2 and everolimus are effective therapy even for heavily pretreated metastatic breast cancer.

The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer.

PURPOSE: The administration of aromatase inhibitors is associated with bone loss in postmenopausal women. We assessed changes in bone mineral density (BMD) from baseline to 60 months of treatment in patients receiving anastrozole as initial adjuvant therapy. METHODS: Postmenopausal women with hormone receptor-positive breast cancer receiving anastrozole as adjuvant therapy at our center since 2004 were enrolled in this study. BMD was assessed by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24, 36, 48 and 60 months. Oral bisphosphonate (Bis) treatment was initiated when patients were diagnosed with osteoporosis having a T-score of -2.5 or lower. RESULTS: Fifty-five patients were enrolled in the study between 2004 and 2011, and the mean follow-up period was 53.6 months. Thirty-five patients were administered Bis (risedronate in 27 patients, alendronate in 8 patients). After 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (LS) and BMD decreased by 1.5% at the femoral neck (FN). However, BMD increased by 1.9% at the LS and BMD decreased by 1.5% at the FN for 60 months of treatment. In patients treated with upfront Bis (n = 19), 5.4% BMD increase from baseline was noted at the LS whereas in those without Bis (n = 21) BMD decreased by 4.3% from baseline within 24 months (P < 0.0001). Fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility fracture. CONCLUSIONS: Upfront treatment of Bis with anastrozole significantly increased BMD at the LS and an optimal use of Bis would not increase bone fractures. TRIAL REGISTRATION: UMIN0000017571.

Prevalence and differentiation of hereditary breast and ovarian cancers in Japan.

BACKGROUND: We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan. MATERIALS AND METHODS: Our study of BRCA1/2 collected data at eight institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March 2012. RESULTS: Among 260 proband cases, 46 (17.7 %) were positive for BRCA1, and 35 (13.5 %) were BRCA2-positive. Therefore, the total pathological mutation rate was 30.7 %. Pathology data after breast surgery were obtained from 37 cases of BRCA1 mutation, 23 (62.2 %) of which were triple negative (TN). On the other hand, 29 cases (82.9 %) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found two cases of large deletion detected by multiplex ligation-dependent probe amplification. One was an entire deletion of exon 20 and the lacked exons 1-9. TN with a family history of ovarian cancer was 11/20 (55 %). TN under 40-year-old (y.o.) 15/23 (65.2 %) and TN with one or more breast cancers in family history 17/32 (53.1 %) showed higher incidences of BRCA1 mutation. CONCLUSION: Hereditary breast and ovarian cancer (HBOC) may have nearly the same prevalence in Japan as in the US or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to develop risk models for BRCA1/2 carriers in Japan.

A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients.

PURPOSE: To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye. METHODS: Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5 mg and SB 15 mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device. RESULTS: We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0-5) for SB alone and 2.2 (1-6) for the combination method. The SLN identification rate was 95.7 % for SB alone and 100 % for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p = 0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8 %) with SB alone and in no patients with the combination method. CONCLUSIONS: ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available.

[Responses to primary systemic therapy for breast cancer as assessed by hormone receptor and HER2 status].

The aim of this study was to investigate responses to primary systemic therapy (PST) for breast cancer, by hormone receptor (HR) and HER2 status. This study included 107 women with T>3 cm and/or node-positive breast cancer who received PST at this department between March 2004 and January 2009. Treatment with epirubicin and cyclophosphamide (EC) followed by docetaxel (DTX) therapy was undertaken up to December 2005. From January 2006, EC followed by weekly paclitaxel (PTX) with or without trastuzumab (T) therapy was performed. From February 2008 and thereafter, the EC-PTX-T therapy was continued in HER2-positive patients, whereas the preceding EC-DTX therapy was administered in HER2-negative patients. Clinical responses of the 107 patients (56 were treated with EC-DTX, 37 with EC-PTX, and 14 with EC-PTX-T) were as follows: CR was achieved in 18 patients, PR in 74 patients, SD in 12 patients, and PD in 3 patients, with a response rate of 86. 0%. Histologically, 14 patients(13. 2%)had pathological CR(pCR)in a limited sense. When these patients were further divided according to HR status, those positive for both estrogen receptor (ER) and progesterone receptor (PgR) accounted for 1. 8%, those positive for ER and negative for PgR accounted for 5. 3%, and those negative for both ER and PgR accounted for a significantly higher percentage of 40. 0% (p<0. 0001) . By HER2 status, pCR was achieved at a significantly higher rate (47. 8%) of HER2-positive patients, compared to 3. 6% of HER2-negative patients (p<0. 0001). Common adverse events included Grade 3/4 leukopenia (57. 9%), neutropenia (67. 3%), and Grade 3 febrile neutropenia (11. 2%). The results show that a higher pCR rate can be expected after PST in HR-negative patients and HER2-positive patients. HER2-positive patients would particularly benefit from preoperative anthracycline chemotherapy followed by a taxane combined with trastuzumab.

A phase II study of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without trastuzumab as primary systemic therapy in locally advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the activity and toxicity of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without trastuzumab as primary systemic therapy in locally advanced breast cancer. PATIENTS AND METHODS: Patients with T2-4 (>3 cm) or N1-3 breast cancer received epirubicin (100 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every three weeks for four cycles followed by paclitaxel (80 mg/m(2)) every week for twelve cycles. Trastuzumab (initially 4 mg/kg, then 2 mg/kg) was added to paclitaxel in HER2-positive patients. The primary endpoint was the pathological complete response (pCR) rate in the breast and axilla, and secondary endpoints were the breast-conserving rate and toxicity. RESULTS: Forty-three patients were enrolled into this study and 3 patients withdrew. The pCR rate was 20.0% (95% confidence interval, 10.5-34.8%). Patients with HER2-positive tumours had a significantly higher pCR rate than the others (62.5% vs. 9.4%; p=0.0008). Twenty-four patients (60.0%) underwent breast-conserving surgery. Grade 4 neutropenia was recorded in 30.0% of the patients, and febrile neutropenia occurred in 7 patients (17.5%). CONCLUSION: Epirubicin and cyclophosphamide followed by weekly paclitaxel, either with or without trastuzumab, was an active and well-tolerated treatment for locally advanced breast cancer.

Successful neoadjuvant therapy with trastuzumab, paclitaxel and epirubicin for an elderly patient with inflammatory breast cancer.

A 75-year old woman presented with diffuse left breast enlargement, redness, edema, and a firm palpable lymph node with skin fixation in the left axilla. The tumor was diagnosed as invasive ductal carcinoma with a strongly positive human epidermal growth factor receptor 2 (HER2) score (3+). She was diagnosed as having inflammatory breast cancer (IBC) (T4d N2M0, stage IIIb). The patient received primary systemic chemotherapy with 4 courses of epirubicin 75 mg/m(2) and cyclophosphamide 500 mg/m(2) every three weeks, then 12 courses of paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (initially 4 mg/kg) weekly. Six months after the start of chemotherapy, a left modified radical mastectomy with axillary dissection was performed. No cancer cells in the breast specimen and no metastases to the axillary nodes were observed, so the therapeutic effect was determined as a pathological complete response (pCR). This report suggests that combination therapy with epirubicin and cyclophosphamide followed by trastuzumab and paclitaxel was useful for HER2-positive IBC.

Epirubicin and cyclophosphamide followed by docetaxel as primary systemic chemotherapy in locally advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the activity and toxicity of epirubicin and cyclophosphamide (EC) followed by docetaxel as primary systemic chemotherapy (PST) in locally advanced breast cancer. PATIENTS AND METHODS: In this phase II trial, 46 patients with locally advanced breast cancer (T > 3 cm or N > 1) received epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks for four cycles, followed by docetaxel (70 mg/m2) every 3 weeks for four cycles. Primary endpoints were pathological and objective response in the breast and axilla, and toxicities. RESULTS: The clinical response rate was 80.4% (95% confidence interval, 68.9-91.9%). Pathological response evaluation revealed 6 complete responses (CR: 13.0%). Patients with ER-negative tumors had a significantly higher rate of pathological CR than the others (33.3% vs. 3.2%; p = 0.0105). Febrile neutropenia occurred in 4 patients (8.7%). CONCLUSION: EC followed by docetaxel is an active and well-tolerated treatment as PST for locally advanced breast cancer.

The combination of epirubicin plus docetaxel as neoadjuvant chemotherapy in locally-advanced breast cancer.

BACKGROUND: The purpose of this study was to evaluate the activity and toxicity of epirubicin plus docetaxel as neoadjuvant chemotherapy for locally advanced breast cancer. PATIENTS AND METHODS: In this single-center, phase II trial, twenty-one patients with locally advanced breast cancer (T>3 cm or N>1) received epirubicin (70 mg/m2) and docetaxel (60 mg/m2) on Day 1 of each cycle for up to 6 cycles. RESULTS: Clinically complete responses (CR) were observed in 5 patients and partial responses were observed in 14 patients. The clinical response rate was 90.5% (95% confidence interval, 78.0-99.9). Eleven patients (52.4%) underwent breast conserving surgery. Pathological response evaluation revealed 2 CR (9.5%). Grade 4 neutropenia was recorded in 81.0% of the patients and febrile neutropenia occurred in 1 patient. CONCLUSION: The combination of epirubicin plus docetaxel was an active and well-tolerated treatment for locally-advanced breast cancer.

Formation characterization of hydroxyapatite on titanium by microarc oxidation and hydrothermal treatment.

Microarc oxidation (MAO) was performed on titanium in an electrolyte containing calcium glycerphosphate (Ca-GP) and calcium acetate (CA) using a direct current power supply. It was found that the MAO method is suitable forming a ceramic coating containing Ca and P using titanium, and that films display a porous and rough structure on their surface. Samples with a Ca/P ratio of 1.71 were hydrothermally treated in water solution whose pH was adjusted to 7.0-11.0 by adding NaOH at 190 degrees C for 10 h in an autoclave. Hydroxyapatite crystals were precipitated on the film surface after the hydrothermal treatment, and the amount of hydroxyapatite precipitated increased with increasing pH of water solution. The oxide film composition was semiquantitatively analyzed with an electron probe microanalyzer. The microstructures on the sample surfaces were observed by scanning electron microscopy before and after the hydrothermal treatment. The topography of the oxide film was imaged with an atomic force microscope. Its cross section was observed by scanning electron microscopy after being coated with a thin Au film. The surface structures of the films were analyzed by X-ray diffraction.

IV-DSA is a new diagnostic tool for axillary lymph node metastasis in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of this study is to know whether intravenous digital subtraction angiography (IV-DSA) is useful to detect axillary lymph node metastasis of breast cancer and to evaluate the anigiogenesis of lymph nodes in the axilla. PATIENTS AND METHODS: Forty three primary breast cancer patients (N0: 26 cases, N1: 5 cases, N2: 2 cases) who underwent IV-DSA between January and November 2000 were included in the study. Infinix CB apparatus (Toshiba, Japan) was used to collect IV-DSA images and when a mass became stained in the axilla, it was considered to be metastatic. The angiogenesis was studied by examining microvessel density (MVD) after lymph node immunostaining for factor VIII. Primary tumor was detected by IV-DSA in all 43 cases. RESULTS: Axillary lymph node metastases were detected by IV-DSA in 34.9% of cases (15/43), and by pathology in 37.2% (16/43). The sensitivity, specificity, and accuracy of the diagnostic method were 75.0% (12/16), 88.9% (24/27), and 83.7% (36/43), respectively. MVD, calculated after immunostaining for factor VIII, was significantly lower in the in metastatic region of lymph nodes identified by DSA (88.5 +/- 35.0) than in metastasis-free lymph nodes (141.1 +/- 34.0, P < 0.0001). CONCLUSIONS: IV-DSA is useful in the diagnosis of axillary lymph node metastasis of breast cancer. Our results suggest that the primary factors involved in the mechanism of DSA display may be different from high/low MVC values.

[Clinical usefulness of UFT and cyclophosphamide as salvage chemotherapy for patients with metastatic breast cancer].

A combination of UFT and cyclophosphamide (CPA) was orally administered to 12 women with previously-treated advanced or recurrent breast cancer. The daily dose of UFT was 400 to 600 mg for tegafur and 100 mg for CPA. Treatment was given orally for 2 weeks followed by 1 week of no treatment, or for 5 days followed by 2 days of no treatment. The response to treatment was CR in 2 patients, PR in 2, and long NC in 2. The response rate was 33.3%, and the clinical benefit 50%. Adverse reactions comprised grade 3 diarrhea requiring admission in 1 patient, over grade 1 leukopenia in 5 patients, and thrombocytopenia in 2 patients. These reactions could be controlled. The combination of UFT and CPA can be given on an outpatient basis and is considered a useful regimen for the management of previously-treated advanced or recurrent breast cancer.

Expression of twist and wnt in human breast cancer.

Twist, a transcription factor of the basic helix-loop-helix class, has been suggested to have oncogenic properties. We reported Twist expression was regulated by Wnt/beta-catenin signaling and that both Wnt-1 and Twist could contribute to mammary tumorigenesis. The aim of this study was to demonstrate the expression of Twist, Wnt-1 and Wnt-2 in human breast cancer tissue. We examined the expression in patients with breast cancer by RT-PCR and immunohistochemistry. RT-PCR of twenty-three pairs of cancer and normal breast tissue revealed that Twist was up-regulated in 69.6% (16/23) of the cancer lesions and 21.7% (5/23) of the normal breast tissues. Wnt-2 was up-regulated in all of the cancer lesions and 13.0% (3/23) of the normal breast tissues, whereas Wnt-1 was expressed in both the cancer and normal breast tissues of the five cases examined. Immunohistochemical analyses revealed that Twist was positively expressed in 52.2% (12/23) of the cancer lesions and 34.8% (8/23) of the normal breast tissues. Twist and Wnt-2 are highly expressed in breast cancer tissue, suggesting that both molecules could play important roles in mammary carcinogenesis.

Outcome of breast-conserving therapy in the Tokyo Women's Medical University Breast Cancer Society experience.

BACKGROUND: The results of BCT in Japanese women have not been fully evaluated. The Tokyo Women's Medical University Breast Cancer Society initiated BCT protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and identify prognostic factors. METHODS: The study population comprised 348 patients (353 breasts) with UICC clinical stage 0,I or II breast cancer, for whom wide excision (n= 294), quadrantectomy (n= 56) and tumorectomy (n= 3) were performed. The final pathological margin states were positive in 102 breasts (cancer cells remained within 5 mm of the surgical margin). The whole breast was irradiated to a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with negative surgical margins. The patients with positive or close margins received 48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All but 2 patients received a radiation boost to the tumor bed and all tumor beds were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240 cases. The median follow-up time was 4.3 years. RESULTS: The 5-year overall, cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%, respectively. Recurrence was observed in 29 patients including 11 patients with loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom were premenopausal. The 5-year local control and loco-regional control rates were 98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant prognostic factor for disease-free survival. No severe morbidity has been observed. Cosmetic results were excellent or good in 73% of patients. CONCLUSION: Our BCT protocols provide a high rate of local control and good cosmetic outcome. Pathologic margin status was not a major prognostic factor for local recurrence. Long term follow-up is required to reach a definite conclusion on optimal BCT protocols.

A case of diabetic mastopathy with multiple lesions mimicking breast cancer.

We report a case of diabetic mastopathy with multiple unilateral lesions in an insulin dependent patient. The patient was a 62-year-old woman with two hard tumors in the right breast, who had been treated with insulin for diabetes mellitus. Mammography revealed a highly dense tumor in the right breast, while ultrasonography showed two irregular hypoechoic lesions with marked posterior acoustical shadowing, suggesting scirrhous carcinoma. On magnetic resonance imaging the two lesions had slightly heterogeneous enhancement. Aspiration breast cytology showed insufficient cellular material for evaluation. Excisional biopsy was performed because the patient wanted confirmation and treatment. Fibrosis with dense lymphocytic infiltration around the lobules and ducts was diagnosed histopathologically. These findings were compatible with diabetic fibrous mastopathy. Although this disease is thought to be a diabetes-induced reaction of autoimmune origin, multiple lesions are rare. This is the first case of unilateral multiple lesions of diabetic mastopathy.

Expression of cyclooxygenase-2 in malignant and benign breast tumors.

Cyclooxygenase-2 (COX-2) is reported to play an important role in carcinogenesis. We examined COX-2 expression in patients with breast cancer and benign breast tumors. Immunohistochemical staining revealed a high level of COX-2 expression in malignant lesions of invasive ductal carcinoma (IDC) at a rate of 40% and a low level of expression in 15% of adjacent normal-appearing breast epithelia. Similarly, in ductal carcinoma in situ (DCIS), a high level of COX-2 expression was found in 80% of malignant lesions and a low level of expression in 50% of normal epithelia. Reverse transcriptional polymerase chain reaction (RT-PCR) performed in 7 of these cases disclosed that COX-2 expression was restricted to the malignant lesion. Further, all 10 cases of fibroadenoma and 10 cases of intraductal papilloma, both of which are benign tumors, had a high level of COX-2 expression. When overexpression of COX-2 was analyzed in relation to the clinicopathological features of the patients, no characteristic correlation was noted. Our results demonstrated that COX-2 is expressed in mammary tissue during tumorigenesis of the breast gland, suggesting that the cyclooxygenase isoenzyme may be a target for the prevention and treatment of breast cancer.

Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer.

BACKGROUND: A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer. METHODS: Docetaxel was administered by intravenous drip infusion over 60 minutes, followed by intravenous bolus injection of CPA every 3-4 weeks. The dosage of docetaxel/CPA was 40/200, 40/400, 50/400, or 60/400 mg/m(2)/day. RESULTS: Fifteen patients were enrolled and received a total of 33 cycles of the combined therapy. The dose limiting toxicities (DLTs) were leukopenia, neutropenia and thrombocytopenia. The MTD was estimated to be docetaxel 60 mg/m(2) in combination with CPA 400 mg/m(2) per day. Plasma clearance of both drugs was similar regardless of dose. The recommended doses of docetaxel/CPA for a phase Utrial are 50/400 mg/m(2)/day every 3-4 weeks. CONCLUSION: The MTD of this combined therapy was docetaxel 60 mg/m(2) and CPA 400 mg/m(2). Neutropenia and leukopeina were common and severe. It is important to stress the need for modification of the dosing scheme.