Staged Prosthetic Reconstruction with Fat Grafting for Severe Depressive Breast Deformation after Breast-conserving Therapy.

Breast-conserving therapy, where radiotherapy is performed after partial mastectomy, is a widely used surgical method that can preserve most of the breast tissue without increasing the recurrence rate of breast cancer. However, without reconstruction, asymmetry of the breast occurs due to the tissue defect and radiation fibrosis, producing in poor cosmetic results. In this case study, we performed staged prosthetic breast reconstruction combined with fat grafting for severe depressive deformation of the breast after breast-conserving therapy. The first surgery involved insertion of a tissue expander and fat grafting, second surgery was the reduction of injected saline volume and fat grafting, and third surgery involved exchange for an implant and fat grafting. The skin in the depressed area, which had atrophied, became soft and flexible; deformation was also improved, and the patient was satisfied with the aesthetic outcome. It is expected that fat grafting will fertilize and qualitatively improve the damaged tissue due to irradiation, reducing the complications related to the tissue expander and implant. We believe that it will be possible to correct a breast deformity after breast-conserving therapy using a tissue expander and implant, which had not been considered as a solution. The results showed that the present method can be an option for delayed reconstruction after breast-conserving therapy.

Vertical breast measurement in East Asian women: A guide for mastopexy and reduction to form nonptotic breasts in unilateral prosthetic breast reconstruction.

BACKGROUND: Following unilateral breast cancer surgery, mastopexy and reduction of the unaffected breast are often performed to obtain symmetrical breasts. The use of implants in breast reconstruction results in a nonptotic breast. To achieve symmetry following the procedure, the unaffected side should be nonptotic too. However, no study has yet reported any indices for the design of mastopexy and reduction in this direction. We present a new method of preoperative design that uses vertical breast measurements to form nonptotic breasts according to individual breast shapes. METHODS: We performed vertical breast measurements of the unaffected breasts of 193 patients scheduled to undergo surgery for unilateral breast cancer. The vertical base dimension (VBD) and vertical surface dimension (VSD) of the ptotic and nonptotic breasts and the height of the nipple in the nonptotic breast were measured in centimeters. RESULTS: The borderline between ptotic and nonptotic breasts was expressed using the formula VSD = 1.13 × VBD + 1.86. The height of the nipple in nonptotic breasts was 0.8 times the distance between the sternal notch and lowest point of the inframammary fold on the midline. From these findings, we formulated a new method for forming a nonptotic breast from a ptotic breast using an inverted T design. CONCLUSION: These results can be used for the design of mastopexy and reduction when forming a nonptotic breast on the unaffected side. These procedures can be performed without significantly lifting the nipple-areolar complex if required during unilateral prosthetic breast reconstruction.

[A patient of the acute phase with severe ischemic enteritis accompanied by portal venous gas who survived conservative treatment].

A 90-year-old man had chest pain. Portal venous gas and ileal edema were noted on abdominal CT, and severe ischemic enteritis was diagnosed. Conservative treatment was performed because of circulatory failure. Later, ileus slowly developed, and ileal stenosis was noted on contrast imaging through an ileus tube. Laparoscopy-assisted small bowel resection was performed and achieved remission. Emergency surgery is performed for portal venous gas in acute celiopathy because it may result in intestinal necrosis, but it is also necessary to consider conservative treatment for maintaining mesenteric blood flow in cases difficult to treat by surgery.

Long-term follow-up results of breast cancer patients with sentinel lymph node biopsy using periareolar injection.

BACKGROUND: Areolar injection for sentinel lymph node biopsy (SLNB) in breast cancer surgery has been adopted by many institutions. However, only one study has reported the follow-up results for patients whose SLNB was performed with this injection method alone. METHODS: Three hundred eighty patients with breast cancer underwent SLNB with periareolar injection of both blue dye and radiotracer. The follow-up consisted of a physical examination every 3 months and annual mammography. RESULTS: Of 380 patients with SLNB, 261 were found to have negative sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39 months (range 13-74), 2 of the 261 patients developed axillary recurrence for an axillary relapse incidence of .77%. Five-year distant disease-free survival was 96.9%, and overall survival was 99.4%. CONCLUSIONS: The incidence of axillary recurrence for the areolar injection method was low and consistent with that reported in other observational studies using other injection methods.

Good response to paclitaxel predicts high rates of pathologic complete response for breast cancer patients treated preoperatively with paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide.

OBJECTIVE: Predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy for breast cancers have been studied extensively. Here, we focused on reduction rate after paclitaxel administration for prediction of pCR to paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). METHODS: This study included 115 patients with tumors > or =3.0 cm or with node-positive disease who were treated preoperatively with paclitaxel (80 mg/m(2), once a week, 12 cycles) followed by FEC (500/75/500 mg/m(2), every three weeks, 4 cycles). Reduction rate was measured with magnetic resonance imaging. RESULTS: Tumor size (< or =5.0 cm) (p = 0.014), estrogen receptor (ER) negativity (p = 0.013), and human epidermal growth factor receptor 2 positivity (p = 0.020), but not histologic type, histologic grade, or progesterone receptor, were significantly associated with pCR, while association of reduction rate > or =80% was highly significant (p = 0.0003). Multivariate analysis identified negative ER (p = 0.022) and reduction rate (p = 0.003) as independent predictors of pCR. Finally, patients with reduction rate > or =80% showed a significantly higher favorable outcome (p = 0.014) than others. CONCLUSIONS: Good response (reduction rate > or =80%) to paclitaxel seems to be a clinically useful predictor of pCR as well as a favorable prognosticator for patients treated preoperatively with paclitaxel followed by FEC.

Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers.

PURPOSE: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro, but their clinical significance remains to be clarified. The aim of this study was to investigate whether cancer stem cells were clinically significant for resistance to chemotherapy in human breast cancers. EXPERIMENTAL DESIGN: Primary breast cancer patients (n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44(+)/CD24(-) tumor cells or ALDH1-positive tumor cells were considered stem cells. RESULTS: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44(+)/CD24(-) tumor cell proportions and pCR rates. Changes in the proportion of CD44(+)/CD24(-) or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR. The proportion of ALDH1-positive tumor cells increased significantly (P < 0.001) after neoadjuvant chemotherapy, but that of CD44(+)/CD24(-) tumor cells did not. CONCLUSIONS: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44(+)/CD24(-), play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker than CD44(+)/CD24(-) for the identification of breast cancer stem cells in terms of resistance to chemotherapy.

Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression.

Recently, aldehyde dehydrogenase (ALDH) 1 has been identified as a reliable marker for breast cancer stem cells. The aim of our study was to investigate the clinicopathological characteristics of breast cancers with ALDH1+ cancer stem cells. In addition, the distribution of ALDH1+ tumor cells was compared on a cell-by-cell basis with that of estrogen receptor (ER)+, Ki67+, or human epidermal growth factor receptor type 2 (HER2)+ tumor cells by means of double immunohistochemical staining. Immunohistochemical staining of ALDH1 was applied to 203 primary breast cancers, and the results were compared with various clinicopathological characteristics of breast cancers including tumor size, histological grade, lymph node metastases, lymphovascular invasion, ER, progesterone receptor, HER2, Ki67, and topoisomerase 2A as well as prognosis. Immunohistochemical double staining of ALDH1 and ER, Ki67, or HER2 was also carried out to investigate their distribution. Of the 203 breast cancers, 21 (10%) were found to be ALDH1+, and these cancers were significantly more likely to be ER- (P = 0.004), progesterone receptor- (P = 0.025), HER2+ (P = 0.001), Ki67+ (P < 0.001), and topoisomerase 2A+ tumors (P = 0.012). Immunohistochemical double staining studies showed that ALDH1+ tumor cells were more likely to be ER-, Ki67-, and HER2+ tumor cells. Patients with ALDH1 (score 3+) tumors showed a tendency (P = 0.056) toward a worse prognosis than did those with ALDH1- tumors. Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are characterized by ER-, Ki67-, and HER2+.

Incidence of joint symptoms and bone fractures in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole.

PURPOSE: Incidence of joint symptoms and bone fractures as well as changes in bone mineral density (BMD) in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole were investigated to determine whether there is an ethnic difference from Caucasian patients in the incidence of these adverse events of anastrozole. METHODS: Adjuvant anastrozole was used to treat 348 postmenopausal breast cancer patients for a median period of 22 months. Adverse events of anastrozole including joint symptoms, loss of BMD, and bone fracture were investigated by means of chart review. RESULTS: Joint symptoms developed in 96 (27.5%) patients. Age (younger than 65) and prior chemotherapy was strongly associated with an increased risk of joint symptoms. Annual fracture incidence was 0.86 and 0.85% and lumbar BMD decreased by 1.3 and 2.8% at 1 and 2 years, respectively. In comparison, the ATAC trial reported corresponding figures of 2.0 and 2.7 and of 2.2 and 4.0%. CONCLUSION: Incidence and risk factors of joint symptoms are similar for Japanese and Caucasian patients, but the former tend to show a smaller decrease in BMD and a lower incidence of bone fractures, probably due to ethnic difference in the hormonal milieu.

Potential of reduction in total tumor volume measured with 3D-MRI as a prognostic factor for locally-advanced breast cancer patients treated with primary chemotherapy.

For accurate assessment of the response to primary chemotherapy (PCT) for locally advanced breast cancer, we measured reduction in total tumor volume (TTV) by using three-dimensional magnetic resonance imaging (3D MRI), and examined the relationship between this reduction and patient prognosis. Fifty-one patients with locally advanced breast cancer were treated with four cycles of docetaxel (60 mg/m(2)) before surgery. Tumor size was measured with calipers, ultrasonography (US) and conventional two-dimensional (2D) MRI before and after chemotherapy. TTV was measured with 3D MRI. These and other clinicopathological parameters were statistically analyzed to determine the prognosis for the patients. Median follow-up time was 46 months (1-64 months). Of the 51 patients, 25 developed distant recurrences. Patients whose TTV decreased by 75% or more after PCT showed significantly better prognosis than others, while tumor size measured with calipers, US and 2D MRI showed no significant relationship with patient prognosis. Of the clinicopathological parameters, only reduction in TTV and histological grade showed a significant association with distant recurrence-free survival (p = 0.03 and 0.02, log-rank test), while stepwise multivariate Cox's proportional hazards analysis identified TTV as the strongest independent prognostic factor. Reduction in TTV measured with 3D MRI can be a useful prognostic factor for patients with locally advanced breast cancer treated with PCT.

Cosmetic outcome and patient satisfaction after skin-sparing mastectomy for breast cancer with immediate reconstruction of the breast.

PURPOSE: We conducted a retrospective study to assess the safety, cosmetic outcome, and patients' satisfaction after skin-sparing (SSM) and nipple-sparing mastectomy (NSM) for breast cancer with immediate reconstruction of the breast (SMIBR). METHODS: The subjects were patients, who underwent SMIBR, breast-conserving surgery (BCS), and total mastectomy (MST) between 2000 and 2004 at Osaka University Hospital. Cosmetic outcome was estimated by 4 reviewers by scoring postoperative photographs of the patients. Patient satisfaction was evaluated with a questionnaire for assessment of quality of life for Japanese breast cancer patients. RESULTS: Of the 74 patients who had undergone SMIBR, 4 developed local recurrences (5%). The local recurrence rate for SMIBR patients was greater than that for BCS (4/178) and MST (3/178, P = .10). The distant recurrence rate was similar for all three types of patients (5% for SMIBR, 5% for BCS, and 9% for MST). The median averaged score by 4 reviewers for the estimated cosmetic outcomes was 7.8 for the SMIBR and 7.5 for the BCS group (P = .20), and for age-adjusted patients, the corresponding scores were 8.2 and 8.0 (P = .70). There was no difference in cosmetic outcome between the SSM and NSM subgroups (P = .09). Average scores for patient satisfaction (social activity, physical aspects, and general condition) were the same for the 3 groups. For body image, the BCS and SMIBR groups had higher scores than the MST group (p < 0.05). Average scores for questions relating to bodily pain and sexual aspects were higher for the BCS than the MST group, but were not different between SMIBR and BCS groups. Similar trends for the 3 groups were observed when patients were divided into subgroups by tumor size or axillary dissection. CONCLUSIONS: SMIBR is safe with a comparatively low local recurrence rate and the same distant recurrence rate as for BCS and MST. Moreover, it results in objective cosmetic outcome and patient satisfaction as good as those for BCS, and greater patient satisfaction with body image than that for MST.

Quantitative assessment of mammographic density and breast cancer risk for Japanese women.

We conducted a case-control study to examine the relationship between breast density (BD) on mammography and breast cancer risk for postmenopausal Japanese women. The mammograms (205 cases and 223 controls) were classified by two doctors employing Wolfe's classification and used to measure BD with original computer software. A weak relationship between breast cancer risk and the parenchymal pattern of Wolfe's classification was found. The BD measured with the computer software, however, showed a significant relationship with breast cancer risk. Analysis after adjustment for epidemiologic factors showed that women in the quintile with the highest BD had a 3.02 times higher risk of breast cancer than those in the quintile with the lowest density. Since mammographic BD is clearly associated with breast cancer risk for postmenopausal Japanese women, our software can be expected to become a useful tool for objective risk assessment of breast cancer.

Preoperative evaluation of residual tumor extent by three-dimensional magnetic resonance imaging in breast cancer patients treated with neoadjuvant chemotherapy.

The purpose of this study was to evaluate the usefulness of three-dimensional magnetic resonance imaging (3D MRI) for the preoperative assessment of residual tumor extent in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Thirty-eight breast cancer patients treated with NAC containing taxane and/or anthracycline for 3-6 months were enrolled in this study. Tumor size was measured by means of calipers, ultrasonography, and dynamic MRI before and after NAC. Three-dimensional maximum intensity projection MRIs to measure the tumor size were created for every case. The tumor size determined by calipers, ultrasonography, and 3D MRI after NAC was compared with that determined by pathologic examination. The tumor size determined by 3D MRI showed a strong correlation with that determined by pathologic examination (r = 0.896). Moderate, but significant correlations were found between measurements obtained with calipers and pathology (r = 0.554), and between ultrasonography and pathology (r = 0.484). The response rates to NAC were estimated at 84.2% with calipers, 58.0% with ultrasonography, and 44.7% with 3D MRI. Calipers and ultrasonography thus tended to overestimate the response to NAC compared to 3D MRI (p < 0.001 and 0.240, respectively). Three-dimensional MRI can visualize residual tumor extent after NAC more accurately than calipers and ultrasonography, and seems to be more reliable than other modalities for estimating response to NAC. It should also help surgeons with decision making for breast-conserving surgery after NAC.

[The feasibility of FEC (75) as adjuvant chemotherapy for Japanese breast cancer patients].

Recently, high-dose FEC (fluorouracil, epirubicin, and cyclophosphamide) has been increasingly used in adjuvant chemotherapy for breast cancer in Japan. However, the safety and tolerability of high-dose FEC are not well evaluated in Japanese breast cancer patients. We studied the feasibility of FEC (75) (fluorouracil: 500 mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6 cycles) as adjuvant chemotherapy for 59 primary breast cancer patients. Out of these patients, 56 (94.9%) finished 6 cycles-FEC. The mean epirubicin dose received was 431.7 mg/m(2) (95.9% of the intended dose of 450 mg/m(2)). Forty-five (76.2%) of 59 patients experienced neutropenia of grade 3 or 4, while the rates of febrile neutropenia (grade 3) and infection (grade 2) were 3.4% and 10.2%, respectively. Anemia (88.2%), fatigue (42.4%), nausea (40.6%), liver dysfunction (40.7%), and vomiting (18.7%) occurred, however most of them were mild and categorized into grade 1 or 2. No patients developed any cardiac failure symptoms. This study shows FEC (75) is well tolerable as adjuvant chemotherapy for Japanese breast cancer patients.

Three-dimensional ultrasound imaging of breast cancer by a real-time intraoperative navigation system.

BACKGROUND: In order to achieve a good cosmetic result without increasing the risk of ipsilateral breast cancer recurrence after breast conserving surgery, it is very important to minimize the resection volume of the breast without compromising the negativity of the surgical margin. For this purpose, it is necessary to obtain precise information on tumor extension. We therefore developed a three-dimensional (3-D) ultrasound navigation system for breast cancer surgery, which can be performed in the operating room just before surgery. METHODS: We obtained 3-D breast tumor images by the 3-D ultrasound navigation system in 40 patients with primary breast cancer (stage 0-II) who underwent mastectomy or breast conserving surgery. The tumor size was measured in a coronal view of the 3-D tumor image and compared with the tumor size obtained from a pathological map of the tumor extension. RESULTS: We obtained 3-D tumor images in 38 patients (success rate=95%). The tumor size in the images showed a very strong correlation with the pathological tumor size (r=0.898). The difference in tumor size between the 3-D images and pathology was less than 1 cm in 29 tumors (76.3%) and less than 2 cm in 36 (94.7%). On the other hand, the difference in tumor size between palpation and pathology was less than 1 cm in 19 out of 38 tumors (50.0%) and less than 2 cm in 29 tumors (76.3%). The absolute difference between the 3-D images and pathology was significantly less than that between palpation and pathology (p=0.0197). CONCLUSIONS: Our 3-D ultrasound navigation system is useful in visualizing breast tumor extension and is more accurate than palpation. The system is expected to be helpful in deciding on the appropriate surgical margin in breast cancer surgery, resulting in a better cosmetic outcome without increasing the risk of surgical margin positivity.

Usefulness of three-dimensional multidetector-row CT images for preoperative evaluation of tumor extension in primary breast cancer patients.

PURPOSE: Usefulness of three dimensional (3D) multidetector-row CT (MDCT) images for preoperative evaluation of tumor extension was studied in primary breast cancer patients. METHODS: 3D-MDCT tumor images of 143 tumors in 143 patients with primary breast cancer were created with the volume rendering method. The transverse tumor size (TS) and vertical tumor size (VS) were then measured in an anterior-posterior view of the 3D-MDCT images. The pathological tumor size was determined according to a map of the tumor spread prepared by pathologists using multi-sliced (3-5 mm intervals) surgical specimens and compared with the tumor size on 3D-MDCT images. RESULTS: First, the optimal method for creating 3D-MDCT tumor images was determined for the first 40 patients (learning set), resulting in a fairly good correlation of tumor size on 3D-MDCT images with pathological tumor size (r = 0.983 for TS and r = 0.958 for VS). We then carried out a validation study on the next 103 patients (validation set). The 3D-MDCT tumor size's strong correlation with the pathological tumor size demonstrated a high rate of accuracy (r = 0.974 for TS and r = 0.977 for VS). Subset analyses according to histological type showed that correlation coefficients were r = 0.979 for TS and r = 0.981 for VS of invasive ductal carcinomas (n = 88), r = 0.948 for TS and r = 0.970 for VS of ductal carcinomas in situ (n = 10), and r = 0.984 for TS and r = 0.976 for VS of invasive lobular carcinomas (n = 5). CONCLUSION: 3D-MDCT images can assess breast cancer tumor extension highly accurately, and thus seems to be useful for planning the extent of resection in breast conserving surgery.

Association of serum estrone levels with estrogen receptor-positive breast cancer risk in postmenopausal Japanese women.

PURPOSE: Several reports have demonstrated the association between high serum estrogens levels and breast cancer risk in postmenopausal women. It is hypothesized that breast cancers arising in postmenopausal women with high serum estrogens levels are more likely to be estrogen receptor (ER)-positive. Thus, we have investigated whether or not high serum estrone (E(1)) levels are associated with ER-positive breast cancer risk in postmenopausal women. EXPERIMENTAL DESIGN: A case-control study was conducted on 71 cases (postmenopausal breast cancer patients) and 73 controls (postmenopausal healthy women). Serum E(1) levels were examined in their association with breast cancer risk after adjustment for the various epidemiological risk factors. In addition, clinicopathological characteristics of breast cancers arising in the women with high E(1) levels were investigated. RESULTS: Women in the high tertile of E(1) levels had a significantly (P < 0.01) increased risk of breast cancer as compared with women in the low tertile [odds ratio (OR), 4.14; 95% confidence interval (CI), 1.44-11.87]. Subset analysis according to the ER status showed that women in the high tertile of E(1) levels had a significantly increased risk for ER-positive breast cancer (OR, 23.79; 95% CI, 3.50-161.59) but not for ER-negative breast cancer (OR, 1.45; 95% CI, 0.41-5.15) as compared with women in the low tertile. Tumor size and lymph node status were not significantly different between women in the high tertile and those in the intermediate and low tertiles. But the frequency of low-histological-grade tumors and ER-positive tumors (88 and 67%, respectively) showed a greater trend toward an increase (P = 0.06 and P = 0.07, respectively) in women in the high tertile than those (69 and 46%, respectively) in the intermediate and low tertiles. In addition, ER levels in ER-positive tumors were significantly (P < 0.05) higher in women in the high tertile (245.3 +/- 37.1 fmol/mg protein) than those in the intermediate and low tertiles (134.0 +/- 31.3 fmol/mg protein). CONCLUSIONS: Postmenopausal women with high serum E(1) levels have a significantly increased risk for ER-positive, but not ER-negative, breast cancer. Breast cancers arising in women with high E(1) levels show a high ER positivity as well as high ER content. Measurement of serum E(1) levels would be clinically useful in the selection of postmenopausal women who can benefit from prophylactic use of tamoxifen because tamoxifen can prevent ER-positive, but not ER-negative, breast cancer.

Aromatase inhibitors for treatment of postmenopausal patients with breast cancer.

The third generation of aromatase inhibitors and inactivators, such as anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin), have become available for treatment of postmenopausal breast cancer patients. Several clinical trials have demonstrated that these new drugs can achieve better treatment results than megestrol acetate (Megace) and may replace tamoxifen for the first-line hormonal therapy for metastatic breast cancer patients. In fact, these drugs are now used in many hospitals and clinics for patients with metastatic breast cancer who were previously given tamoxifen as adjuvant treatment. However, the primary concern is whether they can be used as first-line agents for adjuvant treatment of primary breast cancer or are suitable for breast cancer prevention in view of possible adverse side effects. Recently, the Arimidex and Tamoxifen Alone or in Combination trial demonstrated the superiority in terms of disease-free survival of anastrozole over tamoxifen in adjuvant use for postmenopausal patients with Stage I and II primary breast cancer. The results of this report indicate the potential of anastrozole as an alternative drug in the adjuvant setting, although the mean follow-up time is so far only 47 months. Additional data regarding survival resulting from comparative trials of letrozole and tamoxifen and of exemestane and tamoxifen are expected to be available in a few years. However, limited information is available regarding adverse events caused by long-term administration of aromatase inhibitors. Longer follow-up is needed to determine the efficacy and safety of these new aromatase inhibitors when used for adjuvant treatment of postmenopausal patients with breast cancer.

Influence of adjuvant tamoxifen treatment on bone mineral density and bone turnover markers in postmenopausal breast cancer patients in Japan.

The effect of adjuvant tamoxifen treatment on bone mineral density (BMD) and bone turnover markers was studied in postmenopausal breast cancer patients. The relationship of tamoxifen's effect with the genetic polymorphisms of estrogen receptor (ER)-alpha and ER-beta gene was also studied. Twenty-one postmenopausal breast cancer patients were given tamoxifen (20 mg/day) as the adjuvant treatment after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry) and bone resorption (deoxypyridinoline, aminoterminal telopeptide of type I collagen, and carboxyterminal telopeptide of type I collagen) and formation (propeptide of type I procollagen, osteocalcin, and bone-specific alkaline phosphatase) markers were examined at baseline (before the surgery), 6 and 12 months after the start of tamoxifen treatment. Genetic polymorphisms analyzed were TA dinucleotide repeats polymorphism in the promoter region and PvuII and XbaI restriction fragment length polymorphism for the ER-alpha gene and the CA dinucleotide repeats polymorphism in the intron 5 for the ER-beta gene. Tamoxifen significantly increased BMD of the lumbar spine at both 6 (P<0.01) and 12 months (P<0.01) after the start of tamoxifen as compared with that at baseline. The mean percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All bone resorption and formation markers significantly decreased at both 6 and 12 months. Among the four genetic polymorphisms studied, only ER-beta CA repeat polymorphism was found to be significantly associated with BMD at 12 months, i.e. BMD of the 21 CA repeats allele carriers was significantly higher than that of the non-carriers (P=0.025). These results suggest that tamoxifen increases BMD of the lumbar supine by reducing the bone turnover in postmenopausal breast cancer patients, and this bone restoring effect of tamoxifen is more marked in ER-beta 21 CA repeats allele carriers than non-carriers.

uPA receptor expression in benign and malignant thyroid tumors.

BACKGROUND: Urokinase type plasminogen activator receptor (uPAR) plays an important role in cancer invasion and metastasis. However, the uPAR expression has been rarely investigated in thyroid carcinomas. The aim of this study was to evaluate the clinical relevance of uPAR in thyroid tumors. MATERIALS AND METHODS: Samples included 53 benign tumors (follicular adenoma 34, Graves' disease 8, adenomatous goiter 7 and others 4) and 62 cancers (papillary thyroid cancer (PTC) 47, follicular TC (FTC) 5, medullary TC (MTC) 5 and anaplastic TC (ATC) 5). uPAR expression was prospectively investigated with a labeled streptavidin-biotin method using an anti-uPAR monoclonal antibody. Patients were classified into a low- and high-staining group according to the percentage of positive cells (cut-off value=10%). RESULTS: uPAR was more strongly expressed in thyroid cancers (35.5%) than benign tumors (7.5%). FTC had a significantly higher uPAR expression compared to follicular adenoma (p<0.01). The positivity of uPAR was as follows: PTC 36.2%, FTC 60%, MTC 0% and ATC 40%. In PTC, high uPAR expression was associated with poorly-differentiated PTC (p<0.01) while had a trend to develop more distant metastases than those with low uPAR expression (p=0.17, by the Kaplan-Meier method). CONCLUSION: This study has shown that uPAR expression might be useful for the discrimination between FTC and follicular adenoma and could possibly be used as a prognostic factor in PTC.