Detection of tumor circulating cells by cytokeratin 20 in the blood of patients with endometrial carcinoma.

BACKGROUND: Cytokeratins are constituents of the intermediate filaments of epithelial cells which are expressed in various combinations depending on the epithelial type and the degree of differentiation. Using the reverse transcriptase-polymerase chain reaction technique (RT-PCR) we recently demonstrated that: (1) Cytokertin 20-the most recent discovered cytokeratin-is expressed in endometrial carcinoma tumors but not in the endometrium of patients with benign diseases, and (2) CK-20 is not expressed in blood cells. The aim of this study is to examine whether CK-20 expression in blood can be used as a biomarker for the detection of the dissemination of malignant cells in patients treated for endometrial carcinoma. METHODS: In the present study, we have used RT-PCR to determine the expression of CK-20 in the peripheral blood of the following groups: (1) preop new diagnosed patients (n = 20), (2) patients with no clinical evidence of disease following completion of definitive treatment (n = 33; 17 at low risk; 16 at high risk), (3) patients with recurrent disease (n = 6), and (4) a control group of healthy subjects (n = 16). RNA was extracted from cell pellets and analysed by RT-PCR using primers for CK-20. RESULTS: Of the 20 patients of the first group 7 (35%) were CK-20 positive. Of the 33 patients of the second group 17 (51%) were CK-20 positive. Subdivision of this group showed that 9 of 17 (53%) were positive in the low-risk subgroup, and 8 of 16 (50%) were positive in the high-risk subgroup. All 6 patients with recurrent disease were positive, and all subjects in the control group were negative. CONCLUSION: These results indicate that RT-PCR of CK-20, because of its high sensitivity, is a potential biomarker for detecting metastasis in blood samples of patients with endometrial carcinoma.

Detection of micrometastasis by cytokeratin-20 (reverse transcription polymerase chain reaction) in lymph nodes of patients with endometrial cancer.

BACKGROUND: Cytokeratins are constituents of the intermediate filaments (IFs) of epithelial cells which are expressed in various combinations, depending on the type of epithelium and degree of differentiation. We have reported (R. Zemer, A. Fishman, J. Bernheim, S. Zimlichman, O. Markowitz, M. Altaras, and A. Klein, Gynecol Oncol 70:410-413, 1998) on the determination of cytokeratin-20 (CK-20) by reverse transcription polymerase chain reaction (RT-PCR) in the detection of endometrial cancer cells as a potential biomarker. In that study, we also found that by using immunocytochemistry, most carcinomas were found to be negative for CK-20. The sensitivity and specificity rates obtained by using the RT-PCR method were 94.4 and 91%, respectively. OBJECTIVE: The aim of this study is to investigate the feasibility and potential of the specific mRNA marker, CK-20, to detect endometrial cancer cells-micrometastases (MMs)-by RT-PCR in lymph node (LN) samplings of patients undergoing hysterectomy for endometrial carcinoma. METHOD: We used the RT-PCR method to determine the expression of CK-20 in the LNs of 20 patients [study group (SG)] who were being surgically staged and treated for endometrial carcinoma. The specificity of the mRNA CK-20 marker was examined in LNs obtained from five healthy patients [control group (CG)] who underwent abdominal hysterectomy and bilateral salpingo-oopherectomy for benign gynecologic conditions. The LNs obtained from the SG and CG patients were prepared together before mRNA extraction. RNA of the various cell pellets was extracted and RT-PCR was performed with CK-20 primers. RT-PCR products were analyzed by agarose gel electrophoresis and ethidium bromide staining against PCR size markers. Specificity of the RT-PCR products was examined by Southern blotting. RESULTS: Histopathologic examinations demonstrated the presence of metastases in two (10%) SG patients. These patients were also CK-20 positive. Of the remaining 18 patients with negative histopathologic results, 6 (33%) were CK-20 positive and 12 (67%) were negative. All the CG patients were CK-20 negative (specificity, 100%). CONCLUSIONS: The results obtained in this study suggest that RT-PCR of CK-20 is more sensitive than traditional histopathologic methods in the diagnosis of MMs in LNs of patients with endometrial cancer. Thus, due to the aforementioned characteristics of CK-20, it may be considered a powerful biomarker in the detection of MMs in LNs of patients with endometrial cancer.

Endometrial pathology in postmenopausal tamoxifen treatment: comparison between gynaecologically symptomatic and asymptomatic breast cancer patients.

AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients.

Dose-dependent effect of tamoxifen therapy on endometrial pathologies in postmenopausal breast cancer patients.

To assess whether a higher cumulative tamoxifen dose is associated with increased incidence of various types of endometrial pathologies, we compared cumulative dose of tamoxifen treatment as well as demographic characteristics, risk factors for endometrial cancer, transvaginal ultrasonographic endometrial thickness, and various treatments for the primary breast cancer between 159 postmenopausal breast cancer tamoxifen-treated patients without endometrial pathologies (group I) and 67 similar patients with endometrial pathologies (group II). A similar comparison was made between group I patients and similar patients with proliferative endometrium (group IIa), with endometrial hyperplasia (group IIb), with endometrial polyps (group IIc), and with endometrial cancer (group IId). Overall cumulative tamoxifen dose was significantly higher in group II as compared to group I (27.4+/-33.4 and 17.4+/-20.2, respectively; P<0.0252). Transvaginal ultrasonographic endometrial thickness was significantly higher in group II than in group I patients (16.3+/-11.3 mm and 12.1+/-6.3 mm, respectively; P<0.0147). The frequency of diabetes mellitus, of previous postmenopausal bleeding, and of previous exposure to hormone replacement therapy was significantly higher in group II than in group I patients (P<0.001, P<0.0001 and P<0.001, respectively). There were no significant differences in all parameters tested between group I, group IIa, group IIb, group IIc, and group IId. However, there was an obvious trend for higher cumulative tamoxifen dose in patients with benign endometrial pathologies as compared to those without endometrial pathologies or to those with endometrial cancer (Group I = 17.4+/-20.2 g, group IIa = 22.5+/-18.5 g, group IIb = 28.1+/-20.3 g, group IIc = 31.4+/-42.7 g and group IId = 10.4+/-12.6 g). Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.

Ovarian overstimulation and cystic formation in premenopausal tamoxifen exposure: comparison between tamoxifen-treated and nontreated breast cancer patients.

AIM: Tamoxifen is the antihormonal treatment of choice for premenopausal breast cancer patients with advanced breast disease. Its premenopausal administration has been shown to induce supraphysiological 17beta-estradiol serum levels and to be associated with the presence of persistent, bilateral functional ovarian cysts. However, these abnormalities have not yet been compared to controls. In this study we evaluated the possibility that the above hormonal and/or ovarian abnormalities are more frequent among premenopausal breast cancer patients treated with tamoxifen than among similar nontreated patients, and thus they may be attributed to tamoxifen effect. METHODS: We evaluated serum hormone levels of 17beta-estradiol, follicular-stimulating hormone, luteinizing hormone, and progesterone, the presence of ovarian cysts, and various demographic and clinical characteristics in 20 premenopausal breast cancer patients treated with tamoxifen (study group) and compared them to those observed in 12 similar nontreated patients (control group). RESULTS: Ovarian cysts were found in 80% of the study patients and only in 8.3% of the control patients (P = 0.001). The incidence of oligomenorrhea was nearly significantly higher in the study than in the control group (50 and 16.7%, respectively; P = 0.0651). Various serum hormone levels tested were not found to be significantly different between the two groups, except for 17beta-estradiol serum levels as detected on days 14 and 21 of the menstrual cycle, which were significantly higher among the study than in the control patients. (Day 14 serum estradiol: 757.7 +/- 372.0 pg/mL versus 206.5 +/- 275.0 pg/mL, P = 0.0012. Day 21 serum estradiol: 300.0 +/- 134.5 pg/mL versus 96.5 +/- 71.5 pg/mL, P = 0.0008.) CONCLUSIONS: Tamoxifen treatment increases the incidence of ovarian cysts and the significantly higher 17beta-estradiol serum levels in premenopausal breast cancer patients.

Estrogen and progesterone receptors in benign ovarian tumors of menopausal breast cancer patients treated with tamoxifen.

In order to assess possible ovarian cell potential for interaction with tamoxifen, thus demonstrating possible effects of this agent on the development of ovarian pathologies through growth stimulation and cell proliferation, we measured estrogen receptors (ER) and progesterone receptors (PR) by immunohistochemical method in 16 benign ovarian tumors removed from 11 postmenopausal breast cancer patients treated with tamoxifen (study group). The results were compared with those measured in 7 similar ovarian tumors obtained from 5 similar patients without tamoxifen treatment (control group I), and in 9 similar tumors removed from 9 age-matched postmenopausal women (control group II). There were no significant differences with regard to ER or PR expression between the study group and control group I and II (ER = 18.75, 0.0 and 11%, respectively; PR = 43.75, 28.5 and 44%, respectively; p = NS). There were also no significant statistical differences between the three groups when subdividing the ovarian pathologies according to different histological types. From the results obtained in this study, it seems that tamoxifen probably does not have any direct influence on the ovaries of menopausal breast cancer patients.

Different coexisting gynecological and endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen.

Tamoxifen administration to postmenopausal women has been described as being associated with various endometrial and other gynecological pathologies. However, different coexisting gynecological pathologies in such patients have not yet been described. In the present study, we assessed the histopathological conditions diagnosed in endometrium, myometrium, and ovaries of 28 postmenopausal breast cancer patients who were treated with tamoxifen (study group) and compared the findings to those obtained from 14 similar patients without tamoxifen treatment (control group I) and from 28 age-matched healthy postmenopausal controls (control group II). All specimens were removed by total abdominal hysterectomy and bilateral salpingo-oophorectomy for various indications. The overall incidence of two or more different coexisting gynecological pathologies was significantly higher among the study group (92.9%) than in control group I or in control group II (42.9 and 50%, respectively; p = 0. 0001). There was no significant statistical difference between the control groups. Overall endometrial (and endometrial-like) origin of pathological conditions was significantly more common in the study group (92.6%) than in control group I (50%; p = 0.00072) and control group II (32.1%; p = 0.0000), while there was no significant difference between the latter two groups. These findings suggest that there might be an association between postmenopausal tamoxifen exposure and the development of such different coexisting or specific single gynecological pathologies originating from the endometrium.

Asynchronous replication of homologous alpha-satellite DNA loci in man is associated with nondisjunction.

We tested the hypothesis that loss of replication control of DNA loci associated with human centromeres affects the main centromere function, namely, ensuring proper sister chromatid separation and accurate chromosomal segregation during cell division. Applying one-color fluorescence in situ hybridization (FISH) to interphase nuclei, we studied the replication patterns of homologous DNA loci associated with human centromeres (alpha-satellite sequences) of chromosome pairs 10, 11, 17, and X in PHA-stimulated lymphocytes of female cancer patients with a familial predisposition to malignancy and normal, healthy women. Concomitantly, we measured the rates of aneuploidy for these chromosomes in the same cells. To elucidate the replication patterns of the various centromeric loci, we analyzed the replication-dependent configuration signals obtained following FISH with four chromosome-specific alpha-satellite probes. Our data showed an association between replication timing of alpha-satellite sequences and centromeric function. Chromosome pairs whose homologous alpha-satellite loci replicated highly synchronously revealed low rates of aneuploidy, whereas chromosome pairs with a slightly asynchronous replication pattern (i.e., short intervals between early- and late-replicating loci) revealed intermediate rates of aneuploidy, and chromosome pairs exhibiting asynchrony with long-time intervals between early- and late-replicating loci showed the highest rate of aneuploidy.

Estrogen and progesterone receptors of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen.

Adenomyosis is an ectopic endometrial tissue located in the myometrium. It has been reported to develop at a higher rate among postmenopausal breast cancer patients on tamoxifen (TAM) treatment than in untreated patients. It has also been reported to be stimulated by estrogen. Assessing receptor levels in adenomyotic tissue may indicate the adenomyotic cell's potential to interact with TAM. In the present study the estrogen receptor (ER) and progesterone receptor (PR) were analyzed by an immunohistochemical technique in adenomyotic and the corresponding endometrial tissues of 14 postmenopausal breast cancer patients treated with TAM and in 15 healthy postmenopausal patients who served as controls. All TAM-treated patients had normal postmenopausal serum estradiol levels. Overall the ER and PR contents in adenomyotic tissue (42.9 and 71.4%) and in the endometriotic tissue (64.3 and 78.6%) obtained from the study patients were similar to those obtained from the control group (adenomyosis, ER and PR = 46.7 and 86.7%; endometrium, ER and PR = 40 and 73.3%; p = NS). In the study group, the ER content was lower in the adenomyotic (42.9%) than in the endometriotic tissue (64.3%). No correlation was found between the duration of TAM therapy, the TAM dosage level or the ER or PR content in the adenomyotic or endometrial tissues. The finding of a relatively low ER content in the adenomyotic tissue than in the endometriotic tissue in postmenopausal TAM-treated patients without endogenous estrogens, similar to that observed in healthy premenopausal women, may be attributed to the estrogen-like effect of TAM.

Estrogen and progesterone receptor expression in postmenopausal tamoxifen-exposed endometrial pathologies.

Assessment of receptor levels in tamoxifen-exposed endometrial pathologies may indicate endometrial cells potential for interaction with tamoxifen. To assess this assumption, we analyzed estrogen receptor (ER) and progesterone receptor (PR) expression by an immunohistochemical technique in endometrial specimens with benign hyperplasia, benign polyps, and carcinoma obtained from postmenopausal breast cancer patients treated with tamoxifen (study group) and from age-matched healthy postmenopausal women treated with estrogen replacement therapy (control group I) and not treated with estrogen replacement therapy (control group II). Overall gland and stromal ER expression of benign endometrial hyperplasia and of benign endometrial polyps was significantly higher in control groups I and II than that obtained from the study group (endometrial hyperplasia: P = 0.0274 and 0.00093, respectively, and P = 0.00003 and 0.00001, respectively; benign endometrial polyps: P = 0.02889 and 0.00596, respectively; and P = 0.00228 and 0.00005, respectively), while there were no differences between the two control groups. Overall gland and stromal PR expression was nearly similar in all the three groups (P = NS). There was no correlation between the length of tamoxifen treatment and the presence of ER and PR in various endometrial pathologies in the tamoxifen-treated patients. The significantly lower ER expression in most benign endometrial pathologies obtained from postmenopausal tamoxifen treated patients may further support the weak estrogen-like effect of tamoxifen on the endometrium in the menopause.

Estrogen and progesterone receptors in the endometrium of postmenopausal breast cancer patients treated with tamoxifen and progestogens.

Postmenopausal breast cancer patients who were treated with tamoxifen and progestogens showed a uniform decidual reaction of the endometrium. It is well established that progestogens antagonize the estrogen effect on the endometrium by reducing its receptors in the endometrium. To assess in vivo such a possible effect of progestogens on endometrium primarily exposed to tamoxifen, we analyzed estrogen and progesterone receptors (ER, PR) on endometrial specimens showing decidualization from nine postmenopausal breast cancer patients on tamoxifen and progestogen treatment and on endometrial polyps with areas of decidualization from two other similar patients. ER was weakly detected in the endometrial glands of four (36.4%) patients and in the endometrial stroma of one (9.1%) patient. PR was detected in the endometrial gland of only one (9.1%) patient. No PR was detected in the endometrial stroma. There was no correlation between the length of tamoxifen treatment, the tamoxifen dosage, or the length of progestogen treatment and the ER or PR content, although progestogens were administered for more than 3 consecutive months in all patients. This relatively very low ER and PR content may be attributed to the antagonistic effect of progestogens on the "priming" estrogen-like effect of tamoxifen on the endometrium.

Value of sonohysterography in asymptomatic postmenopausal tamoxifen-treated patients.

A prospective study was performed to assess the efficacy of sonohysterography (SHG) in identifying endometrial pathologies among asymptomatic, postmenopausal breast cancer patients treated with tamoxifen. In this study the uterine cavity of 68 such patients with endometrial thickness of > or = 8 mm was prospectively evaluated by SHG. Forty-six (67.6%) patients in whom SHG did not identify any findings in the uterine cavity (negative group) were followed by diagnostic hysteroscopy. Another 22 (32.4%) who were identified by SHG to have abnormal endometrial findings, such as an echogenic or polypoid mass (positive group), were followed by operative hysteroscopy and by postoperative SHG. In the positive group the basal transvaginal sonogram revealed an endometrial echogenic mass in only 10 (45.5%). In the remaining 12 (54.5%) patients, the transvaginal sonogram identified only thick endometrium. In these latter 12 patients, histological assessment confirmed endometrial polyps in 8 (66.7%) and fibroid in 1 (8.3%). Four (18.2%) patients in the positive group had no histological endometrial pathology. Two (50%) of them had a uterine septum as diagnosed during hysteroscopy, in one (25%) operative hysteroscopy failed to resect the endometrial polyp, and in another (25%) there was a false-positive SHG diagnosis. Overall, SHG accurately diagnosed endometrial and/or other intrauterine pathology in 95.5% of these patients. In the 46 patients with "negative" basal SHG features, diagnostic hysteroscopy confirmed this diagnosis. Thus, there was no SHG false-negative diagnosis. Comparing the results of the basal SHG with those of operative hysteroscopy and/or the histopathological findings in the positive group, the sensitivity of SHG was 1.0, the specificity 0.0, positive predictive value 95.5%, and negative predictive value 0.0. It is suggested that SHG is a useful diagnostic tool for the assessment of specific endometrial pathologies in asymptomatic postmenopausal breast cancer patients treated with tamoxifen who were diagnosed by transvaginal sonography to have thick endometrium.

Ovarian volume in postmenopausal breast cancer patients treated with tamoxifen.

BACKGROUND: Postmenopausal breast cancer patients treated with tamoxifen have been found to have a high incidence of ovarian tumors. Transvaginal ultrasonography is an accurate and reliable method for measuring ovarian size. The purpose of this study was to establish normal values for basal ovarian volume in postmenopausal tamoxifen-treated patients and compare them with those established for healthy, postmenopausal women in the same population with no exposure to hormone treatment. METHODS: In a prospective open pilot study, the ovaries of 65 postmenopausal breast cancer patients treated for at least 6 months with tamoxifen were measured by transvaginal ultrasonography. From the same population, 311 healthy postmenopausal women with no exposure to hormone therapy were examined and served as controls. After matching for menopausal age, ovarian volume was compared between groups. RESULTS: Mean ovarian volume of postmenopausal tamoxifen-treated patients was persistently low through the menopause, whereas the mean ovarian volume of the controls was large, gradually decreasing up to the 10th menopausal year (8.6 +/- 2.3 and 2.8 +/- 2.1 cm3, respectively). Mean ovarian volume of the tamoxifen-treated patients was significantly lower than that of the controls during the initial menopausal years. CONCLUSIONS: An ovarian volume that is considered within normal range for a specific menopausal age in a healthy postmenopausal woman is abnormal for a postmenopausal tamoxifen-treated patient.

High frequency of adenomyosis in postmenopausal breast cancer patients treated with tamoxifen.

Pathologic evaluation for adenomyosis in uterine specimens as well as demographic characteristics, health habits and risk factors for endometrial cancer were compared in 28 postmenopausal breast cancer patients with tamoxifen (TAM) treatment and in 11 similar patients without TAM treatment in order to determine the association between postmenopausal TAM exposure and the frequency of adenomyosis. The same comparison was also made between TAM-treated patients with adenomyosis and TAM-treated patients without adenomyosis. Adenomyosis was histologically diagnosed in 53.6% TAM-treated patients and in 18.2% non-TAM patients. Overall, there were no significant statistical differences in all parameters tested between the 2 groups, as well as between the TAM-treated patients with adenomyosis and the TAM-treated patients without adenomyosis. It can be concluded that adenomyosis was significantly more common among postmenopausal breast cancer patients who were treated with TAM as compared to similar patients without TAM treatment (p = 0.0186). This significant high rate of adenomyosis may be attributed to the continuous and unopposed exposure to TAM. It is, however, impossible to predict which postmenopausal breast cancer patient will develop adenomyosis after treatment with TAM.

Different coexisting endometrial histological features in asymptomatic postmenopausal breast cancer patients treated with tamoxifen.

In an attempt to assess the hypothesis that different endometrial sites may respond differently to tamoxifen exposure in postmenopausal women, hysteroscopic selected endometrial histology was investigated in 175 postmenopausal breast cancer patients who received continuous treatment with tamoxifen, and in 27 similar patients not treated with tamoxifen who served as controls. In the tamoxifen-treated patients 14 (8.0%) developed endometrial polyps. Of 14 patients, 8 (57.2%) each displayed atrophic endometrium in the same histologic specimen, 5 (35.7%) each had coexisting simple hyperplasia, and 1 (7.1%) other had complex hyperplasia. Another 21 (12.0%) developed simple or complex hyperplasia. The endometrial hyperplasia coexisted with atrophic endometrium in all these patients. All these lesions were selectively identified by hysteroscopic examination prior to the endometrial biopsy. In the control group 3 (11.0%) had simple hyperplasia and 2 (7.4%) had endometrial polyps. The above results support the hypothesis that the endometrium of postmenopausal breast cancer patients on tamoxifen treatment may possess different responses to tamoxifen exposure.

Time-dependent effect of tamoxifen therapy on endometrial pathology in asymptomatic postmenopausal breast cancer patients.

Various endometrial lesions were more frequent among asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen for > 48 consecutive months (30.8%) when compared with similar patients who were treated for 6-24 months or for 25-48 months (20.8% and 12.5%, respectively). However, this difference was not statistically significant. There were also no significant differences in the frequency of the various endometrial lesions between these three groups, although endometrial polyps were more frequently found among those treated for > 48 months. Overall, 20.7% of the 164 tamoxifen-treated patients in the study had an endometrial pathology. It can be concluded that there is a slight tendency among those postmenopausal patients who have been treated for > 48 consecutive months to have a higher frequency of endometrial lesions.

Common endometrial decidual reaction in postmenopausal breast cancer patients treated with tamoxifen and progestogens.

In order to assess endometrial reaction to the combined treatment of tamoxifen and progestogens in asymptomatic postmenopausal breast cancer patients, we evaluated all such patients by vaginal ultrasonography and by histological examination of endometrial samplings. All patients were initially treated with tamoxifen, and progestogens were then added when metastases became evident. Of 12 patients included in the study, eight (66.66%) showed evidence of strong endometrial stromal decidualization, while three (25%) had decidual reactions in endometrial polyps. Overall, 11 (91.66%) of the patients had decidual reactions, and all were treated with progestogens for > or = 3 consecutive months. One patient, treated with progestogens for 1 months, had an inactive endometrium. All but three had thickened endometria (> 10 mm) on ultrasonographic evaluation. These data show that postmenopausal breast cancer patients who received progestogens for < or = 3 months, and who concomitantly took tamoxifen, had a uniform decidual reaction in all uteri.

Ovarian tumors in postmenopausal breast cancer patients treated with tamoxifen.

From September 1, 1989, to November 30, 1994, 175 menopausal breast cancer patients treated with tamoxifen were followed at the authors' institutions. During this period. 16 (9.1%) underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, for various indications. Of these, 10 (62.5%) had either uni- or bilateral ovarian tumors. The analysis of surgical findings showed an incidence of 5.7% (10/175) ovarian tumors among all the patients. In 2 (20%), the ovarian masses displayed enlargement over a relatively short period while on treatment. In 5 (50%) patients, the findings were bilateral. All tumors were detectable by ultrasonography, except four serous cystadenomas found in 3 women. The mean duration of tamoxifen treatment was 36.6 +/- 24.9 (range 9-86) months. The rate of 5.7% for ovarian tumors, in this selected group of patients, is four to five times higher than that reported for similar pathologic conditions detected by general screening with ultrasonographic scans among nonselected, asymptomatic, and untreated postmenopausal women. Two possibilities should be considered in the development of ovarian tumors coinciding with tamoxifen treatment; (1) women with breast malignancy are prone to develop benign or malignant ovarian tumors in relation to genetic factors, regardless of tamoxifen treatment; and (2) tamoxifen may stimulate enlargement of such tumors and may even cause them.

Transvaginal color flow imaging in the diagnosis of ovarian tumors.

Transvaginal ultrasonography and color flow imaging, performed to investigate whether there is any diagnostic advantage, were assessed over a 3 year period in 217 patients with adnexal masses prior to explorative laparotomy. Gray scale sonography and color Doppler flow were performed 1 day prior to surgery. Benign tumors were found in 165 patients and flow was detectable in 82 (49.7%); 14 patients had tumors of low malignant potential, 12 (85.7%) of whom showed detectable flow, and 38 had malignant tumors, in 25 (65.8%) of whom flow was detectable. Blood flow velocity was evaluated by the calculation of the resistance index prior to surgery. Mean resistive index was 0.39 +/- 0.05 for malignant tumors, compared with 0.49 +/- 0.06 and 0.55 +/- 0.07 for the low malignant potential and benign tumors, respectively. These differences were statistically significant (P < 0.01). When a resistive index of 0.47 was considered the cut-off value, the sensitivity was 88% and the specificity was calculated to be 85% (using color Doppler flow as the only diagnostic method). With our large cohort of patients, we demonstration the contribution of color Doppler flow examination in differentiating benign from malignant ovarian tumors prior to surgery.