Mario Cordoba

Primary peritoneal papillary serous adenocarcinoma: Clinical and management aspects

From January 1, 1984 to April 30, 1990, 38 patients were surgically found to have an intraabdominal disease resembling epithelial ovarian cancer. This diagnosis was confirmed in 31 patients; the remaining 7 met the criteria of primary peritoneal papillary serous carcinoma. Five of these were diagnosed retrospectively and two during surgery. The mean age at diagnosis was 61.2 years. Tumor histology revealed papillary serous carcinoma in six and mixed (papillary serous and papillary clear cell carcinoma) in one patient. Optimal debulking was achieved in three of seven cases (42.8%). Cisplatin-based combination chemotherapy was administered to all in the study group. Complete response was obtained in four patients, with one surviving for 76 months. The median survival in these patients was 34.5 months (range 6-76 months). Currently, three patients with complete response are alive with clinically undetectable disease. CA-125 assays were available in three cases and blood levels corroborated the clinically determined status of the disease. Tumor steroid hormone receptor status was determined in one case and revealed low levels of estrogen and progesterone receptors. To the best of our knowledge, the usefulness of CA-125 in the diagnosis, management, follow-up, and determination of tumor steroid hormone receptor status, mixed papillary serous and clear cell subtype histological patterns for primary peritoneal papillary serous carcinoma are first described in this report. It seems that this neoplasm may be treated and followed up as in epithelial ovarian cancer, obtaining long-term survival; however, the biologic behavior and management problems of this relatively new entity deserve further clinical experience.

Endometrial changes in postmenopausal women treated with tamoxifen for breast cancer

Objective To evaluate whether risk factors, other than tamoxifen, can be identified for the development of endometrial pathologies in postmenopausal breast cancer patients treated with tamoxifen.

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.

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.

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.

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 ± 20.2g, group IIa = 22.5 ± 18.5g, group IIb = 28.1 ± 20.3g, group IIc = 31.4 ± 42.7g and group IId = 10.4 ± 12.6g).Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.

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.

Doppler flow evaluation of pathologic endometrial conditions in postmenopausal breast cancer patients treated with tamoxifen.

A prospective pilot study was conducted to evaluate the usefulness of uterine artery blood flow in the detection of various pathologic endometrial conditions in 39 asymptomatic postmenopausal breast cancer patients who were treated with tamoxifen. No specific pattern was seen for the uterine artery pulsatility index values in the tamoxifen‐treated patients that could be related to any specific endometrial lesions, nor were any specific changes observed in the pulsatility index value with increasing severity of the pathologic endometrial conditions. Similarly, no correlation was found between ultrasonographically measured endometrial widths and uterine artery pulsatility index values. Thus, although pulsed Doppler flow ultrasonography has been shown previously to be effective in the detection of uterine cancer in non‐tamoxifen‐treated post‐menopausal patients, it probably does not contribute to the assessment of endometrial lesions in post‐menopausal breast cancer patients treated with tamoxifen.

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.

Endometrial decidual changes in a postmenopausal woman treated with tamoxifen and megestrol acetate

Sapir Medical Center Kfar-Saba 4428 1 Israel metrium is related to its capacity to occupy the oestradiol receptor in the endometrial cells. It has been suggested that tamoxifen exerts its effects on the endometrium via the oestrogen receptor, and that it has a long-term, low-grade oestrogenlike effect (Cross & Ismail 1990; Gusberg 1990). In postmenopausal women with breast cancer, an increase in the karyo-picnotic index indicates oestrogenic changes in the vaginal epithelium (Ferrazzi et al. 1977; Boccardo et al. 198 I), and this is supported by the observations of endometrial hyperplasia (Cross & Ismail 1990), or endometrial polyps (Nuovo et al. 1989). Stimulation of endometrial cancer cells in culture by tamoxifen has also been reported (Anzai et al. 1989). Moreover, several groups have observed an increased incidence of endometrial cancer in women with breast cancer and treated with tamoxifen (Killackey et al. 1985; Hardell 1988; Fomander et al. 1989). Hardell et al. (1988) found tamoxifen to be a risk factor for uterine carcinoma, as nearly half of the 23 women with breast cancer in their study who had endometrial