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Background: Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized trial was performed., Methods: One hundred thirty-five eligible postmenopausal women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily) alone or combined with octreotide 150 microg (administered subcutaneously thrice daily). The two groups were well balanced, except the TAM group had higher proportions of patients with visceral disease (50% vs. 37%) and a disease free interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3 levels, and total IGF binding capacity., Results: The median time to progression was estimated to be 14.2 months with TAM and 10.3 months with TAM plus octreotide. The distribution of progression free survival times revealed no significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM + octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution of survival times revealed no significant difference (P = 0.92), and the death hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable or evaluable disease were considered, the objective response rate was 49% with TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The percentage of decline in serum IGF-I, from pretreatment levels to those following 3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus octreotide than with TAM alone., Conclusions: There is no indication that the combination of TAM plus octreotide as administered in this study is substantially more efficacious than TAM alone in the treatment of postmenopausal women with metastatic breast carcinoma. The limited cohort included in IGF-I studies suggests that TAM plus octreotide produces a significantly greater reduction in serum IGF-I levels.

Background: In contrast to female breast carcinoma, information regarding the prevalence and prognostic information of new molecular markers is limited in male breast carcinoma. The objective of this study was to assess the degree of expression and prognostic value of estrogen receptors (ER), progesterone receptors (PR), androgen receptors (AR), bcl-2, p53, HER-2/neu, cyclin D1, and MIB-1 in a cohort of male breast carcinoma patients., Methods: A computerized search of the medical index, tumor registry, and tissue registry was used to identify 111 male patients with a diagnosis of primary adenocarcinoma of the breast seen between 1950-1992 at the Mayo Clinic. Of these, 77 patients had adequate tissue specimens available for the immunohistochemical analysis of the markers. Immunoperoxidase staining was performed by an automated avidin-biotin complex method. Progression free (PFS) and overall (OS) survival distributions were estimated using the Kaplan-Meier method. The log rank test was used to determine whether any patient characteristic, tumor feature, or molecular marker was associated significantly with PFS or OS., Results: The majority of tumor specimens were positive for ER (91%), PR (96%), AR (95%), and bcl-2 (94%). Fewer positive specimens were found for cyclin D1 (58%), MIB-1 (38%), HER-2/neu (29%), and p53 (21%). The 5-year PFS and 10-year OS for the entire patient cohort was estimated to be 66% (95% confidence interval [CI], 57-77%) and 38% (95% CI, 29-50%), respectively. PFS was decreased significantly for those patients with tumors staining positively for MIB-1 (P=0.012) or negatively for cyclin D1 (P=0.009). OS was not found to differ significantly with respect to these markers., Conclusions: The nearly universal expression of hormone receptors in these tumors suggests a central role for endogenous hormones in male breast carcinoma. The high degree of AR expression would suggest that antiandrogen therapy should be explored further. The high frequency of bcl-2 positivity may implicate antiapoptotic mechanisms in the carcinogenesis of male breast carcinoma. The finding of decreased PFS in MIB-1 positive tumors supports the role of proliferative activity as a negative prognostic factor in male breast carcinoma. Positive cyclin D1 expression is associated with increased PFS in male breast carcinoma patients, which suggests that interactions among cell cycle regulatory proteins may be important in this disease.

Background: Despite the availability of clinical and pathologic parameters of prognosis, the behavior of an individual meningioma may be difficult to predict. In a recent review of gross totally resected (GTR) meningiomas, the authors found strong associations between microscopic brain invasion, increased mitotic rate (> or = 4/10 high-power fields), the presence of at least 3 of 4 morphologic variables (sheeting, hypercellularity, macronucleoli, and small cells), and decreased recurrence free survival (RFS). In this study, they assessed the prognostic value of three ancillary techniques: DNA flow cytometry, MIB-1 labeling, and p53 protein expression., Methods: The authors evaluated primary GTR meningiomas from 425 patients with DNA flow cytometry, immunostaining for MIB-1, and determination of p53 protein expression. The patients were followed until death or for a median of 8.9 years., Results: An MIB-1 labeling index (LI) of > or = 4.2%, identified in 8% of cases, was strongly associated with decreased RFS in univariate analysis (P=0.0001). Fourteen percent contained aneuploid cell populations, and 48% exhibited a p53 LI of >10%. Neither variable was associated with decreased RFS. Further analysis revealed a close association between MIB-1 LI and mitotic index, the latter being the parameter of greatest significance in multivariate analysis., Conclusions: MIB-1 LI is a useful adjunct to routine histologic evaluation of meningiomas and appears to be of greatest value in the evaluation of tumors exhibiting borderline atypia. In contrast, our data suggest that, regarding patients with primary GTR meningiomas, neither flow cytometry nor p53 immunohistochemistry provides useful prognostic information.

Background: The incidence of primary central nervous system lymphoma (PCNSL) has increased over time in both immunocompetent and immunodeficient individuals. The reasons for the increase among immunocompetent patients are unclear., Methods: The authors conducted a case-control study of PCNSL at the Mayo Clinic based on cases from local community and referral practices. Cases were all PCNSL patients without immunodeficiency diagnosed between 1975 and 1994 (n = 109). Two groups of controls were selected from the same referral practice, namely, patients with other cancer (cancer controls; n = 101), and patients with a different neurologic disease (neurologic controls; n = 109) seen at our institution during the same time period., Results: PCNSL was significantly associated with lower education when cases were compared with cancer controls but only suggestively when cases were compared with neurologic controls. PCNSL cases were less likely to have had a history of tonsillectomy or oral contraceptive use compared with both control groups. The findings regarding autoimmune disorders and cardiovascular diseases were inconsistent for the two control groups. Neither farming nor prior personal or family history of cancer appeared to be risk factors for PCNSL., Conclusions: The findings of this study warrant further investigation of tonsillectomy and oral contraceptives as possible factors for PCNSL.

Background: It is common practice to utilize a series of different hormonal agents in the treatment of postmenopausal women who, despite disease progression, continue to be candidates for hormonal therapy on a clinical basis. Letrozole is a new highly selective and potent aromatase inhibitor. There are limited data on third-line hormonal therapy in general, and this study was undertaken to evaluate letrozole in this context., Methods: A randomized trial involving two independent Phase II trials of two letrozole dosage levels, 0.5 mg and 2.5 mg per day, was performed. Eligibility requirements included failure on two prior hormonal therapies and measurable or evaluable disease., Results: Ninety-one patients, 46 receiving 0.5 mg and 45 receiving 2.5 mg of letrozole per day, were assessable for response. At the lower dose, 9 patients (20%) achieved an objective response; 6 patients (13%) had this documented on 2 occasions separated by 3 months. At the higher dose, 10 patients (22%) achieved a response; 8 patients (18%) had this documented on 2 occasions separated by 3 months. The median times to progression were 97 days for the lower dose and 154 days for the higher dose. Toxicity was considered acceptable., Conclusions: Letrozole has definite antitumor activity as third-line hormonal therapy for women with metastatic breast carcinoma at doses of 0.5 and 2.5 mg per day. It is an effective and generally well-tolerated hormonal agent.

Background: It has been recommended that cobalt-60 or 4-MV photons be used when treating glottic cancer with radiation therapy. Underdosing may occur when using higher energy photons, particularly when the anterior commissure is involved. The authors report their experience using higher energy photons (6 MV) for the treatment of glottic cancer., Methods: Between January 1975 and July 1991, 73 patients with Tis, T1, T2, or T3 glottic tumors underwent radiation therapy with curative intent. Cobalt-60 or 4-MV photons were used to treat the cancers of 30 patients, and 6-MV photons were used to treat 43 patients. Clinical records were reviewed retrospectively to determine patterns of treatment failure, cancer deaths, and local tumor control in the 43 patients receiving treatment with 6-MV photons. Patients were followed until death or for a minimum of two years., Results: Treatment failures were: local recurrence, one patient; local recurrence and distant metastasis, one patient; delayed neck metastasis, two patients; and delayed neck metastasis with distant metastasis, one patient. Three patients who had treatment failure are alive and free of cancer after salvage treatment. Two patients died of neck and distant metastases. The 2-year initial local tumor control rate was 94.8%., Conclusions: Glottic cancer can be treated successfully with 6-MV photons. Local tumor control is similar to that reported using cobalt-60 or 4-MV photons.

Background: Most cases of granulosa cell tumor of the ovary are characterized by relatively good outcome; however, some tumors behave aggressively, and some tend to recur many years after the initial diagnosis. Because DNA ploidy has been shown to predict biologic behavior better than conventional prognostic variables in many types of genitourinary tumors, the DNA ploidy of granulosa cell tumors was studied to determine if this test correlates with recurrence or survival., Methods: Paraffin embedded tissue blocks were available from the primary ovarian tumors of 40 patients. DNA ploidy, percent S-phase fraction, and proliferative index were determined for each sample and were compared with patient outcome., Results: Of the 40 tumors, 33 were DNA diploid, 5 were DNA near diploid/aneuploid, and 2 were aneuploid. The Kaplan-Meier estimate of the probability of tumors not recurring within 5 years postoperatively was 0.907 (95% confidence interval: 0.811, 1.00)., Conclusions: There is insufficient evidence to claim that the DNA pattern is associated with morphology, stage of disease at diagnosis, or tumor size or that either survival or progression free survival differs with respect to any of the conventional prognostic factors considered. However, progression free survival tends to be shorter for those whose maximal tumor dimension was at least 10 cm (borderline significance, P = 0.0597), and survival time tends to be shorter for those with a high proliferative index (P = 0.0008).