Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

EGFR dependent expression of STAT3 (but not STAT1) in breast cancer.

STAT proteins constitute a family of transcription factors whose activation by cytokine and non-cytokine receptors leads to tyrosine phosphorylation, dimerization and translocation from the cytoplasm to the nucleus. In the nucleus they activate the transcription of specific genes by binding to consensus DNA elements. STATs 1 and 3 can be activated by both cytokine and non-cytokine receptors, and bind as homodimers or heterodimers to viral simian sarcoma virus (sis)-inducible elements such as that found in the c-fos promoter. Activation of c-Src and EGF receptor tyrosine kinases is associated with progression of breast cancer. Both these events lead to activation of STAT proteins, Src kinases activate STAT3 dependent transcription in mammary epithelial cells and EGF receptor activation can lead to activation of STATs 1 and 3. STAT3 activation has been demonstrated to have a role in oncogenesis and increasingly, activated STAT proteins are found to be activated in human cancer. In this study we describe detailed immunohistochemical analysis of nuclear and cytoplasmic STATs 1 and 3 expression in primary breast carcinomas and correlate this with EGFR, HER2, p53, ER, PR, p21/waf1, Bcl-XL and Ki-67 expression. We also compared expression between normal and tumor tissue. We report here a highly significant correlation between nuclear STAT3 expression and breast cancers compared to normal tissue. We also report a very strong correlation between nuclear STAT3 and EGFR expression in breast cancers. These data clearly demonstrate a strong association between STAT3 activation and breast tumorigenesis and strengthen the assertion that STAT3 activation may play an important role in the tumorigenic conversion of breast tissue mediated by tyrosine kinase signaling pathways.

[Acute non-lymphoblastic leukemia in patients treated for Hodgkin's disease. Analysis of 309 cases]. / ANLL in pazienti trattati per morbo di Hodgkin. Analisi di 309 casi.

The analysis of 309 Hodgkin patients treated by radiotherapy alone or in association with chemotherapy, between 1969 and 1979, has shown seven cases of ANLL (acute non lymphoblastic leukemia). The incidence was 2.26% in the overall group and 3.38% in the patients treated with combined therapies. From the frequency and distribution of ANLL in the various treatment groups we can argue that: ANLL may be considered as a second, therapy-induced tumor, correlated with the association of chemotherapy and radiotherapy.

[Ovarian fibrothecoma: MR imaging findings and differential diagnosis]. / Fibrothekom des Ovars: MR-bildgebung und Differentialdiagnose.

We report the preoperative MR imaging of a 70 year old woman with a large tumor of the lower abdomen. MRI shows a extensively large mass with low signal in T2-weighted images. The origin of this tumor was suspected to be either the left ovary or the uterus. In the differential diagnosis a large subserous pedunculated leiomyoma or a low cellular, primarily benign ovarian tumor were considered.

[Radiotherapy of recurrences of adenocarcinoma of the rectum after radical surgery: Galliera Hospitals (1976-1985)]. / La radioterapia delle recidive di adenocarcinoma del retto operato radicalmente: Ospedali Galliera (1976-1985).

From 1976 through 1985, 68 patients were treated with radiation therapy at Ospedali Galliera, Genoa, Italy, for recurrence of radically-operated rectal adenocarcinomas, most of them in Dukes (Astler, Coller) B2, C1, and C2 stages. The average disease-free interval between surgery and recurrence was 12 months (range 2-144) in the whole group, versus only 6 months in stage C2 patients. Pain relief was obtained in 45 patients (66%), and reduction in recurrence size in 22 (32%), with the following global results: disease progression in 16 patients, no progression/regression in 26, partial regression in 19, complete response in 3, and not evaluable in 4. Twenty-one patients had many contemporaneous distant metastases (2 cases) or within a short period of time after the locoregional recurrence (19 cases). These results lead us to believe that radiation therapy should not be employed in so many cases of radical surgery for rectal adenocarcinoma as it is today, but only in case of locoregional recurrences, as an alternative to postoperative radiotherapy, combined, if needed, with adjuvant chemotherapy.

[Radiotherapy of cerebral metastases of breast cancer. Clinical experience with 67 patients]. / La radioterapia delle metastasi cerebrali da carcinoma della mammella. Esperienza clinica su 67 pazienti.

Sixty-seven cases of brain metastases from breast carcinoma treated in the period from January 1969 to June 1986 with radiotherapy (high energies on homogeneous volume, 250-300 kV grid roentgenoherapy) have been evaluated retrospectively. Performance status improvement, evaluated according to Order's stages, with increased quality of life has been obtained in 66% of the patients. Results do not appear to be substantially affected from the different techniques and methods of irradiation. However the importance of implementing and performing the radiotherapy treatment in such a way to keep as high as possible the benefit/risk ratio is stressed, owing to the possibility to observe a few long survival patients after brain metastases occurrence.

[The mammographic images of the irradiated breast after conservative therapy for carcinoma]. / Quadri mammografici della mammella irradiata dopo terapia conservativa per carcinoma.

The mammographic patterns of the patients treated with conservative surgery (quadrantectomy) plus radiotherapy for early breast carcinoma were evaluated to assess treatment-induced changes over time and to improve the differential diagnosis between postirradiation effects and possible tumor recurrences. The mammographic examinations of 79 patients who had undergone quadrantectomy and radiotherapy for breast carcinoma (stage T1-T2) were examined. Skin thickening, edema, fibrosis, distortion and calcifications were considered and classified by comparing the radiographic patterns of the treated breast with those of the contralateral and untreated one. Pattern changes over time were also evaluated and quantified by comparing serial follow-up examinations of the same breast. The percentage of patients with irradiation-induced skin thickening steadily reduced from 100% at 6 months to just above 50% at 4 years. The number of patients showing diffuse irradiation-induced edema decreased from 56% at 6 months to 15% at 1 year and to 0% at 2 years, while the number of cases with localized edema decreased more slowly. The incidence of localized postirradiation breast fibrosis increased to 74% at 4 years, while diffuse fibrosis stabilized around 14%. The patients with no postoperative breast distortion accounted for nearly 33% of the examined cases, while those with minimal distortion approximated 58% and those with gross distortion 9%. In conclusion, the overall results confirmed the value of mammography in the follow-up of the patients treated with QUART.

Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial.

Between 1983 and 1986, the National Institute for Cancer Research in Genoa and affiliated institutions conducted a randomized study to compare two different ways of combining chemotherapy (CT) and radiation therapy (RT). One hundred sixteen patients were randomized to receive neoadjuvant CT followed by definitive RT (treatment arm A) or alternating CT and RT. In treatment arm A, RT consisted of 70 Gy to the involved areas and 50 Gy to the uninvolved neck at 2 Gy/fraction, five fractions per week. In treatment arm B, RT consisted of 60 Gy to involved areas and 50 Gy to the uninvolved neck in three courses of 20 Gy each, 2 Gy/fraction, ten fractions/2 weeks alternated with four courses of CT. CT consisted of vinblastine 6 mg/m2 intravenously followed 6 hours later by bleomycin 30 IU intramuscularly, day 1; methotrexate 200 mg intravenously, day 2; leucovorin rescue, day 3. CT was repeated every 2 weeks up to four courses. The same CT was used in both treatment arms of the study. Fifty-five patients were entered in treatment arm A and 61 in treatment arm B. Complete responses were 7/48 and 19/57 in treatment arms A and B, respectively (P less than 0.03). Four-year progression-free survival was 4% in treatment arm A and 12% in treatment arm B (P less than 0.02), and four-year survival was 10% in A and 22% in B (P less than 0.02). Mucosal tolerance was significantly worse in treatment arm B (P less than 0.00004). The subgroup analysis shows the major improvement of alternating CT and RT in patients with the worst prognostic characteristics.

[Total body irradiation in the preparation of leukemic patients for bone marrow transplantation]. / L'irradiazione corporea totale nella preparazione al trapianto ematomidollare in pazienti leucemici.

Total body irradiation is today the main conditioning method for patients who have bone marrow transplantation. The most diffuse procedure, as proposed at the Fred Hutchinson Cancer Research Center of Seattle, has been employed in this study. Our clinical material comprises 16 patients; 5 with acute lymphoid leukemia; 5 with acute myeloid leukemia; 4 with chronic myeloid leukemia in accelerated fase; and 2 in blastic crisis. Clinical results and toxicity are discussed, with emphasis to interstitial pneumonia.

[High-dose gynecologic endocavitary brachytherapy. Technical and dosimetric aspects]. / Brachiterapia endocavitaria ginecologica ad alta intensità di dose. Aspetti tecnici e dosimetrici.

The technical and dosimetric aspects are presented of high-dose intracavitary brachytherapy in gynecology. Fifty-five patients (203 insertions) were examined over two years with a remote loading Selectron HDR 60Co unit installed in a dedicated bunker. The dose to the rectal and bladder markers on AP and LL films was calculated before every irradiation, in order to allow the necessary corrections to be made. Uniform irradiation conditions were obtained at each treatment set-up for both tumoral target and bladder and rectal doses. High-dose intracavitary brachytherapy proved to be a safe, reliable and versatile method from the technical and dosimetric point of view both in the treatment of unoperated gynecological malignancies and in postoperative therapy.