Clinical and pathological correlations in male breast cancer: intratumoral aromatase expression via tissue microarray

Abstract Background  Male breast cancer (MBC) commonly expresses hormone receptors and there is anecdotal evidence of disease responsivity to aromatase inhibitors in the metastatic setting. Our objectives were to: (i) assess clinical-pathologic characteristics in a consecutive cohort of MBC (ii) evaluate intratumoral aromatase (ITA) expression via tissue microarray (TMA) and (iii) assess the prognostic impact of ITA

Prospective evaluation of fatigue during a course of curative radiotherapy for localised prostate cancer

Abstract Purpose  To prospectively evaluate radiation-induced fatigue among patients undergoing curative radiotherapy at the Toronto Sunnybrook Regional Cancer Centre using two different instruments.

Endoscopic transanal resection provides palliation equivalent to transabdominal resection in patients with metastatic rectal cancer

Abstract  Patients with metastatic rectal cancer precluding curative low anterior resection (LAR) or abdominoperineal resection (APR) can require palliation for impending obstruction. LAR or APR is frequently not optimal because of the associated operative morbidity. Lesser procedures such as diverting colostomy require patients to live with a permanent stoma. Endoscopic transanal resection (ETAR) has been used for excision of rectal lesions. To determine whether ETAR provides palliation equivalent to LAR or APR, we reviewed the outcomes of 49 patients with rectal adenocarcinoma and unresectable liver metastases who required palliative intervention between January 1989 and July 1996. Of these 49 patients, 24 underwent ETAR; the intraluminal tumor was resected using the urologic resectoscope to achieve a hemostatic, patent lumen. The outcomes of these patients were compared to those of the other 25 patients who had palliative LAR, APR, or a Hartmann procedure during the same period. The median distance of the tumors from the anal verge was similar (5 cm; range 1 to 15 cm). ETAR patients had a higher percentage of poorly differentiated tumors (35% vs. 6%, P = 0.034) and higher preoperative alkaline phosphatase values (478 ±75 mg/dl vs. 231 ±24 mg/dl; P<0.015), suggesting more aggressive disease and greater hepatic tumor burden, respectively. Despite these differences, overall survival and time spent outside the hospital were similar in the two groups. The median number of debulking procedures required in the 24 ETAR patients was two (range 1 to 17). Resections in the 25 LAR/APR patients included LAR in 20, APR in two, and Hartmann procedures in three. There was a trend toward more stomas in the LAR/APR group (28% vs. 17%). More important, morbidity was significantly higher in the LAR/APR patients (24% vs. 4%; P = 0.049). In conclusion, ETAR is a safe alternative for the palliation of incurable rectal tumors. Compared to transabdominal resection, ETAR provides equivalent palliation as measured by survival and proportion of the patient’s life spent outside the hospital, with a lower stoma rate and significantly less morbidity. Therefore, in select patients with metastatic rectal cancer, ETAR is an important palliative option.

Adaptation of Estrogen-regulated Genes in Long-term Estradiol Deprived MCF-7 Breast Cancer Cells

Summary  First line treatment of hormone dependent breast cancer initially causes tumor regression but later results in adaptive changes and tumor re-growth. Responses to second line treatments occur but tumors again begin to progress after a period of 12–18 months. In depth understanding of the adaptive process would allow the identification of targets to abrogate the development of hormonal resistance and prolong the efficacy of endocrine therapy. We have developed a model system to examine adaptive changes in human MCF-7 breast cancer cells. Upon deprivation of estradiol for a prolonged period of time, a maneuver analogous to surgical oophorectomy in pre-menopausal women and use of aromatase inhibitors in post-menopausal patients, tumor cells adapt and become hypersensitive to estradiol. We reasoned that the expression pattern of multiple genes would change in response to estradiol deprivation and that cDNA microarrays would provide an efficient means of assessing these changes. Accordingly, we examined the transcriptional responses to estradiol in long-term estradiol deprived (LTED) MCF-7 cells with a cDNA microarray containing 1901 known genes and ESTs. To assess the changes induced by long-term estradiol deprivation, we compared the effects of estradiol administration in LTED cells with those in MCF-7 cells, which we had previously reported, and confirmed with real time PCR using the parental and LTED cells. Seven genes and one EST were induced by estradiol in LTED but not in wild type MCF-7 cells, whereas ten genes were down-regulated by estradiol only in LTED cells. The expression of seven genes increased concurrently and five decreased in response to estradiol in both cell types. From these observations, we generated testable hypotheses regarding several genes including DKFZP, RAP-1, ribosomal protein S6, and TM4SF1. Based upon the known functions of these genes and the patterns of observed changes, we postulate that divergent regulation of these genes may contribute to the different biologic responses to estrogen in these cell lines. These results provide targets for further mechanistic studies in our experimental system. Our findings indicate that long-term estradiol deprivation causes expression changes in multiple genes and emphasizes the complexity of the process of cellular adaptation.

Differential effects of tamoxifen and anastrozole on optic cup size in breast cancer survivors

Abstract Introduction  The main purpose of this study was to determine whether the optic cups of tamoxifen users and anastrozole users differ in size, with the cups of the tamoxifen users being smaller.

Simultaneous Resections of Colorectal Cancer and Synchronous Liver Metastases: A Multi-institutional Analysis

Abstract Background  The safety of simultaneous resections of colorectal cancer and synchronous liver metastases (SCRLM) is not established. This multi-institutional retrospective study compared postoperative outcomes after simultaneous and staged colorectal and hepatic resections.

Complete Clinical Response After Preoperative Chemoradiation in Rectal Cancer: Is a “Wait and See” Policy Justified?

Abstract Purpose  A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of “waiting to see” and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery.