A qualitative systematic review of the evidence base for non-cross-resistance between steroidal and non-steroidal aromatase inhibitors in metastatic breast cancer

Aims

The most effective sequence of tamoxifen and both steroidal (SAIs) and non-steroidal aromatase inhibitors (NSAIs) has been extensively studied in the adjuvant setting. However, treatments for women who have failed initial aromatase inhibitor therapy in the metastatic setting have received relatively little attention. A systematic review was undertaken to assess the use of SAIs and NSAIs in metastatic breast cancer.

Materials and methods

Medline, Embase and the Cochrane library were searched using free text and MeSH terms. Studies assessing the cross-resistance, efficacy and safety of SAIs and NSAIs for postmenopausal women with advanced metastatic breast cancer confirmed by histology/cytology were included. Patients had progressed/relapsed from previous adjuvant, first- or second-line aromatase inhibitor treatment and had undergone treatment with at least two regimens consisting of aminoglutethimide, anastrozole, letrozole and/or exemestane.

Results

Nine studies reported results for patients treated with an SAI after treatment failure with an NSAI. For SAI after NSAI, clinical benefit was the most frequently reported outcome. The clinical benefit for exemestane (SAI) after any NSAI failure or before treatment ranged from 12% (complete response not recorded, partial response 2%, stable disease 10%) to 55% (complete response 6%, partial response 13%, stable disease 35%) Survival outcomes were infrequently reported; four studies reported disease progression. The time to progression ranged from 3.7 to 5.2 months. Only one study reported a median overall survival with exemestane at 15.2 months. Only one study reported information for an NSAI after SAI and an NSAI followed by another NSAI.

Discussion

This review suggests that switching from an NSAI to an SAI is a reasonable option. This would be particularly important for patients who would probably respond to further endocrine manoeuvres; strongly oestrogen receptor-positive disease, non-visceral disease, a good prior response or a long duration of response. Further research to optimise the sequence of endocrine therapies in metastatic breast cancer is needed.     

Dynamic contrast-enhanced magnetic resonance imaging and blood oxygenation level-dependent magnetic resonance imaging for the assessment of changes in tumor biology with treatment

Functional magnetic resonance imaging (MRI) techniques are rapidly gaining importance as methods of exploring the pathophysiological properties of breast carcinomas. In the neoadjuvant setting where the primary tumor remains in situ, functional MRI is able to noninvasively evaluate microenvironmental features such as blood flow and oxygenation. Dynamic contrast-enhanced MRI provides information on tumor vascularity with evidence suggesting a role in predicting response to neoadjuvant chemotherapy. The spatial heterogeneity of response to anti-angiogenic and vascular disrupting agents can also be depicted. There is preliminary data supporting blood oxygenation level-dependent MRI as a potential marker of tumor oxygenation, with the ability to characterize tissue oxygenation changes with neoadjuvant chemotherapy. Additionally, advanced MR sequences such as diffusion-weighted MRI and MR spectroscopy have the potential to provide information relating to cellularity and metabolism, respectively.     

International expert consensus on primary systemic therapy in the management of early breast cancer: highlights of the Fourth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2010)

A panel of international breast cancer experts formulated a declaration of consensus regarding many key issues in the use of primary systemic therapy (PST) either in clinical routine or research practice. The attainment of pathological complete response (pCR), defined as no residual invasive tumor in the surgical specimens both in breast and in axillary nodes, is one of the main goals of PST, and pCR can be used as the primary objective in prospective clinical trials. However, pCR is not a reliable endpoint with all treatment approaches, and alternatives such as Ki67 index of the residual invasive disease or after 2 weeks of PST are also potential endpoints. PST has several advantages: breast conservation and the unique opportunity to obtain information on the interaction between treatment and tumor biology. Changes in tumor biology after PST are an early phenomenon; so, an additional core biopsy performed after 14 days from treatment start should be considered in clinical trials.     

Progression to end-stage liver disease in patients with inherited bleeding disorders and hepatitis C: an international, multicenter cohort study

Prior to 1990, many patients with inherited bleeding disorders were infected with hepatitis C virus (HCV). This study assessed the risk of end-stage liver disease (ESLD) in patients with hemophilia with chronic hepatitis C. Patients were infected between 1961 and 1990 and were followed up to August 2005. Of 847 anti-HCV(+) patients, 160 (19%) spontaneously cleared HCV and 687 (81%) developed chronic hepatitis C. Coinfection with HIV was present in 210 patients. After 35 years of infection the cumulative incidence of ESLD was 11.5% (95% CI, 8.2%-14.8%) in HIV(-) patients and 35.1% (95% CI, 29.2%-41.0%; P < .001) in patients coinfected with HIV. Independent risk factors of ESLD were HIV coinfection (hazard ratio 13.8; 95% CI, 7.5-25.3), older age at infection (hazard ratio 2.3 per 10 years; 95% CI, 2.0-2.8), alcohol abuse (hazard ratio 4.9; 95% CI, 2.5-9.6), and presence of HCV genotype 1 (hazard ratio 2.2; 95% CI, 1.1-4.2). With longer duration of HCV infection, the risk of developing ESLD is emerging in patients with inherited bleeding disorders. Risk factors for rapid progression to ESLD are alcohol abuse, coinfection with HIV, older age at infection, and presence of HCV genotype 1.     

Appendiceal Mucocele. A retrospective Analysis of 19 Cases

Background

Appendiceal mucocele is an infrequent well-recognized entity that can present in a variety of clinical syndromes or can be asymptomatic and discovered incidentally.

Patients and Methods

Nineteen patients with a diagnosis of primary appendiceal mucocele treated in our institution between January 1, 1987 and December 31, 2006 were included in this retrospective analysis.

Results

The histological examination of the specimens revealed simple and hyperplastic appendiceal mucocele in nine cases (47%), mucinous appendiceal cystadenoma in eight cases (42%), and mucinous appendiceal cystadenocarcinoma in two cases (11%). Thirteen patients (68%) underwent appendectomy, five patients (26%) right colectomy, and two patients (6%) underwent right colectomy for invasive appendiceal cystadenocarcinoma and at the same time right nephrectomy and sigmoidectomy, respectively, for concomitant malignancy.

Conclusion

Mucocele of the appendix may be related to a benign or malignant appendiceal process, leading to individualized diagnosis and treatment.