Severe Hypoglycemia Caused by Paraneoplastic Production of IGF-II in Patients With Advanced Gastrointestinal Stromal Tumors: A Report of Two Cases
Authors: Daniel Pink, Dagmar Schoeler, Tanja Lindner, Peter C. Thuss-Patience, Albrecht Kretzschmar, Heike Knipp, Udo Vanhoefer, Peter Reichardt
Journal: Journal of Clinical Oncology (2005)

major shift in management strategy for breast cancer patients and has been taken one step further in a research paper published on behalf of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trials Group. 2 This paper advocates that not only should 5 years of an aromatase inhibitor be the preferred hormonal option for these women, but that anastrozole is the agent of choice.Such conviction may not be fully justified at the present time and in the face of alternative (and potentially interchangeable) aromatase inhibitors and a continued price differential with tamoxifen, which inevitably influences any cost-benefit analysis.The most recent ATAC data at 68 months follow-up shows a continuing divergence of the curves for disease-free survival with evidence of a carry-over effect and a reduction in time to distant recurrence in favor of anastrozole. 2However, there is no difference in overall survival [hazard ratio (HR) 0.97; P ϭ .7]and the relatively good prognostic parameters of patients (61% node-negative) may ultimately obscure translation into a statistically significant benefit for this end point.Furthermore, non-breast cancer-related deaths could be higher in the anastrozole group as effects of aromatase inhibitors on the cardiovascular system and lipid profile remain unclear.These data must be placed in context with those from other adjuvant trials of aromatase inhibitors such as the Intergroup Exemestane (IES), the Italian (ITA), and the Austrian (ABCSG/ARNO) studies, which collectively involve a large number of patients.At a median follow-up of 37 months, the IES trial yields a HR of 0.83 for exemestane with a P value approaching significance (P ϭ .08). 3 This trial could be the first to eventually show a gain in overall survival for use of an aromatase inhibitor within the conventional hormonal treatment span of 5 years.Definitive results are awaited of the BIG-FEMTA trial, which incorporates both a direct comparison of letrozole and tamoxifen (5 years treatment duration) together with sequential regimes of tamoxifen (2 to 3 years) followed by letrozole (2 to 3 years) and vice versa.It seems likely that any blanket policy for adjuvant hormonal therapy in postmenopausal women with early breast cancer is no longer appropriate.A selective strategy based on risk of relapse may prove optimal; there is evidence that patients with estrogen receptor positive but progesterone receptor negative tumors and those with over-expression of HER-2 neu may derive proportionately more benefit from aromatase inhibition (HR 0.48). 4These patients could receive an aromatase inhibitor at the outset that may suppress the amplitude of the hazard peak for recurrence, which is of greater magnitude in those at higher risk of relapse. 5For those patients with lower hazard rates for relapse in the first 2 to 3 years, sequential therapy with tamoxifen (2 to 3 years) followed by an aromatase inhibitor may be more appropriate.Finally, it should be noted that a group of patients may exist for whom the standard 5 years of tamoxifen remains the most cost-effective therapy.Urgent clarification and guidance is demanded on how best to advise and manage patients who are newly diag-nosed with breast cancer or have already received some years of tamoxifen.