The effect of non-oncology drugs on clinical and genomic risk in early luminal breast cancer.

BACKGROUND: An effect of non-oncology medications on cancer outcome has been proposed. In this study, we aimed to systematically examine the impact of commonly prescribed non-oncology drugs on clinical risk and on the genomic risk [based on the Oncotype DX recurrence score (RS)] in early breast cancer (BC). EXPERIMENTAL DESIGN: We collected data on clinical risk (stage and grade), genomic risk (Oncotype DX RS), and on non-oncology medications administered to 1423 patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative BC during the month of their surgery. The influence of various medications on clinical and genomic risks was evaluated by statistical analysis. RESULTS: Out of the multiple drugs we examined, levothyroxine was significantly associated with a high Oncotype DX RS (mean 24.78; P < 0.0001) and metformin with a low Oncotype DX RS (mean 14.87; P < 0.01) compared with patients not receiving other non-oncology drugs (mean 18.7). By contrast, there were no differences in the clinical risk between patients receiving metformin, levothyroxine, or no other non-oncology drugs. Notably, there was no association between the consumption of levothyroxine and metformin and proliferation marker (Ki67) levels, but both drugs were significantly associated with progesterone-related features, suggesting that they influence genomic risk through estrogen-dependent signaling. CONCLUSIONS: The results of this study indicate a significant impact of metformin and levothyroxine on clinical decisions in luminal BC, with potential impact on the clinical course of these patients.

Respective indications for orbital rim, zygomatic arch and orbito-zygomatic osteotomies in the surgical approach to central skull base lesions. Critical, retrospective review in 146 cases.

BACKGROUND: Orbital Rim (ORo) Zygomatic Arch (ZAo) and Orbito-Zygomatic (OZo) osteotomies can be useful adjuncts to the classical Fronto-Pteriono-Temporal craniotomy in facilitating the exposure of deep seated skull base lesions, sparing brain retraction injuries. Based on a review of 146 "operated" cases, the authors suggest their guidelines for patient selection for each of these osteotomies. METHOD: 146 lesions (100 central skull base tumors, 29 deep vascular lesions and 17 mesial temporal epileptogenic foci) were surgically treated by the senior author between 1988-1999 using ORo (59 cases), ZAo (12 cases) and OZo (75 cases). The lesion were radically cured in 85% of the cases. A retrospective critical analysis of patients' records by an independent observer evaluated: 1)--the usefulness and the appropriateness of the performed osteotomy for obtaining an optimal approach to the lesion and 2)--morbidity related to the osteotomy and to brain retraction. FINDINGS: In only one case, the osteotomy (ORo) was found not to be useful. An other 17 patients who underwent OZo would have benefited from a reduced osteotomy (ORo in 15 cases, ZAo in 2 cases). In another case an ORo was found insufficient for an effective exposure of the lesion. Osteotomy-related morbidity rate was 10.2% (15 patients), mostly due to transient Temporo Mandibular Joint dysfunction. In spite of an appropriate approach, 12 patients (8.2%) showed neurological deficits (temporary) and/or CT manifestations attributable to brain retraction. INTERPRETATION: The additional osteotomies were found useful and relatively safe in facilitating the exposure of most of the lesions in this series. A target (rather than pathology) and surgical axis oriented list of indications for ORo, ZAo and OZo is given.

Meningiomas of the anterior cranial fossa floor. Review of 67 cases.

The authors report 67 cases of meningioma of the anterior cranial fossa floor treated surgically between 1978 and 1992. The olfactory groove and tuberculum sellae were the most frequent locations. Mean duration of the clinical history was 30 months. Seventy-three percent of the tumors were large (> 4 cm). All patients were examined with computed tomography and 18 with magnetic resonance imaging as well. Complete removal was performed in 56 cases (84%); in the remaining 11 (16%), partial removal was performed because of encasement of the carotid artery, cavernous sinus, or optic nerves by the tumour. Mortality was 9%. Results at follow-up of the 61 survivors were good in 56 (84%), fair in four (6%), and poor in one (1%). The clinical results were correlated to tumor location and dimension. After review of the literature, the management of these difficult tumours and the preferred surgical technique are discussed. The authors stress the importance of early diagnosis for improving the surgical results.