The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST)

Jiralerspong, Sao; Giordano, S.; Meric‐Bernstam, Funda; Barnett, C. M.; Kau, Shu Wan; Hung, Mien‐Chie; Hortobágyi, G. N.; González-Angulo, Ana M.

doi:10.1200/jco.2008.26.15_suppl.528

Cited by 11 publications

(9 citation statements)

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“…We speculate that hyperinsulinemia can lead to increased growth rates, because malignant tumors often over express insulin‐like growth factor‐1 and insulin receptors 26‐28. There is some evidence that antidiabetic drugs may have direct effects on cancers and may reduce the risk of disease development or recurrence,29‐31 but we do not have data on which medications our diabetic patients were taking; therefore, this hypothesis needs to be tested in a larger population of diabetic patients in which such information is available.…”

Section: Discussionmentioning

confidence: 97%

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer

Varlotto

Recht

Flickinger

et al. 2010

Cancer

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BACKGROUND:The objective of this study was to examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients who undergo potentially curative resection for stage I nonsmall cell lung cancer (NSCLC). METHODS: The study included 306 consecutive patients who were treated from 2000 to 2005 without radiotherapy. Local recurrence was defined either as ''radiation'' (r-LR) (according to previously defined postoperative radiotherapy fields), including the bronchial stump, staple line, ipsilateral hilum, and ipsilateral mediastinum; or as ''comprehensive'' (c-LR), including the same sites plus the ipsilateral lung and contralateral mediastinal and hilar lymph nodes. All recurrences that were not classified as ''local'' were considered to be distal. RESULTS: The median follow-up was 33 months. The proportions of c-LR and r-LR at 2 years, 3 years, and 5 years were 14%, 21%, and 29%, respectively, and 7%, 12%, and 16%, respectively. Significant risk factors for c-LR on multivariate analysis were diabetes, lymphatic vascular invasion, and tumor size; and significant factors for r-LR were resection of less than a lobe and lymphatic vascular invasion. The proportions of distant (nonlocal) recurrence using these definitions at 2 years, 3 years, and 5 years were 10%, 12%, and 18%, respectively, and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the c-LR definition and tumor size when using the r-LR definition. CONCLUSIONS: Local recurrence increased nearly 2-fold when a broad definition was used instead of a narrow definition. The definition also affected which factors were associated significantly with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series.

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Section: Discussionmentioning

confidence: 97%

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer

Varlotto

Recht

Flickinger

et al. 2010

Cancer

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“…The thiazolides result in decreased expression of the antiapoptotic, immunosuppressive, and inflammatory prostaglandin E2 in NSCLC cell lines 26. Furthermore, recent evidence suggests that the antihyperglycemic drug metformin may have therapeutic effects against pancreatic cancer cell lines and breast cancer 27, 28. However, we do not have data regarding the medications our diabetic patients were taking and hence this hypothesis would need to be tested in a larger population of diabetics where such information is available.…”

Section: Discussionmentioning

confidence: 97%

Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer

Varlotto

Recht

Flickinger

et al. 2009

Cancer

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BACKGROUND: This study assessed the impact of surgical, histopathologic and patient‐related factors on the risks of local and distant recurrence and overall survival for patients with stages I through IIIA nonsmall cell lung carcinoma (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy. METHODS: This study included 373 consecutive patients treated between 2000 and 2005 who did not receive adjuvant or neoadjuvant radiotherapy, had at least 3 months of follow‐up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Of these, 52% had pathologic stage IA disease, 30% had stage IB, 5% had stage IIA, 8% had stage IIB and 5% had stage III disease. Forty‐four patients received chemotherapy. RESULTS: The median follow‐up was 33 months. Local failure rates at 2 years, 3 years, and 5 years were 16%, 22%, and 32%, respectively; distant recurrence rates were 13%, 15%, and 21%, respectively. Multivariable analysis revealed that local recurrence was significantly associated with the presence of lymphatic or vascular invasion (LVI), the use of chemotherapy, and having diabetes; distant recurrence was significantly higher in patients with nonsquamous cell histology, those undergoing pneumonectomy, and those with more advanced TNM stage. Survival was significantly associated with age, history of myocardial infarction, performance of a pneumonectomy, histology, LVI, and the number of positive N1 lymph nodes. CONCLUSIONS: Local recurrence was the predominant type of failure in this series. Patient with diabetes or LVI may benefit from close surveillance and aggressive therapy of asymptomatic local recurrences, especially when chemotherapy is given in addition to surgery. Cancer 2009. © 2009 American Cancer Society.

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“…These subsets may be better identified by the use of serum analytes such as fasting insulin, C-peptide, insulin-like growth factor binding protein 1, or adiponectin than by the use of body mass index or other anthropomorphic measurements because the "normal-weight, metabolically obese" phenotype is common in developed countries (30). Although early reports suggest the possibility of clinical relevance (18,19,31), further translational research in this area is needed.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Adiponectin and Metformin on Prostate and Colon Neoplasia Involve Activation of AMP-Activated Protein Kinase

Zakikhani

Dowling

Sonenberg

et al. 2008

Cancer Prevention Research

273

227

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Population studies provide evidence that obesity and insulin resistance are associated not only with elevated serum insulin levels and reduced serum adiponectin levels but also with increased risk of aggressive prostate and colon cancer. We show here that adiponectin activates AMP-activated protein kinase (AMPK) in colon (HT-29) and prostate (PC-3) cancer cells. These results are consistent with prior observations in myocytes, but we show that in epithelial cancer cells AMPK activation is associated with reduction in mammalian target of rapamycin activation as estimated by Ser 2448 phosphorylation, with reduction in p70S6 kinase activation as estimated by Thr 389 phosphorylation, with ribosomal protein S6 activation as estimated by Ser 235/236 phosphorylation, with reduction in protein translation as estimated by [ 35 S]methionine incorporation, and with growth inhibition. Adiponectin-induced growth inhibition is significantly attenuated when AMPK level is reduced using small interfering RNA, indicating that AMPK is involved in mediating the antiproliferative action of this adipokine. Thus, adiponectin has the characteristics of a AMPK-dependent growth inhibitor that is deficient in obesity, and this may contribute to the adverse effects of obesity on neoplastic disease. Furthermore, metformin was observed to activate AMPK and to have growth inhibitory actions on prostate and colon cancer cells, suggesting that this compound may be of particular value in attenuating the adverse effects of obesity on neoplasia.

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The effects of metformin on pathologic complete response (pCR) rates in diabetic breast cancer (BC) patients receiving neoadjuvant systemic therapy (NST)

Cited by 11 publications

References 0 publications

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer

Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer

Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer

The Effects of Adiponectin and Metformin on Prostate and Colon Neoplasia Involve Activation of AMP-Activated Protein Kinase

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