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Stevens Point, WI, United States

Onitilo A.A.,Marshfield Clinic Weston Center | Onitilo A.A.,University of Queensland | Kar P.,Allegiance Health | Engel J.M.,Marshfield Clinic Cancer Care | Glurich I.,Marshfield Clinic Research Foundation
Minerva Medica | Year: 2013

The relative impact of tamoxifen therapy in women with breast cancer on overall survival, especially as it pertains to cardiac and cardiovascular outcomes, remains under debate in the literature. This review focuses specifically on outcomes of studies that examined large clinical trials with longest duration in patient follow-up relative to these parameters in which compliance with therapy could be documented. Over time, evidence supports potential cardioprotective effects and capacity of adjuvant therapy to improve lipid profiles in women treated with tamoxifen. While some benefit to cardiac health is supported, outcomes related to cardiovascular events remain variable across studies and challenging to interpret. In summary, overall survival in women treated with tamoxifen over time has increasingly shown a trend towards positive outcomes in the context of evaluation of post-treatment cardiac and vascular health. Potential mechanisms underlying the cardioprotective effects of tamoxifen are briefly discussed. Source


Onitilo A.A.,Marshfield Clinic Weston Center | Onitilo A.A.,University of Queensland | Engel J.M.,Marshfield Clinic Cancer Care | Stankowski R.V.,Marshfield Clinic Research Foundation | Doi S.A.R.,University of Queensland
Clinical Medicine and Research | Year: 2015

Objectives: Evidence suggests superiority of breast conserving surgery (BCS) plus radiation over mastectomy alone for treatment of early stage breast cancer. Whether the superiority of BCS plus radiation is related to the surgical approach itself or to the addition of adjuvant radiation therapy following BCS remains unclear. Materials and Methods: We conducted a retrospective cohort study of women with breast cancer diagnosed from 1994–2012. Data regarding patient and tumor characteristics and treatment specifics were captured electronically. Kaplan-Meier survival analyses were performed with inverse probability of treatment weighting to reduce selection bias effects in surgical assignment. Results: Data from 5335 women were included, of which two-thirds had BCS and one-third had mastectomy. Surgical decision trends changed over time with more women undergoing mastectomy in recent years. Women who underwent BCS versus mastectomy differed significantly regarding age, cancer stage/grade, adjuvant radiation, chemotherapy, and endocrine treatment. Overall survival was similar for BCS and mastectomy. When BCS plus radiation was compared to mastectomy alone, 3-, 5-, and 10-year overall survival was 96.5% vs 93.4%, 92.9% vs 88.3% and 80.9% vs 67.2%, respectively. Conclusion: These analyses suggest that survival benefit is not related only to the surgery itself, but that the prognostic advantage of BCS plus radiation over mastectomy may also be related to the addition of adjuvant radiation therapy. This conclusion requires prospective confirmation in randomized trials. © 2015 Marshfield Clinic Health System. Source


Onitilo A.A.,University of Queensland | Onesti J.K.,Grand Rapids Medical Education Partners | Single R.M.,University of Vermont | Engel J.M.,Marshfield Clinic Cancer Care | And 5 more authors.
PLoS ONE | Year: 2013

Background: Treatment with neoadjuvant chemotherapy (NAC) has made it possible for some women to be successfully treated with breast conservation therapy (BCT ) who were initially considered ineligible. Factors related to current practice patterns of NAC use are important to understand particularly as the surgical treatment of invasive breast cancer has changed. The goal of this study was to determine variations in neoadjuvant chemotherapy use in a large multi-center national database of patients with breast cancer. Methods: We evaluated NAC use in patients with initially operable invasive breast cancer and potential impact on breast conservation rates. Records of 2871 women ages 18-years and older diagnosed with 2907 invasive breast cancers from January 2003 to December 2008 at four institutions across the United States were examined using the Breast Cancer Surgical Outcomes (BRCASO) database. Main outcome measures included NAC use and association with pre-operatively identified clinical factors, surgical approach (partial mastectomy [PM] or total mastectomy [TM]), and BCT failure (initial PM followed by subsequent TM). Results: Overall, NAC utilization was 3.8%l. Factors associated with NAC use included younger age, pre-operatively known positive nodal status, and increasing clinical tumor size. NAC use and BCT failure rates increased with clinical tumor size, and there was significant variation in NAC use across institutions. Initial TM frequency approached initial PM frequency for tumors >30-40mm; BCT failure rate was 22.7% for tumors >40mm. Only 2.7% of patients undergoing initial PM and 7.2% undergoing initial TM received NAC. Conclusions: NAC use in this study was infrequent and varied among institutions. Infrequent NAC use in patients suggests that NAC may be underutilized in eligible patients desiring breast conservation. © 2013 Onitilo et al. Source


Onitilo A.A.,Marshfield Clinic Weston Center | Onitilo A.A.,University of Queensland | Berg R.L.,Marshfield Clinic Research Foundation | Engel J.M.,Marshfield Clinic Cancer Care | And 4 more authors.
PLoS ONE | Year: 2013

Background:Historically, studies exploring the association between type 2 diabetes mellitus (DM) and cancer lack accurate definition of date of DM onset, limiting temporal analyses. We examined the temporal relationship between colon cancer risk and DM using an electronic algorithm and clinical, administrative, and laboratory data to pinpoint date of DM onset.Methods:Subjects diagnosed with DM (N = 11,236) between January 1, 1995 and December 31, 2009 were identified and matched at a 5:1 ratio with 54 365 non-diabetic subjects by age, gender, smoking history, residence, and diagnosis reference date. Colon cancer incidence relative to the reference date was used to develop Cox regression models adjusted for matching variables, body mass index, insurance status, and comorbidities. Primary outcomes measures included hazard ratio (HR) and number needed to be exposed for one additional person to be harmed (NNEH).Results:The adjusted HR for colon cancer in men before DM onset was 1.28 (95% CI 1.04-1.58, P = 0.0223) and the NNEH decreased with time, reaching 263 at DM onset. No such difference was observed in women. After DM onset, DM did not appear to alter colon cancer risk in either gender.Conclusions:Colon cancer risk is increased in diabetic men, but not women, before DM onset. DM did not alter colon cancer risk in men or women after clinical onset. In pre-diabetic men, colon cancer risk increased as time to DM onset decreased, suggesting that the effects of the pre-diabetes phase on colon cancer risk in men are cumulative. © 2013 Onitilo et al. Source


Onitilo A.A.,Marshfield Clinic Weston Center | Onitilo A.A.,Marshfield Clinic Research Foundation | Onitilo A.A.,University of Queensland | Engel J.M.,Marshfield Clinic Cancer Care | And 4 more authors.
Cancer Causes and Control | Year: 2012

An association between type 2 diabetes mellitus (DM) and cancer has long been postulated, but the biological mechanism responsible for this association has not been defined. In part one of this review, we discussed the epidemiological evidence for increased risk of cancer, decreased cancer survival, and decreased rates of cancer screening in diabetic patients. Here we review the risk factors shared by cancer and DM and how DM medications play a role in altering cancer risk. Hyperinsulinemia stands out as a major factor contributing to the association between DM and cancer, and modulation of circulating insulin levels by DM medications appears to play an important role in altering cancer risk. Drugs that increase circulating insulin, including exogenous insulin, insulin analogs, and insulin secretagogues, are generally associated with an increased cancer risk. In contrast, drugs that regulate insulin signaling without increasing levels, especially metformin, appear to be associated with a decreased cancer risk. In addition to hyperinsulinemia, the effect of DM medications on other shared risk factors including hyperglycemia, obesity, and oxidative stress as well as demographic factors that may influence the use of certain DM drugs in different populations are described. Further elucidation of the mechanisms behind the association between DM, cancer, and the role of DM medications in modulating cancer risk may aid in the development of better prevention and treatment options for both DM and cancer. Additionally, incorporation of DM medication use into cancer prediction models may lead to the development of improved risk assessment tools for diabetic patients. © 2012 Springer Science+Business Media B.V. Source

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