Research Spotlight

Posted March 15th 2016

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

Robert G. Mennel M.D.

Robert G. Mennel, M.D.

Harris, L. N., N. Ismaila, L. M. McShane, F. Andre, D. E. Collyar, A. M. Gonzalez-Angulo, E. H. Hammond, N. M. Kuderer, M. C. Liu, R. G. Mennel, C. van Poznak, R. C. Bast and D. F. Hayes (2016). “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.” J Clin Oncol. Feb 8. [Epub ahead of print]

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PURPOSE: To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. METHODS: A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. RECOMMENDATIONS: In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.


Posted March 15th 2016

Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.

William C. Roberts M.D.

William C. Roberts, M.D.

Roberts, W. C., S. A. Hall, J. M. Ko, P. A. McCullough and B. Lima (2016). “Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.” Am J Cardiol 117(5): 878-879.

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Described are findings in a 70-year-old man who had heart transplantation 4 years after treatment with a left ventricular assist device, and surgical closure of his previously replaced aortic valve. The result was a totally nonfunctioning left ventricle resulting in severe atrophy.


Posted March 15th 2016

Proliferation of Online Medical Journals.

William C. Roberts M.D.

William C. Roberts, M.D.

Roberts, W. C. (2016). “Proliferation of Online Medical Journals.” Am J Cardiol 117(4): 699-700.

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Almost daily on my emails there is a new open access (online) medical journal requesting a manuscript from me, or asking that I review a manuscript received by them. During a recent 2-month period, I counted at least 26 heart-related journals (Table 1) and at least 75 non-heart related journals (Table 2). Most do not have a physician as editor and few are included on PubMed. Medicine went from a physician editor of international distinction to a non-physician editor of unknown qualifications. Most of the online journals charge authors to publish their manuscripts and not the readers for reading them, the reverse of hundreds of years of publishing. Some of these online journals not only request reviews from physicians of the submitted manuscripts but also request that physicians recommend names of appropriate reviewers, and some request that physicians actually manage groups of manuscripts as visiting editors. A young investigator might be tempted to submit his/her manuscript to one of the open-access journals after receiving a gracious invitation to do so rather than submit the manuscript to an established journal. I realize that online publishing without print publishing will probably be the future for most present-day print journals but that change has not occurred yet so I recommend staying with the print journals as long as they use that medium. Academic careers will not be built by publishing in the open access journals with non-physician editors.


Posted March 15th 2016

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy, M.D.

Krekow, L. K., B. A. Hellerstedt, R. P. Collea, S. Papish, S. M. Diggikar, R. Resta, S. J. Vukelja, F. A. Holmes, P. K. Reddy, L. Asmar, Y. Wang, P. S. Fox, S. R. Peck and J. O’Shaughnessy (2016). “Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.” J Clin Oncol. Feb 16. [Epub ahead of print]

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PURPOSE: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. PATIENTS AND METHODS: Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for >/= 1 year were treated with letrozole (2.5 mg) daily for >/= 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. RESULTS: The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naive patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. CONCLUSION: These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.


Posted March 15th 2016

Phase II, Multicenter, Single-Arm, Feasibility Study of Eribulin Combined With Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive, Early-Stage Breast Cancer.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy, M.D.

Smith, J. W., 2nd, S. Vukelja, A. D. Hoffman, V. E. Jones, K. McIntyre, E. Berrak, J. X. Song and J. O’Shaughnessy (2016). “Phase II, Multicenter, Single-Arm, Feasibility Study of Eribulin Combined With Capecitabine for Adjuvant Treatment in Estrogen Receptor-Positive, Early-Stage Breast Cancer.” Clin Breast Cancer 16(1): 31-37.

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BACKGROUND: The present phase II, open-label, multicenter study explored the feasibility, safety, and tolerability of eribulin, a novel non-taxane microtubule inhibitor, plus capecitabine as adjuvant therapy. PATIENTS AND METHODS: Postmenopausal women with early-stage, human epidermal growth factor receptor 2 (HER2)-negative, estrogen-receptor (ER)-positive breast cancer received four 21-day cycles of treatment with eribulin mesylate (1.4 mg/m(2) intravenously on days 1 and 8 of each cycle) combined with capecitabine (900 mg/m(2) orally twice daily on days 1-14 of each cycle [standard schedule] or 1500 mg orally twice daily using a 7-days on/7-days off schedule [weekly schedule]). Feasibility was determined by the relative dose intensity (RDI) of the combination using prespecified criteria for 80% of patients achieving an RDI of >/= 85%, with a lower 95% confidence boundary > 70%. RESULTS: The mean RDI was 90.6%, and the feasibility rate was 81.3% among women (n = 67, mean age, 61.3 years) receiving the standard schedule and 95.6% and 100% among women (n = 10, mean age 62.3 years) receiving the weekly schedule. Dose reductions, missed doses, and withdrawals due to adverse events (most commonly hand-foot syndrome) ascribed to capecitabine led to a higher RDI (93.5% vs. 87.8%) and feasibility rate (82.8% vs. 71.9%) for eribulin than for capecitabine using the standard dosing schedule. The most common adverse events were alopecia and fatigue. CONCLUSION: Eribulin plus capecitabine with standard or weekly dosing schedules is feasible in patients with early-stage, HER2-negative, ER-positive breast cancer. Full-dose eribulin (1.4 mg/m(2) on days 1 and 8) with capecitabine (1500 mg orally twice daily, 7 days on/7 days off) is recommended as a regimen for further evaluation.