Publications by authors named "Helen Krontiras"

49 Publications

Less Toxic Chemotherapy in Locally Advanced Breast Cancer.

South Med J 2020 11;113(11):559-563

From the Division of Hematology/Oncology, the Department of Radiation Oncology, the Department of Surgery, the Division of Preventive Medicine, and the UAB Comprehensive Cancer, University of Alabama at Birmingham, Birmingham.

Objectives: Preoperative chemotherapy produces tumor shrinkage in most patients with locally advanced breast cancer, including some pathological complete responses (pCRs). We attempted this using a much less toxic sequential regimen, given with concurrent bevacizumab.

Methods: Patients with locally advanced breast cancer received 3 intravenous doses each of preoperative sequential liposome encapsulated doxorubicin 25 mg/m, paclitaxel 175 mg/m, and cyclophosphamide 600 mg/m, with concurrent bevacizumab every 2 weeks without growth factor support.

Results: Between March 2008 and December 2009, 32 patients received treatment. There was no cardiotoxicity, and other toxicity was mild (no grade 4 or 5 toxicity). No long-term toxicity, including cardiotoxicity, has been observed. Every patient had ≥30% reduction in tumor size; 9 of 31 patients who completed chemotherapy had pCR at operation. Seven years later, 22 of 32 patients remain free of recurrence and 27 of 32 are alive.

Conclusions: The preoperative chemotherapy used appears to be comparably effective, but much less toxic than that used in most conventional regimens and should be studied further. Concurrent treatment with bevacizumab (reported separately) did not provide any additional benefit.
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http://dx.doi.org/10.14423/SMJ.0000000000001169DOI Listing
November 2020

Expectations of Surveillance for Non-BRCA Gene Mutation Carriers at Increased Risk for Breast Cancer.

J Surg Res 2020 12 23;256:267-271. Epub 2020 Jul 23.

Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Background: The University of Alabama at Birmingham Preventative Care Program for Women's Cancer provides genetic testing, risk evaluation, and screening for breast cancer. Women diagnosed with high-risk mutations may opt to undergo active surveillance or prophylactic surgery. This decision requires understanding of the surveillance process and its potential outcomes. In this study, we report specifically on women with non-BRCA1 or BRCA2 mutations.

Methods: A retrospective, cross-sectional study was conducted of women enrolled in our program identified as high risk because of non-BRCA mutations. Events regarding genetic mutations, method of detection of suspicious lesions, number of biopsies, results of those biopsies, prophylactic surgery, and cancer diagnosis were collected.

Results: We identified 78 patients with asymptomatic non-BRCA deleterious mutations. Sixteen mutations were identified, with the most common being ATM, CHEK2, and PALB2. In total, 11.5% underwent prophylactic surgery and 88.5% underwent active surveillance. In the surveillance group, 63.8% had no examination or imaging to warrant biopsy, 24.6% had biopsy with benign result, and 11.6% had biopsy with malignant result. For the nine women who developed breast cancer during surveillance, six were diagnosed with ductal carcinoma in situ, two with stage I, and one with stage IIA cancer.

Conclusions: Women with non-BRCA mutations enroll in prevention clinics with hopes of early detection of breast cancer. Because of increased screening, this population undergoes biopsy more frequently; however, during surveillance most do not require a biopsy. For those that do, the result is typically benign. This information can further allow women to make informed decisions about surveillance and establish realistic expectations regarding the likelihood of tissue sampling.
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http://dx.doi.org/10.1016/j.jss.2020.06.029DOI Listing
December 2020

A Randomized, Placebo-Controlled, Double-Blind, Dose Escalation, Single Dose, and Steady-State Pharmacokinetic Study of 9cUAB30 in Healthy Volunteers.

Cancer Prev Res (Phila) 2019 12 4;12(12):903-912. Epub 2019 Sep 4.

University of Wisconsin Carbone Cancer Center, Madison, Wisconsin.

9cUAB30 is a synthetic analogue of 9-cis retinoic acid with chemoprevention activity in cell lines and animal models. The purpose of this phase I placebo-controlled, double-blinded, dose escalation study of 9cUAB30 was to evaluate its safety, pharmacokinetics, and determine a dose for future phase II studies. Participants received a single dose of study drug (placebo or 9cUAB30) on day 1 followed by a 6-day drug-free period and then 28 days of continuous daily dosing starting on day 8. Fifty-three healthy volunteers were enrolled into five dose cohorts (20, 40, 80, 160, and 240 mg). Participants were randomized within each dose level to receive either 9cUAB30 ( = 8) or placebo ( = 2). 9cUAB30 was well tolerated, with no dose limiting toxicities reported and no evidence of persistent elevations in serum triglycerides or cholesterol. Treatment-emergent grade 3 hypertension occurred in 1 of 8 participants at the 20 mg dose level and in 2 of 8 at the 240 mg dose level, all considered unlikely related to study agent; no other grade 3 adverse events were observed. The AUC increased, as expected, between day 1 (single dose) and day 36 (steady state). Pharmacokinetics were linear in dose escalation through 160 mg. 9cUAB30 administered by daily oral dosing has a favorable safety and pharmacokinetic profile. On the basis of the observed safety profile and lack of linearity in pharmacokinetics at doses greater than 160 mg, the recommended phase II dose with the current formulation is 160 mg once daily.
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http://dx.doi.org/10.1158/1940-6207.CAPR-19-0310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008944PMC
December 2019

Randomized trial of weight loss in primary breast cancer: Impact on body composition, circulating biomarkers and tumor characteristics.

Int J Cancer 2020 05 5;146(10):2784-2796. Epub 2019 Sep 5.

O'Neal Comprehensive Cancer Center at UAB, Birmingham, AL.

Obesity adversely impacts overall and cancer-specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits cancer progression; however, feasibility and effects in patients are unknown. A two-arm, single-blinded, randomized controlled weight-loss trial was undertaken presurgery among 32 overweight/obese, Stage 0-II breast cancer patients. The attention control arm (AC) received basic nutritional counseling and upper-body progressive resistance training whereas the weight loss intervention (WLI) arm received identical guidance, plus counseling on caloric restriction and aerobic exercise to promote 0.68-0.92 kg/week weight loss. Anthropometrics, body composition, blood and survey data were collected at baseline and presurgery ∼30 days later. Tumor markers (e.g., Ki67) and gene expression were assessed on biopsy and surgical specimens; sera were analyzed for cytokines, growth and metabolic factors. Significant WLI vs. AC differences were seen in baseline-to-follow-up changes in weight (-3.62 vs. -0.52 kg), %body fat (-1.3 vs. 0%), moderate-to-vigorous physical activity (+224 vs. +115 min/week), caloric density (-0.3 vs. 0 kcal/g), serum leptin (-12.3 vs. -4.0 ng/dl) and upregulation of tumor PI3Kinase signaling and cell cycle-apoptosis related genes (CC-ARG; all p-values <0.05). Cytolytic CD56 NK cell expression was positively associated with weight loss; CC-ARG increased with physical activity. Increased tumor (nuclear) TNFα and IL-1β, CX3CL1 and CXCL1 gene expression was observed in the WLI. Tumor Ki67 did not differ between arms. Feasibility benchmarks included 80% accrual, 100% retention, no adverse effects and excellent adherence. Short-term weight loss interventions are feasible; however, mixed effects on tumor biology suggest unclear benefit to presurgical caloric restriction, but possible benefits of physical activity.
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http://dx.doi.org/10.1002/ijc.32637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155016PMC
May 2020

The Impact of Breast Lumpectomy Tray Utilization on Cost Savings.

J Surg Res 2019 01 27;233:32-35. Epub 2018 Jul 27.

Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Background: Right-sizing instrument trays reduce processing and replacement costs, physical strain, and turnover times. Historically, a 98-instrument head and neck tray has been used for breast lumpectomy cases at our institution. Observations revealed that many instruments on the tray were not used during the breast cases. With the significant number of surgical breast lumpectomies performed annually, tray downsizing could significantly reduce costs and physical strain.

Methods: Surgical technicians identified instruments needed for a standard breast lumpectomy. Breast surgeons reviewed the list and made final recommendations. Three of 13 existing head and neck trays were converted to breast lumpectomy trays. The number of breast lumpectomies in 2017 was pulled from the institution's health information system. Instrument quantities were verified using instrument management software. Weights were taken on a digital scale, and processing cost was estimated by a consultant.

Results: The new breast trays included 51 instruments rather than the standard 98-instrument trays. Reprocessing cost decreased from $49.98 to $26.01. With 449 breast lumpectomies performed at the institution in 2017, the annual reprocessing savings totaled $10,763. The tray weight was reduced from 27 to 16 pounds. Setup time decreased from 7 to 4 min per use (22.5 h saved annually).

Conclusions: Downsizing from a head and neck tray to a specific breast lumpectomy tray demonstrated a reduction in reprocessing cost, tray weight, and setup time. Lighter trays allow for safer handling and transport by surgical personnel. In the current health-care environment, it is important to maximize operating room efficiency and minimize cost.
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http://dx.doi.org/10.1016/j.jss.2018.06.063DOI Listing
January 2019

Treatment patterns for ductal carcinoma in situ with close or positive mastectomy margins.

J Surg Res 2018 11 1;231:36-42. Epub 2018 Jun 1.

Department of Surgery, The University of Alabama at Birmingham, Birmingham, Alabama. Electronic address:

Background: Mastectomy remains an effective treatment for ductal carcinoma in situ (DCIS) but whether further therapy is warranted for close or positive margins is controversial. We aim to characterize the treatment practices of DCIS throughout the United States in patients who undergo mastectomy with close or positive margins to better understand the use of postmastectomy radiation therapy (PMRT).

Materials And Methods: Using the 2004-2013 National Cancer Database, we identified all female patients with a diagnosis of DCIS who underwent mastectomy. Distributional characteristics were summarized for overall and margin-stratified samples. Characteristic differences were assessed by region and receipt of radiation. Chi-square and independent sample t-tests were used to assess differences for categorical and continuous variables, respectively.

Results: In 21,591 patients who met inclusion criteria, 470 patients with close/positive margins were identified. Sixteen percent of patients with close/positive margins received PMRT compared to 1.5% with negative margins (P < 0.01). There was no difference in PMRT and patient race, insurance status, treatment facility, or endocrine therapy. Patients with close/positive margins who received PMRT were more likely to be in an urban setting from the Midwest (24.6%) and Northeast (21.8%) compared to the West (11.0%) and South (10.7%) (P < 0.01).

Conclusions: Use of PMRT for DCIS following mastectomy with close/positive margins differs across the country. Regional variations in treatment patterns reinforce a need to determine whether PMRT improves survival to establish treatment guidelines.
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http://dx.doi.org/10.1016/j.jss.2018.05.007DOI Listing
November 2018

Breast Cancer Genetics and Indications for Prophylactic Mastectomy.

Surg Clin North Am 2018 Aug 30;98(4):677-685. Epub 2018 May 30.

Division of Surgical Oncology, Department of Surgery, University of Alabama at Birmingham, Faculty Office Tower Suite 1153, 1720 2nd Avenue South, Birmingham, AL 35294-3411, USA.

As more genetic information becomes available to inform breast cancer treatment, screening, and risk-reduction approaches, clinicians must become more knowledgeable about possible genetic testing and prevention strategies, including outcomes, benefits, risks, and limitations. The aim of this article is to define and distinguish high- and moderate-risk breast cancer predisposition genes, summarize the clinical recommendations that may be considered based on the identification of pathogenic variants (mutations) in these genes, and indications for risk-reducing and contralateral prophylactic mastectomy.
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http://dx.doi.org/10.1016/j.suc.2018.03.004DOI Listing
August 2018

A Structured Compensation Plan Improves But Does Not Erase the Sex Pay Gap in Surgery.

Ann Surg 2018 09;268(3):442-448

University of Alabama at Birmingham, Department of Surgery, Birmingham, AL.

Objective: The aim of this study is to examine the relationship between the sex pay gap in a large academic department of surgery and a recently instituted structured compensation plan.

Summary Of Background Data: A recent large study found that after controlling for measures of academic and clinical productivity, male physicians earned nearly $20,000 more annually than female physicians. Increased salary transparency has been proposed as a method to reduce this disparity.

Methods: A new structured compensation plan was developed to improve transparency of compensation and financial viability of each division. The total compensations of each faculty member before and after the new compensation plan were calculated. Salaries were compared with the Association of Academic Medical Colleges (AAMC) median value based on specialty, region, academic rank, stratified by sex and compared. Work relative value units (wRVUs) were calculated for each faculty member during the entire study period, stratified by sex and compared.

Results: Among 44 eligible surgeons (33 men and 11 women), a sex pay gap existed with male surgeon salaries significantly higher than female surgeon salaries [56% (8 to 213) vs 26% (1 to 64); P < 0.00001] despite similar RVU production (men 8725 ± 831 vs women 7818 ± 911, P = 0.454). The new compensation plan did not significantly change male surgeon salaries [56% (8 to 213) vs 58% (26 to 159); P = 0.552] but did significantly increase the salaries of female surgeons [26% (1 to 64) vs 42% (10 to 80); P = 0.026].

Conclusion: A structured compensation plan can improve the sex pay gap in a short period of time. More transparency in surgical compensation plans is essential to understand the most equitable way to compensate all surgeons.
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http://dx.doi.org/10.1097/SLA.0000000000002928DOI Listing
September 2018

Select Choices in Benign Breast Disease: An Initiative of the American Society of Breast Surgeons for the American Board of Internal Medicine Choosing Wisely Campaign.

Ann Surg Oncol 2018 Oct 2;25(10):2795-2800. Epub 2018 Jul 2.

Gundersen Medical Foundation, La Crosse, WI, USA.

Background: Up to 50% of all women encounter benign breast problems. In contrast to breast cancer, high-level evidence is not available to guide treatment. Management is therefore largely based on individual physician experience/training. The American board of internal medicine (ABIM) initiated its Choosing Wisely campaign to promote conversations between patients and physicians about challenging the use of tests or procedures which may not be necessary. The American society of breast surgeons (ASBrS) Patient safety and quality committee (PSQC) chose to participate in this campaign in regard to the management of benign breast disease.

Methods: The PSQC solicited initial candidate measures. PSQC surgeons represent a wide variety of practices. The resulting measures were ranked by modified Delphi appropriateness methodology in two rounds. The final list was approved by ASBrS and endorsed by the ABIM.

Results: The final five measures are as follows. (1) Don't routinely excise areas of pseuodoangiomatous stromal hyperplasia (PASH) of the breast in patients who are not having symptoms from it. (2) Don't routinely surgically excise biopsy-proven fibroadenomas that are < 2 cm. (3) Don't routinely operate for a breast abscess without an initial attempt to percutaneously aspirate. (4) Don't perform screening mammography in asymptomatic patients with normal exams who have less than a 5-years life expectancy. (5) Don't routinely drain nonpainful, fluid-filled cysts.

Conclusions: The ASBrS Choosing Wisely measures that address benign breast disease management are easily accessible to patients via the internet. Consensus was reached by PSQC regarding these recommendations. These measures provide guidance for shared decision-making.
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http://dx.doi.org/10.1245/s10434-018-6584-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512861PMC
October 2018

Benchmarking the American Society of Breast Surgeon Member Performance for More Than a Million Quality Measure-Patient Encounters.

Ann Surg Oncol 2018 Feb 22;25(2):501-511. Epub 2017 Nov 22.

Columbia University Medical Center, New York, NY, USA.

Background: Nine breast cancer quality measures (QM) were selected by the American Society of Breast Surgeons (ASBrS) for the Centers for Medicare and Medicaid Services (CMS) Quality Payment Programs (QPP) and other performance improvement programs. We report member performance.

Study Design: Surgeons entered QM data into an electronic registry. For each QM, aggregate "performance met" (PM) was reported (median, range and percentiles) and benchmarks (target goals) were calculated by CMS methodology, specifically, the Achievable Benchmark of Care™ (ABC) method.

Results: A total of 1,286,011 QM encounters were captured from 2011-2015. For 7 QM, first and last PM rates were as follows: (1) needle biopsy (95.8, 98.5%), (2) specimen imaging (97.9, 98.8%), (3) specimen orientation (98.5, 98.3%), (4) sentinel node use (95.1, 93.4%), (5) antibiotic selection (98.0, 99.4%), (6) antibiotic duration (99.0, 99.8%), and (7) no surgical site infection (98.8, 98.9%); all p values < 0.001 for trends. Variability and reasons for noncompliance by surgeon for each QM were identified. The CMS-calculated target goals (ABC™ benchmarks) for PM for 6 QM were 100%, suggesting that not meeting performance is a "never should occur" event.

Conclusions: Surgeons self-reported a large number of specialty-specific patient-measure encounters into a registry for self-assessment and participation in QPP. Despite high levels of performance demonstrated initially in 2011 with minimal subsequent change, the ASBrS concluded "perfect" performance was not a realistic goal for QPP. Thus, after review of our normative performance data, the ASBrS recommended different benchmarks than CMS for each QM.
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http://dx.doi.org/10.1245/s10434-017-6257-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758679PMC
February 2018

NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer.

Clin Cancer Res 2017 Aug 7;23(15):4055-4065. Epub 2017 Mar 7.

Pfizer Pharmaceuticals, New York, New York.

Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. Eligible patients with clinical stage II/III ER/HER2 breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%). Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression. Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. .
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http://dx.doi.org/10.1158/1078-0432.CCR-16-3206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555232PMC
August 2017

Exploring effects of presurgical weight loss among women with stage 0-II breast cancer: protocol for a randomised controlled feasibility trial.

BMJ Open 2016 09 15;6(9):e012320. Epub 2016 Sep 15.

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Introduction: Obesity is a known risk factor for postmenopausal breast cancer and is associated with poorer prognosis for premenopausal and postmenopausal patients; however, the aetiological mechanisms are unknown. Preclinical studies support weight loss via caloric restriction and increased physical activity as a possible cancer control strategy, though few clinical studies have been conducted. We undertook a feasibility trial among women recently diagnosed with stage 0-II breast cancer hypothesising that presurgical weight loss would be feasible, safe and result in favourable changes in tumour markers and circulating biomarkers.

Methods And Analysis: A two-arm randomised controlled trial among 40 overweight or obese women, newly diagnosed with stage 0-II breast cancer and scheduled for surgery was planned. The attention control arm received upper body progressive resistance training and diet counselling to correct deficiencies in nutrient intake; the experimental arm received the same plus counselling on caloric restriction and aerobic exercise to achieve a weight loss of 0.68-0.919 kg/week. In addition to achieving feasibility benchmarks (accruing and retaining at least 80% of participants, and observing no serious adverse effects attributable to the intervention), we will explore the potential impact of an acute state of negative energy balance on tumour proliferation rates (Ki-67), as well as other tumour markers, serum biomarkers, gene expression, microbiome profiles and other clinical outcomes (eg, quality of life). Outcomes for the 2 study arms are compared using mixed models repeated-measures analyses.

Ethics And Dissemination: Ethics approval was received from the University of Alabama at Birmingham Institutional Review Board (Protocol number F130325009). Study findings will be disseminated through peer-reviewed publications. Given that this is one of the first studies to investigate the impact of negative energy balance directly on tumour biology in humans, larger trials will be pursued if results are favourable.

Trial Registration Number: NCT02224807; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2016-012320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030610PMC
September 2016

Measures of Appropriateness and Value for Breast Surgeons and Their Patients: The American Society of Breast Surgeons Choosing Wisely (®) Initiative.

Ann Surg Oncol 2016 10 22;23(10):3112-8. Epub 2016 Jun 22.

OasisMD, San Diego, CA, USA.

Background: Current breast cancer care is based on high-level evidence from randomized, controlled trials. Despite these data, there continues to be variability of breast cancer care, including overutilization of some tests and operations. To reduce overutilization, the American Board of Internal Medicine Choosing Wisely (®) Campaign recommends that professional organizations provide patients and providers with a list of care practices that may not be necessary. Shared decision making regarding these services is encouraged.

Methods: The Patient Safety and Quality Committee of the American Society of Breast Surgeons (ASBrS) solicited candidate measures for the Choosing Wisely (®) Campaign. The resulting list of "appropriateness" measures of care was ranked by a modified Delphi appropriateness methodology. The highest-ranked measures were submitted to and later approved by the ASBrS Board of Directors. They are listed below.

Results: (1) Don't routinely order breast magnetic resonance imaging in new breast cancer patients. (2) Don't routinely excise all the lymph nodes beneath the arm in patients having lumpectomy for breast cancer. (3) Don't routinely order specialized tumor gene testing in all new breast cancer patients. (4) Don't routinely reoperate on patients with invasive cancer if the cancer is close to the edge of the excised lumpectomy tissue. (5) Don't routinely perform a double mastectomy in patients who have a single breast with cancer.

Conclusions: The ASBrS list for the Choosing Wisely (®) campaign is easily accessible to breast cancer patients online. These measures provide surgeons and their patients with a starting point for shared decision making regarding potentially unnecessary testing and operations.
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http://dx.doi.org/10.1245/s10434-016-5327-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999471PMC
October 2016

Translation of a Tissue-Selective Rexinoid, UAB30, to the Clinic for Breast Cancer Prevention.

Curr Top Med Chem 2017 ;17(6):676-695

901 14th street south, Birmingham Al 35294, United States.

This review focuses on our efforts to translate a low-toxicity retinoid X receptor-selective agonist, UAB30, to the clinic for the prevention of breast cancers. The review is divided into several sections. First, the current status of breast cancer prevention is discussed. Next, preclinical studies are presented that support translation of rexinoids to the clinic for cancer prevention. While current FDAapproved retinoids and rexinoids demonstrate profound effects in treating cancers, they lack sufficient safety for long term use in the high risk population that is otherwise disease free. The review stresses the need to identify cancer preventive drugs that are effective and safe in order to gain wide use in the clinic. Due to the heterogeneity of the disease, UAB30 is evaluated for the prevention of ER-positive and ER-negative mammary cancers. Since selective estrogen receptor modulators and aromatase inhibitors are used clinically to prevent and treat ER-positive breast cancers, preclinical studies also must demonstrate efficacy of UAB30 in combination with existing drugs under use in the clinic. To support an Investigational New Drug Application to the FDA, data on pharmacology and toxicity as well as mutagenicity is gathered prior to human trials. The review concludes with a discussion of the outcomes of human Phase 0/1 clinical trials that determine the safety and pharmacology of UAB30. These studies are essential before this agent is evaluated for efficacy in phase 2 trials. Success in phase 2 evaluation is critical before long-term and costly phase 3 trials are undertaken. The lack of surrogate biomarkers as endpoints for phase 2 evaluation of rexinoid preventive agents is discussed.
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http://dx.doi.org/10.2174/1568026616666160617093604DOI Listing
February 2017

Prognostic Impact of 21-Gene Recurrence Score in Patients With Stage IV Breast Cancer: TBCRC 013.

J Clin Oncol 2016 07 21;34(20):2359-65. Epub 2016 Mar 21.

Tari A. King, Jaclyn P. Lyman, Mithat Gonen, Amy Voci, Marina De Brot, Camilla Boafo, Larry Norton, Monica Morrow, and Clifford A. Hudis, Memorial Sloan Kettering Cancer Center, New York, NY; Amy Pratt Sing, Genomic Health, Redwood City; Michael D. Alvarado, University of California San Francisco Comprehensive Cancer Center, San Francisco, CA; E. Shelley Hwang, Duke University School of Medicine, Durham, NC; Minetta C. Liu, Georgetown University Medical Center, Washington, DC; Judy C. Boughey, Mayo Clinic, Rochester, MN; Kandace P. McGuire, University of Pittsburgh, Pittsburgh, PA; Catherine H. Van Poznak, University of Michigan Medical School, Ann Arbor, MI; Lisa K. Jacobs, Johns Hopkins University School of Medicine, Baltimore, MD; Ingrid M. Meszoely, Vanderbilt University Medical Center, Nashville, TN; Helen Krontiras, University of Alabama at Birmingham School of Medicine, Birmingham, AL; and Gildy V. Babiera, The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: The objective of this study was to determine whether the 21-gene Recurrence Score (RS) provides clinically meaningful information in patients with de novo stage IV breast cancer enrolled in the Translational Breast Cancer Research Consortium (TBCRC) 013.

Patients And Methods: TBCRC 013 was a multicenter prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. From July 2009 to April 2012, 127 patients from 14 sites were enrolled; 109 (86%) patients had pretreatment primary tumor samples suitable for 21-gene RS analysis. Clinical variables, time to first progression (TTP), and 2-year overall survival (OS) were correlated with the 21-gene RS by using log-rank, Kaplan-Meier, and Cox regression.

Results: Median patient age was 52 years (21 to 79 years); the majority had hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (72 [66%]) or hormone receptor-positive/HER2-positive (20 [18%]) breast cancer. At a median follow-up of 29 months, median TTP was 20 months (95% CI, 16 to 26 months), and median survival was 49 months (95% CI, 40 months to not reached). An RS was generated for 101 (93%) primary tumor samples: 22 (23%) low risk (< 18), 29 (28%) intermediate risk (18 to 30); and 50 (49%) high risk (≥ 31). For all patients, RS was associated with TTP (P = .01) and 2-year OS (P = .04). In multivariable Cox regression models among 69 patients with estrogen receptor (ER)-positive/HER2-negative cancer, RS was independently prognostic for TTP (hazard ratio, 1.40; 95% CI, 1.05 to 1.86; P = .02) and 2-year OS (hazard ratio, 1.83; 95% CI, 1.14 to 2.95; P = .013).

Conclusion: The 21-gene RS is independently prognostic for both TTP and 2-year OS in ER-positive/HER2-negative de novo stage IV breast cancer. Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset.
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http://dx.doi.org/10.1200/JCO.2015.63.1960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981976PMC
July 2016

Impact of a behavioral weight loss intervention on comorbidities in overweight and obese breast cancer survivors.

Support Care Cancer 2016 08 5;24(8):3285-93. Epub 2016 Mar 5.

University of California, San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093, USA.

Purpose: Comorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss.

Methods: ENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses.

Results: At 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p < 0.001); however, by 24 months, there was no longer a significant difference. No difference was observed in each of the four conditions for which non-cancer medications were prescribed, hospital visits, or emergency visits at either 12 or 24 months.

Conclusions: These results support a short-term benefit of modest weight loss on the likelihood of comorbid conditions; however, recidivism and weight regain likely explain no benefit at 1-year postintervention follow-up.
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http://dx.doi.org/10.1007/s00520-016-3141-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323258PMC
August 2016

Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY)-randomized weight loss trial among breast cancer survivors.

Breast Cancer Res Treat 2015 Nov 31;154(2):329-37. Epub 2015 Oct 31.

Department of Health Policy & Management and Medicine, Schools of Public Health and Medicine, University of California - Los Angeles, Los Angeles, CA, 90095, USA.

Obesity is a poor prognostic factor and is negatively related to quality of life (QOL) in breast cancer survivors. Exercise and Nutrition to Enhance Recovery and Good Health for You is the largest weight loss trial completed among cancer survivors. Percent losses in body weight with an intensive group-based intervention versus an attention control were 6.0 versus 1.5 % (p < 0.0001) and 3.7 versus 1.3 % (p < 0.0001) at 12 and 24 months, respectively. ENERGY also was designed to answer the research question: Does weight loss significantly improve vitality and physical function (key components of QOL)? 692 breast cancer survivors (BMI: 25-45 kg/m(2)) at 4 US sites were randomized to a year-long intensive intervention of 52 group sessions and telephone counseling contacts versus a non-intensive (control) of two in-person counseling sessions. Weight, self-reported QOL, and symptoms were measured semi-annually for two years. Significant decreases in physical function and increases in symptoms were observed among controls from baseline to 6 months, but not in the intervention arm, -3.45 (95 % Confidence Interval [CI] -6.10, -0.79, p = 0.0109) and 0.10 (95 %CI 0.04, 0.16, p = 0.0021), respectively. Improvements in vitality were seen in both arms but trended toward greater improvement in the intervention arm -2.72 (95 % CI -5.45, 0.01, p = 0.0508). These differences diminished over time; however, depressive symptoms increased in the intervention versus control arms and became significant at 24 months, -1.64 (95 % CI -3.13, -0.15, p = 0.0308). Increased QOL has been reported in shorter term diet and exercise trials among cancer survivors. These longer term data suggest that diet and exercise interventions improve some aspects of QOL, but these benefits may diminish over time.
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http://dx.doi.org/10.1007/s10549-015-3627-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654570PMC
November 2015

Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancers.

J Med Chem 2015 Oct 22;58(19):7763-74. Epub 2015 Sep 22.

Departments of †Chemistry, ‡Biochemistry and Molecular Genetics, §Vision Sciences, and ∥Surgery, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.

(2E,4E,6Z,8Z)-8-(3',4'-Dihydro-1'(2H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,3,6-octatrienoinic acid (UAB30) is currently undergoing clinical evaluation as a novel cancer prevention agent. In efforts to develop even more highly potent rexinoids that prevent breast cancer without toxicity, we further explore here the structure-activity relationship of two separate classes of rexinoids. UAB30 belongs to the class II rexinoids and possesses a 9Z-tetraenoic acid chain bonded to a tetralone ring, whereas the class I rexinoids contain the same 9Z-tetraenoic acid chain bonded to a disubstituted cyclohexenyl ring. Among the 12 class I and class II rexinoids evaluated, the class I rexinoid 11 is most effective in preventing breast cancers in an in vivo rat model alone or in combination with tamoxifen. Rexinoid 11 also reduces the size of established tumors and exhibits a therapeutic effect. However, 11 induces hypertriglyceridemia at its effective dose. On the other hand rexinoid 10 does not increase triglyceride levels while being effective in the in vivo chemoprevention assay. X-ray studies of four rexinoids bound to the ligand binding domain of the retinoid X receptor reveal key structural aspects that enhance potency as well as those that enhance the synthesis of lipids.
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http://dx.doi.org/10.1021/acs.jmedchem.5b00829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928877PMC
October 2015

Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors.

J Clin Oncol 2015 Oct 17;33(28):3169-76. Epub 2015 Aug 17.

Cheryl L. Rock, Shirley W. Flatt, Bilgé Pakiz, and Barbara A. Parker, University of California, San Diego, Moores Cancer Center, La Jolla; Patricia A. Ganz, Jonsson Comprehensive Cancer Center and the Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA; Tim E. Byers, Anthony Elias, Rebecca L. Sedjo, and Holly Wyatt, University of Colorado Denver, Aurora, CO; Graham A. Colditz, Jingxia Liu, and Michael Naughton, Washington University School of Medicine, St Louis, MO; Wendy Demark-Wahnefried and Helen Krontiras, University of Alabama Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL; and Kathleen Y. Wolin, Coeus Health, Scale Down, and Northwestern University, Chicago, IL.

Purpose: Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date.

Methods: In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time.

Results: At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P<.001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P<.001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women.

Conclusion: A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.
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http://dx.doi.org/10.1200/JCO.2015.61.1095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582146PMC
October 2015

Breast Cancer Risk Reduction, Version 2.2015.

J Natl Compr Canc Netw 2015 Jul;13(7):880-915

Breast cancer is the most frequently diagnosed malignancy in women in the United States and is second only to lung cancer as a cause of cancer death. To assist women who are at increased risk of developing breast cancer and their physicians in the application of individualized strategies to reduce breast cancer risk, NCCN has developed these guidelines for breast cancer risk reduction.
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http://dx.doi.org/10.6004/jnccn.2015.0105DOI Listing
July 2015

TBCRC 019: A Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel with or without the Anti-Death Receptor 5 Monoclonal Antibody Tigatuzumab in Patients with Triple-Negative Breast Cancer.

Clin Cancer Res 2015 Jun 16;21(12):2722-9. Epub 2015 Mar 16.

Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore, Maryland.

Purpose: Tigatuzumab (TIG), an agonistic anti-DR5 antibody, triggers apoptosis in DR5(+) human tumor cells without crosslinking. TIG has strong in vitro/in vivo activity against basal-like breast cancer cells enhanced by chemotherapy agents. This study evaluates activity of TIG and chemotherapy in patients with metastatic triple-negative breast cancer (TNBC).

Experimental Design: Randomized 2:1 phase II trial of albumin-bound paclitaxel (nab-PAC) ± TIG in patients with TNBC stratified by prior chemotherapy. Patients received nab-PAC weekly × 3 ± TIG every other week, every 28 days. Primary objective was within-arm objective response rate (ORR). Secondary objectives were safety, progression-free survival (PFS), clinical benefit, and TIG immunogenicity. Metastatic research biopsies were required.

Results: Among 64 patients (60 treated; TIG/nab-PAC n = 39 and nab-PAC n = 21), there were 3 complete remissions (CR), 8 partial remissions (PR; 1 almost CR), 11 stable diseases (SD), and 17 progressive diseases (PD) in the TIG/nab-PAC arm (ORR, 28%), and no CRs, 8 PRs, 4 SDs, and 9 PDs in the nab-PAC arm (ORR, 38%). There was a numerical increase in CRs and several patients had prolonged PFS (1,025+, 781, 672, 460, 334) in the TIG/nab-PAC arm. Grade 3 toxicities were 28% and 29%, respectively, with no grade 4-5. Exploratory analysis suggests an association of ROCK1 gene pathway activation with efficacy in the TIG/nab-PAC arm.

Conclusions: ORR and PFS were similar in both. Preclinical activity of TIG in basal-like breast cancer and prolonged PFS in few patients in the combination arm support further investigation of anti-DR5 agents. ROCK pathway activation merits further evaluation.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-2780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186432PMC
June 2015

Local recurrence rates are low in high-risk neoadjuvant breast cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657).

Ann Surg Oncol 2014 Sep 1;21(9):2889-96. Epub 2014 May 1.

University of California San Francisco, San Francisco, CA, USA.

Background: Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS.

Methods: We analyzed data from the I-SPY 1 Trial. Women with tumors ≥3 cm from nine clinical breast centers received neoadjuvant doxorubicin, cyclophosphamide and paclitaxel followed by definitive surgical therapy, and radiation at physician discretion. LR following mastectomy and BCS were analyzed in relation to clinical characteristics and response to therapy as measured by residual cancer burden.

Results: Of the 237 patients enrolled in the I-SPY 1 Trial, 206 were available for analysis. Median tumor size was 6.0 cm, and median follow-up was 3.9 years. Fourteen patients (7 %) had LR and 45 (22 %) had distant recurrence (DR). Of the 14 patients with LR, nine had synchronous DR; one had DR > 2 years later. Only four (2 % of evaluable patients) had LR alone. The rate of LR was low after mastectomy and after BCS, even in the setting of significant residual disease.

Conclusions: Overall, these patients at high risk for early recurrence, treated with maximal multidisciplinary treatment, had low LR. Recurrence was associated with aggressive biological features such as more advanced stage at presentation, where LR occurs most frequently in the setting of DR.
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http://dx.doi.org/10.1245/s10434-014-3721-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303244PMC
September 2014

S-(-)equol producing status not associated with breast cancer risk among low isoflavone-consuming US postmenopausal women undergoing a physician-recommended breast biopsy.

Nutr Res 2014 Feb 18;34(2):116-25. Epub 2013 Dec 18.

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA; The UAB Comprehensive Cancer Center, Birmingham, AL, USA. Electronic address:

Soy foods are the richest sources of isoflavones, mainly daidzein and genistein. Soy isoflavones are structurally similar to the steroid hormone 17β-estradiol and may protect against breast cancer. S-(-)equol, a metabolite of the soy isoflavone daidzein, has a higher bioavailability and greater affinity for estrogen receptor β than daidzein. Approximately one-third of the Western population is able to produce S-(-)equol, and the ability is linked to certain gut microbes. We hypothesized that the prevalence of breast cancer, ductal hyperplasia, and overall breast pathology will be lower among S-(-)equol producing, as compared with nonproducing, postmenopausal women undergoing a breast biopsy. We tested our hypothesis using a cross-sectional study design. Usual diets of the participants were supplemented with 1 soy bar per day for 3 consecutive days. Liquid chromatography-multiple reaction ion monitoring mass spectrometry analysis of urine from 143 subjects revealed 25 (17.5%) as S-(-)equol producers. We found no statistically significant associations between S-(-)equol producing status and overall breast pathology (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.23-1.89), ductal hyperplasia (OR, 0.84; 95% CI, 0.20-3.41), or breast cancer (OR, 0.56; 95% CI, 0.16-1.87). However, the mean dietary isoflavone intake was much lower (0.3 mg/d) than in previous reports. Given that the amount of S-(-)equol produced in the gut depends on the amount of daidzein exposure, the low soy intake coupled with lower prevalence of S-(-)equol producing status in the study population favors toward null associations. Findings from our study could be used for further investigations on S-(-)equol producing status and disease risk.
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http://dx.doi.org/10.1016/j.nutres.2013.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028846PMC
February 2014

What is a clear margin in breast conserving cancer surgery?

Curr Treat Options Oncol 2014 Mar;15(1):79-85

Department of Surgery, University of Alabama School of Medicine, Birmingham, AL, USA,

Opinion Statement: Team work is the key to successful breast conservation therapy. Patient education and the informed consent process should include a discussion about the importance of margin status. Specimen management is critically important to obtain the highest quality information about margins. Operating technique should avoid trauma to or disruption of the specimen surface. The specimen should be oriented for the pathologist using standard techniques including sutures, clips, or colored inks. Specimen radiography is mandatory to confirm complete resection of the target tissues and can be used to direct additional margin resections during the initial procedure. With a well-designed and oriented specimen, the pathologist can give an accurate description of the margin distance for both the invasive and in situ components of the cancer. In most cases, decision-making about margins will be straightforward. Positive margins should be re-excised or the treatment is converted to mastectomy. Clear margins (>5 mm) require no further surgical therapy. "Close" margins (1-4 mm) will remain a point of controversy because of conflicting reports from clinical series. At UAB, decision for re-excision is made on a case-by-case basis. Routinely 2 mm is considered adequate, however, volume of disease and intraductal component are important considerations when making recommendations.
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http://dx.doi.org/10.1007/s11864-013-0270-4DOI Listing
March 2014

Socioeconomic disparities in breast cancer treatment among older women.

J Womens Health (Larchmt) 2014 Apr 19;23(4):335-41. Epub 2013 Dec 19.

1 Division of Cancer Prevention and Control, National Center for Chronic Disease and Health Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia .

Background: Racial disparities in breast cancer treatment among Medicare beneficiaries have been documented. This study aimed to determine whether racial disparities exist among white and black female Medicare beneficiaries in Alabama, an economically disadvantaged U.S. state.

Methods: From a linked dataset of breast cancer cases from the Alabama Statewide Cancer Registry and fee-for-service claims from Medicare, we identified 2,097 white and black females, aged 66 years and older, who were diagnosed with stages 1-3 breast cancer from January 1, 2000, to December 31, 2002. Generalized estimating equation (GEE) models were used to determine whether there were racial differences in initiating and completing National Comprehensive Cancer Network Clinical Practice guideline-specific treatment.

Results: Sixty-two percent of whites and 64.7% of blacks had mastectomy (p=0.27); 34.6% of whites and 30.2% of blacks had breast conserving surgery (BCS) (p=0.12). Among those who had BCS, 76.8% of whites and 83.3% of blacks started adjuvant radiation therapy (p=0.33) and they equally completed adjuvant radiation therapy (p=0.29). For women with tumors over 1 centimeter, whites and blacks were equally likely to start (16.1% of whites and 18.3% of black; p=0.34) and complete (50.6% of whites and 46.3% of black; p=0.87) adjuvant chemotherapy. There were still no differences after adjusting for confounders using GEE. However, differences were observed by area-level socioeconomic status (SES), with lower SES residents more likely to receive a mastectomy (odds ratio [OR]=1.26; 95% confidence interval [CI]: 1.01-1.57) and initiate radiation after BCS (OR=2.24; 95% CI: 1.28-3.93).

Conclusions: No racial differences were found in guideline-specific breast cancer treatment or treatment completion, but there were differences by SES. Future studies should explore reasons for SES differences and whether similar results hold in other economically disadvantaged U.S. states.
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http://dx.doi.org/10.1089/jwh.2013.4460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991993PMC
April 2014

Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.

Ann Surg Oncol 2013 Aug 17;20(8):2590-9. Epub 2013 Mar 17.

Divisions of Surgical Oncology and Plastic Surgery, UCSD Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Background: Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance.

Methods: A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept.

Results: A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept.

Conclusion: [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.
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http://dx.doi.org/10.1245/s10434-013-2887-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705144PMC
August 2013

Harvest for health gardening intervention feasibility study in cancer survivors.

Acta Oncol 2013 Aug 26;52(6):1110-8. Epub 2013 Feb 26.

Department of Nutrition Sciences, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.

Background: Cancer survivors are at increased risk for second malignancies, cardiovascular disease, diabetes, and functional decline. Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population.

Methods: We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake, physical activity, quality-of-life, and physical function. Throughout the year-long study period, the survivor-Master Gardener dyads worked together to plan/plant three gardens, harvest/rotate plantings, and troubleshoot/correct problems. Data on diet, physical activity, and quality-of-life were collected via surveys; anthropometrics and physical function were objectively measured. Acceptability of the intervention was assessed with a structured debriefing survey.

Results: The gardening intervention was feasible (robust enrollment; minimal attrition) and well-received by cancer survivors and Master Gardeners. Improvement in three of four objective measures of strength, agility, and endurance was observed in 90% of survivors, with the following change scores [median (interquartile range)] noted between baseline and one-year follow-up: hand grip test [+ 4.8 (3.0, 6.7) kg], 2.44 meter Get-Up-and-Go [+ 1.0 (+ 1.8, + 0.2) seconds], 30-second chair stand [+ 3.0 (+ 1.0, 5.0) stands], and six-minute walk [+ 11.6 (6.1, 48.8) meters]. Increases of ≥ 1 fruit and vegetable serving/day and ≥ 30 minutes/week of physical activity were observed in 40% and 60%, respectively.

Conclusion: These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption, physical activity, and physical function in cancer survivors. A larger randomized controlled trial is needed to confirm our results.
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http://dx.doi.org/10.3109/0284186X.2013.770165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3718632PMC
August 2013

How do I screen patients for breast cancer?

Curr Treat Options Oncol 2013 Mar;14(1):88-96

Department of Surgery, Section of Surgical Oncology, University of Alabama at Birmingham, 1922 7th Avenue South KB 321, Birmingham, AL 35294, USA.

Breast cancer is a complex, heterogeneous disease. Approximately 230,000 women are diagnosed with breast cancer in the United States each year and approximately 40,000 women die each year with breast cancer. Although prevention of the disease would be preferred, no real prospects are available in the near future that would be applicable to the majority of women who are at risk for breast cancer. Early detection remains an effective way to decrease mortality from breast cancer, treating it at an early stage when it is likely curable. Unfortunately, screening does have its limitations. Not all breast cancers can be identified with routine screening. Some breast cancers despite early detection still result in poor outcomes. Furthermore, false-positive results are not infrequently seen in women undergoing screening mammography. Most patients experience significant anxiety when called back for additional studies or a biopsy. Not to mention the additional cost and potential side effects and complications of invasive procedures. In addition, there are breast cancers that may be indolent and otherwise not a threat to patients. In fact, some studies show that up to one quarter of cancers detected by screening may represent overdiagnosis. Currently, however, there are no proven methods to discern with complete certainty the cancers that would progress to lethal disease from those that would not. Women should be counseled regarding the risks and benefits of screening. Women at average risk should initiate screening mammography annually at the age of 40 years. Women at significant increased risk for breast cancer should be screened earlier. MRI has been shown to increase detection of breast cancer in women at increased risk and should be used as an adjunct to mammography in this high-risk patient population.
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http://dx.doi.org/10.1007/s11864-012-0218-0DOI Listing
March 2013

Reducing breast cancer recurrence with weight loss, a vanguard trial: the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial.

Contemp Clin Trials 2013 Mar 22;34(2):282-95. Epub 2012 Dec 22.

University of California, La Jolla, CA 92093, USA.

Breast cancer is the most common invasive cancer among women in developed countries. Obesity is a major risk factor for breast cancer recurrence and mortality in both pre- and postmenopausal women. Co-morbid medical conditions are common among breast cancer survivors. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is a 4-year randomized clinical trial of 693 overweight/obese women aged ≥21years diagnosed with any early stage breast cancer (stages I[≥1cm]-III) within the previous five years, designed to demonstrate the feasibility of achieving sustained weight loss and to examine the impact of weight loss on quality of life and co-morbidities, and to enable future exploration of biochemical mechanisms linking obesity to lower likelihood of disease-free survival. This trial is strategically designed as a vanguard for a fully-powered trial of women who will be evaluated for breast cancer recurrence and disease-free survival. Participants were recruited between 2010 and 2012 at four sites, had completed initial therapies, and had a body mass index between 25 and 45kg/m(2). The intervention featured a group-based cognitive-behavioral weight loss program with telephone counseling and tailored newsletters to support initial weight loss and subsequent maintenance, with the goal of 7% weight loss at two years. This study has high potential to have a major impact on clinical management and outcomes after a breast cancer diagnosis. This trial initiates the effort to establish weight loss support for overweight or obese breast cancer survivors as a new standard of clinical care.
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http://dx.doi.org/10.1016/j.cct.2012.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593786PMC
March 2013

Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657.

J Clin Oncol 2012 Sep 29;30(26):3242-9. Epub 2012 May 29.

Breast Care Center, University of California at San Francisco, 1600 Divisadero St, 2nd Floor, Box 1710, San Francisco, CA 94115, USA.

Purpose: Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.

Patients And Methods: Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.

Results: In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.

Conclusion: In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.
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http://dx.doi.org/10.1200/JCO.2011.39.2779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434983PMC
September 2012