Publications by authors named "Victor R Grann"

51 Publications

A Pilot Study of Interpersonal Psychotherapy for Depressed Women with Breast Cancer.

Am J Psychother 2014;68(4):489-95

Department of Psychiatry, New York State Psychiatric Institute/Columbia University. 1051 Riverside Drive, Unit 69, New York, NY 10032, USA.

This study sought to examine the feasibility and preliminary efficacy of interpersonal psychotherapy (IPT) in the treatment of major depressive disorder (MDD) among women with breast cancer. Seven women with breast cancer and MDD received 12 sessions of IPT. Outcome measures included changes in depression severity, as measured by the Hamilton Rating Depression Scale (HAM-D), and global functioning, as measured by the Global Assessment Scale (GAF). Mixed linear models were used to examine whether change in depressive symptoms mediated change in global functioning. The HAM-D decreased from 21.3 (SD 8.1) to 11.1 (9.6) (p 0.02), whereas the GAF improved from 56.7 (5.5) to 70.3 (15.6) (p 0.049). A mixed regression model indicated that change in HAM-D scores predicted change in GAF scores (p 0.03). These results suggest that IPT is a promising treatment for depression in women with breast cancer. Randomized controlled trials are warranted to confirm the results of this study.
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http://dx.doi.org/10.1176/appi.psychotherapy.2014.68.4.489DOI Listing
January 2014

Portrayal of complementary and alternative medicine for cancer by top online news sites.

J Altern Complement Med 2012 May 2;18(5):487-93. Epub 2012 May 2.

New York University School of Medicine, New York, NY, USA.

Background: Medical research news provided through the World Wide Web is easily accessible to the general public. Thus, it is necessary to understand how research findings released from online news sources are portrayed.

Methods: The sample includes articles (n=205) published between January 1, 2010 and June 18, 2010 in top online news sites with competitive traffic rankings in the United States as determined by Alexa.com. Google Reader was used to find health-related news articles corresponding to the relevant news sources. Data analysis was performed using SPSS with two-tailed significance values of the χ(2) statistic.

Results: A content analysis (n=205 stories) revealed that the majority of complementary and alternative medicine (CAM) modalities for cancer discussed in top online news sources are classified as nutritional therapeutics, and the cancer topic that appeared most frequently was that of prevention. General oncology was the most frequently cited cancer type that was discussed with regard to CAM. Medical journals were the most frequently cited source in CAM/cancer news articles. The majority of news stories on CAM/cancer were neutral in tone, and the relationship between tone and evidence type reported was statistically significant. Observational studies rather than randomized controlled trials were the predominant form of evidence provided for research findings.

Conclusions: Overall, the quality of how online news sources report research findings on complementary and alternative medicine therapies for cancer is fairly high. However, certain top online media sources are more reliable and informative than others when it comes to reporting about CAM remedies for cancer.
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http://dx.doi.org/10.1089/acm.2011.0110DOI Listing
May 2012

Association between prescription co-payment amount and compliance with adjuvant hormonal therapy in women with early-stage breast cancer.

J Clin Oncol 2011 Jun 23;29(18):2534-42. Epub 2011 May 23.

Herbert Irving Comprehensive Cancer Center, College of Physiciansand Surgeons, Columbia University, New York, NY, USA.

Purpose: Noncompliance with adjuvant hormonal therapy among women with breast cancer is common. Little is known about the impact of financial factors, such as co-payments, on noncompliance.

Patients And Methods: We conducted a retrospective cohort study by using the pharmacy and medical claims database at Medco Health Solutions. Women older than age 50 years who were taking aromatase inhibitors (AIs) for resected breast cancer with two or more mail-order prescriptions, from January 1, 2007, to December 31, 2008, were identified. Patients who were eligible for Medicare were analyzed separately. Nonpersistence was defined as a prescription supply gap of more than 45 days without subsequent refill. Nonadherence was defined as a medication possession ratio less than 80% of eligible days.

Results: Of 8110 women younger than age 65 years, 1721 (21.1%) were nonpersistent and 863 (10.6%) were nonadherent. Among 14,050 women age 65 years or older, 3476 (24.7%) were nonpersistent and 1248 (8.9%) were nonadherent. In a multivariate analysis, nonpersistence (ever/never) in both age groups was associated with older age, having a non-oncologist write the prescription, and having a higher number of other prescriptions. Compared with a co-payment of less than $30, a co-payment of $30 to $89.99 for a 90-day prescription was associated with less persistence in women age 65 years or older (odds ratio [OR], 0.69; 95% CI, 0.62 to 0.75) but not among women younger than age 65, although a co-payment of more than $90 was associated with less persistence both in women younger than age 65 (OR, 0.82; 95% CI, 0.72 to 0.94) and those age 65 years or older (OR, 0.72; 95% CI, 0.65 to 0.80). Similar results were seen with nonadherence.

Conclusion: We found that higher prescription co-payments were associated with both nonpersistence and nonadherence to AIs. This relationship was stronger in older women. Because noncompliance is associated with worse outcomes, future policy efforts should be directed toward interventions that would help patients with financial difficulties obtain life-saving medications.
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http://dx.doi.org/10.1200/JCO.2010.33.3179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138633PMC
June 2011

High-deductible plans: What if you can't afford your share?: Comment on "Health care use and decision-making among lower-income families in high-deductible health plans".

Authors:
Victor R Grann

Arch Intern Med 2010 Nov;170(21):1925

Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA.

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http://dx.doi.org/10.1001/archinternmed.2010.417DOI Listing
November 2010

Prophylactic pancreatectomy for intraductal papillary mucinous neoplasm does not negatively impact quality of life: a preliminary study.

J Gastrointest Surg 2010 Nov 8;14(11):1847-52. Epub 2010 Sep 8.

Department of Surgery, College of Physicians and Surgeons, Columbia University, 161 Fort Washington Avenue, Suite 820, New York, NY 10032-3784, USA.

Background: Uncertainties remain over whether prophylactic surgery or surveillance is the better management option for intraductal papillary mucinous neoplasm of the pancreas. The aim of this preliminary study was to determine if differences in anxiety and quality of life exist between patients who have surgery or undergo surveillance.

Methods: Recruited patients were given the Hospital Anxiety and Depression Scale, a general survey that evaluates anxiety, and the Functional Assessment of Cancer Therapy-Pancreas, a disease-specific survey that assesses quality of life. Questionnaires were scored by standardized algorithms and compared using Student's t test or Wilcoxon rank-sum test.

Results: Sixteen patients had surgery and 16 patients were undergoing surveillance. Mean age was 66.8 ± 19.9 years. Responses from both groups were remarkably similar. Surgery patients scored higher on the anxiety questionnaire than surveillance patients, although not statistically significant (p = 0.09). Surgery patients scored lower on the functional well-being domain of the quality-of-life instrument (p = 0.03), though there were no differences in overall quality of life.

Conclusion: Prophylactic surgery does not reduce quality of life, and a protocol of surveillance does not appear to generate undue anxiety in this select patient group. Further investigation with more patients is required to validate these findings.
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http://dx.doi.org/10.1007/s11605-010-1346-0DOI Listing
November 2010

Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers.

Breast Cancer Res Treat 2011 Feb 20;125(3):837-47. Epub 2010 Jul 20.

Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.

Unlabelled: Comparative effectiveness research has become an integral part of health care planning in most developed countries. In a simulated cohort of women, aged 30-65, who tested positive for BRCA1 or BRCA2 mutations, we compared outcomes of mammography with and without MRI, prophylactic oophorectomy with and without mastectomy, mastectomy alone, and chemoprevention.

Methods: Using Treeage 9.02 software, we developed Markov models with 25,000 Monte Carlo simulations and conducted probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence, and mortality rates, and costs in terms of 2009 dollars, on published studies and data from the Surveillance, Epidemiology, and End RESULTS (SEER) Program and the Centers for Medicare and Medicaid Services. We used preference ratings obtained from mutation carriers and controls to adjust survival for quality of life (QALYs).

Results: For BRCA1 mutation carriers, prophylactic oophorectomy at $1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic oophorectomy, at $4,587 per QALY, was more cost effective than both surgeries. Without quality adjustment, both mastectomy and BSO surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost effective than screening because screening modalities were costly.

Conclusion: Our analysis suggested that among BRCA1/2 mutation carriers, prophylactic surgery would dominate or be cost effective compared to chemoprevention and screening. Annual screening with MRI and mammography was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive.
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http://dx.doi.org/10.1007/s10549-010-1043-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615889PMC
February 2011

Erasing barriers to minority participation in cancer research.

Authors:
Victor R Grann

J Womens Health (Larchmt) 2010 May;19(5):837-8

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http://dx.doi.org/10.1089/jwh.2010.1985DOI Listing
May 2010

Pancreatic proteolytic enzyme therapy compared with gemcitabine-based chemotherapy for the treatment of pancreatic cancer.

J Clin Oncol 2010 Apr 17;28(12):2058-63. Epub 2009 Aug 17.

Columbia University Mailman School of Public Health, 722 W 168th St, Rm 734, New York, NY 10032, USA.

PURPOSE Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma; thus, many patients seek alternative treatments. The National Cancer Institute, in 1998, sponsored a randomized, phase III, controlled trial of proteolytic enzyme therapy versus chemotherapy. Because most eligible patients refused random assignment, the trial was changed in 2001 to a controlled, observational study. METHODS All patients were seen by one of the investigators at Columbia University, and patients who received enzyme therapy were seen by the participating alternative practitioner. Of 55 patients who had inoperable pancreatic cancer, 23 elected gemcitabine-based chemotherapy, and 32 elected enzyme treatment, which included pancreatic enzymes, nutritional supplements, detoxification, and an organic diet. Primary and secondary outcomes were overall survival and quality of life, respectively. Results At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P < .001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P < .01). CONCLUSION Among patients who have pancreatic cancer, those who chose gemcitabine-based chemotherapy survived more than three times as long (14.0 v 4.3 months) and had better quality of life than those who chose proteolytic enzyme treatment.
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http://dx.doi.org/10.1200/JCO.2009.22.8429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860407PMC
April 2010

Breast cancer-related preferences among women with and without BRCA mutations.

Breast Cancer Res Treat 2010 Jan 26;119(1):177-84. Epub 2009 Mar 26.

Herbert Irving Comprehensive Cancer Center, Department of Medicine, and Joseph L. Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Preference ratings are used to quantify quality of life in analyses used for health care policy making. Subjects indicated how many years of their life expectancy they would trade to avoid BRCA mutations, breast/ovarian cancer, and five preventive measures including prophylactic surgery, annual mammograms, and annual magnetic resonance imaging (MRI). Among 243 respondents, both the 83 women with mutations and the 160 controls rated mammography highest (most favorably), MRI next highest, having a child with a mutation lowest, and ovarian cancer next lowest. Controls rated prophylactic surgery higher than cancer (P < 0.01), but women with mutations did not. In logistic regression, controls were twice as willing as women with mutations to trade time except for screening modalities; younger, lower-income, and non-white women were more willing to trade time than older, higher-income, and white women. Our findings support the use of average-risk individuals' time trade-off preference ratings for health care policy development.
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http://dx.doi.org/10.1007/s10549-009-0373-6DOI Listing
January 2010

Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean.

Br J Haematol 2008 Oct 15;143(2):288-93. Epub 2008 Aug 15.

Departments of Medicine, Epidemiology, and Health Policy, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.

Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.
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http://dx.doi.org/10.1111/j.1365-2141.2008.07335.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2655355PMC
October 2008

Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin's lymphoma.

J Clin Oncol 2008 Jul;26(19):3159-65

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Purpose: Anthracycline-based chemotherapy, which improves survival for patients with non-Hodgkin's lymphoma, is often withheld from elderly patients because of its cardiotoxicity. We studied the cardiac effects of doxorubicin in a population-based sample of older patients with diffuse large B-cell lymphoma (DLBCL).

Patients And Methods: Among patients age > or = 65 years diagnosed with DLBCL from 1991 to 2002 in the Surveillance, Epidemiology, and End Results-Medicare database, we developed logistic regression models of the associations of doxorubicin with demographic, clinical, and cardiac variables. We then developed Cox proportional hazards models of the association between doxorubicin and subsequent congestive heart failure (CHF), taking predictors of CHF into account.

Results: Of 9,438 patients with DLBCL, 3,164 (42%) received doxorubicin-based chemotherapy. Any doxorubicin use was associated with a 29% increase in risk of CHF (95% CI, 1.02 to 1.62); CHF risk increased with number of doxorubicin claims, increasing age, prior heart disease, comorbidities, diabetes, and hypertension; hypertension intensified the effect of doxorubicin on risk of CHF (hazard ratio = 1.8; P < .01). In the 8 years after diagnosis, the adjusted CHF-free survival rate was 74% in doxorubicin-treated patients versus 79% in patients not treated with doxorubicin.

Conclusion: Among patients receiving chemotherapy for DLBCL, those with prior heart disease were less likely than others to be treated with doxorubicin, and those who received doxorubicin were more likely than others to develop CHF. Various cardiac risk factors increased CHF risk, but only hypertension was synergistic with doxorubicin. Doxorubicin has dramatically improved survival of DLBCL patients; nonetheless, some subgroups may benefit from efforts to reduce doxorubicin-related CHF risk.
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http://dx.doi.org/10.1200/JCO.2007.14.1242DOI Listing
July 2008

Comparing genetic ancestry and self-described race in african americans born in the United States and in Africa.

Cancer Epidemiol Biomarkers Prev 2008 Jun;17(6):1329-38

Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA.

Genetic association studies can be used to identify factors that may contribute to disparities in disease evident across different racial and ethnic populations. However, such studies may not account for potential confounding if study populations are genetically heterogeneous. Racial and ethnic classifications have been used as proxies for genetic relatedness. We investigated genetic admixture and developed a questionnaire to explore variables used in constructing racial identity in two cohorts: 50 African Americans and 40 Nigerians. Genetic ancestry was determined by genotyping 107 ancestry informative markers. Ancestry estimates calculated with maximum likelihood estimation were compared with population stratification detected with principal components analysis. Ancestry was approximately 95% west African, 4% European, and 1% Native American in the Nigerian cohort and 83% west African, 15% European, and 2% Native American in the African American cohort. Therefore, self-identification as African American agreed well with inferred west African ancestry. However, the cohorts differed significantly in mean percentage west African and European ancestries (P < 0.0001) and in the variance for individual ancestry (P < or = 0.01). Among African Americans, no set of questionnaire items effectively estimated degree of west African ancestry, and self-report of a high degree of African ancestry in a three-generation family tree did not accurately predict degree of African ancestry. Our findings suggest that self-reported race and ancestry can predict ancestral clusters but do not reveal the extent of admixture. Genetic classifications of ancestry may provide a more objective and accurate method of defining homogenous populations for the investigation of specific population-disease associations.
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http://dx.doi.org/10.1158/1055-9965.EPI-07-2505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2507870PMC
June 2008

Neutropenia in 6 ethnic groups from the Caribbean and the U.S.

Cancer 2008 Aug;113(4):854-60

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, New York 10032, USA.

Background: Low white blood cell counts (WBC) or absolute neutrophil counts (ANC) may delay or prevent the completion of appropriate chemotherapy, especially among women receiving adjuvant therapy for breast and colon cancer, and affect cancer survival. Because race/ethnicity is also associated with survival, the authors compared WBC and ANC in healthy American-born women of African descent and European descent, and women from Barbados/Trinidad-Tobago, the Dominican Republic, Haiti, and Jamaica.

Methods: Blood samples from 261 healthy women ages 20 to 70 years were tested for WBC with differential, cytokine and growth factor levels, and ancestry informative and neutrophil elastase polymorphisms. The authors analyzed the association between neutropenia and serum WBC growth factor levels, cytokine levels, and neutrophil elastase c199a polymorphism.

Results: The median WBC and ANC differed among the 6 groups (P < .01 for WBC and P < .0001 for ANC). Dominicans were found to have higher median WBC and ANC than all other groups (P < .03). Neutropenia (ANC < 1500 cu/mm) was observed among 2.7% to 12.5% of the groups of predominantly African descent; no other groups were found to have neutropenia (P < .05). Granulocyte-colony-stimulating factor was found to be lower in white women, but tumor necrosis factor-alpha and C-reactive protein were not found to be correlated with ethnicity. Women of African origin were more likely to have polymorphisms of African ancestry (P < .001) and c199a alleles (P < .0001), which were also associated with low ANC levels.

Conclusions: In the current study, the authors observed a strong association between neutropenia and African descent among asymptomatic women from the U.S. and the Caribbean. Among women of African descent who develop a malignancy, this association may contribute to racial disparities in treatment and outcomes.
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http://dx.doi.org/10.1002/cncr.23614DOI Listing
August 2008

Surgeon characteristics and receipt of adjuvant radiotherapy in women with breast cancer.

J Natl Cancer Inst 2008 Feb 29;100(3):199-206. Epub 2008 Jan 29.

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Background: Adjuvant radiotherapy following breast conservation surgery (BCS) is considered to be an indicator of quality of care for the majority of women with breast cancer, but many women do not receive adjuvant radiotherapy. We investigated the association of surgeon-related factors with receipt of adjuvant radiotherapy after BCS.

Methods: We used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database to identify women aged 65 years or older with stage I/II breast cancer who were diagnosed between 1991 and 2002 and underwent BCS. We collected demographic and clinical data from SEER and treatment information from Medicare claims data. The American Medical Association Masterfile was used to obtain information on surgeons' characteristics, including sex, medical school location (United States or elsewhere), and type of degree (MD or Doctorate in Osteopathic Medicine [DO]). The associations of patient (age, race, rural vs urban residence, comorbidities, marital status), tumor (hormone receptor status, grade, stage), and surgeon-related factors with receipt of adjuvant radiotherapy were analyzed using Generalized Estimating Equations to control for clustering. All statistical tests were two-sided.

Results: Of 29,760 women in our sample, 22,207 (75%) received radiotherapy. Patients who received adjuvant radiotherapy were younger, had fewer comorbidities, and were more likely to be white, married, from an urban area, and diagnosed in a later year compared with those who did not. They were also more likely to have a surgeon who was female (79% vs 73%), had an MD degree (75% vs 68%), or was US trained (75% vs 70%). The multivariable analysis confirmed the association of radiotherapy with having a surgeon who was female (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.06 to 1.27), had an MD degree (OR = 1.55; 95% CI = 1.24 to 1.91), was US trained (OR = 1.12; 95% CI = 1.01 to 1.25), or had more than 15 patients (OR = 1.18; 95% CI = 1.10 to 1.28).

Conclusions: Surgeon characteristics were associated with patients' receipt of adjuvant radiotherapy after BCS after controlling for patient and tumor characteristics, although the individual effect sizes were small for surgeon sex, location of training, and type of medical degree. More research is warranted to confirm the associations to determine whether they reflect surgeon behavior, patient response, or physician-patient interactions.
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http://dx.doi.org/10.1093/jnci/djm320DOI Listing
February 2008

Arsenic exposure and anemia in Bangladesh: a population-based study.

J Occup Environ Med 2008 Jan;50(1):80-7

Department of Epidemiology, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

Objective: The purpose of this study was to examine the association between arsenic exposure and anemia, based on blood hemoglobin concentration.

Methods: Hemoglobin measures, skin lesions, arsenic exposure, and nutritional and demographic information were collected from 1954 Bangladeshi participants in the Health Effects of Arsenic Longitudinal Study. We used general linear modeling to assess the association between arsenic exposure and hemoglobin concentration, examining men and women separately.

Results: Arsenic exposure (urinary arsenic >200 microg/L) was negatively associated with hemoglobin among all men and among women with hemoglobin <10 d/L. Other predictors of anemia in men and women included older age, lower body mass index, and low intake of iron. Among women, the use of contraceptives predicted higher hemoglobin.

Conclusions: The study suggests an association between high arsenic exposure and anemia in Bangladesh.
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http://dx.doi.org/10.1097/JOM.0b013e31815ae9d4DOI Listing
January 2008

Racial disparities in treatment and survival of male breast cancer.

J Clin Oncol 2007 Mar;25(9):1089-98

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Purpose: Black women with breast cancer have poorer survival than do white women, but little is known about racial disparities in male breast cancer. We analyzed race and other predictors of treatment and survival among men with stage I-III breast cancer.

Patients And Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Medicare database to identify men 65 years of age or older diagnosed with stage I-III breast cancer from 1991 to 2002. Multivariate regression was used to compare those treated with those not treated with either chemotherapy or radiation therapy, adjusting for known clinical and demographic factors. Cox proportional hazards regression models were used to analyze survival.

Results: Of 510 male breast cancer cases (456 white, 34 black), 94% underwent mastectomy, 28% received adjuvant chemotherapy, and 29% received radiation therapy. Among those with known hormone receptors, 95% had hormone-sensitive tumors. In a multivariate analysis, chemotherapy was associated with younger age, advanced stage, and hormone receptor-negative tumors. Radiation therapy was associated with younger age and advanced stage. Black men were approximately 50% less likely to undergo consultation with an oncologist and subsequently receive chemotherapy; however, the results did not reach statistical significance. The breast cancer-specific mortality hazard ratio was more than tripled for black versus white men (hazard ratio = 3.29; 95% CI, 1.10 to 9.86).

Conclusion: After adjustment for known clinical, demographic, and treatment factors, there was an association of black race with increased male breast cancer-specific mortality. Although male breast cancer is rare, the reasons for these disparities need to be better understood.
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http://dx.doi.org/10.1200/JCO.2006.09.1710DOI Listing
March 2007

Radiation therapy, cardiac risk factors, and cardiac toxicity in early-stage breast cancer patients.

Int J Radiat Oncol Biol Phys 2007 May 2;68(1):82-93. Epub 2007 Mar 2.

Department of Epidemiology, Mailman School of Public, College of Physicians and Surgeons, Columbia University, New York Presbyterian Hospital, New York, NY, USA.

Purpose: The benefits of adjuvant radiation therapy (RT) for breast cancer may be counterbalanced by the risk of cardiac toxicity. We studied the cardiac effects of RT and the impact of pre-existing cardiac risk factors (CRFs) in a population-based sample of older patients with breast cancer.

Methods And Materials: In the Surveillance, Epidemiology and End-Results (SEER)-Medicare database of women > or = 65 years diagnosed with Stages I to III breast cancer from January 1, 1992 to December 31, 2000, we used multivariable logistic regression to model the associations of demographic and clinical variables with postmastectomy and postlumpectomy RT. Using Cox proportional hazards regression, we then modeled the association between treatment and myocardial infarction (MI) and ischemia in the 10 or more years after diagnosis, taking the predictors of treatment into account.

Results: Among 48,353 women with breast cancer; 19,897 (42%) were treated with lumpectomy and 26,534 (55%) with mastectomy; the remainder had unknown surgery type (3%). Receipt of RT was associated with later year of diagnosis, younger age, fewer comorbidities, nonrural residence, and chemotherapy. Postlumpectomy RT was also associated with white ethnicity and no prior history of heart disease (HD). The RT did not increase the risk of MI. Presence of MI was associated with age, African American ethnicity, advanced stage, nonrural residence, more than one comorbid condition, a hormone receptor-negative tumor, CRFs and HD. Among patients who received RT, tumor laterality was not associated with MI outcome. The effect of RT on the heart was not influenced by HD or CRFs.

Conclusion: It appears unlikely that RT would increase the risk of MI in elderly women with breast cancer, regardless of type of surgery, tumor laterality, or history of CRFs or HD, for at least 10 years.
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http://dx.doi.org/10.1016/j.ijrobp.2006.12.019DOI Listing
May 2007

Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy.

J Natl Cancer Inst 2007 Feb;99(3):196-205

Department of Medicine and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Background: Recently, increasing numbers of women receiving adjuvant chemotherapy for breast cancer have also received granulocyte colony-stimulating factors (G-CSFs) or granulocyte-macrophage colony-stimulating factors (GM-CSFs). Although these growth factors support chemotherapy, their long-term safety has not been evaluated. We studied the association between G-CSF use and incidence of leukemia in a population-based sample of breast cancer patients.

Methods: Among women aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database who were diagnosed with stages I-III breast cancer from January 1, 1991, to December 31, 1999, we identified those who received G-CSF or GM-CSF concurrently with chemotherapy. We used Cox proportional hazards models to estimate hazard ratios for the association of treatment with G-CSF or GM-CSF and subsequent (through December 31, 2003) diagnosis of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). All statistical tests were two-sided.

Results: Of 5510 women treated with chemotherapy, 906 (16%) received G-CSF or GM-CSF therapy, and 64 (1.16%) were subsequently diagnosed with either MDS or AML before a cancer recurrence. Use of G-CSF and GM-CSF was associated with more recent diagnosis, younger age, urban residence, fewer comorbidities, receipt of radiation therapy, positive lymph nodes, and cyclophosphamide treatment. Of the 906 patients who were treated with G-CSF, 16 (1.77%) developed AML or MDS; of the 4604 patients not treated with G-CSF, 48 (1.04%) developed AML or MDS. The hazard rate ratio for AML or MDS among those treated with G-CSF or GM-CSF compared with those who were not was 2.14 (95% confidence interval [CI] = 1.12 to 4.08). AML or MDS developed within 48 months of breast cancer diagnosis in 1.8% of patients who received G-CSF or GM-CSF but only in 0.7% of patients who did not (hazard ratio = 2.59, 95% CI = 1.30 to 5.15).

Conclusions: The use of G-CSF was associated with a doubling in the risk of subsequent AML or MDS among the population that we studied, although the absolute risk remained low. Even if this association is confirmed, the benefits of G-CSF may still outweigh the risks. Meanwhile, however, G-CSF use should not be assumed to be risk free.
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http://dx.doi.org/10.1093/jnci/djk028DOI Listing
February 2007

Inequality of care and cancer survival.

Authors:
Victor R Grann

Virtual Mentor 2007 Jan 1;9(1):48-51. Epub 2007 Jan 1.

College of Physicians and Surgeons and Mailman School of Public Health, both at Columbia University in New York City.

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http://dx.doi.org/10.1001/virtualmentor.2007.9.1.pfor3-0701DOI Listing
January 2007

Timing of adjuvant chemotherapy initiation after surgery for stage III colon cancer.

Cancer 2006 Dec;107(11):2581-8

Department of Medicine, Mailman School of Public Health, Columbia University, New York, New York, USA.

Background: An important advance in medical oncology has been the use of adjuvant chemotherapy for lymph node-positive colon cancer. However, to the authors' knowledge, the effect of the interval between surgery and the initiation of chemotherapy on survival has not been investigated.

Methods: The authors analyzed predictors and outcomes of time intervals to treatment after surgery among patients older than 65 years who were diagnosed with stage III colon cancer between 1992 and 1999 using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear and logistic regression analyses were used to model predictors of delay, and Cox proportional hazards models were used to analyze the impact of treatment timing on survival.

Results: Among 4382 patients with colon cancer, 1122 patients (26%) began adjuvant chemotherapy within 1 month, 2391 patients (55%) began adjuvant chemotherapy in 1 to 2 months, 454 patients (10%) began adjuvant chemotherapy in 2 to 3 months, and 415 patients (9%) began adjuvant chemotherapy >/=3 months after surgery. Intervals of >/=3 months (delay) were associated with older age, increased comorbid conditions, well/moderately differentiated grade, and being unmarried. Colon cancer-specific mortality was associated with a delay in the initiation of chemotherapy (hazards ratio [HR], 1.48; 95% confidence interval [95% CI], 1.15-1.92), advanced age, increased comorbidity, poorly differentiated tumor grade, the presence of >/=4 positive lymph nodes, and undergoing surgery in a nonteaching hospital. All-cause mortality was associated with intervals >2 months between surgery and chemotherapy (2 to 3 months: HR, 1.41; 95% CI, 1.15-1.74; >/=3 months: HR, 1.62; 95% CI, 1.31-1.99) compared with <1 month.

Conclusions: In the older population that was studied, only 9% of patients initiated adjuvant chemotherapy >3 months after the date of curative surgery. However, delay in initiation was associated with both cancer-specific and all-cause mortality. Determining whether these results were because of chemotherapy timing or other associated factors will require further study.
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http://dx.doi.org/10.1002/cncr.22316DOI Listing
December 2006

Outcomes and diffusion of doxorubicin-based chemotherapy among elderly patients with aggressive non-Hodgkin lymphoma.

Cancer 2006 Oct;107(7):1530-41

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA.

Background: In the past 25 years, clinical trials have demonstrated the benefits of chemotherapy for patients with aggressive non-Hodgkin lymphoma. The authors analyzed the predictors and outcomes of chemotherapy among elderly patients with lymphoma.

Methods: Patients age >/=65 years who were diagnosed with Stage III and IV diffuse large B-cell lymphoma [according to the SEER Summary Staging Manual, 2000] between 1991 and 1999 in the Surveillance, Epidemiology, and End Results-Medicare data base were categorized by treatment: no chemotherapy, a doxorubicin-containing regimen, a regimen without doxorubicin, or chemotherapy not otherwise specified. Among the patients who survived for >6 weeks after diagnosis and who had a chemotherapy regimen specified, logistic regression analysis was used to identify predictors of doxorubicin-based treatment, and Cox proportional-hazards regression was used to analyze outcomes.

Results: Less than 66% of patients received any chemotherapy in the 6 months after diagnosis, and 42% of untreated patients died within 6 weeks. Older age, congestive heart failure, and other comorbidities were strong predictors of treatment without doxorubicin. From 1991 to 1999, the proportion of patients who received doxorubicin increased from <20% to >50%. Patients who received doxorubicin survived more than twice as long (24.4 months) as patients who did not receive doxorubicin (11.2 months). Survival was no better among patients who received chemotherapy without doxorubicin than among patients who received no chemotherapy.

Conclusions: By 1999, doxorubicin-based chemotherapy had gained general acceptance for use among the elderly, although nearly 50% of elderly patients still were not receiving it. Given the clinical trial-based evidence of its benefits, in the absence of specific contraindications, most patients, including the elderly, should be treated with regimens that include doxorubicin.
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http://dx.doi.org/10.1002/cncr.22188DOI Listing
October 2006

Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival.

Int J Radiat Oncol Biol Phys 2006 Aug 9;65(5):1353-60. Epub 2006 Jun 9.

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, New York, NY 10032, USA.

Purpose: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival.

Patients And Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling.

Results: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91).

Conclusions: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.
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http://dx.doi.org/10.1016/j.ijrobp.2006.03.048DOI Listing
August 2006

Breast biopsy and race/ethnicity among women without breast cancer.

Cancer Detect Prev 2006 18;30(2):129-33. Epub 2006 Apr 18.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA.

Background: Breast biopsy is essential for definitive breast cancer diagnosis, but may also play a role in determining eligibility for breast cancer preventive measures or clinical trials. In addition, the prevalence of a history of negative breast biopsy can be viewed as an indicator of the adequacy or intensity of health care in a given population. We therefore analyzed the association of a history of breast biopsy with race/ethnicity and other factors in a cohort of women without a cancer diagnosis who completed a risk assessment form for participation in the Study of Tamoxifen and Raloxifene (STAR) and a sociodemographic questionnaire.

Methods: Subjects were recruited at our large, urban teaching hospital. We developed a logistic regression model with biopsy (ever/never) as the outcome and age, race/ethnicity, educational attainment, and insurance coverage as the independent variables.

Results: Among 805 unaffected predominantly minority subjects, white women were more than three times as likely as black and Hispanic women (OR=3.3, 95% CI 1.9-5.9), and insured women were twice as likely as uninsured women (OR=2.0, 95% CI 1.4-2.9) to have had a biopsy. Biopsy results were also associated with race/ethnicity.

Discussion: We view these observations as hypothesis-generating rather than definitive. If confirmed, the associations we observed between negative biopsies and insurance status may reflect disparities in the timeliness and effectiveness of follow-up of suspicious lesions found via mammography. Our findings may also be relevant to the well-known association of breast cancer stage at diagnosis with low income and minority race/ethnicity.
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http://dx.doi.org/10.1016/j.cdp.2006.02.002DOI Listing
November 2006

Duration of adjuvant chemotherapy for colon cancer and survival among the elderly.

J Clin Oncol 2006 May 17;24(15):2368-75. Epub 2006 Apr 17.

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, New York, NY 10032, USA.

Purpose: In randomized trials, patients with stage III colon cancer who received 6 months of fluorouracil (FU)-based adjuvant chemotherapy had better survival than patients who did not. However, little is known about the predictors of, or the survival associated with, duration of chemotherapy in the community.

Patients And Methods: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify individuals > or = 65 years of age diagnosed with stage III colon cancer between 1995 and 1999. We used logistic and Cox proportional hazards regression models to analyze factors associated with early discontinuation of FU-based chemotherapy among these elderly colon cancer patients.

Results: Among 1,722 patients who received 1 to 7 months of FU-based chemotherapy, older age, being unmarried, and having comorbid conditions were associated with receiving less than 5 months of treatment. Among the 1,579 patients who survived > or = 8 months, the 1,091 (69.1%) who received 5 to 7 months of treatment had lower overall (hazard ratio [HR], 0.59; 95%, CI 0.49 to 0.71) and colon cancer-specific (HR, 0.53; 95% CI, 0.43 to 0.66) mortality than the 488 (30.9%) who received 1 to 4 months of treatment.

Conclusion: More than 30% of elderly patients who initiated FU-based chemotherapy for stage III colon cancer and survived for at least 8 months discontinued treatment early. Mortality rates among such patients were nearly twice as high as among patients who completed 5 to 7 months of treatment. If the association we observed between duration of treatment and survival is confirmed, additional investigation is warranted to determine whether dose-intensity, cumulative dose, or other factors related to receipt of full adjuvant treatment are responsible.
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http://dx.doi.org/10.1200/JCO.2005.04.5005DOI Listing
May 2006

Delay of adjuvant chemotherapy initiation following breast cancer surgery among elderly women.

Breast Cancer Res Treat 2006 Oct 1;99(3):313-21. Epub 2006 Apr 1.

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons Columbia University, 161 Ft Washington Room 1068, New York, NY 10032, USA.

Background: Delay in the diagnosis of breast cancer is associated with worse stage distribution at diagnosis and decreased survival. However, the occurrence of delay in the delivery of adjuvant therapy and its impact on prognosis is not well understood.

Methods: To investigate the timeliness of initiation of adjuvant chemotherapy following surgery for breast cancer, we used data from the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. Among women > or = 65 years diagnosed between 1992 and 1999 with stages I-II breast cancer, we used linear regression and Cox proportional hazards models to investigate the time intervals between surgery and initiation of adjuvant chemotherapy, factors associated with delay, and the effect of delay on survival.

Results: Our sample consisted of 5003 women who received adjuvant chemotherapy. Of these, 47% initiated chemotherapy within 1 month, 37% between 1 and 2 months, 6% between 2 and 3 months and 10% >3 months (delay) following surgery. Delay was associated with increasing age, residing in a rural location, being unmarried, earlier tumor stage, hormone receptor positivity, mastectomy, and non-receipt of radiation therapy. Survival did not differ among patients who initiated chemotherapy within 1, 2, or 3 months after surgery. Delay beyond 3 months was, however, associated with increased disease-specific mortality (HR 1.69; 95% CI 1.31-2.19) and overall mortality (HR 1.46; 95% CI 1.21-1.75).

Conclusions: Among older patients, moderate delays in the receipt of adjuvant chemotherapy occur frequently, but long delays (>3 months) are uncommon. While early initiation of therapy is no benefit, significant delays are associated with increased mortality. Whether this reflects the medical impact of the delay of chemotherapy or factors associated with delay is unclear, but until this is clarified, patients should be encouraged to initiate treatment without significant delay.
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http://dx.doi.org/10.1007/s10549-006-9206-zDOI Listing
October 2006

Cost-effectiveness of preventive strategies for women with a BRCA1 or a BRCA2 mutation.

Ann Intern Med 2006 Mar;144(6):397-406

Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Joseph L. Mailman School of Public Health, Columbia University, and New York Presbyterian Hospital, New York, New York 10032, USA.

Background: For BRCA1 or BRCA2 mutation carriers, decision analysis indicates that prophylactic surgery or chemoprevention leads to better survival than surveillance alone.

Objective: To evaluate the cost-effectiveness of the preventive strategies that are available to unaffected women carrying a single BRCA1 or BRCA2 mutation with high cancer penetrance.

Design: Markov modeling with Monte Carlo simulations and probabilistic sensitivity analyses.

Data Sources: Breast and ovarian cancer incidence and mortality rates, preference ratings, and costs derived from the literature; the Surveillance, Epidemiology, and End Results (SEER) Program; and the Health Care Financing Administration (now the Centers for Medicare & Medicaid Services).

Target Population: Unaffected carriers of a single BRCA1 or BRCA2 mutation 35 to 50 years of age.

Time Horizon: Lifetime.

Perspective: Health policy, societal.

Interventions: Tamoxifen, oral contraceptives, bilateral salpingo-oophorectomy, mastectomy, both surgeries, or surveillance.

Outcome Measures: Cost-effectiveness.

Results Of Base-case Analysis: For mutation carriers 35 years of age, both surgeries (prophylactic bilateral mastectomy and oophorectomy) had an incremental cost-effectiveness ratio over oophorectomy alone of 2352 dollars per life-year for BRCA1 and 100 dollars per life-year for BRCA2. With quality adjustment, oophorectomy dominated all other strategies for BRCA1 and had an incremental cost-effectiveness ratio of 2281 dollars per life-year for BRCA2.

Results Of Sensitivity Analysis: Older age at intervention increased the cost-effectiveness of prophylactic mastectomy for BRCA1 mutation carriers to 73,755 dollars per life-year. Varying the penetrance, mortality rates, costs, discount rates, and preferences had minimal effects on outcomes.

Limitations: Results are dependent on the accuracy of model assumptions.

Conclusion: On the basis of this model, the most cost-effective strategies for BRCA mutation carriers, with and without quality adjustment, were oophorectomy alone and oophorectomy and mastectomy, respectively.
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http://dx.doi.org/10.7326/0003-4819-144-6-200603210-00006DOI Listing
March 2006

Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.

J Clin Oncol 2005 Dec;23(34):8597-605

Department of Medicine and Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, 161 Ft Washington, Rm 1068, New York, NY 10032, USA.

Purpose: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up.

Patients And Methods: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy.

Results: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis.

Conclusion: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.
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http://dx.doi.org/10.1200/JCO.2005.02.5841DOI Listing
December 2005

Racial disparities in treatment and survival among women with early-stage breast cancer.

J Clin Oncol 2005 Sep;23(27):6639-46

Department of Medicine and the Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, New York, NY, USA.

Purpose: Black women with breast cancer are known to have poorer survival than white women. Suboptimal treatment may compromise the survival benefits of adjuvant chemotherapy. We analyzed the association of race and survival with duration of treatment and number of treatment cycles among women receiving chemotherapy for early-stage breast cancer.

Patients And Methods: Patients were women in the Henry Ford Health System tumor registry who were diagnosed with stage I/II breast cancer between January 1, 1996, and December 31, 2001, who received adjuvant chemotherapy. We calculated an observed/expected ratio of treatment duration and of completed chemotherapy cycles for each patient. Using Cox proportional hazards models, we analyzed the association of early treatment termination and treatment duration with all-cause mortality, controlling for age, race, stage, hormone receptor status, grade, comorbidity score, and doxorubicin use.

Results: Of 472 eligible patients, 28% (31% black, 23% white; P = .03) received fewer cycles of treatment than expected. Black race, receipt of < or = 75% of the expected number of cycles, increasing age, hormone receptor negativity, and a comorbidity score of more than 1 were associated with poorer survival. Among the 344 patients receiving the expected number of cycles, 60% experienced delays. These delays did not reduce survival.

Conclusion: This study is the first to find that a substantial fraction of women with early-stage breast cancer terminated their chemotherapy prematurely and that early termination was associated with both black race and poorer survival. A better understanding of the determinants of suboptimal treatment may lead to interventions that can reduce racial disparities and improve breast cancer outcomes for all women.
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http://dx.doi.org/10.1200/JCO.2005.12.633DOI Listing
September 2005
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