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Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

ABSTRACT: Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype.This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had PAM50 assays and were diagnosed with American Joint Committee on Cancer stage I through III breast cancer from 1996 to 2013. Patients reported weight and height. Cox regression models were adjusted for age, menopause, race/ethnicity, stage, and chemotherapy.Over a median of 9 years (maximum, 19 years), 378 women developed recurrent disease, and 312 died from breast cancer. Overall, BMI was not associated with breast cancer recurrence or survival when controlling for subtype (eg, the hazard ratio per 5?kg/m2 of BMI was 1.05 [95% confidence interval, 0.95-1.15] for breast cancer-specific death). However, associations varied by subtype. Among women with luminal A cancers, those who had class II/III obesity, but not class I obesity or overweight, had worse outcomes. When women who had a BMI ?35?kg/m2 were compared with those who had a BMI from 18.5 to <25?kg/m2 , the hazard ratio was 2.24 (95% confidence interval,1.22-4.11) for breast cancer-specific death and 1.24 (95% confidence interval, 1.00-1.54) for recurrence. There was no association within luminal B, basal-like or human epidermal growth factor over-expressing subtypes.Among patients who had accurately classified breast cancer subtypes based on gene expression, a BMI ?35?kg/m2 was adversely associated with outcomes only among those who had luminal A cancers. Research is needed into whether tailoring recommendations for weight management to tumor characteristics will improve outcomes. Cancer 2017;123:2535-42. © 2017 American Cancer Society.

SUBMITTER: Cespedes Feliciano EM

PROVIDER: S-EPMC5474169 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

Cespedes Feliciano Elizabeth M EM Kwan Marilyn L ML Kushi Lawrence H LH Chen Wendy Y WY Weltzien Erin K EK Castillo Adrienne L AL Sweeney Carol C Bernard Philip S PS Caan Bette J BJ

Cancer 20170313 13

<h4>Background</h4>Studies of obesity and survival among patients with breast cancer produce conflicting results, possibly because of heterogeneity by molecular subtype.<h4>Methods</h4>This study examined whether the association of body mass index (BMI) at diagnosis with breast cancer recurrence and survival varied across subtypes defined by PAM50 (Prediction Analysis of Microarray 50) gene expression. Included were 1559 Kaiser Permanente Northern California members ages 18 to 79 years who had P ...[more]

PMID: 28295245

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Project description:ImportanceBlack women in the United States have higher breast cancer (BC) mortality rates than White women. The combined role of multiple factors, including body mass index (BMI), age, and tumor subtype, remains unclear.ObjectiveTo assess the association of race and ethnicity with survival among clinical trial participants with early-stage BC (eBC) according to tumor subtype, age, and BMI.Design, setting, and participantsThis cohort study analyzed survival data, as of November 12, 2021, from participants enrolled between 1997 and 2010 in 4 randomized adjuvant chemotherapy trials: Cancer and Leukemia Group B (CALGB) 9741, 49907, and 40101 as well as North Central Cancer Treatment Group (NCCTG) N9831, legacy groups of the Alliance of Clinical Trials in Oncology. Median follow-up was 9.8 years.ExposuresNon-Hispanic Black and Hispanic participants were compared with non-Hispanic White participants within subgroups of subtype (hormone receptor positive [HR+]/ERBB2 [formerly HER2] negative [ERBB2-], ERBB2+, and HR-/ERBB2-), age (<50, 50 to <65, and ≥65 years), and BMI (<18.5, 18.5 to <25.0, 25.0 to <30.0, and ≥30.0).Main outcomes and measuresRecurrence-free survival (RFS) and overall survival (OS).ResultsOf 9479 participants, 436 (4.4%) were Hispanic, 871 (8.8%) non-Hispanic Black, and 7889 (79.5%) non-Hispanic White. The median (range) age was 52 (19.0-89.7) years. Among participants with HR+/ERBB2- tumors, non-Hispanic Black individuals had worse RFS (hazard ratio [HR], 1.49; 95% CI, 1.04-2.12; 5-year RFS, 88.5% vs 93.2%) than non-Hispanic White individuals, although the global test for association of race and ethnicity with RFS was not significant within any tumor subtype. There were no OS differences by race and ethnicity in any subtype. Race and ethnicity were associated with OS in young participants (age <50 years; global P = .008); young non-Hispanic Black participants (HR, 1.34; 95% CI, 1.04-1.71; 5-year OS, 86.6% vs 92.0%) and Hispanic participants (HR, 1.62; 95% CI, 1.16-2.29; 5-year OS, 86.2% vs 92.0%) had worse OS than young non-Hispanic White participants. Race and ethnicity were associated with RFS in participants with BMIs of 25 to less than 30, with non-Hispanic Black participants having worse RFS (HR, 1.81; 95% CI, 1.23-2.68; 5-year RFS, 83.2% vs 87.3%) than non-Hispanic White participants.Conclusions and relevanceIn this cohort study, racial and ethnic survival disparities were identified in patients with eBC receiving standardized initial care, and potentially at-risk subgroups, for whom focused interventions may improve outcomes, were found.

Project description:BackgroundObesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status.MethodsWe conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study and the San Francisco Bay Area Breast Cancer SPORE/San Francisco Mammography Registry. Our pooled analysis contained 1538 ER-positive and 285 ER-negative invasive breast cancer cases and 4720 controls matched on age, menopausal status at time of mammogram, and year of mammogram. Percent density was measured on digitized film mammograms using computer-assisted techniques. We used polytomous logistic regression to evaluate the association between percent density and ER subtype by BMI subgroup (normal/underweight, < 25 kg/m2 versus overweight/obese, ≥ 25 kg/m2). We used Wald chi-squared tests to assess for interactions between percent density and BMI. Our analysis was stratified by menopausal status and hormone therapy usage at the time of index mammogram.ResultsPercent density was associated with increased risk of overall breast cancer regardless of menopausal status or BMI. However, when analyzing breast cancer across ER subtype, we found a statistically significant (p = 0.008) interaction between percent density and BMI in premenopausal women only. Specifically, elevated percent density was associated with a higher risk of ER-negative than ER-positive cancer in overweight/obese premenopausal women [OR per standard deviation increment 2.17 (95% CI 1.50-3.16) vs 1.33 (95% CI 1.11-1.61) respectively, Pheterogeneity = 0.01]. In postmenopausal women, elevated percent density was associated with similar risk of ER-positive and ER-negative cancers, and no substantive differences were seen after accounting for BMI or hormone therapy usage.ConclusionsThe combination of overweight/obesity and elevated breast density in premenopausal women is associated with a higher risk of ER-negative compared with ER-positive cancer. Eighteen percent of premenopausal women in the USA have elevated BMI and breast density and may benefit from lifestyle modifications involving weight loss and exercise.

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Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

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Body mass index, PAM50 subtype, recurrence, and survival among patients with nonmetastatic breast cancer.

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