Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance)

Jennifer A. Ligibel, Constance T. Cirrincione, Minetta C Liu, Marc Citron, James N. Ingle, William Gradishar, Silvana Martino, William Sikov, Richard Michaelson, Elaine Mardis, Charles M. Perou, Matthew Ellis, Eric Winer, Clifford A. Hudis, Donald Berry, William T. Barry

Research output: Contribution to journalArticle

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Abstract

Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4kg/m<sup>2</sup>. After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95% confidence interval [CI] = 1.02 to 1.14, P =. 01) and OS (adjusted HR = 1.08, 95% CI = 1.01 to 1.14, P =. 02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. Conclusions: BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes.

Original languageEnglish (US)
Article numberdjv179
JournalJournal of the National Cancer Institute
Volume107
Issue number9
DOIs
StatePublished - Sep 1 2015

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Body Mass Index
Breast Neoplasms
Confidence Intervals
Weights and Measures
Drug Therapy
Paclitaxel
Estrogen Receptors
Doxorubicin
Cyclophosphamide
Weight Loss
Neoplasms
Obesity
Body Weight
Phenotype
Recurrence
Survival
Research
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ligibel, J. A., Cirrincione, C. T., Liu, M. C., Citron, M., Ingle, J. N., Gradishar, W., ... Barry, W. T. (2015). Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance). Journal of the National Cancer Institute, 107(9), [djv179]. https://doi.org/10.1093/jnci/djv179

Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer : CALGB 9741 (Alliance). / Ligibel, Jennifer A.; Cirrincione, Constance T.; Liu, Minetta C; Citron, Marc; Ingle, James N.; Gradishar, William; Martino, Silvana; Sikov, William; Michaelson, Richard; Mardis, Elaine; Perou, Charles M.; Ellis, Matthew; Winer, Eric; Hudis, Clifford A.; Berry, Donald; Barry, William T.

In: Journal of the National Cancer Institute, Vol. 107, No. 9, djv179, 01.09.2015.

Research output: Contribution to journalArticle

Ligibel, JA, Cirrincione, CT, Liu, MC, Citron, M, Ingle, JN, Gradishar, W, Martino, S, Sikov, W, Michaelson, R, Mardis, E, Perou, CM, Ellis, M, Winer, E, Hudis, CA, Berry, D & Barry, WT 2015, 'Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance)', Journal of the National Cancer Institute, vol. 107, no. 9, djv179. https://doi.org/10.1093/jnci/djv179
Ligibel, Jennifer A. ; Cirrincione, Constance T. ; Liu, Minetta C ; Citron, Marc ; Ingle, James N. ; Gradishar, William ; Martino, Silvana ; Sikov, William ; Michaelson, Richard ; Mardis, Elaine ; Perou, Charles M. ; Ellis, Matthew ; Winer, Eric ; Hudis, Clifford A. ; Berry, Donald ; Barry, William T. / Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer : CALGB 9741 (Alliance). In: Journal of the National Cancer Institute. 2015 ; Vol. 107, No. 9.
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abstract = "Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4kg/m2. After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95{\%} confidence interval [CI] = 1.02 to 1.14, P =. 01) and OS (adjusted HR = 1.08, 95{\%} CI = 1.01 to 1.14, P =. 02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. Conclusions: BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes.",
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AU - Ligibel, Jennifer A.

AU - Cirrincione, Constance T.

AU - Liu, Minetta C

AU - Citron, Marc

AU - Ingle, James N.

AU - Gradishar, William

AU - Martino, Silvana

AU - Sikov, William

AU - Michaelson, Richard

AU - Mardis, Elaine

AU - Perou, Charles M.

AU - Ellis, Matthew

AU - Winer, Eric

AU - Hudis, Clifford A.

AU - Berry, Donald

AU - Barry, William T.

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N2 - Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4kg/m2. After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95% confidence interval [CI] = 1.02 to 1.14, P =. 01) and OS (adjusted HR = 1.08, 95% CI = 1.01 to 1.14, P =. 02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. Conclusions: BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes.

AB - Background: Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. Methods: CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Results: Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4kg/m2. After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95% confidence interval [CI] = 1.02 to 1.14, P =. 01) and OS (adjusted HR = 1.08, 95% CI = 1.01 to 1.14, P =. 02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. Conclusions: BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes.

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