Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

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Abstract

Introduction

Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.

Methods

We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.

Results

Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.

Conclusions

Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

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Most cited references 25

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Breast cancer and hormone-replacement therapy in the Million Women Study.

Valerie Beral (2003)

Current use of hormone-replacement therapy (HRT) increases the incidence of breast cancer. The Million Women Study was set up to investigate the effects of specific types of HRT on incident and fatal breast cancer. 1084110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death. Half the women had used HRT; 9364 incident invasive breast cancers and 637 breast cancer deaths were registered after an average of 2.6 and 4.1 years of follow-up, respectively. Current users of HRT at recruitment were more likely than never users to develop breast cancer (adjusted relative risk 1.66 [95% CI 1.58-1.75], p<0.0001) and die from it (1.22 [1.00-1.48], p=0.05). Past users of HRT were, however, not at an increased risk of incident or fatal disease (1.01 [0.94-1.09] and 1.05 [0.82-1.34], respectively). Incidence was significantly increased for current users of preparations containing oestrogen only (1.30 [1.21-1.40], p<0.0001), oestrogen-progestagen (2.00 [1.88-2.12], p<0.0001), and tibolone (1.45 [1.25-1.68], p<0.0001), but the magnitude of the associated risk was substantially greater for oestrogen-progestagen than for other types of HRT (p<0.0001). Results varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increased separately for oral, transdermal, and implanted oestrogen-only formulations (1.32 [1.21-1.45]; 1.24 [1.11-1.39]; and 1.65 [1.26-2.16], respectively; all p<0.0001). In current users of each type of HRT the risk of breast cancer increased with increasing total duration of use. 10 years' use of HRT is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 users of oestrogen-only preparations and 19 (15-23) additional cancers per 1000 users of oestrogen-progestagen combinations. Use of HRT by women aged 50-64 years in the UK over the past decade has resulted in an estimated 20000 extra breast cancers, 15000 associated with oestrogen-progestagen; the extra deaths cannot yet be reliably estimated. Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.

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Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

Rowan Chlebowski, Susan L Hendrix, Robert D. Langer … (2003)

The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography. To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations. Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter. Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure. In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration. Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.

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Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study.

Pamela J Goodwin, Marguerite Ennis, Kathleen Pritchard … (2002)

Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer. A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained. Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P <.001), which, in turn, was associated with distant recurrence and death (P <.001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively. Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.

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Author and article information

Contributors

Bella Pajares

Marina Pollán

Miguel Martín

John R Mackey

Ana Lluch

Joaquín Gavila

Charles Vogel

Manuel Ruiz-Borrego

Lourdes Calvo

Tadeusz Pienkowski

Álvaro Rodríguez-Lescure

Miguel Angel Seguí

Olivier Tredan

Antonio Antón

Manuel Ramos

María del Carmen Cámara

César Rodríguez-Martín

Eva Carrasco

Emilio Alba

Journal

Journal ID (nlm-ta): Breast Cancer Res

Journal ID (iso-abbrev): Breast Cancer Res

Title: Breast Cancer Research : BCR

Publisher: BioMed Central

ISSN (Print): 1465-5411

ISSN (Electronic): 1465-542X

Publication date (Print): 2013

Publication date (Electronic): 6 November 2013

Volume: 15

Issue: 6

Page: R105

Affiliations

[1 ]Medical Oncology Department, Hospital Clínico Universitario Virgen de la Victoria, Málaga, Spain

[2 ]Epidemiology Nacional Center, Instituto de Salud Carlos III, Madrid, Spain

[3 ]Medical Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain

[4 ]Medical Oncology Department, Medical Cross Cancer Institute, Edmonton, AB, Canada

[5 ]Hematology-Oncology Department, Hospital Clínico Universitario de Valencia- INCLIVA Health Research Institute, University of Valencia, Valencia, Spain

[6 ]Medical Oncology Department, Instituto Valenciano de Oncología, Valencia, Spain

[7 ]Medical Oncology Department, Sylvester Comprehensive Cancer at Deerfield; Miller School of Medicine; Univ. of Miami- Deerfield Bch, Miami, FL, USA

[8 ]Medical Oncology Department, Hospital Virgen del Rocío, Sevilla, Spain

[9 ]Medical Oncology Department, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain

[10 ]Medical Oncology Department, European Health Center, Otwock, Poland

[11 ]Medical Oncology Department, Hospital General Universitario de Elche, Alicante, Spain

[12 ]Medical Oncology Department, Corporación Sanitaria Parc Taulí, Sabadell, Spain

[13 ]Medical Oncology Department, Centre Léon Bérard, Lyon, France

[14 ]Medical Oncology Department, Hospital Miguel Servet, Zaragoza, Spain

[15 ]Medical Oncology Department, Centro Oncológico de Galicia, A Coruña, Spain

[16 ]Spanish Breast Cancer Research Group, GEICAM, Madrid, Spain

Article

Publisher ID: bcr3572

DOI: 10.1186/bcr3572

PMC ID: 3978725

PubMed ID: 24192331

SO-VID: 3e0b2125-0360-4370-ab55-8ace72923644

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

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Abstract

Introduction

Methods

Results

Conclusions

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Karger: Oncology

Most cited references 25

Breast cancer and hormone-replacement therapy in the Million Women Study.

Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study.

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