Metabolic Syndrome and Postmenopausal Breast Cancer

Systematic Review and Meta-analysis

Katherine Esposito, MD, PhD, Paolo Chiodini, PhD, Annalisa Capuano, MD, Giuseppe Bellastella, MD, Maria Ida Maiorino, MD, Concetta Rafaniello, MD, and Dario Giugliano, MD, PhD


Menopause. 2013;20(12):1301-1309. 

In This Article

Abstract and Introduction


Objective: The role of metabolic syndrome (MS) and its individual components in postmenopausal breast cancer (PBC) risk is still unclear. We reviewed and summarized epidemiological studies assessing the association of MS with the risk of PBC.

Methods: We conducted an electronic search, without restrictions, for articles published before October 31, 2012. Every included study was to report risk estimates with 95% CIs for the association between MS and PBC. Studyspecific estimates were pooled using random-effects models.

Results: Nine articles (with 6,417 cancer cases), all published in English, were included in the meta-analysis. MS was associated with a 52% increase in cancer risk (P < 0.001)—for the most part confined to noncohort studies (109% increased risk); the risk estimates changed little, depending on populations (United States and Europe) and definition of the syndrome (traditional vs nontraditional). The risk estimates for PBC were 1.12 (P = 0.068) for higher values of body mass index/waist circumference, 1.19 (P = 0.005) for hyperglycemia (higher fasting glucose or diabetes), 1.13 (P = 0.027) for higher blood pressure, 1.08 (P = 0.248) for higher triglycerides, and 1.39 (P = 0.008) for lower high-density lipoprotein cholesterol. All these estimates were lower than those associated with MS in the same studies.

Conclusions: MS is associated with a moderately increased risk of PBC. No single component explains the risk conveyed by the full syndrome.


Carcinoma of the breast is the most commonly occurring cancer (with the exception of nonmelanomatous skin cancers) in American women and the second most common cause of cancer-related deaths (after lung cancer).[1] In all European Union countries (EU-27), female breast cancer ranks first in both incidence and mortality.[2] Breast cancer is the second most commonly diagnosed cancer worldwide.[3] There are, however, variations in incidence and mortality rates among the different racial and ethnic groups in the American population.[1] Large regional inequalities in cancer incidence across the European Union also exist.[2]

It has been estimated that approximately one third of cancer deaths occurring in the United States each year are caused by poor nutrition, physical inactivity, and excess weight.[1] Metabolic syndrome (MS) has become a major public health problem in several countries and represents a common clinical condition in countries with a high incidence of obesity and western dietary patterns.[4] It is a cluster of risk factors for cardiovascular disease and type 2 diabetes, including abdominal adiposity, hyperglycemia, increased blood pressure, elevated triglycerides, and low high-density lipoprotein cholesterol (HDL-C) levels.

Epidemiological studies have reported associations of breast cancer risk with individual components of MS, including obesity, type 2 diabetes, and dyslipidemia.[5,6,7] The involvement of MS per se in breast cancer risk is still unclear. Two reviews[8,9] published in 2007 concluded that the relation between MS and breast cancer risk had not been considered in any observational study. A recent meta-analysis[10] based on nine observational data sets published since 2008 yielded a 14% (nonsignificant) increased risk of breast cancer associated with MS. However, it is still unclear whether the risk associated with the full syndrome is greater than the sum of its parts; moreover, the role specifically played by postmenopause status has never been extensively investigated. In the present article, we performed a thorough review and meta-analysis of studies assessing the impact of MS on postmenopausal breast cancer (PBC) risk, paying particular attention to the strength of the association by each component of the syndrome, as compared with that conveyed by the full syndrome. To our knowledge, no previous metaanalysis has specifically evaluated the role of hypertension, high triglycerides, and low HDL-C in PBC risk.