Abstract

Breast cancer affected more than 2.3 million women in 2022 and is the most diagnosed cancer among women worldwide. The incidence rates are greater in developed regions and are significantly higher among women with higher education and socioeconomic status. Therefore, it is reasonable to assume that the way women live their lives may impact their risk of being diagnosed with breast cancer. This systematic review aimed to identify what is known about the causes and risk factors of breast cancer, excluding genetic causes. A comprehensive systematic search identified 2387 systematic reviews, 122 were included and six overall themes identified. In our “top list” with the 36 most important findings, a study of breast density had the highest effect size for increasing the risk of breast cancer, and a high sex-hormone-binding globulin level was the most protective factor. Many of the included studies investigating the same topics had conflicting results. The conclusion from this evidence synthesis reveals a lack of consensus of factors associated with the causes and risk of breast cancer. These findings suggest that recommendations about lifestyle and breast cancer should be made with caution.

Introduction

Breast cancer affected more than 2.3 million women in 2022 and is the most diagnosed cancer among women worldwide [1,2]. Breast cancer is also the number one cause of death from cancer in women; 670,000 women died from this disease in 2022 [2]. That is approximately 7% of all cancer deaths worldwide. The incidence rates are greater than 80 per 100,000 in developed regions of the world, such as Europe and North America, Australia, and New Zealand, and less than 40 per 100,000 in developing countries [3,4]. However, statistics from some developing countries may be attributed to underreporting [5]. The differences in incidence between countries could be due to changes in exposure to environmental risk factors, behavior, and lifestyle factors of different population groups [6]. These facts provide good reasons to study the causes and risk factors of breast cancer.

The causes of breast cancer in women are still unclear, and nonhereditary causes and risk factors predominate [7]. These include early menarche, hormone intake, nutrition, alcohol consumption, smoking, and obesity, all of which are commonly reported as risk factors [6]. Heredity accounts for only 5–۱۰% of breast cancer cases, with germline mutations in BRCA1 or BRCA2 accounting for 30% of inheritable breast cancer cases [7]. Several researchers are working on the identification of specific genes as a cause of breast cancer, while others are conducting studies on the combinations of genes and other factors [8]. A study published in the Lancet in 2005 concluded that 21% of all breast cancer deaths worldwide were attributable to physical inactivity, overweight and obesity, and alcohol use [9]. An update from 2017 examined the connection between breast cancer incidence and environmental factors such as chemicals and radiation and found that exposure to these substances may lead to an increased risk of developing breast cancer [10]. However, numerous studies have identified late age of first full-term (if any) pregnancy, short periods of breast-feeding, dietary habits, quality and composition of meals, physiologic factors, lower age at menarche, and later menopause as causes and risk factors of breast cancer in women [11].

Conclusions

Six overall themes and more than 27 topics were identified. In our “top list” of the 36 most important findings, high breast density had the highest effect size for increasing the risk of breast cancer, and a high sex-hormone-binding globulin level was identified as the most protective factor in decreasing breast cancer risk. Notwithstanding the comprehensive work in performing these studies, there is still a large degree of uncertainty with respect to what exactly triggers or may influence or cause breast cancer. Unfortunately, this extensive work has not provided a clear and convincing answer as to why women develop breast cancer. Based on our review, however, it is important to point out this lack of consensus because the recommendations from some health authorities use several uncertain consensus statements to guide us to a healthy lifestyle. We therefore argue that this review of systematic reviews provides a valuable contribution to the research portfolio regarding breast cancer in women. We also argue that it highlights that health professionals should be careful because there still remains a great deal of uncertainty regarding the risk factors and causes of breast cancer in women.