Causes and Risk Factors
Breast cancer occurs almost exclusively in women. About 2,500 men and 250,000 women are diagnosed each year in the United States (ACS 2017a). Age is also a critical risk factor (PDQ Screening Prevention Editorial Board 2017a). At age 40, women have a 1.4% chance of being diagnosed with breast cancer in the next 10 years. By age 70, that chance rises to 3.9% (U.S. Cancer Statistics Working Group 2017).
Family History and Genetics
Women with a family history of breast cancer are at increased risk. Having a first-degree relative diagnosed with breast cancer can increase the risk two- to four-fold (Davidson 2016). A family history of cancer may result from inheritance of a gene mutation. The most well-known genes mutated in breast cancer are called BRCA1 and BRCA2. Women with a mutation in one of these genes have a 50% to 85% lifetime risk of developing breast cancer (Davidson 2016; Antoniou 2003; Kuchenbaecker 2017). Not all women with these mutations develop breast cancer, and most women with breast cancer do not have these mutations.
Other Breast Conditions
Breasts with more stroma and epithelial tissue and less fat are described as dense (ACS 2017b). These characteristics can be seen on a mammogram. Women with very dense breasts have a four-fold or even higher risk for breast cancer (Boyd 2009; McCormack 2006; Cecchini 2012). Also, high breast density can make it harder to detect tumors with a mammogram (Lee, Chen 2017). Benign or non-invasive breast conditions such as atypical hyperplasias can also increase the risk of cancer (Davidson 2016).
Various factors influencing the level of estrogen exposure to the breast tissue can influence breast cancer risk. Women who start puberty early or enter menopause later have a slightly higher risk (Davidson 2016; Kotsopoulos 2010). In one large analysis, complete pregnancy reduced the risk of breast cancer by about 7%. In the same analysis, every 12 months of breastfeeding also reduced the risk of breast cancer by about 4% (Collaborative Group on Hormonal Factors in Breast Cancer 2002). Women who have a first childbirth later in life are at increased risk (Kotsopoulos 2010).
Women treated with conventional estrogen-progestin hormone replacement therapy (HRT) for menopause have been shown to have an increased risk of breast cancer compared with women using estrogen-only HRT (Davidson 2016; DeBono 2017). However, the increased risk is primarily attributable to forms of HRT containing medroxyprogesterone acetate (MPA), a synthetic form of progesterone (Palacios 2016). In contrast, natural progesterone does not appear to increase the risk of breast cancer (Lieberman 2017). Unopposed estrogen replacement (estrogen therapy without any form of progesterone) also does not appear to increase the risk of breast cancer (Manson 2013; DeBono 2017). In fact, some data suggest estrogen alone may decrease the risk of invasive breast cancer (Nelson 2012). Oral forms of estrogen replacement can increase risk of stroke and coronary artery disease, but estrogen absorbed through the skin (transdermal) is considered to be safer (Cobin 2017).
The type of estrogen used in hormone replacement therapy preparations may also influence risk. There are three primary types of estrogen: estrone, estradiol, and estriol. Estradiol is the dominant estrogen throughout most of a woman’s life, but estriol takes a more prominent role during pregnancy. Some preliminary evidence suggested that estriol may be protective against breast cancer risk (Takahashi 2000; Melamed 1997; Weiderpass 1999), and thus would be a preferable form of estrogen to use in hormone replacement therapy preparations. However, not all older studies supported this notion (Lippman 1977; Marmorston 1965), and more recent studies and analyses appear less conclusive (Ali 2017; Perkins 2017). Overall, more long-term, randomized, controlled trials are needed to test whether hormone replacement with estriol reduces breast cancer risk relative to other forms of hormone replacement therapy.
The association of HRT with breast cancer risk remains a controversial area. More information about the nuances of HRT in the context of breast cancer risk is available in the Female Hormone Restoration protocol.
The relationship between oral contraceptive use and breast cancer risk is controversial as well. Oral contraceptives may slightly increase the risk of breast cancer (Gierisch 2013; Davidson 2016). A recent study included data from 1.8 million women (Morch 2017). Women who were currently or recently using hormonal contraception were 20% more likely to develop breast cancer than those who had never used hormonal contraception. Although this increased risk was statistically significant, the authors of the study clarify that their analysis suggests only about one additional breast cancer for every 7,690 women using hormonal contraception for one year.
Other Health Parameters
Obesity increases the risk of breast cancer (Davidson 2016; Kabat 2017). In a study of almost 100,000 women, body mass index and weight gain during adulthood were both associated with increased risk of breast cancer (Huang 1997). Most evidence suggests obesity after menopause is particularly problematic, increasing risk two- to four-fold (van den Brandt 2000; Davidson 2016; Cordina-Duverger 2016). Additional related conditions such as high fasting glucose, high cholesterol, diabetes, or high blood pressure may further increase the risk among obese women (Kabat 2017; Park 2017; Michels 2003; Maskarinec 2017; Ronco 2012). Life Extension Magazine® published an article in 2013 summarizing the association between elevated glucose levels and greater breast cancer risk.
Radiation to the chest for another cancer, such as Hodgkin’s lymphoma, may also increase breast cancer risk later in life (Sud 2017; Schaapveld 2015).