Each breast contains 15 to 20 lobes, each made up of several smaller sections called lobules (NCCN 2016; PDQ Adult Treatment Editorial Board 2017). Breast milk is produced in the lobules and travels through the ducts to the nipple (Figure 1).
The tissue around the lobes and ducts is called stroma. Within the stroma, vessels carry a clear fluid called lymph. Lymph delivers immune cells, water, and nutrients to the breast tissue and drains to nearby lymph nodes (NCCN 2016). Healthy breasts also contain fat tissue, connective tissue, nerves, and blood vessels.
Figure 1. Breast Anatomy (OpenStax College 2013)
The hormones estrogen and progesterone are important for the development and function of the breast during puberty and pregnancy (Hilton 2017). Estrogen is primarily produced by the ovaries before menopause, but some is produced by the adrenal glands and, in smaller amounts, in fat tissue and the liver (McNamara 2016). Estrogen can also be produced in the breast tissue itself by a process called aromatization (Yaghjyan 2011). There are two main types of estrogen receptors: estrogen receptor alpha and estrogen receptor beta (McNamara 2016). Activation of estrogen receptors plays a role in breast growth and in many cases of breast cancer.
The breasts can develop several non-cancerous conditions, some of which may cause symptoms similar to breast cancer. Cysts, fibroadenomas, and calcifications are common benign or non-cancerous breast diseases (Neal 2014; Mayo Clinic 2018). Another condition, hyperplasia, is a condition in which the cells in the duct or lobe are dividing too frequently (Davidson 2016). Women with so called atypical hyperplasias are at increased risk for developing breast cancer (Dion 2016; Farshid 2017).
Breast cancer can develop from cells in either the ducts or lobes, but ductal tumors are more common (NCCN 2016; PDQ Adult Treatment Editorial Board 2017). The cells acquire mutations that cause them to divide too rapidly or survive too long. One mutation in breast cancer leads to increased signaling through the HER2 growth factor receptor pathway (Davidson 2016). Cells with extra copies of the HER2 gene can grow more quickly (Petrelli 2017). Some people inherit or develop a mutation in the BRCA1 or BRCA2 genes, which are involved in DNA repair (Takaoka 2017; Davidson 2016). Presence of certain BRCA1 and BRCA2 mutations increase breast and ovarian cancer risk (Toland 2017).
As breast cells acquire more mutations, they begin to look less normal under a microscope. They can divide quickly and are less likely to die when normal cells would (NCCN 2016). Over time, they form a mass or tumor.
Tumors that are small and confined to the lobular or ductal tissue are called non-invasive (Davidson 2016; Posner 1992). Ductal carcinoma in situ (DCIS) is a non-invasive tumor that may become invasive (Rakovitch 2012). DCIS is typically detected by a mammogram (PDQ Screening Prevention Editorial Board 2017b). While some studies found that many DCIS lesions would not progress even without treatment, some of them may become invasive tumors over time. DCIS is normally treated with surgery and radiation, and the prognosis is excellent (NCCN 2017b; PDQ Adult Treatment Editorial Board 2017; Lee 2012; Jones 2006; Vatovec 2014).
Lobular carcinoma in situ (LCIS) is less common than DCIS and less likely to become an invasive tumor (Venkitaraman 2010; Frykberg 1999). LCIS does not normally require standard breast cancer treatments, although these are sometimes used, depending on the patient’s characteristics, but all women diagnosed with LCIS should be carefully monitored and make lifestyle changes to reduce their risk of developing breast cancer (see, “Dietary and Lifestyle Considerations”) (NCCN 2017b; Davidson 2016; Cutuli 2015).
Tumors that have grown into the nearby stromal tissue in the breast are called invasive (NCCN 2016). In some cases, tumor cells are able to move away from the original tumor and invade nearby lymph nodes (Davidson 2016; NCCN 2016). Beyond the lymph nodes, breast cancer may spread to distant sites such as the bones, lungs, liver, or brain (Rostami 2016; Chen 2017).
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).
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.
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.
Life Extension Health Concens
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.
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)
