Breast cancer is the most common cancer in females in the United States and the second most common cause of cancer death in women. Approximately one-half of newly diagnosed breast cancers can be explained by known risk factors, such as age at menarche, first live birth, menopause, and proliferative breast disease. An additional 10% are associated with a positive family history. Risk factors for breast cancer may be modified by demographic, lifestyle, and environmental factors.
So, what increases our risk? What can we change? What do have no control over?
Age: the risk of breast cancer increases with older age. In recent surveillance risk stratifies as such: Birth to age 39 - 1 in 203 women; Age 40 to 59 - 1 in 27 women; Age 60 to 69 - 1 in 28 women; Age 70 and older - 1 in 15 women; Birth to death - 1 in 8 women.
Female gender: Breast cancer occurs 100 times more frequently in women than in men. In the United States, over 200,000 women are diagnosed with invasive breast cancer each year, compared with approximately 2000 cases that occur annually in men.
Caucasian race: the highest rate of breast cancer occurs among white women, although breast cancer remains the most common cancer among women of every major ethnic group.
Weight: Obesity (defined body mass index ≥30 kg/m2) is associated with an overall increase in morbidity and mortality. However, the risk of breast cancer associated with BMI appears to depend on the menopausal status of women.
Postmenopausal women: A higher body mass index (BMI) and/or perimenopausal weight gain have been consistently associated with a higher risk of breast cancer among postmenopausal women. The association for risk can be explained by higher estrogen levels resulting from the adipose tissue to estrogen.
Premenopausal women: Unlike postmenopausal women, an increased BMI is associated with a lower risk of breast cancer in premenopausal women. The explanation of this finding remains unclear.
Tall stature: Increased height is associated with a higher risk of breast cancer in both premenopausal and postmenopausal women. The mechanism underlying this association is unknown, but may reflect the influence of nutritional exposures during childhood and puberty.
Estrogen levels: High endogenous estrogen levels increase the risk of breast cancer (particularly hormone receptor-positive breast cancer) in both postmenopausal and premenopausal women. For postmenopausal women, the correlation between an increased risk for breast cancer and increasing hormone levels (eg, estradiol, estrone) has been consistent.
Benign breast disease: A wide spectrum of pathologic entities is included in the category of benign breast disease. Among these, proliferative lesions (especially those with histologic atypia) are associated with an increased risk of breast cancer.
Dense breast tissue: The density of breast tissue reflects the relative amount of glandular and connective tissue (parenchyma) to adipose tissue. Breast density is a measure of the extent of radiodense fibroglandular tissue. Women with mammographically dense breast tissue, generally defined as dense tissue comprising ≥75 percent of the breast, have a 4 to 5 times risk of breast cancer compared with women of similar age with less or no dense tissue. It is unclear whether screening recommendations should differ for women with dense breasts in the absence of other risk factors.
Bone mineral density: Because bone contains estrogen receptors and is highly sensitive to circulating estrogen levels, bone mineral density (BMD) is considered a surrogate marker for long-term exposure to endogenous and exogenous estrogen. In multiple studies, women with higher bone density have a higher breast cancer risk.
Androgens: Elevated androgen (ie, testosterone) levels have been associated with an increased risk of postmenopausal and premenopausal breast cancer.
Insulin pathway and related hormones: Although diabetes is not considered a breast cancer risk factor, a large pooled analysis drawing from 17 prospective studies suggested that insulin growth factor-1 was associated with breast cancer risk in both premenopausal and postmenopausal women.
In utero exposure to diethylstilbestrol: Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) that was given to their mothers to prevent pregnancy complications. Whether these women are also at an increased risk for breast cancer is unclear.
Exogenous hormones: Much of the available evidence supports a causal relationship between menopausal hormone replacement therapy and breast cancer. The duration of use and type of hormone formulation seem to be important factors in the risk for breast cancer. While long-term use has been associated with the highest risk, short-term use of combined estrogen-progestin therapy (<3 administration="" an="" appear="" as="" associated="" breast="" cancer.="" clearly="" contraceptives="" does="" estrogen="" exogenous="" for="" hormones="" however="" in="" increase="" increased="" induction="" is="" nbsp="" not="" of="" or="" oral="" ovulation="" premenopausal="" previous="" purpose="" risk="" significantly="" span="" the="" to="" users="" with="" years="">3>
Earlier menarche or later menopause: Early age at menarche is associated with a higher risk of breast cancer. Women with menarche at or after age 15 years of age were less likely to develop estrogen receptor/progesterone receptor positive breast cancer compared with women who experienced menarche before the age of 13 years. Women with menarche at or after age 15 years also had a 16 percent decreased risk of estrogen receptor/progesterone receptor negative breast cancer.
Nulliparity: Nulliparous women are at increased risk for breast cancer compared with parous women, however, the protective effect of pregnancy is not seen until after 10 years following delivery.
Increasing age at first pregnancy: Women who become pregnant later in life have an increased risk of breast cancer. One study showed when compared with nulliparous women at or near menopause, the cumulative incidence of breast cancer (up to age 70) was 20 percent lower, 10 percent lower, and 5 percent higher among women who delivered their first child at age 20, 25, or 35 years, respectively. A later age at first birth may confer a greater risk than nulliparity because of the additional proliferative stimulation placed on breast cells that are more likely to be fully developed and perhaps more prone to cell damage.
Personal history of breast cancer: A personal history of ductal carcinoma in situ (DCIS) or invasive breast cancer increases the risk of developing an invasive breast cancer in the contralateral breast. A 2010 study using Surveillance, Epidemiology, and End-Results (SEER) data that included almost 340,000 women with a primary breast cancer found the incidence of invasive contralateral breast cancer was 4% during an average follow-up of 7.5 years.
Family history of breast cancer: The risk associated with a positive family history of breast cancer is strongly affected by the number of female first-degree relatives with and without cancer. In addition to a family history of breast cancer, the age at diagnosis of the affected first-degree relative also influences the risk for breast cancer. Women have a threefold higher risk if the first-degree relative was diagnosed before age 30, but only 1.5-fold increased if the affected relative was diagnosed after age 60.
Inherited genetic mutations: Specific genetic mutations that predispose to breast cancer are rare; only 5 to 6 % of all breast cancers are directly attributable to inheritance of a breast cancer susceptibility gene such as BRCA1, BRCA2, p53, ATM, and PTEN.
Alcohol: Alcohol consumption in early life as well as later adult life is associated with an increased risk of breast cancer development. There appears to be a significant dose-response relationship between alcohol consumption (eg, beer, wine, liquor) and an increased risk of breast cancer, which begins with alcohol intake as low as three drinks per week compared with abstainers. The risk appears to increase with greater alcohol consumption and additive with the use of menopausal hormone therapy. There does not appear to be a difference by type of alcohol (wine versus beer versus liquor).
Smoking: The relationship between cigarette smoking and breast cancer is complicated by the interaction of smoking with alcohol and endogenous hormonal influences. Although results have varied widely, multiple studies suggest there is a modestly increased risk of breast cancer in smokers.
Night shift work: Night shift work is recognized by International Agency for Research on Cancer and the World Health Organization (IARC/WHO) as a probable carcinogen. This association may be related to nocturnal light exposure, which results in the suppression of nocturnal melatonin production by the pineal gland. Evidence to support this comes from the finding that low levels of 6-sulfatoxymelatonin (the major melatonin metabolite) are associated with an increased risk of breast cancer.
Exposure to therapeutic ionizing radiation: Exposure to ionizing radiation of the chest at a young age, as occurs with treatment of Hodgkin lymphoma or in survivors of atomic bomb or nuclear plant accidents, is associated with an increased risk of breast cancer. The most vulnerable ages appear to be between 10 to 14 years (prepuberty), although excess risk is seen in women exposed as late as 45 years of age. After age 45, there does not appear to be any increased risk.
So what can we do to help ourselves?
In addition to modifying some of the risk factors above and spreading awareness, some protective factors that may also reduce breast cancer risk are breastfeeding, soy/phytoestrogens (such as soybeans, legumes and lignans) and increased physical activity.
Let us be your resource for concerns or questions about your breast health--that is what we are here for!
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-Maansi Piparia, MD