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Factors that modify breast cancer risk in females

Factors that modify breast cancer risk in females
Author:
Rowan T Chlebowski, MD, PhD
Section Editors:
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Daniel F Hayes, MD
Deputy Editor:
Sadhna R Vora, MD
Literature review current through: Apr 2025. | This topic last updated: Mar 07, 2025.

INTRODUCTION — 

Globally, breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer death in females [1]. In the United States, breast cancer is the most common cancer and the second most common cause of cancer death in females [2]. Approximately half of breast cancers can be explained by known risk factors, like reproductive factors and proliferative breast disease. An additional 10 percent are associated with family history and genetics. In addition, risk may be modified by demographic, lifestyle, and environmental factors.

This topic will review risk factors that modify breast cancer risk in females. Pharmacologic interventions for breast cancer risk reduction (tamoxifen, raloxifene, aromatase inhibitors) are reviewed separately. Screening for breast cancer and risk prediction models are discussed separately.

●(See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

●(See "Screening for breast cancer: Strategies and recommendations", section on 'Breast cancer risk determination'.)

●(See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Risk assessment models'.)

FACTORS ASSOCIATED WITH GREATER BREAST CANCER RISK

Increasing age — Breast cancer risk increases with age. In the Surveillance, Epidemiology, and End Results (SEER) database, the probability of a female developing breast cancer in the United States between 2013 and 2015 was [2]:

●Birth to age 49 – 2.1 percent (1 in 49)

●Age 50 to 59 – 2.4 percent (1 in 42)

●Age 60 to 69 – 3.5 percent (1 in 28)

●Age 70 and older – 7 percent (1 in 14)

●Birth to death – 12.9 percent (1 in 8)

Female sex — Breast cancer occurs 100 times more frequently in females than in males. In the United States, over 280,000 females are diagnosed with invasive breast cancer each year, compared with fewer than 3000 cases that occur annually in males [2].

Race and ethnicity — In the United States, the highest breast cancer risk occurs among White females, although breast cancer remains the most common cancer among females of every major ethnic/racial group [2].

Many of the racial differences in breast cancer rates are attributable to factors associated with lifestyle. In analyses in a cohort of over 156,000 postmenopausal females, the age adjusted incidence of breast cancer for White females was higher than for other groups, but adjustment for breast cancer risk factors accounted for the differences for all but Black females [3].

In a separate analysis, using population-based cancer registries from the National Program of Cancer Registries and SEER, the rate of newly diagnosed breast cancer (per 100,000 females) was 124 and 122 for White and Black females, respectively [4]. Despite this, Black females more commonly presented with regional or advanced disease (46 versus 36 percent) and had a 41 percent higher breast cancer-specific mortality rate (30 versus 21 deaths per 100,000 females). In one analysis, breast cancers in females <40 years old and triple-negative breast cancers are more common among Black females than White females [5]. In summary, while Black females have 5 percent fewer breast cancers than White females, they have 44 percent greater breast cancer mortality [6].

Weight and body fat in postmenopausal females — Obesity (defined as body mass index [BMI] ≥30 kg/m2) is associated with an overall increase in morbidity and mortality [7]. However, the risk of breast cancer associated with BMI differs by menopausal status. (See "Overweight and obesity in adults: Health consequences".)

●Postmenopausal females – A higher BMI and/or perimenopausal weight gain have been consistently associated with a higher risk of breast cancer among postmenopausal females [8-10]. As examples:

•In a meta-analysis of more than 1000 epidemiologic studies, females with a higher BMI experienced a higher risk of postmenopausal breast cancer (relative risk [RR] 1.1 per 5 BMI units, 95% CI 1.1-1.2), particularly estrogen receptor (ER)-positive breast cancer [11].

•In a separate meta-analysis of 50 studies, for each 5-kg increase in adult weight gain, the RR for postmenopausal breast cancer among no- or low-menopausal hormone therapy users was 1.11 (95% CI 1.08-1.13) [12].

The association between a higher BMI and postmenopausal breast cancer risk may be mediated by higher estrogen levels resulting from the peripheral conversion of estrogen precursors (from adipose tissue) to estrogen [13,14]. In addition, hyperinsulinemia may also represent a mediator of the obesity-breast cancer relationship because a high BMI is associated with higher insulin levels [15]. (See 'Others' below.)

Even among females with normal BMI, a higher body-fat percentage is associated with higher breast cancer risk. In a secondary analysis of the Women's Health Initiative (WHI) cohort, among 3460 postmenopausal females with normal BMI, the multivariable-adjusted hazard ratios (HRs) for breast cancer risk among those with the highest quartile of body fat versus the lowest was 1.89 (95% CI 1.21-2.95) [14]. Similarly, studies are comparing variables other than BMI with respect to breast cancer prediction. In two reports, the number of metabolic syndrome components were stronger predictors of breast cancer mortality than BMI [16,17].

In addition, hyperinsulinemia may also contribute to the obesity-breast cancer relationship because a high BMI is associated with higher insulin levels [15]. (See 'Others' below.)

Of note, estrogen plus progestin increased breast cancer risk in all BMI groups in the WHI randomized trial [18]. (See "Menopausal hormone therapy: Benefits and risks".)

●Inverse relationship in premenopausal females – Unlike postmenopausal females, an increased BMI is associated with a lower risk of breast cancer in premenopausal females, particularly in early adulthood [19,20]. In a multicenter analysis using pooled individual-level data from approximately 760,000 premenopausal females from 19 prospective cohorts, there was a 4.2-fold increased risk between the lowest and highest BMI categories (BMI <17 versus ≥35) at ages 18 to 24 years [20]. 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 females [21,22]. In one study, females who were >175 cm (69 inches) tall were 20 percent more likely to develop breast cancer than those <160 cm (63 inches) tall [23]. The mechanism underlying this association is unknown but may reflect the influence of nutritional exposures during childhood and puberty [24].

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. (See "Overview of benign breast diseases".)

Dense breast tissue — The density of breast tissue reflects the relative amount of glandular and connective tissue (parenchyma) to adipose tissue [25]. Females with mammographically dense breast tissue, generally defined as dense tissue comprising ≥75 percent of the breast, have a higher breast cancer risk compared with females of similar age with less or no dense tissue [26-28]. (See "Breast density and screening for breast cancer", section on 'Breast density and breast cancer risk'.)

In addition, longitudinal increases (or slower decreases in breast density) are associated with an increased risk of breast cancer, while decreases (particularly more rapid ones) are associated with a decreased risk [29,30]. It is unclear whether screening recommendations should differ for females with dense breasts. (See "Screening for breast cancer: Strategies and recommendations".)

Although breast density is a largely inherited trait, other factors can influence density [31-34]. For example, lower density has been associated with higher levels of physical activity [33] and with a low-fat, high-carbohydrate diet [34]. In postmenopausal females, estrogen and progesterone increase breast density [35-37], while the ER antagonist tamoxifen decreases breast density [38,39]. Despite the association of exogenous hormones with breast density, breast density is not strongly correlated with endogenous hormone levels [40].

Bone mineral density — Because bone contains estrogen receptors and is highly sensitive to circulating estrogen levels, bone mineral density (BMD) is considered a surrogate for long-term exposure to endogenous and exogenous estrogen. In multiple studies, females with higher bone density have a higher breast cancer risk [41-43].

In a meta-analysis of eight prospective cohort and two nested-control studies that included over 70,000 postmenopausal females, of whom 1889 developed breast cancer, females in the highest hip BMD category were more likely to develop breast cancer compared with females in the lowest BMD category (RR 1.62, 95% CI 1.17-2.06) [44]. In a 2008 study from the WHI (including 9941 postmenopausal females), each unit increase in the total hip BMD T-score was associated with a higher breast cancer risk (HR 1.25, 95% CI 1.11-1.40) [43]. (See "Clinical manifestations, diagnosis, and evaluation of osteoporosis in postmenopausal women", section on 'T-score'.)

Hormonal factors

Endogenous estrogen and hormone therapy

●Higher endogenous estrogen levels – Higher endogenous estrogen levels are associated with higher breast cancer risk (particularly hormone receptor-positive disease) in both postmenopausal and premenopausal females. For postmenopausal females, the correlation between a higher breast cancer risk and higher hormone levels (estradiol, estrone) has been consistent [45-48]. Supporting this concept is the finding that reducing estrogen levels with aromatase inhibitors in postmenopausal females reduces breast cancer risk.

Estrogen level associations with breast cancer risk among premenopausal females are limited by menstrual cycle variations. In a pooled analysis from seven studies, including 767 premenopausal females with breast cancer and 1699 controls, concentrations of estradiol, calculated free estradiol, estrone, androstenedione, dehydroepiandrosterone, and testosterone were positively associated with breast cancer risk [49]. For example, every twofold increase in estradiol concentration was associated with an odds ratio for breast cancer of 1.19 (95% CI 1.06-1.35). Concentrations of luteal-phase progesterone and calculated free testosterone were not significantly associated with such risk.

●Menopausal hormone therapy – In the WHI randomized trial, including 16,608 postmenopausal females, after 5.6 years intervention and through >20 years follow-up, estrogen plus progestin increased breast cancer incidence, which was not limited to ER-positive cancers [18]. By contrast, in the WHI randomized trial, including 16,608 postmenopausal females with prior hysterectomy, after 7.2 years intervention and through >20 years follow-up, estrogen alone use reduced breast cancer incidence and breast cancer mortality [18]. The relationship between menopausal hormone therapy and breast cancer is reviewed in detail elsewhere. (See "Menopausal hormone therapy and the risk of breast cancer" and "Menopausal hormone therapy: Benefits and risks".)

●Contraceptives – Breast cancer risk is increased with current or recent use of combined oral contraceptives, but this association disappeared within two to five years of discontinuation. Additional information on the risks of estrogen-progestin contraceptives are discussed separately. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Breast cancer'.)

Others

●Androgens – Preclinical data suggest that androgens (in particular, testosterone) exert dual effects on mammary tumor development, with a proliferative effect mediated by the estrogen receptor and an antiproliferative effect mediated by the androgen receptor [50]. Elevated androgen (testosterone) levels are associated with higher postmenopausal and premenopausal breast cancer risk [45,49,51].

Testosterone association with breast cancer subtypes has not been consistently seen. Some studies suggest that elevated testosterone levels increase breast cancer risk specifically for hormone receptor-positive breast cancers [51-54], while one study suggests elevated testosterone levels are associated with a lower risk of hormone receptor-negative breast cancers [48].

●Insulin pathway and related factors – In reports from the WHI, higher insulin resistance levels were associated with higher breast cancer incidence (HR 1.34, 95% CI 1.12-1.61), as well as higher all-cause mortality and higher all-cancer-specific mortality [55,56]. In addition, although diabetes is not considered a breast cancer risk factor [57], in a large pooled analysis from 17 prospective studies, insulin growth factor-1 was associated with breast cancer risk in both premenopausal and postmenopausal females [58].

Reproductive factors

Earlier menarche or later menopause — Early age at menarche is associated with a higher breast cancer risk [24,59]. Females with menarche at or after 15 years of age were less likely to develop hormone receptor-positive breast cancer compared with females who experienced menarche before the age of 13 years (HR 0.76, 95% CI 0.68-0.85) [24]. They also had a 16 percent lower risk of hormone receptor-negative breast cancer. In one study, for every one-year delay in the onset of menarche, breast cancer risk was 5 percent lower [59]. In addition, later age at menopause is associated with higher breast cancer risk.

Nulliparity — Nulliparous females are at higher risk for breast cancer compared with parous females (RR from 1.2 to 1.7) [60,61]. Although parous females have an increased risk for developing breast cancer within the first few years of delivery relative to nulliparous females, parity confers a protective effect decades after delivery. Whether multiparity confers protection against breast cancer is controversial, because it is difficult to separate the effects of multiparity from early first full-term pregnancy; however, studies suggest a decreased risk with increasing number of pregnancies [59,61,62].

Increasing age at first full-term pregnancy — The effect of parity also differs depending upon the age of first full-term birth. Females who become pregnant later in life have a higher risk of breast cancer [59,61,62]. In the Nurses' Health Study, compared with nulliparous females at or near menopause, the cumulative incidence of breast cancer (up to age 70) was 20 percent lower among females who delivered their first child at age 20; 10 percent lower for those with their first child at age 25 years; and 5 percent higher among those delivering their first child at 35 years [60]. The risk for a nulliparous female of any age was similar to that of a female with a first full-term birth at age 35.

It has been proposed that full cellular differentiation, which occurs in the gland during and after pregnancy, protects the breast from breast cancer development [63]. 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.

The relationship between infertility and breast cancer is controversial and is discussed below. (See 'Infertility' below.)

In vitro fertilization does not appear to be associated with breast cancer risks. (See "Assisted reproductive technology: Pregnancy and maternal outcomes", section on 'Breast cancer'.)

Personal and family history of breast cancer

●Personal history of breast cancer – A personal history of either invasive or in situ breast cancer increases the risk of developing an invasive breast cancer in the contralateral breast.

A 2010 study using SEER data that included almost 340,000 females with a primary breast cancer found the incidence of invasive contralateral breast cancer (CBC) was 4 percent during an average follow-up of 7.5 years [64]. The risk of a CBC varied by age at the time of the index breast cancer diagnosis (those <30 years at diagnosis and those with ER-negative cancers were at higher risk; however, these rates have been decreasing over time.

In a separate study, risks of CBC among those with hormone receptor-positive breast cancer were approximately 0.2 percent per year for the first five years after diagnosis (during adjuvant endocrine therapy), 0.5 percent per year for the subsequent five years (after endocrine treatment), and somewhere between these estimates for the following 5 to 10 years [65].

In the setting of a personal history of breast cancer, a family history of breast cancer further increases CBC risk. For example, in a case-control study of females with CBC matched with females with unilateral breast cancer as controls, having a first-degree relative with breast cancer increased risk of CBC by almost twofold [66]. Risks were further increased if the relative was diagnosed at age <40 years.

●Family history and genetic mutations – The risk associated with a positive family history of breast cancer is strongly affected by the number of female first-degree relatives with breast cancer and the age when diagnosed.

In a pooled analysis of over 50,000 females with breast cancer and 100,000 controls, the risk of breast cancer was [67]:

•Increased almost twofold in someone with one affected first-degree relative

•Increased threefold in someone with two affected first-degree relatives

The age at diagnosis of the affected first-degree relative also influences breast cancer risk [67]. Females have a threefold higher risk if the first-degree relative was diagnosed before age 30 (RR 3, 95% CI 1.8-4.9), but the risk is only 1.5-fold higher if the affected relative was diagnosed after age 60. (See "Screening for breast cancer: Strategies and recommendations", section on 'Models predicting pathogenic BRCA1/2 mutations'.)

Family history is still an important risk factor even with relatives with a later age at diagnosis. In a cohort study of over 400,000 females, family history of breast cancer in a first-degree relative was associated with a higher breast cancer risk, regardless of whether the relative was diagnosed before or after 50 years of age [68]. Criteria for genetic screening are discussed elsewhere. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Criteria for genetic risk evaluation'.)

Specific genetic mutations that predispose to breast cancer are rare; as an example, only approximately 6 percent of all breast cancers are directly attributable to inheritance of a BRCA1/2 pathogenic variant. These and other variants are discussed in more detail elsewhere. (See "Cancer risks in BRCA1/2 carriers" and "Overview of hereditary breast and ovarian cancer syndromes".)

Alcohol use and smoking — Alcohol consumption is associated with a higher breast cancer risk. This topic is discussed in detail elsewhere. (See "Overview of the risks and benefits of alcohol consumption", section on 'Breast cancer'.)

Although results have not been uniform, multiple studies suggest there is a modestly increased risk of breast cancer in smokers [69-74]. For example, in a meta-analysis of 27 prospective observational studies, the risk of breast cancer was higher among females with any smoking history (summary RR 1.10, 95% CI 1.02-1.14) [69]. The relationship between cigarette smoking and breast cancer is complicated; as many as 50 percent of females who smoke also consume alcohol, a known breast cancer risk factor [69]. However, even in females who did not drink alcohol, there was still a higher breast cancer risk associated with smoking [69].

Studies regarding passive smoking and breast cancer risk have been inconclusive, but evidence for an increase in risk with passive smoking is emerging [71,75,76].

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 [77-79]. The most vulnerable ages appear to be between 10 to 14 years (prepuberty), although excess risk is seen in females exposed as late as 45 years of age [80]. After age 45, risk is attenuated. (See "Second malignancies after treatment of classic Hodgkin lymphoma".)

FACTORS ASSOCIATED WITH DECREASED BREAST CANCER RISK

Medical and surgical risk reduction strategies — Chemoprevention with aromatase inhibitors in postmenopausal females, or tamoxifen in pre- or postmenopausal females, reduces breast cancer risks. Mastectomy also greatly decreases breast cancer risks, and is an appropriate option for select patients at high risk, for example BRCA carriers. These strategies, as well as appropriate candidates, are discussed in detail elsewhere. (See "Cancer risks in BRCA1/2 carriers" and "Overview of hereditary breast and ovarian cancer syndromes" and "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention" and "Contralateral prophylactic mastectomy".)

The effect of oophorectomy on breast cancer risk in the general population and among BRCA carriers is discussed elsewhere. (See "Elective oophorectomy or ovarian conservation at the time of hysterectomy" and "Cancer risks in BRCA1/2 carriers", section on 'Bilateral salpingo-oophorectomy'.)

Chestfeeding — A protective effect of chestfeeding has been shown in multiple case-control and cohort studies and meta-analyses, the magnitude of which depends on the duration of chestfeeding and on the confounding factor of parity [81,82].

A large pooled analysis that included individual data from 47 epidemiologic studies (approximately 50,000 females with invasive breast cancer and 97,000 controls) estimated that for every 12 months of chestfeeding, there was 4.3 percent reduction in the relative risk (RR) of breast cancer [81]. In another meta-analysis, this association was stronger for hormone receptor-negative breast cancers [82]. A postulated mechanism for this protective effect is delay in re-establishment of ovulatory cycles.

Physical activity — While randomized clinical trial evidence is lacking, observational study results strongly suggest that physical activity is associated with lower breast cancer risk [83-86]. In a 2016 review of epidemiologic studies, risk of breast cancer was lower among the most physically active compared with the least active females (RR 0.88, 95% CI 0.85-0.90) [83]. Another meta-analysis of 139 prospective and retrospective studies evaluated physical activity and weight loss in approximately 237,000 breast cancer cases and 4 million controls. Higher physical activity levels were associated with lower breast cancer risk (odds ratio [OR] 0.78, 95% CI 0.76-0.81) with similar findings in pre-and postmenopausal females and for light- and high-intensity physical activity [87].

Given the paradoxical effect of weight in premenopausal and postmenopausal females, the lower breast cancer risk seen with exercise is unlikely to be mediated through weight control alone [88-91]. Increased physical activity may reduce breast cancer risk through hormonal influences such as reducing serum estrogens, insulin, and insulin growth factor-1 levels [92-94]. (See 'Weight loss in postmenopausal females' below and 'Low-fat dietary pattern in postmenopausal females' below and 'Hormonal factors' above.)

Weight loss in postmenopausal females — While not seen in all studies [14,95], weight loss in postmenopausal females may reduce breast cancer risk [9,87,96-101], as observed in the examples below:

●In the meta-analysis of prospective and retrospective studies discussed above, including approximately 237,000 cases and 4 million controls, weight loss was associated with lower breast cancer risk (OR 0.82, 95% CI 0.67-0.97) [87].

●Among prospective studies, the Nurses' Health Study assessed weight change since menopause among approximately 50,000 females followed for up to 24 years. Females with no prior hormone therapy use who maintained a weight loss of ≥10 kg were at lower breast cancer risk than females who did not (RR 0.43, 95% CI 0.21-0.86) [9]. More recently, in roughly 61,000 postmenopausal females in the Women's Health Initiative (WHI), those who lost ≥5 percent of body weight in the three years from study entry had a lower breast cancer incidence over a mean of 11.4 years compared with females who did not (hazard ratio [HR] 0.88, 95% CI 0.78-0.98) [96].

●Retrospective studies have shown similar results. Among almost 34,000 participants in the Iowa Women's Health Study reporting recalled weight over a 35 year period, those with intentional weight loss ≥20 pounds had lower breast cancer risk (RR 0.81, 95% CI 0.66-1) [100], with similar significant findings in a subsequent analysis (RR 0.77, 95% CI 0.55-0.93) [99].

Low-fat dietary pattern in postmenopausal females — The low-fat dietary pattern, which includes increased intake of fruits, vegetables, and grains evaluated in the WHI Dietary Modification (DM) randomized trial, involves dietary moderation and is similar to the Dietary Approaches to Stop Hypertension diet, but with somewhat more emphasis on fat intake reduction [102,103]. This pattern has been associated with reducing deaths following breast cancer diagnosis [104], with potential mediating mechanisms, including reducing metabolic syndrome components and estradiol [14,105].

The WHI DM trial randomly assigned 48,835 postmenopausal females with no previous breast cancer to a usual diet comparison group or a low-fat dietary pattern, with every-three-week group sessions in the first year, and quarterly maintenance sessions throughout the 8.5-year intervention period [105,106]. The dietary intervention reduced fat intake to 24 percent calories from fat, and increased the intake of fruit, vegetables, and grains, resulting in modest weight loss (3 percent). After cumulative follow-up of nearly 20 years, the dietary group experienced fewer deaths from breast cancer (0.037 versus 0.047 percent; HR 0·79, 95% CI 0·64-0·97). This finding did not change by addition of time-dependent weight change and was mediated, in part, by a reduction in poor prognosis, estrogen receptor-positive, progesterone receptor-negative breast cancers (HR 0.77, 95% CI 0.64-0.94). In a secondary analysis of the WHI DM trial, females in the intervention group with 3 to 4 metabolic syndrome components at entry had a 69 percent reduction in breast cancer mortality (HR 0.31, 95% CI 0.14-0.69) [107].

The influence of dietary fat, as a single component of diet, on breast cancer risks is discussed below. (See 'Other dietary factors' below.)

INCONCLUSIVE FACTORS

Diet rich in fruits and vegetables, fish, and olive oil (eg, Mediterranean diet) — A Mediterranean diet, characterized by an abundance of plant foods, fish, and olive oil, may decrease breast cancer risk, but further study is needed.

In the PREDIMED clinical trial, 4282 postmenopausal females were randomly assigned to a Mediterranean diet supplemented with (1) extra-virgin olive oil, or (2) mixed nuts, or (3) a control diet with a primary outcome of cardiovascular disease (CVD) [108]. As a secondary analysis, through 4.8 years of follow-up, there were fewer breast cancer cases in the Mediterranean diet with olive oil versus the control group (hazard ratio [HR] 0.32, 95% CI 0.13-0.79). The original report on findings for CVD was retracted in 2018 due to "irregularities in randomization procedures" involving 1588 participants (37 percent of the total randomized), which were excluded from a new analysis [109]. Importantly, as the original breast cancer findings were based on only 35 incident cases and no revision of breast cancer findings has been published, the PREDIMED trial does not provide randomized clinical evidence of Mediterranean diet influence on breast cancer incidence [110].

Observational studies have been conflicting regarding whether a Mediterranean diet is associated with lower incidence of all breast cancer or only estrogen receptor (ER)-negative breast cancers.

●In a systematic review, three of four cohort studies examining Mediterranean diet adherence and breast cancer showed inverse associations with postmenopausal ER-negative, but not ER-positive, breast cancers [111].

●In the same time frame, a meta-analysis of five cohort studies examining Mediterranean diet and breast cancer in postmenopausal females found a 6 percent lower risk for all breast cancers, which was of borderline significance (relative risk [RR] 0.94, 95% CI 0.88-1.01) [112].

●In the Nurses' Health Study, the association of alternate Mediterranean Diet score (aMed) with breast cancer risk was examined [113]. With 3580 cases of breast cancer, the highest quintile of aMed was associated with similar rates of total and ER-positive breast cancer to the lowest quintile, but lower rates of ER-negative breast cancer.

Other dietary factors — With rare exception, data gathered largely from observational studies suggest that certain dietary factors may modify breast cancer risk. However, methodologic issues regarding the measurement of nutritional intake and the contribution of other factors (such as alcohol use) complicate the interpretation of studies. The concept of studies designed to evaluate foods and/or nutrients in isolation is being challenged by the concept that evaluation of overall dietary patterns may better reflect the nature of the actual dietary exposure in a population [114]. Information regarding dietary patterns and breast cancer risk is found above. (See 'Low-fat dietary pattern in postmenopausal females' above and 'Diet rich in fruits and vegetables, fish, and olive oil (eg, Mediterranean diet)' above.)

A summary of what is known about specific dietary factors and breast cancer risk is discussed below.

●Fruits and vegetables – Data regarding the contribution of fruits and vegetables on breast cancer risk are inconclusive, with some evidence suggesting no effect and other studies suggesting a lower breast cancer risk in females with higher fruit and vegetable intakes.

In a prospective study of over 993,000 females observed for 11 to 20 years, no association between total fruit and vegetable intake and overall risk of breast cancer was identified [115]. However, other studies have suggested a decreased breast cancer risk in diets high in fruits and vegetables [105,116-118]. A 2010 meta-analysis of studies evaluating breast cancer risk reported that high consumption of a diet composed predominantly of fruits and vegetables was associated with lower breast cancer risk (odds ratio [OR] 0.89, 95% CI 0.82-0.99) [117].

Randomized clinical trials incorporating a pattern of increased fruits and vegetables are discussed above. (See 'Low-fat dietary pattern in postmenopausal females' above and 'Diet rich in fruits and vegetables, fish, and olive oil (eg, Mediterranean diet)' above.)

●Fat intake – Observational studies evaluating dietary fat intake as a single dietary component provide inconsistent results regarding breast cancer risk [119]. However, a low-fat dietary pattern, including increase in fruit, vegetables, and grains may reduce breast cancer mortality, as discussed above [105]. (See 'Low-fat dietary pattern in postmenopausal females' above.)

A meta-analysis of cohort studies found no significant association between dietary fat intake and breast cancer risk (RR 1.03, 95% CI 0.76-1.40) [119]. However, in the AARP Diet and Health Study, females in the highest fat intake quintile had breast cancer rates 11 to 22 percent higher compared with females in the lowest quintile [120]. In a more recent meta-analysis of 15 prospective cohort studies, breast cancer mortality was higher for females with the highest compared with lowest saturated fat intake (HR 1.5, 95% CI 1.09-2.09; p <0.01), but no such association was seen with total fat intake [121].

These inconsistent results could reflect limitations of the dietary assessment methodology [122]. In this regard, one study found dietary fat intake significantly associated with breast cancer incidence only when intake was based on food diaries rather than the food frequency questionnaires most commonly used in observational studies [123]. (See "Dietary fat", section on 'Cancer'.)

●Soy/phytoestrogens – Phytoestrogens are naturally occurring plant substances with a chemical structure similar to 17-beta estradiol. They consist mainly of isoflavones (found in high concentrations in soybeans and other legumes) and lignans (found in a variety of fruits, vegetables, and cereal products). There is only low-quality evidence that soy-rich diets in Western societies prevent breast cancer.

A 2014 meta-analysis of eight studies evaluating the impact of soy food intake and breast cancer risk reported that [124]: in pooled studies in Asian countries soy isoflavone has a protective effect in both pre- and postmenopausal females (OR 0.59, 95% CI 0.48-0.69; OR 0.59, 95% CI 0.44-0.74, respectively); in pooled studies in postmenopausal females in Western countries soy isoflavone intake has only a marginally protective effect (OR 0.92, 95% CI 0.83-1). However, further analyses stratifying by study design found no statistically significant association.

●Red meat and processed meat – Red meat and processed meat have been suggested to increase breast cancer risk, but data are inconclusive. Two meta-analyses found processed meat associated with higher breast cancer incidence, with no association with red meat [125,126]. In the 2010 meta-analysis discussed above, there was no influence on breast cancer risk among females with high intake of red/processed meats. Meanwhile, an association between intake of red meat (>5 servings per week) and premenopausal breast cancer has been reported in a few studies, but the evidence linking this to breast cancer risk is weaker than that for other cancers [127-129].

The suggested relationship has been based on iron content, estrogen use as a supplement for cattle, and mutagens created by cooking. However, further data are needed.

●Fiber intake – In a meta-analysis of 24 epidemiologic studies, dietary fiber intake was associated with a 12 percent relative risk reduction in breast cancer incidence, with dose-response analysis suggesting that every 10 gram/day increment in dietary fiber intake was associated with a 4 percent relative risk reduction in breast cancer [130].

Geographic residence — Globally, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females. Breast cancer incidence rates are highest in North America, Australia/New Zealand, and in western and northern Europe and lowest in Asia and sub-Saharan Africa [1]. Despite the decreases in incidence rates in North America, breast cancer incidence has been increasing in other parts of the world, such as Asia and Africa. These international differences are thought to be related to societal changes occurring during industrialization (eg, changes in fat intake, body weight, age at menarche, and/or lactation and reproductive patterns such as fewer pregnancies and later age at first birth).

In the United States, geographic cluster regions with high breast cancer incidence rates have been identified, such as Cape Cod, Massachusetts; Long Island, New York; and Marin County, California [131-133]. These clusters are most likely due to regional differences in established breast cancer risk factors, but studies are ongoing to better understand these clusters [134]. Studies of migration patterns of females from low-risk areas to the United States are consistent with the importance of cultural and/or environmental changes [135]. In general, incidence rates of breast cancer are greater in second-generation migrants and increase further in third- and fourth-generation migrants.

Air pollution — There is no clear link between breast cancer and air pollution.

In a meta-analysis, including 11 cohort studies, there was a trend toward increase in breast cancer incidence associated with a 10 mcg/m3 increase in exposure to fine particulate matter, but it did not reach statistical significance (HR 1.05, 95% CI 1.00-1.10) [136]. In one of the studies included in the meta-analysis, which included almost 60,000 female patients followed for an average of 19.3 years, fine particulate matter (PM2.5) exposure was associated with an increased incidence of breast cancer (HR per 10 mcg/m3 1.28, 95% CI 1.08-1.51), with no heterogeneity in regards to race, ethnicity, and hormone receptor status. Further data are needed to establish and quantitate a potential risk between air pollution and breast cancer.

Exposure to diagnostic radiation — Whether there is a link between breast cancer risk and diagnostic levels of irradiation (eg, mammography, chest radiographs, diagnostic spine imaging, computed tomography scans) in females without an inherited predisposition is controversial [137-139]. However, the risk of breast cancer associated with diagnostic radiation in females with an inherited BRCA1/2 mutation appears to be increased [140-142]. (See "Screening for breast cancer: Evidence for effectiveness and harms", section on 'Radiation'.)

Medications — Several medication classes may have a modifying effect on breast cancer risk. However, the evidence to support their association to breast cancer is weak. These include the following:

Calcium/vitamin D — Although observational studies have suggested that higher plasma 25-hydroxyvitamin D levels may be associated with lower breast cancer risk in postmenopausal (but not premenopausal) females [143], randomized trials of vitamin D supplementation have not shown a protective effect [144].

In a Women's Health Initiative (WHI) randomized trial, among over 36,000 postmenopausal females, those assigned to 1000 mg of elemental calcium with 400 international units of vitamin D3 did not have higher rates of invasive breast cancer relative to placebo, during the seven years of intervention and 4.9 years of postintervention follow-up [145,146]. Similarly, the randomized VITAL trial of over 25,000 people found no significant effect of vitamin D (2000 international units) with or without omega-3 supplements on breast cancer incidence, or on total invasive cancer and major cardiovascular disease events (the coprimary study outcomes) [147,148].

Nonsteroidal anti-inflammatory drugs — The data regarding a possible protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk are mixed:

●In a meta-analysis of 49 studies, use of any NSAID was associated with a lower breast cancer risk (OR 0.82, 95% CI 0.77-0.88), with similar findings for aspirin, acetaminophen, cyclooxygenase-2 inhibitors, and, to a lesser extent, ibuprofen [149]. By contrast, in a Nurses' Health Study, there was no association between use of aspirin, NSAIDs, or acetaminophen and breast cancer incidence [150]. Finally, in a randomized trial evaluating low-dose aspirin (100 mg every other day), after 10-years (mean) follow-up, no effect on incidence of breast cancer or all cancer was seen [151].

Bisphosphonates — Oral bisphosphonates are commonly used for the treatment of osteoporosis therapy and for females with breast cancer with bone loss attributed to aromatase inhibitors. Whether their use is a true protective factor for those without a history of breast cancer is unclear (see "Bisphosphonate therapy for the treatment of osteoporosis"). Although some studies have shown a lower breast cancer risk with bisphosphonates by approximately one-third [152-155], other studies, including a large observational cohort of over 64,000 postmenopausal females followed for approximately seven years, have not seen an association [156]. Low bone mineral density may reflect a lower-estrogen environment, so the decreased risk observed with bisphosphonates in some studies may reflect a population that is at lower risk of getting breast cancer. (See 'Bone mineral density' above.)

The protective effect of bisphosphonates in the adjuvant setting for breast cancer is an ongoing area of research. (See "Use of osteoclast inhibitors in early breast cancer".)

Phthalates — Phthalates are chemicals found in medical supplies, food containers, cosmetics, toys, and medications, particularly those with suspended-release formulations [157,158]. They have been reported to have hormonal effects [159], but the effect on breast cancer risk is unclear. For example, in a nested case-control study of postmenopausal participants in the prospective WHI, there was no association between urinary metabolites of phthalates and breast cancer incidence [160]. However, in a nationwide Danish cohort study of females at risk for cancer, high levels of phthalate exposure from medications (≥10,000 cumulative mg, calculated from prescriptions filled) was associated with an approximately twofold increase in the rate of ER-positive breast cancer (but not ER-negative breast cancer) [161]. The association was stronger among premenopausal females. At this point, more conclusive data are needed to determine whether high-level exposure, as through long-term use of phthalate-containing medications, is a breast cancer risk factor.

Infertility — The association between infertility and breast cancer risk is controversial. In several epidemiologic studies, infertility due to anovulatory disorders was associated with lower breast cancer risk [62,162,163]. However, in other studies, either no association or a slight increase in risk was associated with infertility after adjusting for prior pregnancy history and age at first delivery [162,164].

Night-shift work — Night-shift work is recognized by the International Agency for Research on Cancer and the World Health Organization as a probable carcinogen [165], although evidence is mixed [165-168]. This association may be related to nocturnal light exposure, which results in the suppression of nocturnal melatonin production by the pineal gland [169]. Evidence to support this comes from the finding that low levels of 6-sulfatoxymelatonin (the major melatonin metabolite) are associated with higher breast cancer risk [169,170]. (See "Pharmacotherapy for insomnia in adults", section on 'Melatonin'.)

FACTORS THAT DO NOT INFLUENCE BREAST CANCER RISK

Abortion — Both a large pooled analysis [171] and population-based cohort studies [172-176] do not support an association between abortion (induced or spontaneous) and breast cancer risk. The effect of age of first full-term birth is discussed above. (See 'Increasing age at first full-term pregnancy' above.)

Chemicals — Organochlorines include polychlorinated biphenyls, dioxins, and organochlorine pesticides such as dichlorodiphenyltrichloroethane. These compounds are weak estrogens, highly lipophilic, and capable of persisting in body tissues for years. However, an association with breast cancer has not been demonstrated [177,178].

Antioxidants — There is no evidence for an effect of intake of vitamin A, E, or C or beta-carotene on breast cancer risk [179,180].

Tubal ligation — Early observational studies reported inconsistent results on the association between tubal ligation and breast cancer risk. A meta-analysis of 77,249 postmenopausal, cancer-free females found no association between tubal ligation and breast cancer risk (odds ratio 0.97, 95% CI 0.84-1.09) [181].

Caffeine — A number of studies have failed to show any association between caffeine intake and breast cancer risk [182,183]. (See "Benefits and risks of caffeine and caffeinated beverages".)

Other — Well-done epidemiologic studies have failed to find any association between cosmetic breast implants, electromagnetic fields, electric blankets, and hair dyes and breast cancer risk [178,184].

For patients undergoing in vitro fertilization, there does not appear to be an increased long-term risk of breast cancer. This is discussed in detail elsewhere. (See "Assisted reproductive technology: Pregnancy and maternal outcomes", section on 'Breast cancer'.)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Factors that affect breast cancer risk in women (Beyond the Basics)")

SUMMARY

●Non-modifiable risk factors for breast cancer – Non-modifiable factors associated with higher breast cancer risk include increasing age, female sex, being from a White population, family history, certain genetic alterations, breast atypia, and dense breast tissue. (See 'Factors associated with greater breast cancer risk' above.)

●Reproductive risk factors – Reproductive factors that increase breast cancer risk include early menarche, later age at the time of first pregnancy (>35 years old), absence of chestfeeding, and nulliparity. (See 'Reproductive factors' above.)

●Modifiable risk factors

•For postmenopausal females, obesity is associated with a higher breast cancer risk, which is ameliorated by weight loss. However, a higher body mass index has been associated with a lower risk of breast cancer in premenopausal females. (See 'Weight and body fat in postmenopausal females' above.)

•Combined estrogen/progesterone menopausal hormone therapy in females with intact uteri has been clearly shown to increase risk of subsequent estrogen receptor-positive breast cancer. However, in females with prior hysterectomy, single-agent estrogen replacement has not been associated with increased risk of breast cancer (and is actually associated with reduced risks). (See "Menopausal hormone therapy and the risk of breast cancer".)

•Alcohol use and current smoking are associated with higher risks of breast cancer. (See 'Alcohol use and smoking' above.)

•A low-fat dietary pattern, which includes increase in fruits, vegetables, and grains, may reduce risk of death from breast cancer in postmenopausal females. (See 'Other dietary factors' above and 'Low-fat dietary pattern in postmenopausal females' above.)

•Regular, moderate physical activity may provide modest protection against breast cancer. (See 'Physical activity' above.)

●Factors that do not influence breast cancer risk – A number of other variables, including abortion, caffeine intake, in vitro fertilization, cosmetic breast implants, and hair dyes are not associated with increased risks of breast cancer. (See 'Factors that do not influence breast cancer risk' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Wendy Y Chen, MD, MPH, who contributed to an earlier version of this topic review.

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  136. Wu AH, Wu J, Tseng C, et al. Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study. J Clin Oncol 2025; 43:273.
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  140. Narod SA, Lubinski J, Ghadirian P, et al. Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Lancet Oncol 2006; 7:402.
  141. Pijpe A, Andrieu N, Easton DF, et al. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK). BMJ 2012; 345:e5660.
  142. Andrieu N, Easton DF, Chang-Claude J, et al. Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators' Group. J Clin Oncol 2006; 24:3361.
  143. Bauer SR, Hankinson SE, Bertone-Johnson ER, Ding EL. Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine (Baltimore) 2013; 92:123.
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  145. Chlebowski RT, Johnson KC, Kooperberg C, et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 2008; 100:1581.
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  151. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA 2005; 294:47.
  152. Chlebowski RT, Chen Z, Cauley JA, et al. Oral bisphosphonate use and breast cancer incidence in postmenopausal women. J Clin Oncol 2010; 28:3582.
  153. Rennert G, Pinchev M, Rennert HS. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol 2010; 28:3577.
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Topic 792 Version 90.0

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39 : Tamoxifen and breast density in women at increased risk of breast cancer.

40 : Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women.

41 : Bone mass and the risk of breast cancer among postmenopausal women.

42 : Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures. Study of Osteoporotic Fractures Research Group.

43 : Hip bone density predicts breast cancer risk independently of Gail score: results from the Women's Health Initiative.

44 : Bone mineral density and risk of breast cancer in postmenopausal women.

45 : Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

46 : Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women.

47 : Endogenous sex hormones, breast cancer risk, and tamoxifen response: an ancillary study in the NSABP Breast Cancer Prevention Trial (P-1).

48 : Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers.

49 : Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies.

50 : [Dual effects of androgens on mammary gland].

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56 : Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women's Health Initiative.

57 : Diabetes mellitus and breast cancer.

58 : Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies.

59 : Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies.

60 : Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses' Health Study.

61 : Reproductive risk factors in a prospective study of breast cancer: the Nurses' Health Study.

62 : Reproductive factors and breast cancer.

63 : Models of breast cancer show that risk is set by events of early life: prevention efforts must shift focus.

64 : Declining incidence of contralateral breast cancer in the United States from 1975 to 2006.

65 : 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.

66 : Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women's Environmental Cancer and Radiation Epidemiology Study.

67 : Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease.

68 : Family History and Breast Cancer Risk Among Older Women in the Breast Cancer Surveillance Consortium Cohort.

69 : Smoking and Risk of Breast Cancer in a Racially/Ethnically Diverse Population of Mainly Women Who Do Not Drink Alcohol: The MEC Study.

70 : Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.

71 : Active and passive smoking and risk of breast cancer: a meta-analysis.

72 : Active smoking and breast cancer risk: original cohort data and meta-analysis.

73 : Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009).

74 : Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

75 : Passive cigarette smoke exposure during various periods of life, genetic variants, and breast cancer risk among never smokers.

76 : Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

77 : Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer.

78 : Breast cancer in Belarus and Ukraine after the Chernobyl accident.

79 : Breast cancer incidence following low-dose rate environmental exposure: Techa River Cohort, 1956-2004.

80 : Radiation and other environmental exposures and breast cancer.

81 : Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease.

82 : Breastfeeding and breast cancer risk by receptor status--a systematic review and meta-analysis.

83 : Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.

84 : Recreational Physical Activity Is Associated with Reduced Breast Cancer Risk in Adult Women at High Risk for Breast Cancer: A Cohort Study of Women Selected for Familial and Genetic Risk.

85 : Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study.

86 : International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

87 : Physical Activity and Weight Loss Reduce the Risk of Breast Cancer: A Meta-analysis of 139 Prospective and Retrospective Studies.

88 : Summary of the workshop: Workshop on Physical Activity and Breast Cancer, November 13-14, 1997.

89 : Summary of the workshop: Workshop on Physical Activity and Breast Cancer, November 13-14, 1997.

90 : Physical activity and the risk of breast cancer.

91 : A prospective study of age-specific physical activity and premenopausal breast cancer.

92 : Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors.

93 : Effects of exercise training on fasting insulin, insulin resistance, insulin-like growth factors, and insulin-like growth factor binding proteins in postmenopausal breast cancer survivors: a randomized controlled trial.

94 : Randomized controlled trial of aerobic exercise on insulin and insulin-like growth factors in breast cancer survivors: the Yale Exercise and Survivorship study.

95 : Adult weight change and incidence of premenopausal breast cancer.

96 : Weight loss and breast cancer incidence in postmenopausal women.

97 : Sustained Weight Loss and Risk of Breast Cancer in Women 50 Years and Older: A Pooled Analysis of Prospective Data.

98 : Genetic Factors, Adherence to Healthy Lifestyle Behavior, and Risk of Invasive Breast Cancer Among Women in the UK Biobank.

99 : Association of gain and loss of weight before and after menopause with risk of postmenopausal breast cancer in the Iowa women's health study.

100 : Intentional weight loss and incidence of obesity-related cancers: the Iowa Women's Health Study.

101 : Adiposity, adult weight change and breast cancer risk in postmenopausal Japanese women: the Miyagi Cohort Study.

102 : Eating Pattern Response to a Low-Fat Diet Intervention and Cardiovascular Outcomes in Normotensive Women: The Women's Health Initiative.

103 : A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.

104 : Association of Low-Fat Dietary Pattern With Breast Cancer Overall Survival: A Secondary Analysis of the Women's Health Initiative Randomized Clinical Trial.

105 : Dietary Modification and Breast Cancer Mortality: Long-Term Follow-Up of the Women's Health Initiative Randomized Trial.

106 : Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

107 : Low-fat dietary pattern and breast cancer mortality by metabolic syndrome components: a secondary analysis of the Women's Health Initiative (WHI) randomised trial.

108 : Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial: A Randomized Clinical Trial.

109 : Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts.

110 : PREDIMED trial of Mediterranean diet: retracted, republished, still trusted?

111 : Associations between Diet Quality Scores and Risk of Postmenopausal Estrogen Receptor-Negative Breast Cancer: A Systematic Review.

112 : Mediterranean diet adherence and risk of postmenopausal breast cancer: results of a cohort study and meta-analysis.

113 : Diet quality is associated with the risk of estrogen receptor-negative breast cancer in postmenopausal women.

114 : Dietary patterns and breast cancer risk: a study in 2 cohorts.

115 : Fruit and vegetable intake and risk of breast cancer by hormone receptor status.

116 : Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study.

117 : Dietary patterns and breast cancer risk: a systematic review and meta-analysis.

118 : Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.

119 : Summary and meta-analysis of prospective studies of animal fat intake and breast cancer.

120 : Dietary fat and postmenopausal invasive breast cancer in the National Institutes of Health-AARP Diet and Health Study cohort.

121 : Dietary fat and breast cancer mortality: A systematic review and meta-analysis.

122 : Epidemiological assessment of diet: a comparison of a 7-day diary with a food frequency questionnaire using urinary markers of nitrogen, potassium and sodium.

123 : Are imprecise methods obscuring a relation between fat and breast cancer?

124 : Association between soy isoflavone intake and breast cancer risk for pre- and post-menopausal women: a meta-analysis of epidemiological studies.

125 : Consumption of red and processed meat and breast cancer incidence: A systematic review and meta-analysis of prospective studies.

126 : Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis.

127 : Dietary fat and breast cancer risk revisited: a meta-analysis of the published literature.

128 : Red meat intake and risk of breast cancer among premenopausal women.

129 : Meat consumption and risk of breast cancer in the UK Women's Cohort Study.

130 : Dietary fibre intake and risk of breast cancer: A systematic review and meta-analysis of epidemiological studies.

131 : Breast cancer in Marin County.

132 : Spatial analysis of lung, colorectal, and breast cancer on Cape Cod: an application of generalized additive models to case-control data.

133 : Breast cancer clusters in the northeast United States: a geographic analysis.

134 : Geographic variation in mortality from breast cancer among white women in the United States.

135 : Geographic variation in mortality from breast cancer among white women in the United States.

136 : Air Pollution and Breast Cancer Incidence in the Multiethnic Cohort Study.

137 : Radiation exposure to patients receiving routine scoliosis radiography measured at depth in an anthropomorphic phantom.

138 : Breast cancer in women with scoliosis exposed to multiple diagnostic x rays.

139 : Radiation-Induced Breast Cancer Incidence and Mortality From Digital Mammography Screening: A Modeling Study.

140 : Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study.

141 : Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK).

142 : Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators' Group.

143 : Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies.

144 : The effect of vitamin D supplementation on the risk of breast cancer: a trial sequential meta-analysis.

145 : Calcium plus vitamin D supplementation and the risk of breast cancer.

146 : Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.

147 : Calcium plus vitamin D supplementation and health outcomes five years after active intervention ended: the Women's Health Initiative.

148 : Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials.

149 : Effect of COX-2 inhibitors and other non-steroidal inflammatory drugs on breast cancer risk: a meta-analysis.

150 : Use of aspirin, other nonsteroidal anti-inflammatory drugs, and acetaminophen and postmenopausal breast cancer incidence.

151 : Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial.

152 : Oral bisphosphonate use and breast cancer incidence in postmenopausal women.

153 : Use of bisphosphonates and risk of postmenopausal breast cancer.

154 : Bisphosphonate use after estrogen receptor-positive breast cancer and risk of contralateral breast cancer.

155 : Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk.

156 : Use of Bisphosphonates and Risk of Breast Cancer in a French Cohort of Postmenopausal Women.

157 : Levels of seven urinary phthalate metabolites in a human reference population.

158 : Medications as a source of human exposure to phthalates.

159 : Urinary bisphenol A, phthalates, and couple fecundity: the Longitudinal Investigation of Fertility and the Environment (LIFE) Study.

160 : Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

161 : Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study.

162 : Risk of breast cancer in a cohort of infertile women.

163 : Infertility and breast cancer: a population-based case-control study.

164 : Cancer incidence in a cohort of infertile women.

165 : Cancer incidence in a cohort of infertile women.

166 : Case-control study of shift-work and breast cancer risk in Danish nurses: impact of shift systems.

167 : Night Shift Work and Breast Cancer Incidence: Three Prospective Studies and Meta-analysis of Published Studies.

168 : A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer.

169 : Urinary melatonin levels and breast cancer risk.

170 : Urinary 6-sulfatoxymelatonin levels and risk of breast cancer in postmenopausal women.

171 : Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries.

172 : Induced abortion and the risk of breast cancer.

173 : Breast cancer risk in relation to abortion: Results from the EPIC study.

174 : Induced and spontaneous abortion and breast cancer risk: results from the E3N cohort study.

175 : Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study.

176 : Abortions and breast cancer: record-based case-control study.

177 : Organochlorines and breast cancer risk.

178 : Organochlorines and breast cancer risk.

179 : Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial.

180 : Dietary beta-carotene, vitamin C and E intake and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

181 : Tubal sterilization and breast cancer incidence: results from the cancer prevention study II nutrition cohort and meta-analysis.

182 : Coffee intake and breast cancer risk in the NIH-AARP diet and health study cohort.

183 : Coffee, tea, caffeine intake, and the risk of cancer in the PLCO cohort.

184 : Cancer among Scandinavian women with cosmetic breast implants: a pooled long-term follow-up study.