Cadmium exposure and the risk of breast cancer in Japanese women

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case–control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 μg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 μg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 μg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.     

Racial disparities in red meat and poultry intake and breast cancer risk

Purpose

Research on the role of red meat and poultry consumption in breast carcinogenesis is inconclusive, but the evidence in African-American (AA) women is lacking. The association between consuming meat and breast cancer risk was examined in the Women’s Circle of Health Study involving 803 AA cases, 889 AA controls, 755 Caucasian cases, and 701 Caucasian controls.

Methods

Dietary information was collected using a Food Frequency Questionnaire. Odds ratios (OR) and 95 % confidence intervals (CI) were obtained from logistic regression models adjusting for potential covariates.

Results

Comparing the fourth versus the first quartiles, among Caucasian women, processed meat (OR = 1.48; 95 % CI 1.07–2.04), unprocessed red meat (OR = 1.40; 95 % CI 1.01–1.94), and poultry intakes (OR = 1.42; 95 % CI 1.01–1.99) increased breast cancer risk. Risk associated with poultry intake was more dominant in premenopausal women (OR = 2.33; 95 % CI 1.44–3.77) and for women with ER? tumors (OR = 2.55; 95 % CI 1.29–5.03) in the Caucasian group. Associations in AA women were mostly null except for a significant increased risk trend with processed meat consumption for ER+ tumors (OR = 1.36; 95 % CI 0.94–1.97, p trend = 0.04).

Conclusions

Overall, associations between breast cancer risk and consumption of red meat and poultry were of different magnitude in AA and Caucasian women, with further differences noted by menopausal and hormone receptor status in Caucasian women. This is the first study to examine racial differences in meat and breast cancer risk and represents some of the first evidence in AA women.     

Hypothesized role of pregnancy hormones on HER2+ breast tumor development

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR? = ER? and PR?) expression and HER2 status: HR+/HER2?, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2? tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2? cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12–2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08–2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.     

Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer

Molecular and morphological alterations related to carcinogenesis have been found in terminal duct lobular units (TDLUs), the microscopic structures from which most breast cancer precursors and cancers develop, and therefore, analysis of these structures may reveal early changes in breast carcinogenesis and etiologic heterogeneity. Accordingly, we evaluated relationships of breast cancer risk factors and tumor pathology to estrogen receptor (ER) and progesterone receptor (PR) expression in TDLUs surrounding breast cancers. We analyzed 270 breast cancer cases included in a population-based breast cancer case–control study conducted in Poland. TDLUs were mapped in relation to breast cancer: within the same block as the tumor (TDLU-T), proximal to tumor (TDLU-PT), or distant from (TDLU-DT). ER/PR was quantitated using image analysis of immunohistochemically stained TDLUs prepared as tissue microarrays. In surgical specimens containing ER-positive breast cancers, ER and PR levels were significantly higher in breast cancer cells than in normal TDLUs, and higher in TDLU-T than in TDLU-DT or TDLU-PT, which showed similar results. Analyses combining DT?/PT TDLUs within subjects demonstrated that ER levels were significantly lower in premenopausal women versus postmenopausal women (odds ratio [OR] = 0.38, 95 % confidence interval [CI] = 0.19, 0.76, P = 0.0064) and among recent or current menopausal hormone therapy users compared with never users (OR = 0.14, 95 % CI = 0.046–0.43, P _trend = 0.0006). Compared with premenopausal women, TDLUs of postmenopausal women showed lower levels of PR (OR = 0.90, 95 % CI = 0.83–0.97, P _trend = 0.007). ER and PR expression in TDLUs was associated with epidermal growth factor receptor (EGFR) expression in invasive tumors (P = 0.019 for ER and P = 0.03 for PR), but not with other tumor features. Our data suggest that TDLUs near breast cancers reflect field effects, whereas those at a distance demonstrate influences of breast cancer risk factors on at-risk breast tissue. Analyses of mapped TDLUs may provide information about the sequence of molecular changes occurring in breast carcinogenesis.     

Association of race/ethnicity,socioeconomic status,and breast cancer subtypes in the National Cancer Data Base (2010–2011)

To estimate the odds of breast cancer subtypes in minority populations versus non-Hispanic (NH) whites stratified by socioeconomic status (SES) [a composite of individual-level SES (insurance status) and area-level SES (median household income quartile from 2000 U.S. Census data)] using a large nationwide cancer database. We used the National Cancer Data Base to identify breast cancer cases diagnosed in 2010 and 2011, the only 2 years since U.S. cancer registries uniformly began collecting HER2 results. Breast cancer cases were classified into five subtypes based on hormone receptor (HR) and HER2 status: HR+/HER2?, HR+/HER2+, HR?/HER2+ (HER2-overexpressing), HR?/HER2? (TN), and unknown. A polytomous logistic regression was used to estimate odds ratios (ORs) comparing the odds of non-HR+/HER2-subtypes to HR+/HER2? for racial/ethnic groups controlling for and stratifying by SES, using a composite of insurance status and area-level income. Compared with NH whites, NH blacks and Hispanics were 84 % (OR = 1.84; 95 % CI 1.77–1.92) and 17 % (OR = 1.17; 95 % CI 1.11–1.24) more likely to have TN subtype versus HR+/HER2?, respectively. Asian/Pacific Islanders (API) had 1.45 times greater odds of being diagnosed with HER2-overexpressing subtype versus HR+/HER2? compared with NH whites (OR = 1.45; 95 % CI 1.31–1.61). We found similar ORs for race in high and low strata of SES. In a large nationwide hospital-based dataset, we found higher odds of having TN breast cancer in black women and of HER2-overexpressing in API compared with white women in every level of SES.     

Contribution of clinical and socioeconomic factors to differences in breast cancer subtype and mortality between Hispanic and non-Hispanic white women

Purpose

To assess tumor subtype distribution and the relative contribution of clinical and sociodemographic factors on breast cancer survival between Hispanic and non-Hispanic whites (NHWs).

Methods

We analyzed data from the California Cancer Registry, which included 29,626 Hispanic and 99,862 NHW female invasive breast cancer cases diagnosed from 2004 to 2014. Logistic regression was used to assess ethnic differences in tumor subtype, and Cox proportional hazard modeling to assess differences in breast cancer survival.

Results

Hispanics compared to NHWs had higher odds of having triple-negative (OR = 1.29; 95% CI 1.23–1.35) and HER2-overexpressing tumors (OR = 1.19; 95% CI 1.14–1.25 [HR?] and OR = 1.39; 95% CI 1.31–1.48 [HR+]). In adjusted models, Hispanic women had a higher risk of breast cancer mortality than NHW women (mortality rate ratio [MRR] = 1.24; 95% CI 1.19–1.28). Clinical factors accounted for most of the mortality difference (MRR = 1.05; 95% CI 1.01–1.09); however, neighborhood socioeconomic status (SES) and health insurance together accounted for all of the mortality difference (MRR = 1.01; 95% CI 0.97–1.05).

Conclusions

Addressing SES disparities, including increasing access to health care, may be critical to overcoming poorer breast cancer outcomes in Hispanics.

     

Dietary patterns and breast cancer risk among Chinese women

Objective

The present study aimed to examine the relationship between dietary patterns and breast cancer risk among Chinese women.

Methods

Four hundred and thirty-eight cases with histologically confirmed primary breast cancer and 438 controls were consecutively recruited. Cases were frequency matched to controls on 5-year age group and rural?Curban residence. A validated food frequency questionnaire was used to assess dietary intake by face-to-face interviews. Dietary patterns were identified by factor analysis. Multivariate odds ratios (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression adjusted for various potential confounders.

Results

Two diet patterns were identified: vegetable?Cfruit?Csoy?Cmilk?Cpoultry?Cfish pattern and refined grain?Cmeat?Cpickle pattern. After adjustment for confounders, a 74% decreased risk was observed among women in the highest quartile of the vegetable?Cfruit?Csoy?Cmilk?Cpoultry?Cfish dietary pattern relative to the lowest quartile (OR = 0.26, 95% CI = 0.17?C0.42). The refined grain?Cmeat?Cpickle pattern was positively associated with breast cancer risk (OR = 2.58, 95% CI = 1.53, 4.34). Women with a high intake of the vegetable?Cfruit?Csoy?Cmilk?Cpoultry?Cfish pattern and a low intake of the refined grain?Cmeat?Cpickle pattern showed a decreased risk of breast cancer (adjusted OR = 0.26, 95% CI = 0.17?C0.41).

Conclusions

These results indicated that a diet characterized by a high consumption of vegetable/fruit/soy/milk/poultry/fish and a low consumption of refined grain/red meat/pickle is associated with a lower risk of breast cancer in Chinese women.     

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy

It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43–2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32–1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05–1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ER? tumors (p = 0.062). In a case–case multivariate analysis, a statistically significant association between ESR1 and ER? tumors was found (OR = 1.88; 95 % CI: 1.03–3.49; p = 0.039). Overall, our data, based on a large and well-characterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.     

Single-nucleotide polymorphisms in DNA bypass polymerase genes and association with breast cancer and breast cancer subtypes among African Americans and Whites

DNA damage recognition and repair is a complex system of genes focused on maintaining genomic stability. Recently, there has been a focus on how breast cancer susceptibility relates to genetic variation in the DNA bypass polymerases pathway. Race-stratified and subtype-specific logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between 22 single-nucleotide polymorphisms (SNPs) in seven bypass polymerase genes and breast cancer risk in the Carolina Breast Cancer Study, a population-based, case–control study (1,972 cases and 1,776 controls). We used SNP-set kernel association test (SKAT) to evaluate the multi-gene, multi-locus (combined) SNP effects within bypass polymerase genes. We found similar ORs for breast cancer with three POLQ SNPs (rs487848 AG/AA vs. GG; OR = 1.31, 95 % CI 1.03–1.68 for Whites and OR = 1.22, 95 % CI 1.00–1.49 for African Americans), (rs532411 CT/TT vs. CC; OR = 1.31, 95 % CI 1.02–1.66 for Whites and OR = 1.22, 95 % CI 1.00–1.48 for African Americans), and (rs3218634 CG/CC vs. GG; OR = 1.29, 95 % CI 1.02–1.65 for Whites). These three SNPs are in high linkage disequilibrium in both races. Tumor subtype analysis showed the same SNPs to be associated with increased risk of Luminal breast cancer. SKAT analysis showed no significant combined SNP effects. These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer.     

Impact of familial risk and mammography screening on prognostic indicators of breast disease among women from the Ontario site of the Breast Cancer Family Registry

Although several studies have found screen-detected cancers in women with familial breast cancer risk have favorable prognostic features compared with symptomatic cancers, the impact of level of familial risk is unknown. A cohort of 899 first-degree female relatives of cases of breast cancer from the Ontario site of the Breast Cancer Family Registry was followed for 2 years. Logistic regression analyses compared diagnoses of breast cancer or benign breast disease (BBD) between women at high (n = 258, 28.7 %) versus low/moderate (n = 641, 71.3 %) familial risk. Similar analyses compared prognostic features of invasive cancers and BBD by level of familial risk and mammography screening status. Among 899 women, 44 (4.9 %) were diagnosed with invasive breast cancer and/or ductal carcinoma in situ, and 56 (6.2 %) with BBD. Women with high familial risk were significantly more likely to be diagnosed with breast cancer [odds ratio (OR) = 2.84, 95 % confidence interval (CI) 1.50–5.38] than low/moderate risk women, particularly if diagnosed at age ≥50 (OR = 2.99, 95 % CI 1.37–6.56) or screened with mammography (OR = 3.33, 95 % CI 1.54–7.18). High risk women were more likely to be diagnosed with BBD (OR = 1.94, 95 % CI 1.03–3.66). Level of familial risk was not associated with prognostic features. Cancers among unscreened women were larger (OR = 9.72, 95 % CI 1.01–93.61) and diagnosed at stage II or above (OR = 7.80, 95 % CI 1.18–51.50) compared with screen-detected cancers. Screening mammography may be effective for women with a first-degree family history of breast cancer, irrespective of level of familial risk.     

Three novel functional polymorphisms in the promoter of FGFR2 gene and breast cancer risk: a HuGE review and meta-analysis

Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21–1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18–1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11–1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18–1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55–1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. CC/CT: OR = 0.55, 95 % CI: 0.38–0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35–0.76; TT vs. CT: OR = 0.58, 95 % CI: 0.40–0.85), especially among Asians. Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.     

The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis

Many epidemiological studies have found that leptin correlates to body fat extent and breast cancer. Leptin exerts its physiological action through the leptin receptor (LEPR). However, published data on the association between LEPR alleles and breast cancer occurrence have led to in contradictory results. A total of 10 studies were identified to the meta-analysis, including 4,644 cases and 5,485 controls for LEPR rs1137101 polymorphism, 5 studies with 2,759 cases and 4,464 controls for rs1137100 polymorphism, and 2 studies for rs8051542, rs8051542, and rs8051542 polymorphisms. The pooled odds ratios (OR) with 95 % confidence intervals (CI) for breast cancer risk associated with LEPR genotypes were estimated. Elevated breast cancer risk was associated with LEPR rs1137101 polymorphism when all studies were pooled in the meta-analysis (allele contrast model: OR = 0.71, 95 % CI = 0.551–0.997). In the stratified analysis by ethnicity, significantly increased risks were also found among Asians for allele contrast model (OR 0.414, 95 % CI 0.312–0.550) and dominant model (OR 0.537, 95 % CI 0.370–0.781); for Africans, significantly increased risks were also found for allele contrast model (OR 0.716, 95 % CI 0.595–0.861), homozygote codominant (OR 0.537, 95 % CI 0.370–0.781) and dominant model (OR 1.595, 95 % CI 1.207–2.108). And significantly elevated breast cancer risk was associated with LEPR rs1137100 polymorphism for allele contrast (OR = 0.666, 95 % CI = 0.603–0.720) and homozygote codominant models (OR = 0.344, 95 % CI = 0.282–0.421). For LEPR rs8179183, rs4655537, and rs3762274 polymorphisms, no significant associations were detected in all comparison models. This pooled analysis suggested that rs1137101 and rs1137100 polymorphisms were significantly correlated with breast cancer risk and the A allele of LEPR rs1137101 variant and the G allele of LEPR rs1137100 variant were low-penetrant risk factors for developing breast cancer. Further, no significant associations existed between LEPR rs8179183, rs4655537, and rs3762274 polymorphisms and risk of breast cancer.     

Radial scars and subsequent breast cancer risk: results from the Nurses’ Health Studies

Radial scars (RS) are benign proliferative lesions associated with an increased risk of subsequent breast cancer. However, it remains unclear whether RS are an independent risk factor for breast cancer or whether their association with breast cancer is due to their common occurrence with other proliferative lesions known to increase breast cancer risk. We performed an updated analysis of the association between RS and subsequent breast cancer risk in a nested case–control study among 460 cases and 1,792 controls with benign breast disease (BBD) in the Nurses’ Health Studies. Logistic regression was used to estimate associations between RS in BBD biopsy specimens and breast cancer risk, adjusted for matching factors and breast cancer risk factors, including histologic category of concurrent BBD. In multivariable models prior to adjustment for histologic category of BBD, RS were associated with a twofold increased risk of breast cancer (odds ratio (OR) = 2.0; 95 % confidence interval (95 % CI) 1.4, 2.8). This association was attenuated but still significant after adjustment for BBD histologic category (OR = 1.6; 95 % CI 1.1, 2.3). In models adjusted for BBD histologic category and other covariates, risk appeared greater among women with multiple RS (1 RS, OR = 1.5; 95 % CI 0.9, 2.3; ≥2 RS, OR = 2.7; 95 % CI 1.5, 5.0; p-heterogeneity = 0.12). There were also suggestions of a greater risk associated with RS among women age ≥50 years at biopsy (p-heterogeneity = 0.07) and for estrogen receptor-negative/progesterone receptor-negative tumors compared with other hormone receptor subtypes (p-heterogeneity = 0.19). RS appear to be an independent histologic risk factor for breast cancer. Larger studies are needed to further evaluate whether risk is increased when multiple RS are present and whether associations vary by age at biopsy or by hormone receptor status of the breast tumor.     

Serum insulin-like growth factor (IGF)-1 and IGF binding protein-3 in relation to breast cancer among Hispanic and white, non-Hispanic women in the US Southwest

Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case–control study of women living in the U.S. Southwest. Serum levels of IGF-1 and IGFBP-3 were measured in fasting blood samples, and associations among IGF-1, IGFBP-3, and breast cancer were calculated using logistic regression, adjusting for age, study center, ethnicity, education, recent hormone exposure, body mass index, parity, total energy expenditure, total calories, and cholesterol. Both IGF-1 and IGFBP-3 were statistically significantly associated with breast cancer overall (highest vs. lowest quartile (Q4 vs. Q1) for IGF-1: odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.07–3.43); for IGFBP-3: OR = 3.04, 95% CI = 1.63–5.67). Positive associations were observed for both premenopausal breast cancer and postmenopausal breast cancer. IGF-1 was associated with breast cancer in NHW women (Q4 vs. Q1: OR = 2.82, 95% CI = 1.36–5.83), but not in Hispanic women (Q4 vs. Q1: OR = 0.81, 95% CI = 0.29–2.27). IGFBP-3 was associated with breast cancer in both ethnic groups (Q4 vs. Q1 for NHW: OR = 3.32, 95% CI = 1.45–7.60; Q4 vs. Q1 for Hispanics: OR = 2.15, 95% CI = 0.76–6.04). In conclusion, the association between IGF-1 and breast cancer differed by ethnicity, while no ethnic differences were observed in IGFBP-3-associated breast cancer.     

Legume intake and the risk of cancer: a multisite case–control study in Uruguay

Background

Previous studies have suggested that a high intake of legumes may decrease the risk of stomach and prostate cancer and some other cancers. However, the evidence is still limited. To further explore the association between legume intake and cancer risk we conducted a case–control study of 11 cancer sites in Uruguay between 1996 and 2004, including 3,539 cancer cases and 2,032 hospital controls.

Results

The highest versus the lowest tertile of legume intake was associated with a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.48, 95% CI: 0.34–0.68), esophagus (OR = 0.54, 95% CI: 0.38–0.77), larynx (OR = 0.55, 95% CI: 0.40–0.77), upper aerodigestive tract (OR = 0.50, 95% CI: 0.40–0.63), stomach (OR = 0.69, 95% CI: 0.49–0.97), colorectum (OR = 0.43, 95% CI: 0.32–0.59), kidney (OR = 0.41, 95% CI: 0.24–0.71), and all sites combined (OR = 0.68, 95% CI: 0.59–0.78). No significant association was observed between legume intake and cancers of the lung (OR = 1.03, 95% CI: 0.83–1.27), breast (OR = 0.89, 95% CI: 0.65–1.20), prostate (OR = 0.87, 95% CI: 0.64–1.18) or bladder (OR = 0.82, 95% CI: 0.57–1.17). Similar results were found for both beans and lentils.

Conclusion

Higher intake of legumes was associated with a decreased risk of several cancers including those of the upper aerodigestive tract, stomach, colorectum, and kidney, but not lung, breast, prostate or bladder. Further investigations of these associations in prospective cohort studies are warranted.     

A case–control study of lifetime light intensity physical activity and breast cancer risk

Purpose

Physical activity reduces breast cancer risk, although most evidence is for activity in the moderate-to-vigorous intensity range. The effect of light intensity physical activity (LIPA) is unknown. We aimed to determine the association between self-reported lifetime LIPA and pre- and post-menopausal breast cancer risk. Our secondary objective was to analyze risk stratified by estrogen and progesterone tumor receptor status.

Methods

Data were from a case–control study of 1,110 incident breast cancer cases (388 pre-menopausal; 722 post-menopausal) and 1,172 controls (442 pre-menopausal; 730 post-menopausal) recruited at two Canadian sites. Lifetime leisure-time, household, and occupational physical activity and covariates were assessed by questionnaire. Mean minutes per day of LIPA for each of the age periods 12–17, 18–34, 35–49, ≥50, and the total lifetime were calculated. Odds ratios were calculated using unconditional logistic regression for overall breast cancer risk and using polytomous logistic regression for estrogen receptor (ER)/progesterone receptor (PR)-defined tumor subtypes and were adjusted for moderate-to-vigorous physical activity and other confounders.

Results

LIPA was not associated with breast cancer risk at any age period across the life course: odds ratio (OR) = 0.81; 95 % CI 0.53–1.24 for pre-menopausal women and OR = 0.87; 95 % CI 0.64–1.19 for post-menopausal women in the highest vs. lowest categories of total lifetime LIPA. No heterogeneity in risk by ER/PR tumor status was observed.

Conclusions

Our results suggest that light intensity physical activity is not associated with breast cancer risk reduction. This finding is important for physical activity recommendations for breast cancer prevention.     

Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers

Immune signatures in breast tumors differ by estrogen receptor (ER) status. The purpose of this study was to assess associations between ER phenotypes and circulating levels of cytokines that co-ordinate cell-mediated [T-helper type 1 (Th1)] and humoral [T-helper type 2 (Th2)] immunity. We conducted a case–case comparison of 523 women with newly diagnosed breast cancer to evaluate associations between 27 circulating cytokines, measured using Luminex XMap technology, and breast cancer phenotypes [ER^? vs. ER⁺; triple negative breast cancer (TNBC) vs. luminal A (LumA)]. Ratios of Th1 to Th2 cytokines were also evaluated. Levels of interleukin (IL)-5, a Th-2 cytokine, were higher in ER^? than in ER⁺ tumors. The highest tertile of IL-5 was more strongly associated with ER^? (OR = 2.33, 95 % CI 1.40–3.90) and TNBCs (OR = 2.78, 95 % CI 1.53–5.06) compared to ER⁺ and LumA cancers, respectively, particularly among premenopausal women (OR = 4.17, 95 % CI 1.86–9.34, ER^? vs. ER⁺; OR = 5.60, 95 % CI 2.09–15.01, TNBC vs. LumA). Elevated Th1 cytokines were also detected in women with ER^? and TNBCs, with women in the highest tertile of interferon α2 (OR = 2.39, 95 % CI 1.31–4.35) or tumor necrosis factor-α (OR = 2.27, 95 % CI 1.21–4.26) being twice as likely to have TNBC versus LumA cancer. When cytokine ratios were examined, women with the highest ratios of Th1 cytokines to IL-5 levels were least likely to have ER^? or TNBCs compared to ER⁺ or LumA cancers, respectively. The strongest associations were in premenopausal women, who were up to 80 % less likely to have TNBC than LumA cancers (IL-12p40/IL-5, OR = 0.19, 95 % CI 0.07–0.56). These findings indicate that immune function is associated with ER^? and TNBC and may be most relevant among younger women, who are likely to be diagnosed with these aggressive phenotypes.     

A case–control study of lifetime occupational sitting and likelihood of breast cancer

Purpose

Sedentary behavior may be a unique risk factor for some cancers, including breast cancer. The objective of this study was to determine the association between lifetime occupational sitting and likelihood of breast cancer.

Methods

A case–control study of 2,452 women was conducted in Alberta, Canada, between 1995 and 1997. A comprehensive measure of lifetime physical activity assessed frequency and duration of sedentary jobs. Logistic regression estimated the odds of being diagnosed with breast cancer across quartiles of lifetime occupational sitting, by menopausal status and family history of breast cancer, and within body mass index categories and physical activity quartiles.

Results

There was no association between occupational sitting and breast cancer among pre-menopausal women and women with a family history of breast cancer. Unexpectedly, higher amounts of occupational sitting were associated with lower odds of breast cancer in post-menopausal women (top versus bottom categories of occupational sitting OR = 0.71, 95 % CI 0.52, 0.97), women without a family history of breast cancer (OR = 0.77, 95 % CI 0.60, 1.00), and women in the third highest quartile of total lifetime physical activity (OR = 0.57, 95 % CI 0.33, 0.97).

Conclusion

Occupational sitting levels were lower than would be expected in a contemporary study. Exposures may have been insufficient to make a determinable contribution to breast cancer risk.     

Patterns of relapse and metastatic spread in HER2-overexpressing breast cancer according to estrogen receptor status

Purpose

The primary aim of this study was to compare the relapse patterns of estrogen receptor (ER)-positive and ER-negative patients with HER2-overexpressing breast cancer. A secondary aim was to distinguish the preferential primary site of metastases in HER2-overexpressing breast cancer.

Methods

Out of 886 patients treated for metastatic breast cancer (MBC) between January 1995 and December 2006, 269 patients with HER2-positive tumors were identified. Of these, 198 patients with relapsed breast cancer following surgery were included in this study. Rates and patterns of relapse and metastatic spread in HER2+/ER+ and HER2+/ER? patients were analyzed. This analysis was evaluated by the validation patients’ cohort of our institute prospectively.

Results

Median relapse-free survival was longer in the HER2+/ER+ group than in the HER2+/ER? group (32.0 vs. 19.5 months, p = 0.0012). The peak of recurrence occurred at 12 months after surgery in the HER2+/ER? patients. The peak of relapse was later and the level was lower in the HER2+/ER+ patients (66 and 78 months following surgery) than in the HER2+/ER? patients (33 and 39 months following surgery, respectively). This result was reproduced by the validation cohort with great similarity. Young age [hazard ratio (HR) 1.59, p = 0.002], TNM stage 3 (HR 1.51, p = 0.005), and ER-negativity (HR 1.68, p < 0.0001) were identified as independent risk factors for relapse. Severe bone metastasis (HR 4.48, p = 0.028) and massive hepatic metastasis (HR 5.24, p = 0.043) were identified as independent risk factors for early relapse.

Conclusions

Our study shows that HER2-overexpressing breast cancer displays characteristic patterns of relapse and metastatic spread depending on ER status.     

Total energy intake and breast cancer risk in sisters: the Breast Cancer Family Registry

Energy restriction inhibits mammary tumor development in animal models. Epidemiologic studies in humans generally do not support an association between dietary energy intake and breast cancer risk, although some studies suggest a more complex interplay between measures of energy intake, physical activity, and body size. We examined the association between total energy intake jointly with physical activity and body mass index (BMI) and the risk of breast cancer among 1,775 women diagnosed with breast cancer between 1995 and 2006 and 2,529 of their unaffected sisters, enrolled in the Breast Cancer Family Registry. We collected dietary data using the Hawaii–Los Angeles Multiethnic Cohort food frequency questionnaire. Using conditional logistic regression to estimate the odds ratios (OR) and 95 % confidence intervals (CI) associated with total energy intake, we observed an overall 60–70 % increased risk of breast cancer among women in the highest quartile of total energy intake compared to those in the lowest quartile (Q4 vs. Q1: OR = 1.6, 95 % CI: 1.3–2.0; P _trend < 0.0001); these associations were limited to pre-menopausal women or women with hormone receptor-positive cancers. Although the associations were slightly stronger among women with a higher BMI or lower level of average lifetime physical activity, we observed a positive association between total energy intake and breast cancer risk across different strata of physical activity and BMI. Our results suggest that within sisters, high energy intake may increase the risk of breast cancer independent of physical activity and body size. If replicated in prospective studies, then these findings suggest that reductions in total energy intake may help in modifying breast cancer risk.