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INTRODUCTION The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. METHODS In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. RESULTS Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. CONCLUSIONS Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight. [ABSTRACT FROM AUTHOR]

Experimental evidence indicates that exercise performed at different times of the day may affect circadian rhythms and circadian disruption has been linked to breast and prostate cancer. We examined in a population‐based case‐control study (MCC‐Spain) if the time‐of‐day when physical activity is done affects prostate and breast cancer risk. Lifetime recreational and household physical activity was assessed by in‐person interviews. Information on time‐of‐day of activity (assessed approximately 3 years after the assessment of lifetime physical activity and confounders) was available for 781 breast cancer cases, 865 population female controls, 504 prostate cases and 645 population male controls from 10 Spanish regions, 2008‐2013. We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for different activity timings compared to inactive subjects using unconditional logistic regression adjusting for confounders. Early morning (8‐10 am) activity was associated with a protective effect compared to no physical activity for both breast (OR = 0.74, 95% CI = 0.48‐1.15) and prostate cancer (OR = 0.73, 95% CI = 0.44‐1.20); meta‐OR for the two cancers combined 0.74 (95%CI = 0.53‐1.02). There was no effect observed for breast or prostate cancer for late morning to afternoon activity while a protective effect was also observed for evening activity only for prostate cancer (OR = 0.75, 95% CI = 0.45‐1.24). Protective effects of early morning activity were more pronounced for intermediate/evening chronotypes for both cancers. This is the first population‐based investigation identifying a differential effect of timing of physical activity on cancer risk with more pronounced effects for morning hour activity. Our results, if confirmed, may improve current physical activity recommendations for cancer prevention. What's new?: Exercise protects against a variety of cancers, but does time of day matter? Disrupting the body's circadian rhythm can boost cancer risk. Here, the authors compared breast and prostate cancer risk among people who exercised in the early morning, late morning, afternoon, and evening. They conducted a population‐based case‐control study, in which participants filled out a questionnaire about their patterns of sleeping, eating, and exercising. Exercising in the early morning appeared to be more strongly protective against breast and prostate cancer than exercising later in the day. Evening exercise appeared to have a moderate protective effect on prostate cancer. [ABSTRACT FROM AUTHOR]

Introduction: Phototype has been associated with an increased risk of prostate cancer, and it is yet unknown if it is related to other hormone-dependent cancers, such as breast cancer or whether this association could be considered causal. Methods: We examined the association between the phototype and breast and prostate cancers using a Mendelian randomization analysis. We studied 1,738 incident cases of breast cancer and another 817 cases of prostate cancer. To perform a Mendelian randomization analysis on the phototype—cancer relationship, a genetic pigmentation score was required that met the following criteria: (1) the genetic pigmentation score was associated with phototype in controls; (2) the genetic pigmentation score was not associated with confounders in the relationship between phototype and cancer, and (3) the genetic pigmentation score was associated with cancer only through its association with phototype. Once this genetic score is available, the association between genetic pigmentation score and cancer can be identified as the association between phototype and cancer. Results: The association between the genetic pigmentation score and phototype in controls showed that a higher genetic pigmentation score was associated with fair skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian randomization analysis, we verified that there was no association between the genetic pigmentation score and cancers of the breast and prostate. Conclusions: Phototype is not associated with breast or prostate cancer. [ABSTRACT FROM AUTHOR]

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations. [ABSTRACT FROM AUTHOR]

Introduction: The evidence on the relationship between breast cancer and different types of antihypertensive drugs taken for at least 5 years is limited and inconsistent. Furthermore, the debate has recently been fueled again with new data reporting an increased risk of breast cancer among women with a long history of use of antihypertensive drugs compared with nonusers. Methods: In this case-control study, we report the antihypertensive drugs–breast cancer relationship in 1,736 breast cancer cases and 1,895 healthy controls; results are reported stratifying by the women’s characteristics (i.e., menopausal status or body mass index category) tumor characteristics and length of use of antihypertensive drugs. Results: The relationship among breast cancer and use of calcium channel blockers (CCB) for 5 or more years had odds ratio (OR) = 1.77 (95% CI, 0.99 to 3.17). Stratifying by BMI, the OR increased significantly in the group with BMI ≥ 25 (OR 2.54, 95% CI, 1.24 to 5.22). CCBs were even more strongly associated with more aggressive tumors, (OR for invasive tumors = 1.96, 95% CI = 1.09 to 3.53; OR for non ductal cancers = 3.97, 95% CI = 1.73 to 9.05; OR for Erbb2+ cancer = 2.97, 95% CI: 1.20 to 7.32). On the other hand, premenopausal women were the only group in which angiotensin II receptor blockers may be associated with breast cancer (OR = 4.27, 95% CI = 1.32 to 13.84) but this could not be identified with any type or stage. Use of angiotensin-converting-enzyme inhibitors, beta blockers and diuretics were not associated with risk. Conclusions: In this large population-based study we found that long term use of calcium channel blockers is associated with some subtypes of breast cancer (and with breast cancer in overweight women). [ABSTRACT FROM AUTHOR]

There is limited evidence of phenolic compounds acting as protective agents on several cancer types, including breast cancer (BC). Nevertheless, some polyphenol classes have not been investigated and there is a lack of studies assessing the effect on menopausal status and hormone receptor status as influenced by these compounds. The objective of this study is to evaluate the association between the intake of all polyphenol classes in relation to the BC risk by menopausal and hormone receptor status. We used data from a population-based multi-case-control study (MCC-Spain) including 1472 BC cases and 1577 controls from 12 different regions of Spain. The odds ratios (ORs) with 95% CI were calculated using logistic regression of mixed effects by quartiles and log2 of polyphenol intakes (adjusted for the residual method) of overall BC, menopausal and receptor status. No associations were found between total intake of polyphenols and BC risk. However, inverse associations were found between stilbenes and all BC risk (ORQ4 vs. Q1: 0.70, 95%CI: 0.56–0.89, Ptrend = 0.001), the consumption of hydroxybenzaldehydes (ORQ4 vs. Q1: 0.75, 95%CI: 0.59–0.93, Ptrend = 0.012) and hydroxycoumarins (ORQ4 vs. Q1: 0.73, 95%CI: 0.57–0.93; Ptrend = 0.005) were also inversely associated. The intake of stilbenes, hydroxybenzaldehydes and hydroxycoumarins can contribute to BC reduction risk on all menopausal and receptor statuses. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Inflammation and antioxidant capacity have been associated with colorectal and breast cancer. We computed the dietary inflammatory index (DII®), and the total dietary non-enzymatic antioxidant capacity (NEAC) and associated them with colorectal and breast cancer risk in the population-based multi case-control study in Spain (MCC-Spain). We included 1852 colorectal cancer and 1567 breast cancer cases, and 3447 and 1486 population controls, respectively. DII score and NEAC were derived using data from a semi-quantitative validated food frequency questionnaire. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for energy-adjusted DII (E-DII), and a score combining E-DII and NEAC. E-DII was associated with colorectal cancer risk (OR = 1.93, highest quartile versus lowest, 95%CI:1.60–2.32; p-trend: <0.001); this increase was observed for both colon and rectal cancer. Less pronounced increased risks were observed for breast cancer (OR = 1.22, highest quartile versus lowest, 95%CI:0.99–1.52, p-trend: >0.10). The combined score of high E-DII scores and low antioxidant values were associated with colorectal cancer risk (OR = 1.48, highest quartile versus lowest, 95%CI: 1.26–1.74; p-trend: <0.001), but not breast cancer. This study provides evidence that a pro-inflammatory diet is associated with increased colorectal cancer risk while findings for breast cancer were less consistent. [ABSTRACT FROM AUTHOR]

Background Breast cancer is the main cause of cancer mortality among women. Green spaces have been recently associated with reduced cancer mortality among women. Mechanisms explaining the beneficial effect of green spaces include increased levels of physical activity and reduced exposure to air pollution, which have been both associated with cancer development. Objectives To investigate the associations between presence of urban green areas, presence of agricultural areas and surrounding greenness and risk of breast cancer, and to assess whether these associations are mediated by physical activity and/or air pollution levels. Methods We geocoded the current residence of 1129 breast cancer cases and 1619 controls recruited between 2008 and 2013 in ten provinces of Spain, as part of the MCC-Spain study. We assigned different indicators of exposure to green spaces in a buffer of 300 m, and in nested buffers of 100 m and 500 m around the residence: presence of urban green areas according to Urban Atlas, presence of agricultural areas according to CORINE Land Cover 2006, and surrounding greenness according to the average of the Normalized Difference Vegetation Index. We used logistic mixed-effects regression models with a random effect for hospital adjusting for potential confounders. We explored the effect of several potential effect modifiers. We assessed mediation effect by physical activity and levels of air pollution. Results Presence of urban green areas was associated with reduced risk of breast cancer after adjusting for age, socio-economic status at individual and at area level, education, and number of children [OR (95%CI) = 0.65 (0.49–0.86)]. There was evidence of a linear trend between distance to urban green areas and risk of breast cancer. On the contrary, presence of agricultural areas and surrounding greenness were associated with increased risk of breast cancer [adjusted OR (95%CI) = 1.33 (1.07–1.65) and adjusted OR (95%CI) = 1.27 (0.92–1.77), respectively]. None of the associations observed were mediated by levels of physical activity or levels or air pollution. Conclusions The association between green spaces and risk of breast cancer is dependent on land-use. The confirmation of these results in other settings and the study of potential mechanisms for the associations observed are needed to advance the understanding on the potential effects of green spaces on health. [ABSTRACT FROM AUTHOR]

Objective: To analyse the relationship of the risk of breast cancer (BC) to meat intake, preference regarding degree of cooking ('doneness') and cooking methods, using data from a population-based case-control study (MCC-Spain).Study Design: 1006 Histologically confirmed incident BC cases and 1370 controls were recruited in 10 Spanish provinces. Participants were 23-85 years old. They answered an epidemiological survey and a food frequency questionnaire. BC risk was assessed overall, by menopausal status and by pathological subtypes, using logistic and multinomial regression mixed models adjusted for known confounding factors and including province as a random effects term.Main Outcome Measures: Breast cancer and pathological subtype.Results: High total intake of meat (ORQ4-Q1 (95% IC) = 1.39 (1.03-1.88)) was associated with increased BC risk among post-menopausal women. Similar results were found for processed/cured meat (ORQ4-Q1 (95% IC) = 1.47 (1.10-1.97)), and this association was particularly strong for triple-negative tumours (ER-, PR- and HER2-) (ORQ4-Q1 (95% IC) = 2.52 (1.15-5.49)). Intakes of well-done (ORwell-donevsrare (95% CI) = 1.62 (1.15-2.30)) and stewed (OR (95% CI) = 1.49 (1.20-1.84)) red meat were associated with increased BC risk, with a high risk observed for HR+ tumours (ER+/PR+ and HER2-). Pan-fried/bread-coated fried white meat, but not doneness preference, was associated with an increased BC risk for all women (OR (95% CI) = 1.38 (1.14-1.65)), with a stronger association for pre-menopausal women (OR (95% CI) = 1.78 (1.29-2.46)).Conclusion: The risk of developing BC could be reduced by moderating the consumption of well-done or stewed red meat, pan-fried/bread-coated fried white meat and, especially, processed/cured meat. [ABSTRACT FROM AUTHOR]