Relationship of established risk factors with breast cancer subtypes

McCarthy, Anne Marie; Friebel-Klingner, Tara; Ehsan, Sarah; He, Wei; Welch, Michaela; Chen, Jinbo; Kontos, Despina; Domchek, Susan M.; Conant, Emily F.; Semine, Alan; Hughes, Kevin S.; Bardia, Aditya; Lehman, Constance D.; Armstrong, Katrina

doi:10.1002/cam4.4158

Cited by 58 publications

(44 citation statements)

References 55 publications

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“…However, to our knowledge, no study has specifically evaluated the association of circulating SHBG with risk of triple-negative breast cancer, which differs from other common types of breast cancer in many risk factors. 45,46 In particular, several reproductive factors related to a high estrogen exposure (such as age at menarche, nulliparity, and age at first full-term pregnancy) were not associated with risk of triple-negative breast cancer, 47,48 suggesting that triple-negative breast cancer may have a different etiologic profile from other breast cancer subtypes.…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes

Chen

Wen

Long

et al. 2022

Intl Journal of Cancer

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Many risk factors have been identified for breast cancer. The potential causality for some of them remains uncertain, and few studies have comprehensively investigated these associations by molecular subtypes. We performed a two-sample Mendelian randomization (MR) study to evaluate potential causal associations of 23 known and suspected risk factors and biomarkers with breast cancer risk overall and by molecular subtypes using data from the Breast Cancer Association Consortium. The inversevariance weighted method was used to estimate odds ratios (OR) and 95% confidence interval (CI) for association of each trait with breast cancer risk. Significant associations with breast cancer risk were found for 15 traits, including age at menarche, age at menopause, body mass index, waist-to-hip ratio, height, physical activity, cigarette smoking, sleep duration, and morning-preference chronotype, and six blood biomarkers (estrogens, insulin-like growth factor-1, sex hormone-binding globulin [SHBG], telomere length, HDL-cholesterol and fasting insulin). Noticeably, an increased circulating SHBG was associated with a reduced risk of estrogen receptor (ER)-positive cancer (OR = 0.83, 95% CI: 0.73-0.94), but an elevated risk of ER-negative (OR = 1.12, 95% CI: 0.93-1.36) and triple negative cancer (OR = 1.19, 95% CI: 0.92-1.54) (P heterogeneity = 0.01). Fasting insulin was most strongly associated with an increased risk of HER2-negative cancer (OR = 1.94, 95% CI: 1.18-3.20), but a reduced risk of HER2-enriched cancer (OR = 0.46, 95% CI: 0.26-0.81) (P heterogeneity = 0.006). Results from sensitivity analyses using MR-Egger and MR-PRESSO were generally consistent. Our study provides strong evidence supporting potential causal associations of several risk factors for breast cancer and suggests potential heterogeneous associations of SHBG and fasting insulin levels with subtypes of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes

Chen

Wen

Long

et al. 2022

Intl Journal of Cancer

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“…54,55 In addition, there are some identified prognostically unfavorable genetic mutations and other aggressive characteristics that are more common in cancers diagnosed among people of African ancestry and may contribute to survival disparities for some cancers. [56][57][58] The underrepresentation of people of color in clinical trials, which limits knowledge about the efficacy of new therapeutic agents in these populations specifically as well as the population at large, is also likely a factor. [59][60][61][62] From 2014 to 2018, Black individuals represented 14% of the US population but only 7% of participants in clinical trials supporting US Food and Drug Administration approval of cancer drugs.…”

Section: Stage At Diagnosis and Survivalmentioning

confidence: 99%

“…For example, diabetes is more common in Black people than in White people and is associated with an increased risk of cancer death 54,55 . In addition, there are some identified prognostically unfavorable genetic mutations and other aggressive characteristics that are more common in cancers diagnosed among people of African ancestry and may contribute to survival disparities for some cancers 56‐58 . The underrepresentation of people of color in clinical trials, which limits knowledge about the efficacy of new therapeutic agents in these populations specifically as well as the population at large, is also likely a factor 59‐62 .…”

Section: Select Findingsmentioning

confidence: 99%

Cancer statistics for African American/Black People 2022

Giaquinto

Miller

Tossas

et al. 2022

CA A Cancer J Clinicians

336

228

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African American/Black individuals have a disproportionate cancer burden, including the highest mortality and the lowest survival of any racial/ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2018), mortality (through 2019), survival, screening, and risk factors using population‐based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2022, there will be approximately 224,080 new cancer cases and 73,680 cancer deaths among Black people in the United States. During the most recent 5‐year period, Black men had a 6% higher incidence rate but 19% higher mortality than White men overall, including an approximately 2‐fold higher risk of death from myeloma, stomach cancer, and prostate cancer. The overall cancer mortality disparity is narrowing between Black and White men because of a steeper drop in Black men for lung and prostate cancers. However, the decline in prostate cancer mortality in Black men slowed from 5% annually during 2010 through 2014 to 1.3% during 2015 through 2019, likely reflecting the 5% annual increase in advanced‐stage diagnoses since 2012. Black women have an 8% lower incidence rate than White women but a 12% higher mortality; further, mortality rates are 2‐fold higher for endometrial cancer and 41% higher for breast cancer despite similar or lower incidence rates. The wide breast cancer disparity reflects both later stage diagnosis (57% localized stage vs 67% in White women) and lower 5‐year survival overall (82% vs 92%, respectively) and for every stage of disease (eg, 20% vs 30%, respectively, for distant stage). Breast cancer surpassed lung cancer as the leading cause of cancer death among Black women in 2019. Targeted interventions are needed to reduce stark cancer inequalities in the Black community.

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“…Once investigative teams began to oversample or enroll a disproportionately high percentage of minorities and younger women [27], include multiple breast cancer subtypes by additional IHC markers [39] or transcriptomic analysis, record pre-or postmenopausal status at the time of diagnosis, and use multiple measures of obesity, our understanding of obesity's impact on risk became even more complex. In studies such as the Carolina Breast Cancer Study (CBCS) or consortia such as AMBER (African American Breast Cancer Epidemiology and Risk, which includes CBCS), obesity in premenopausal women was reported to be a risk factor for breast cancer, especially for triple-negative breast cancer (TNBC) [34,[40][41][42][43]. In contrast, several studies have not supported these findings, showing null results or moderately reduced risk ratios for obesity risk in premenopausal women.…”

Section: Obesity and Breast Cancermentioning

confidence: 99%

The role of obesity and bariatric surgery-induced weight loss in breast cancer

Bohm

Sipe

Pye

et al. 2022

Cancer Metastasis Rev

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Obesity is a complex metabolic condition considered a worldwide public health crisis, and a deeper mechanistic understanding of obesity-associated diseases is urgently needed. Obesity comorbidities include many associated cancers and are estimated to account for 20% of female cancer deaths in the USA. Breast cancer, in particular, is associated with obesity and is the focus of this review. The exact causal links between obesity and breast cancer remain unclear. Still, interactions have emerged between body mass index, tumor molecular subtype, genetic background, and environmental factors that strongly suggest obesity influences the risk and progression of certain breast cancers. Supportive preclinical research uses various diet-induced obesity models to demonstrate that weight loss, via dietary interventions or changes in energy expenditure, reduces the onset or progression of breast cancers. Ongoing and future studies are now aimed at elucidating the underpinning mechanisms behind weight-loss-driven observations to improve therapy and outcomes in patients with breast cancer and reduce risk. This review aims to summarize the rapidly emerging literature on obesity and weight loss strategies with a focused discussion of bariatric surgery in both clinical and preclinical studies detailing the complex interactions between metabolism, immune response, and immunotherapy in the setting of obesity and breast cancer.

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Relationship of established risk factors with breast cancer subtypes

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 58 publications

References 55 publications

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes

Cancer statistics for African American/Black People 2022

The role of obesity and bariatric surgery-induced weight loss in breast cancer

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