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BREAST CANCER

Alcohol and Smoking

  • A study of postmenopausal CTS participants found that women who consumed alcohol while they were using hormone therapy had an elevated risk of breast cancer. Once women stopped using hormone therapy, their consumption of alcohol was no longer associated with breast cancer risk.  Read more here. 
     

  • Researchers combined data from the CTS and 19 other cohort studies to examine the relationship between drinking alcohol and developing breast cancer. Within these studies, alcohol consumption was positively associated with the risk of developing estrogen-receptor-positive (ER+) and estrogen-receptor-negative (ER-) breast cancer, even among women with high folate intake.  Read more here
     

  • Heavy alcohol use may increase the risk of breast cancer. CTS participants who had two or more drinks per day had an increased risk of invasive breast cancer. This risk was further elevated among postmenopausal women in the cohort, and was highest for participants who were postmenopausal and had a history of benign breast disease or who used combination hormone replacement therapy.  Read more here.
     

  • Smoking may play a role in the development of breast cancer among CTS participants. Postmenopausal participants who were exposed to high levels of sidestream smoke (smoke from others’ tobacco products) had a small increased risk of breast cancer.  Read more here.

     

Body Size

  • Researchers pooled data from 159 prospective cohort studies, including the California Teachers Study, to study the relationship between adult health and risk of breast cancer. Their study found that adult height may be a risk factor for breast cancer in women, and suggested that there may be underlying genetic pathways that affect both a woman’s height and the pathogenesis (biological mechanisms that lead to disease) of breast cancer.  Read more here

  • A 2014 study found the relationship between body size (BMI and waist-to-hip ratio) and breast cancer patients’ risk of death varied across racial/ethnic groups. Using data from the California Breast Cancer Survivorship Consortium, researchers found that non-Latina white participants who were underweight (BMI <18.5) or morbidly obese (BMI ≥ 40) had an increased risk of dying from breast cancer. Among Latina participants, only the morbidly obese had a higher risk of death. This study did not find any association between BMI and breast cancer mortality among African American or Asian American study participants.  Read more here.

  • Among CTS participants, obesity, greater abdominal adiposity (excessive fat around the stomach), gaining 40 or more pounds as an adult, and greater height increased study participants’ risk of developing estrogen-receptor-positive progesterone-receptor-positive (ER+PR+) breast cancer. Postmenopausal obesity was associated with an increased risk of ER+PR+ breast cancer, but only among study participants who did not use hormone therapy when they joined the CTS. Obesity, abdominal adiposity, and height were not associated with CTS participants’ risk of developing estrogen-receptor-negative progesterone-receptor-negative (ER-PR-) tumors.  Read more here

Comorbidities

  • Using data from the California Breast Cancer Survivorship Consortium, researchers examined the role of comorbidities in the survival of patients with breast cancer. This 2015 study found that the risk of dying from breast cancer increased among study participants with breast cancer who also had a history of diabetes or myocardial infarction (heart attack). Read more here.

Diet

  • When researchers examined the recent diets of CTS participants, they found that energy, fat, fiber, antioxidant vitamins, and phytoestrogens were not associated with participants’ risk of breast cancer. However, they did find that participants who drank an average of 20 or more grams of alcohol per day (approximately two or more glasses of wine) had an increased risk of breast cancer.  Read more here

  • CTS participants who ate a plant-based diet (high in fruits and vegetables) had a reduced risk of breast cancer. The risk reduction was greatest for ER-PR- tumors.  Read more here
     

  • A 2012 study concerning intake of carotenoids α-Carotene, β-carotene, and lutein/zeaxanthin revealed that increased consumption of these pigments was associated with a lower risk of ER-negative breast cancer, though not ER-positive breast cancer. It is unclear whether the carotenoids themselves lend to the effect or if other components in the same food sources do.  Read more here.
     

  • A 2013 study found no association between total fruit and vegetable intake and risk of overall breast cancer. However, increased vegetable consumption was correlated with lower risk of ER-negative breast cancer.  Read more here.

Environmental Factors

  • Researchers studied the relationship between neighborhood environment (the social and human-made (“built”) physical attributes of an individual's surroundings), BMI, and mortality after breast cancer diagnosis. Using pooled data from the California Breast Cancer Consortium and the California Neighborhoods Data System, researchers found that neighborhood environment was associated with obesity and mortality after breast cancer diagnoses, but that these associations varied across racial/ethnic groups.  Read more here. 
     

  • A 2015 study found that CTS participants who had long-term, low-dose exposure to ambient cadmium compounds (chemical compounds in the environment containing cadmium, a type of metal) had an elevated risk of breast cancer, specifically hormone-responsive-negative tumors. Read more here

  • A 2014 study examined the relationship between indoor and outdoor light at night and CTS participants’ risk of breast cancer. CTS participants who lived in areas with the highest quintile (measure) of outdoor light-at-night had an increased risk of developing breast cancer.  Read more here. 
     

  • California women who lived in areas of high agricultural pesticide use between 1988 and 1997 do not have higher than expected rates of breast cancer.  Read more here. 
     

  • Researchers found that CTS participants from the San Francisco Bay area and the Southern Coastal areas had a higher rate of breast cancer than the rest of California. These residents were noted to have socioeconomic, urbanization, and personal risk factor variables that were associated with higher risk. However, even when these were controlled for, risk was still elevated in these two areas.  Read more here.
     

  • Researchers examined the relationship between breast cancer incidence and concentrations of air pollutants shown to be mammary gland carcinogens (MGCs), modeled by annual average air concentrations though not other sources of inhalation. There was no relationship found between MGC concentration and increased risk of breast cancer.  Read more here.
     

  • A 2018 study found no evidence that serum polyfluoroalkyl substances (PFASs) measured post-diagnosis had any relation to breast cancer risk.  Read more here.
     

  • Researchers compared the blood serum of women diagnosed with invasive breast cancer and women with no diagnosis. Using post-diagnostic data, researchers did not find evidence that higher PBE-related chemical (BDE-47, BDE-100, and BDE-153) presence in blood was associated with increased breast cancer risk.  Read more here.

Genetics

  • Using data from the Breast Cancer Association Consortium, of which the CTS is a member, researchers constructed a Type 2 diabetes genetic risk score (GRS) for study participants using risk variants from 33 known independent Type 2 diabetes susceptibility loci (regions on chromosomes that are susceptible to mutation). They found that while the diabetes type 2 GRS was not associated with breast cancer risk overall, several genetic risk variants were associated with the risk of both type 2 diabetes and breast cancer.  Read more here
     

  • In 2014, researchers evaluated the relationship between estrogen plus progestin therapy (EPT) and mammographic density (MD) among CTS participants. MD is a strong biomarker of breast cancer risk. Researchers examined the associations between polymorphisms (genetic variation within a population) in hormone metabolism pathway genes and changes in mammographic density after study participants quit EPT.  Read more here

  • Using data from 24 studies of the Breast Cancer Association Consortium, researchers studied whether 10 risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) modified the relative risk of breast cancer associated with 23 single nucleotide polymorphisms for study participants of European ancestry.  They found that the risk of breast cancer associated with some common genetic variants varied by risk factor.  Read more here
     

  • A susceptibility locus is an allele that influences risk but isn’t sufficient nor necessary to stop/cause expression of the disease. A 2012 study identified three new susceptibility loci at chromosomes 12p11, 12q24, and 21q21. Read more here.
     

  • A single nucleotide polymorphism (SNP) is a variation in a single DNA building block, also known as a nucleotide. A 2012 study researched SNP rs2046210, which has previously been associated with increased risk of breast cancer in Asian women but the role of which is uncertain in European women. European studies have identified a different SNP, rs12662670, for this locus (6p25.1). This study found that SNP rs2046210 was associated with a greater risk of ER- than ER+ breast cancer in Europeans; in Asians, there was no clear leaning towards a specific ER receptor style. Each SNP was associated with risk after adjusting for the other SNP,  suggesting the presence of two variants at 6q25.1, each independently associated with breast cancer risk in Asians and in Europeans. The variant tagged by rs2046210 was associated with a greater risk of ER- tumors.  Read more here.
     

  • Researchers identified two novel susceptibility loci for breast cancer at chromosomes 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with increased risk of ER-negative breast cancer but showed a weaker association with overall breast cancer and no association with ER-positive breast cancer. SNP rs17530068 at 6q14 was associated with increased risk of overall breast cancer, ER-negative, and ER-positive breast cancer. Three loci previously associated with greater ER-negative (19p13) and both ER-negative and ER-positive breast cancer risk (6p25 and 12p11) were confirmed.  Read more here.
     

  • The 19p13.1 breast cancer susceptibility locus modifies breast cancer risk in BRCA1 mutation carriers and is also established to be associated with greater risk of ovarian cancer. A 2012 study found no evidence that 19p13.1 variants were associated with either overall breast cancer or ER-positive breast cancer; however, they were associated with greater risk of ER-negative breast cancer and triple negative (ER-, PR-, HER2-negative) at rs8170. Furthermore, once adjusted for triple negative breast cancer, rs8170 was no longer associated with ER-negative breast cancer risk, and a significant genome-wide association was found between rs8170 and triple negative breast cancer. These findings provide evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct pathways. Read more here.
     

  • Researchers have identified a new breast cancer susceptibility locus at chromosome 9q31.2: rs865686. A 2012 study found this susceptibility locus was inversely associated with breast cancer risk among women of European descent. The association was strongest for ER+ breast cancer, which lends further support to the theory that genetic susceptibility varies according to tumor subtype.  Read more here.
     

  • A 2013 genome-wide association study (GWAS) examined susceptibility loci specific to ER-negative breast cancer. This study identified SNPs at four loci that were associated with associated with ER-negative, but not ER-positive, breast cancer risk. These four loci were MDM4 and LGR6 at chromosomes 1q32.1, 2p24.1, and FTO at chromosome 16q12.2.  Read more here.
     

  • A 2013 study identified three independent risk signals within the 10q26 locus in the second intron of FGFR2, the locus shown to be most strongly associated with estrogen-receptor-positive breast cancer in genome-wide association studies. Researchers also identified rs35054928, rs2981578, and rs45631563 as putative functional SNPs. Chromatin immunoprecipitation, a technique used to investigate the interaction between proteins and DNA in a cell, showed that FOXA1 preferentially bound to the risk-associated allele (C) of rs2981578 and E2F1 preferentially bound the risk variant of rs35054928.  Read more here.
     

  • A 2014 study found that while FGFR2 has been identified as a breast cancer susceptibility gene, other variations in fibroblast growth factor receptors (FGFR1, FGFR3, FGFR4, FGFRL1) were not associated with risk of breast cancer to the same degree. The strongest association besides FGFR2 was FGFR3 in European women, with an estimated per-allele odds ratio of 1.05, which was still much lower than observed for SNPs in FGFR2.  Read more here.
     

  • Using data from 50 case-control studies, researchers mapped the 2q35 breast cancer susceptibility locus using 1,560 genotyped and imputed single nucleotide polymorphisms (SNPs). They found that rs4442975 is associated with allele-specific FOXA1 binding, chromatin looping and IGFBP5 expression, suggesting that the g-allele of rs4442975 may increase breast cancer susceptibility through reduced IGFBP5 expression.  Read more here.
     

  • Genetic variations in the SNPs of microRNA (miRNA) or in the miRNA binding sites may affect the miRNA-dependent DNA expression/regulation. This could consequently affect many cancers, including breast cancer, and may alter individual risk to the disease. Combining nine genome-wide association studies, researchers found five miRNA binding site SNPs significantly associated with breast cancer risk. These SNPs are rs1045494, rs1052532, rs10719, rs4687554, and rs3134615, located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1 respectively.  Read more here.
     

  • A 2014 study did not find evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs (2.5 billion possible two SNP combinations) and the large sample size. Boolean operation-based screening and testing was used to evaluate each two SNP combination.  Read more here.
     

  • A 2014 study identified 25 new loci associated with risk of triple-negative breast cancer.  Read more here
     

  • Variants in mitotic genes (genes directly involved in mitosis or in regulating its process) were investigated for association with breast cancer risk and grade of tumor tissue. While no SNPs were individually associated with high-grade cancer, which is more undifferentiated and often fatal, the gene TACC2 was identified as an area of interest. Analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk.  Read more here.
     

  • Genome-wide association studies have previously identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. Researchers genotyped 428 SNPs using data from the Breast Cancer Association Consortium to identify the most causal SNPs. A 2015 study identified four sets of iCHAV variants, three of which were located within ZNF365. The most strongly associated SNP, rs10995201 in iCHAV1, was linked with both decreased ER-positive and ER-negative breast cancer risk, and was associated with decreased percent mammographic density. iCHAV2 and iCHAV3 were associated with both ER-positive and ER-negative breast cancer, though iCHAV4, located 5’ of ADO, was associated with only ER-positive breast cancer. A haplotype in iCHAV2 was found to function as a silencer of an NRBF2 promoter, suggesting a role in the development of breast cancer.  Read more here.
     

  • A 2015 study found that DNA damage response genes, including the first common variant of BRCA1, were associated with natural age at menopause. Later natural age at menopause increases breast cancer risk (approximately 6% increase in risk per year) but this is likely caused by prolonged sex hormone exposure, rather than DNA damage response gene mechanisms.  Read more here.
     

  • Researchers analyzed genetic variants across 5q11.2, a chromosome known to have associations with breast cancer risk. The study revealed four cancer risk allele candidates (rs74345699 and rs62355900 [iCHAV1], rs16886397 [iCHAV2a], and rs17432750 [iCHAV3]) that increased expression of the MAP3K1 gene, suggesting that MAP3K1 is the likely gene of focus in 5q11.2.  Read more here.
     

  • Researchers have previously identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. A 2015 study found that two independent association signals at 4q24 - variants rs62331150 and rs73838678 residing in the promoter of gene TET2 - are in linkage disequilibrium with rs9790517, meaning that sets of linked genes do not occur at the expected frequency. TET2 appears to play an important role in tumor suppression, and therefore these variants may be associated with breast cancer risk through their regulation of TET2 gene expression.  Read more here.
     

  • Previous studies have suggested that gene variations in CASP8 on chromosome 2 are associated with breast cancer risk. A 2015 genotyping study found an association between increased breast cancer risk and intron SNP rs1830298 in ALS2CR12for European subjects. Three additional independent breast cancer associations with other intron SNPs were also identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475).  Read more here.
     

  • Researchers created a polygenic risk score (PRS) that examined multiplicative interactions between 77 breast-cancer associated SNPs and derived absolute breast cancer risk from relative risk estimates and UK incidence and mortality rates. This study found that the risk of developing breast cancer for women in the highest 1% of the PRS was three times higher than the risk of women in the middle quintile of PRS.  Read more here.
     

  • A 2015 genome wide association study found 15 new susceptibility loci for breast cancer. Likely genes of interest were identified in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1.  Read more here.
     

  • Single nucleotide polymorphisms (SNPs) rs676256, rs865686, rs10816625, and rs13294895 in chromosomes 9p31.2 were found to be associated with ER-positive breast cancer. These SNPs were also found to interact with known drivers of hormone driven breast cancer, including including ER-α, FOXA1 and GATA-3. SNPs rs10816625 and rs13294895 appeared to have allele-specific effects on enhancer activity and could interact with the KLF4 gene locus.  Read more here.
     

  • A 2016 study identified TRM61B and WDR43 at chromosome 2p23.2 and PPIL3 at chromosome 2q33 as susceptibility loci for ER-negative breast cancer.  Read more here.
     

  • A 2016 genome-wide association study tested whether breast, ovarian and prostate cancers, which are all hormone-related cancers, had a shared genetic basis. This study found seven new cross-cancer loci: three loci associated with susceptibility to all three cancers, two loci associated with breast and ovarian cancer risk, and two loci associated with breast and prostate cancer risk.  Read more here.
     

  • Previous research has identified SNP rs10771399 at chromosome 12p11 as associated with breast cancer risk. A 2016 fine-scale mapping study revealed four more independent association signals at 12p11(rs7297051, rs805510 and rs113824616, and rs1871152) among participants of European descent.  Read more here.
     

  • A 2017 study examined the relationship between exonic variation and many breast cancer subtypes (ER, PR, HER2). No new exonic variants were found to be statistically significantly associated with breast cancer risk.  Read more here.
     

  • A 2017 genome-wide association study identified 65 new loci associated with breast cancer risk among women of European and East Asian descent. Researchers used in silico data (computer simulation of cell behavior) to predict target genes in breast cells at each locus.  Read more here.
     

  • A 2017 study focused on susceptibility variants for ER-negative breast cancer among women of European origin and identified ten variants at nine new loci associated with ER- breast cancer risk.  Read more here.
     

  • Researchers found that for women with a history of preeclampsia, the T allele of IGF1R variant rs2016347 was associated with a lower risk of breast cancer. This effect was most noticeable for HR+ breast cancer and in women whose age at first birth was younger than 30 years.  Read more here.
     

  • A 2017 study qualified BRCA2 isoforms (functionally similar proteins with similar amino acid sequences) retaining or missing exon 3 and assessed the cancer risk associated with the BRCA2 c.68‐7T > A variant. Although exon 3 exclusion was 4.5 times higher among variant carriers than controls, researchers did not find evidence of increased risk of breast cancer when co-occurring with pathogenic variants. Results from the study suggest the nonpathogenicity of the BRCA2 c.68‐7T > A, meaning the variant is not likely associated with disease.  Read more here.
     

  • A 2018 transcriptome wide association study identified 48 genes associated with breast cancer risk, including 14 genes at loci not yet reported for breast cancer.  Read more here.
     

  • A 2019 study evaluated associations between germline variants and breast cancer-specific mortality. Researchers did not find any germline variants directly associated with breast cancer-specific mortality, even if there were variants on chromosome 7 close to genes for which there is evidence of breast cancer association.  Read more here.
     

  • A 2018 transcriptome wide association study identified 48 genes associated with breast cancer risk, including 14 genes at loci not yet reported for breast cancer.  Read more here.

Incidence

  • A 2013 study applied the Rosner-Colditz breast cancer incidence model to the CTS population. Researchers affirmed that there was a statistically significant higher incidence of breast cancer in the CTS compared with the Nurses’ Health Study (NHS), and that the model worked consistently well when applied to an independent data set. Read more here.
     

  • The incidence of advanced breast cancer in premenopausal women has increased in the recent decades, unlike rates in postmenopausal women. The Premenopausal Breast Cancer Collaboration is a cooperative group of 20 cohort studies with the aim of identifying contributors to and reducing these rates. Read more here.

Medication

  • Although NSAIDs were found to have no association with breast cancer risk, long term (>= 5 years) daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. Long term daily ibuprofen use was furthermore associated with an increased risk of breast cancer.  Read more here
     

  • A 2010 study suggested that declines in breast cancer are largely attributable to the decrease in hormone therapy use. Breast cancer incidence in the California Teachers Study decreased sharply (30.6% from 2003 to 2005) among women who stopped taking hormone therapy, but remained generally consistent in the population who had never taken hormone therapy.  Read more here.
     

  • Researchers evaluated SNPs in growth factor genes associated with changes in mammographic density among non-Latina white CTS participants who had stopped estrogen-progestin combined therapy (EPT). The associations found were slight and potentially useful but not statistically significant.  Read more here.

Physical Activity

  • For California Teachers Study participants, strenuous recreational physical activity was associated with lower breast cancer risk, especially triple negative breast cancer (TNBC ER-/PR-/HER2-). Participants who were consistently physically active for more than 3.51 hours per week per year had the lowest risk of breast cancer compared with participants who exercised less than 0.50 hours per week per year.  Read more here

  • Within the CTS, participants who engaged in long-term strenuous physical activity had a reduced risk of invasive breast cancer and in situ breast cancer. Strenuous and moderate long-term activities were also associated with a reduced risk of developing estrogen-receptor-negative (ER-) but not estrogen-receptive-positive (ER+) breast cancer.  Read more here

Racial/Ethnic Disparities in Survival

  • Researchers combined data from the California Teachers Study and five other California-based breast cancer studies to examine the racial and ethnic disparities in breast cancer deaths in the United States. Physical activity, body size, and comorbidities (having two or more diseases or health conditions at the same time) may influence mortality from breast cancer, but these factors did not explain why women from different racial and ethnic groups died from breast cancer at different rates.  Read more here

  • Using data from the California Breast Cancer Survivorship Consortium, researchers examined the associations between race/ethnicity, education, neighborhood measures of socioeconomic status (nSES) and all-cause and breast cancer-specific mortality. In this study, white study participants with high-education and low-SES had higher all-cause mortality; African American study participants with low SES, regardless of their education level, had higher all-cause mortality.  Read more here. 
     

  • Cohort data from six California-based cancer studies were pooled together to examine overall breast-cancer mortality in other ethnicities relative to non-Latina Whites. The study found that African Americans had higher breast cancer-specific mortality than non-Latina Whites, although overall mortality was similar. Overall and breast cancer-specific mortality in Latinas and Asian Americans was considerably lower than in non-Latina Whites.  Read more here.

Reproductive Health

  • Researchers combined data from the CTS and the Women’s Contraceptive and Reproductive Experiences (CARE) Study to examine the relationship between oral contraceptive use and breast cancer survival. In this study, oral contraceptive use was not associated with all-cause or breast cancer specific mortality among study participants with invasive breast cancer.  Read more here
     

  • A 2010 study found that CTS participants who reported 15 or more years of estrogen therapy (ET) had a 19% greater risk of breast cancer risk, and study participants who reported 15 or more years of estrogen plus progestin (EPT) therapy had an 83% greater risk of breast cancer than woman who had not used hormone therapy.  These risks were confined to ER+PR+ and HER2+ tumors.  Read more here

  • Within the CTS, long-term (≥5 years) use of antihypertensive medication was associated with a small increased risk of invasive breast cancer. This increased risk appeared to be confined to estrogen-receptor-positive (ER +) breast cancer and younger women.  Read more here

  • Compared with CTS participants who had never been pregnant, parous CTS participants had a reduced risk for breast carcinoma in situ (CIS) and invasive breast cancer. The risk reduction grew with an increasing number of full-term pregnancies. The age at which participants had their first-full term pregnancy was also associated with breast cancer risk. Participants whose first full-term pregnancy occurred at age 35 or later had a 115% greater risk for breast CIS and a 27% greater risk for invasive breast cancer than participants whose first full-term pregnancy occurred before age 21.  Read more here. 
     

  • A 2008 study found that there was no statistically significant association between incomplete pregnancy (i.e. miscarriage or abortion) and the risk of breast cancer for California Teachers Study participants. Read more here.
     

  • A 2002 study found that CTS participants had a higher incidence rate of breast, ovarian, and endometrial cancer than comparable California women. These three cancers share several risk factors that may be more common among California female teachers, including low parity, short duration of breastfeeding, and use of postmenopausal hormones.  Read more here.
     

  • A 2014 study found that the association between SNP rs10235235 (locus CYP3A, chromosome 7q22.1) and breast cancer varied by age at menarche. The modest protective effect of rs10235235 only occurred in women with an older age at menarche (>or=15 years) and was not found for women with an age at menarche of <or=11 years, consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. This relationship between later menarche and reduced risk can likely be attributed to changes in hormone circulation patterns.  Read more here.

 
 
 
 
 
 
 
 
 
 
 

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