In 2009 the Agency for Healthcare Research and Quality (AHRQ) published the Evidence Report/Technology Assessment, Diagnosis and Management of Ductal Carcinoma in Situ (DCIS) (AHRQ, 2009). The report is a systematic synthesis of the published evidence about the incidence, risk factors, and the management options for women with ductal carcinoma in situ (DCIS) of the breast.
While no causual relationships have been found, multiple risk factors have been proposed. Here we outline the AHRQ findings for 4 risk factor categories: (1) demographic factors, (2) reproductive factors, (3) biological risk factors such as family history, (4) behavioral risk factors
- Age-specific incidence:
- DCIS is strongly related to age in U.S. women
- incidence of DCIS is extremely uncommon prior to age 35
- incidence increases after 35, peaking between 65-69, decreasing thereafter
- The incidence of DCIS is highest in Caucasians and lower in African Americans, Asian-Pacific Islanders and Hispanics. The lower rates of DCIS for African American, Asian, and Hispanic women is coupled with lower rates of invasive cancer. The lower rates of DCIS in nonwhites should not be viewed as indicating a failure to diagnose breast cancer early but could be related to lower underlying risk of breast cancer.
- After 1973 the incidence of of DCIS increased for both urban and rural women. However, the increase was greater for urban women.
- Urban and rural Australian women experienced a similar increase in DCIS over the same time period.
- Limited data suggests that women with < high school education had a greater cumulative incidence of DCIS than women who had higher education
- Limited data suggests that women of the lowest socio-economic status had a lower cumulative incidence of DCIS than women with the highest status
- Age at menarche:
- There is little evidence to support an association between DCIS and early onset of menarche
- Age at menopause
- Limited evidence supports an increased risk of DCIS in women experiencing onset of menopause after 55 years compared with women who are 45 at onset.
- Hormone replacement therapy
- Evidence associating HRT use and DCIS is mixed
- Current users of hormone replacement therapy for less than 5 years compared to never users had significantly less risk of DCIS
- Current users of HRT for more than 5 years were found to have a greater risk of DCIS compared to never users
- Oral contraceptives
- A significant association between OC use and the risk of DCIS has not been found
- First live birth after 20 years of age increases the risk of DCIS
- Three or more births may provide a protective effect but the statisitcs are mixed
- Breast density
- Extreme density increases risk of DCIS
- Fatty breasts develop DCIS less often
- Body Composition
- Evidence of association between BMI and DCIS is mixed.
- Family history
- Evidence of association between first degree relatives with breast cancer and DCIS is mixed.
- DCIS incidence is increased for women with the BRCA1/2 mutation plus a high famial risk
- Polymorphisms rs4415084 and rs10941679 located on n chromosome 5p12 increased the odds of DCIS
- Benign breast conditions
- Previous breast biopsy is not associated with increased incidence of DCIS
- Previous diagnosis of benign breast disease is associated with increased risk of DCIS
Behavioral risk factors
- the evidence of alcohol association with increased risk of DCIS is mixed
- Dietary betacarotene
- Modest evidence indicates that increased dietary beta carotene may reduce the risk of DCIS
- Vitamin D deficiency
- A deficiency in vitamin D is associated with tumor progression and metastasis in breast cancer
- Vitamin D supplements may provide a protective anti-breast cancer effect. Bauer et al. (2013) examined prospective studies of the circulating plasma vitamin D3, active metabolite (25-hydroxyvitamin D (25[OH]D)), and its relationship to breast cancer risk. These researchers were compared 5206 female subjects with breast cancer and 6450 female control subjects. They found that 25(OH)D levels of ≥27 ng/mL to 35 ng/mL lowered the risk of breast cancer in post-menopausal women by 12%. The anti-cancer benefits did not increase at levels beyond 35 ng/mL.
Shao, Klein and Grossbard (2012) found a 60% lower risk of cancer of all types including breast cancer with the addition of vitamin D supplements in a study but with a small (n=19) incidence of breast cancer.
- The 2014 U.S. Surgeon General Report estimates that a history of ever smoking may increase the risk for breast cancer by an average of 10%
- Limited evidence indicates no association between cigarette smoking and risk of DCIS
- Physical activity
- Women with a physically active lifestyle had a significantly reduced risk of DCIS compared to sedentary women.
- Nonsteroidal anti-inflammatory agents
- The relative risk of DCIS was significantly lower among frequent aspirin users compared to nonusers.
- Ibuprofen users did not receive the same benefit.
It is not clear exactly what triggers the cellular changes that result in DCIS.
It is likely that preventable and non-preventable influences are responsible. A 2011 study by Schnabel, Chun, Billig et al., found no statistically significant differences for the following risk factors between women diagnosed with DCIS or IDC:
- Median age at diagnosis
- Family history of breast cancer
- Age at menarche
- Age at menopause
- Age at first birth
- Breast feeding
- Body Mass Index
Oral contraceptives are known to increase the risk of DCIS.
Agency for Healthcare Research and Quality (2009). Diagnosis and Management of Ductal Carcinoma in Situ (DCIS). Evidence Report/Technology Assessment Number 185. Accessed 12/25/16. http://www.ahrq.gov/sites/default/files/wysiwyg/research/findings/evidence-based-reports/dcis-evidence-report.pdf
Bauer, S.R., Hankinson, S.E., Bertone-Johnson, E.R., et al (2013). Plasma vitamin D levels, menopause, and risk of breast cancer: dose-response meta-analysis of prospective studies. Medicine 92,123-131.
Kabat G.C., Kim M., Kakani C., Tindle H., Wactawski-Wende J. , Ockene J.K., Luo J., Wassertheil-Smoller S., Rohan T.E. (2010) Cigarette Smoking in Relation to Risk of Ductal Carcinoma In Situ of the Breast in a Cohort of Postmenopausal Women. American Journal of Epidemiology, 172 (5): 591-599. Accessed online 11/22/15 http://aje.oxfordjournals.org/content/172/5/591.
Schnabel F., Chun K., Billig J., et al. (2011) Poster Session 4 - Epidemiology, Risk, and Prevention: Risk Factors and Modeling. Risk Factor Profiles of Women with DCIS and Invasive Ductal Breast Cancers. Cancer Research. December 15, 2011
U.S. Department of Health & Human Services (2014) Surgeon General Reports. The Health Consequences of Smoking 50 Years of Progress: A Report of the Surgeon General, 2014 http://www.surgeongeneral.gov/library/reports/50-years-of-progress
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