Table F2Original epidemiologic studies of risk factors for DCIS

StudyPatientsDefinition of DCIS and Control for Bias
Weiss, 199664
Country: USA
Design: Case control
Evidence: II-2B
Time Period: May 1, 1990- December 31, 1992
Length of followup/months: N/A
Data source: Cancer registry in Atlanta, Georgia, Seattle/Puget Sound, Washington, and central New Jersey
Inclusion criteria: Breast cancer patients 20–44 years old diagnosed during the period of May 1, 1990, through December 31, 1992 identified in cancer registry in Atlanta, Georgia, Seattle/Puget Sound, Washington, and central New Jersey. Population based controls were identified by random-digit dialing among the residents of the same states.
Exclusion: Not having residential phone number
Inclusion Age: 20–44 Mean age: NR
Sample size: 3,152
Definition: DCIS identified in cancer registry with histological confirmation in SEER database or hospital records in New Jersey
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age at diagnosis, study site, smoking, number of mammographs in 5 year period, family history of breast cancer, race, parity, and BMI
Kerlikowske, 199765
Country: USA
Design: Cross-sectional
Evidence: II-2B
Time Period: April 1985 - September 1995
Length of followup/months: 1
Data source: University of California San Francisco Mobile Mammography Screening Program
Inclusion criteria: All 39,542 women aged 30 years and older who underwent a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program in April 1985 – September 1995 who had her records linked to the regional Surveillance, Epidemiology, and End Results cancer registry
Exclusion: History of breast cancer or mastectomy
Inclusion Age: >30 Mean age:
Sample size: 39,542
Definition: DCIS identified after biopsy
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age, age at first birth, family history of breast cancer, age at menarche, BMI, parity, and previous breast surgery
Elmore, 199866
Country: USA
Design: Well-designed nested case-control study (retrospective cohort)
Evidence: II-2C
Time Period: 1985–1993
Length of followup/months: 96
Data source: Yale-New Haven Hospital Tumor Registry
Inclusion criteria: All Black female patients of all ages with a first diagnosis of breast carcinoma verified by tissue pathology at Yale-New Haven Hospital from January 1, 1985-December 31, 1993, were selected from the hospital tumor registry. White control patients with breast carcinoma were selected randomly and matched to each black patient by the year of breast carcinoma diagnosis in a 3:1ratio.
Exclusion: From medical records for 120 black and 346 white patients were reviewed; 20 black patients were excluded (6 had a history of breast carcinoma prior to January 1, 1985, 1 did not have breast carcinoma, 1 had an incorrect race designated, and 12 were duplicate names). 46 white patients were excluded (32 had breast carcinoma prior to January 1, 1985, 1 had no evidence of breast carcinoma, 6 had an incorrect race designated, 1 had inadequate records, and 6 were duplicate names).
Inclusion Age: N/S Mean age: N/S
Sample size: 400
Definition: DCIS recorded as a medical diagnosis in Tumor registry
Masking of outcome assessment: Not reported
Control for bias: Adjusted for race, age, insurance status, income, and method of detection (screening mammogram, clinical breast examination, patient noted)
Elkhadrawy, 199867
Country: USA
Design: Case control study
Evidence: IIB
Time Period: January 1, 1989 - December 31, 1993
Length of followup/months: N/A
Data source: Columbia Presbyterian Medical Center (CPMC)
Inclusion criteria: All cases of female DCIS registered in CPMC cancer registry between January 1, 1989 and December 31, 1993. Controls were randomly selected females who underwent surgery for different benign conditions that are not associated with serum cholesterol at CPMC at the same time.
Exclusion: N/S
Inclusion Age: NS Mean age: 58.6
Sample size: 394
Definition: DCIS
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age, serum cholesterol, serum albumin, menopausal status
Bohlke, 199868
Country: USA
Design: Case control study
Evidence: IIB
Time Period: January 1, 1993- August 30, 1997
Length of followup/months: 18.5
Data source: the Massachusetts Cancer Registry
Inclusion criteria: DCIS cases diagnosed between January 1, 1993, and August 30, 1997, through the Massachusetts Cancer Registry, younger than 50 years, residing in eastern Massachusetts, premenopausal. Controls were randomly selected from annually published Massachusetts town lists. 94 cases with DCIS and 76 controls were included
Exclusion: Pregnancy, breastfeeding, taking exogenous hormones during the preceding 3 months, chemotherapy or radiation to the pelvis
Inclusion Age: <50 Mean age: NR
Sample size: 170
Definition: DCIS
Masking of outcome assessment: Not reported
Control for bias: Matching controls to cases by age (within 2 years) and precinct of residence. Adjustment for age (years), ethnic group (white, black, Hispanic, Asian), body mass index [weight (kg) per height squared (m2)], height (cm), parity (parous, nulliparous), age at menarche (years), age at first birth (years; among parous women), first-degree family history of breast cancer (present, absent), and estradiol level (pg per ml).
Gapstur, 199969
Country: USA
Design: Prospective cohort study
Evidence: II-2A
Time Period: January 1986 - December 1996
Length of followup/months: 132
Data source: The Iowa Women’s Health Study
Inclusion criteria: The Iowa Women’s Health Study is a prospective cohort study designed to examine the effect of several risk factors on the incidence of cancer in postmenopausal women aged 55 to 69 years at baseline. Randomly selected from the 1985 Iowa Department of Transportation driver’s license list (94% of all Iowa women) were invited in January 1986 to participate, 42% from 98,029 eligible women responded and consented.
Exclusion: Women with low risk of breast cancer who at baseline (1) were premenopausal (n = 569), (2) reported a previous total or partial mastectomy (n = 1870), or (3) reported a personal history of non skin cancer (n = 2293).
Inclusion Age: 55-69 Mean age:
Sample size: 37,105
Definition: DCIS identified using the Health Registry of Iowa, part of the National Cancer Institute’s Surveillance, Epidemiology and End Results program
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age (continuous variable), body mass index, body mass index at age 18 years, waist-to-hip ratio, age at menarche, age at menopause, age at first birth, parity, family history of breast cancer in a first-degree relative, type of menopause, and alcohol intake using Cox proportional hazards regression
Trentham-Dietz, 200070
Country: USA
Design: Case control study
Evidence: II-3
Time Period: 1988–1990
Length of followup/months: N/A
Data source: Wisconsin’s mandatory cancer registry
Inclusion criteria: All female residents of Wisconsin with a new diagnosis of in situ or invasive breast cancer who were 75 years of age.
Cases were identified by Wisconsin’s mandatory cancer registry (fifth digit behavior code=2; 8500, 8501, 8503, 8504, 8010, and 8140) from April 1988-December 1990. Eligibility was limited to cases with listed telephone numbers and known dates of diagnosis. The data for 301 in situ cases (85%) were available for analysis.
Community controls were randomly selected from two sampling frames: those under age 65 years were selected from a list of licensed drivers, and controls ages 65–75 years were selected from a roster of Medicare beneficiaries compiled by the Health Care Financing Administration. Computer files of potential controls were obtained annually. Controls had no previous diagnosis of breast cancer, listed telephone number. Of the 4,445 potential controls, 49 (1%) were deceased, 21 (<1%) could not be located, and 376 (9%) refused to participate. The overall response rate for control subjects was 90% (n =3,999).
Exclusion: 65 years of age without a driver’s license (by self- report)
Inclusion Age: 18–74, Mean age: N/S
Sample size: 3,999
Definition: Ductal/nonlobular carcinoma (ICD codes 8500, 8501, 8503, 8504, 8010, and 8140)
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age, age at first birth, family history of breast cancer, age at menopause, and education.
Claus, 200171
Country: USA
Design: Case control study
Evidence: IIB
Time Period: September 15, 1994-March 14, 1998
Length of followup/months: N/A
Data source: Rapid-case-ascertainment shared resource of the Yale Cancer Center (Yale University, New Haven, CT)
Inclusion criteria: All case patients with DCIS or LCIS ages 20–79 years at the time of diagnosis diagnosed among female residents of Connecticut from September 15, 1994, through March 14, 1998. Controls were female Connecticut residents selected by random-digit dialing methods by an outside consulting firm (Northeast Research, Oreno, ME).The final study population included 1,068 case patients and 999 control subjects, with overall estimated response rates of 76% and 70% for case patients and control subjects
Exclusion: Out-of-state residency,(8 patients), non-English speaking (21 patients), history of breast cancer/biopsy of unknown outcome (181 patients), age older than 79 years (31 patients), mixed histology (DCIS+LCIS)
Inclusion Age: NS Mean age: 56.6 ± 11.4
Sample size: 1,874
Definition: DCIS
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age (continuous), college education (yes/no), history of at least one screening mammogram 1 year before interview, body mass index, and ethnicity (white/other), age at menarche, previous breast biopsy, family history of breast cancer, parity, age at first live birth, age at menopause, external hormone use, ever smoke, and ever drink
Cuzick, 200272
Country: UK, Australia, New Zealand
Design: randomized controlled clinical trial
Evidence: I
Time Period: 1992–2001
Length of followup/months: 50
Data source: IBIS (International Breast Cancer Intervention Study) center Inclusion criteria: Women ages 35–70 years with risk factors for breast cancer indicating at least a twofold relative risk if they were 45–70 years of age, a fourfold relative risk if they were 40–44 years of age, or a 10- fold relative risk if they were 35–39 years of age. Women were eligible from age 45 years if they had 1) a mother or sister diagnosed with breast cancer before the age of 50 years, 2) two first- or second-degree relatives with breast cancer at any age, or 3) a first-degree relative with breast cancer at any age, and either were nulliparous or had a previous hyperplastic benign lesion. Women were eligible from the age of 40 years if they had 1) atypical ductal or lobular hyperplasia, 2) a first first-degree relative with bilateral breast cancer at any age, or 3) two first- or second- degree relatives with breast cancer, one of whom was diagnosed before age 50 years. Women were eligible from the age of 35 years if they had either 1) lobular carcinoma in situ or 2) two first first-degree relatives with breast cancer, both diagnosed before the age of 50 years. Any women with an estimated 10-year risk of 5% or more were also eligible as risk equivalent after approval by the study chairman.
Exclusion: Any previous invasive cancer (except non- melanoma skin cancer), a previous deep-vein thrombosis or pulmonary embolism, current use of anticoagulants, or a life expectancy judged to be <10 years, present or planned pregnancy.
Inclusion Age: 35–70 Mean age: 50.7
Sample size: 7,152
Definition: DCIS
Masking of outcome assessment: Double blind
Control for bias: Intention to treat, after exclusion of the 13 women found to have breast cancer at baseline The mean age was 50.8 years (SD 6.9); 54.7% of the women were between the ages of 45 and 54 ; 49% were postmenopausal and 41% had previously used hormone- replacement therapy.
Frank, 200273
Country: USA
Design: Retrospective cohort
Evidence: II-2C
Time Period: 1996–1999
Length of followup/months: 36
Data source: Myriad Genetic Laboratories and Myriad Genetics, Inc, Salt Lake City, UT.
Inclusion criteria: Retrospective study of consecutive tests performed in a clinical setting in 10,000 individuals analyzed by Myriad Genetic Laboratories over a 3-year period. 7,461 were analyzed for the coding sequences of BRCA1 and BRCA2 and 2,539 analyzed only for three specific founder mutations prevalent in individuals of Ashkenazi Jewish ancestry.
Exclusion: Non completed by health care provider information to specify the ancestry of the proband, the family history (including breast, ovarian, and other cancers, age of diagnosis, and relationship to patient), whether the proband had not been diagnosed with cancer, or whether there was a history of breast, ovarian, or other cancers, including the age of diagnosis of each.
Inclusion Age: 18–96 Mean age: 49 (median)
Sample size: 9,090
Definition: DCIS
Masking of outcome assessment: Not reported
Control for bias: Age and family history
Johnson, 200274
Country: USA
Design: Prospective cohort study
Evidence: IIA
Time Period: 1992-December 31, 1999
Length of followup/months: 72
Data source: The Iowa Women’s Health Study cohort. Breast cancer incidence was ascertained by linkage to the State Health Registry of Iowa, which is part of the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program
Inclusion criteria: The Iowa Women’s Health Study is a prospective cohort study designed to examine the effect of several risk factors on the incidence of cancer in postmenopausal women ages 55 to 69 years at baseline. Randomly selected from the 1985 Iowa Department of Transportation driver’s license list (94% of all Iowa women) were invited in January 1986 to participate, 42% from 98,029 eligible women responded and consented. Exclusion: Premenopausal status, cancer other than skin cancer, a previous total or partial mastectomy, lobular carcinoma in situ
Inclusion Age: 55 and 69 Mean age:
Sample size: 27,616
Definition: DCIS identified in cancer registry with histological confirmation in SEER database
Masking of outcome assessment: Not reported
Control for bias: Adjustment for age (continuous), BMI (continuous), estrogen use (current or not current), family history of breast cancer (yes or no), benign breast disease (yes or no), multivitamin use (yes or no), mammography (yes or no), and waist: hip ratio (continuous). Aspirin analyses are adjusted for NSAIDs, and NSAID analyses are adjusted for aspirin use.
Claus, 200375
Country: USA
Design: Case control study
Evidence: II-3
Time Period: September 15, 1994-March 14, 1998
Length of followup/months: 42
Data source: The Rapid Case Ascertainment (RCA); Yale cancer center; Connecticut Tumor Registry
Inclusion criteria: All cases of female breast carcinoma in situ between the ages of 20 and 79 years at the time of diagnosis diagnosed among residents of the state of Connecticut from September 15, 1994-March 14, 1998 identified through the Rapid Case Ascertainment (RCA) Shared Resource of the Yale Cancer Center as well as the Connecticut Tumor Registry. Controls were female Connecticut residents selected by random-digit-dialing methods by an outside consulting firm (Northeast Research) and were frequency matched by 5-year age intervals to the cases
Exclusion: Previous history of breast cancer and/or a breast biopsy of unknown outcome. Cases with mixed or other pathology (i.e. both DCIS and LCIS, invasive, or no identifiable disease)
Inclusion Age: 20–79 Mean age: 55
Sample size: 1,998
Definition: DCIS, non-infiltrating identified in pathology report and confirmed via a uniform review by the study pathologist
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age, ethnicity (white/other), family history of breast cancer (yes/no), age at first menstrual period, number of full-term pregnancies, number of screening mammograms one year prior to interview (0, 1, 2+), history of previous breast biopsy (yes/no), and a history of hormone replacement therapy (yes/no)
Claus, 200376
Country: USA
Design: Case control study Evidence: II-3
Time Period: September 15, 1994- March 14, 1998
Length of followup/months: 42
Data source: The Rapid Case Ascertainment (RCA); Yale cancer center; Connecticut Tumor Registry
Inclusion criteria: All women with breast carcinoma in situ between the ages of 20 and 79 years at time of diagnosis identified through the Rapid Case Ascertainment (RCA) Shared Resource of the Yale Cancer Center as well as the Connecticut Tumor Registry from September 15, 1994- March 14, 1998. Controls were randomly selected among female Connecticut residents using random-digit-dialing methods by an outside consulting firm (Northeast Research). Exclusion: Previous history of breast cancer and/or a breast biopsy of unknown outcome.1,606 cases and 1,445 controls were identified, 241 cases were ineligible due to out-of-state residency (8), language (21), a history of previous breast cancer/biopsy of unknown outcome (181) or age-group (31). 74 controls were ineligible due to out-of state residency (3), language (18), a history of previous breast cancer/biopsy of unknown outcome (51), or age-group (2). The final sample included 1,068 case and 999 control subjects, with overall response rates of 76 and 70% for cases and controls, respectively.
Inclusion Age: 20–79 Mean age: 55
Sample size: 1,998
Definition: DCIS by pathology report and confirmed via a uniform review by the study pathologist
Masking of outcome assessment: Not reported
Control for bias: Adjusted for age, ethnicity (white/other), family history of breast cancer (yes/no), age at first menstrual period, number of full-term pregnancies, number of screening mammograms one year prior to interview (0, 1, 2+), history of previous breast biopsy (yes/no), and a history of hormone replacement therapy(yes/no).
Kerlikowske, 200377
Country: USA
Design: Prospective cohort study
Evidence: IIA
Time Period: January 1996–December 2000
Length of followup/months: 12
Data source: 6 mammography registries that participate in the Breast Cancer Surveillance Consortium (http:​//breastscreening.cancer.gov) funded by the National Cancer Institute: (1) San Francisco Mammography Registry, San Francisco, CA; (2) Group Health Cooperative, Seattle, WA; (3) Colorado Mammography Advocacy Project, Denver, CO; (4) Vermont Breast Cancer Surveillance System, Burlington, VT; (5) New Hampshire Mammography Network, Lebanon, NH; and (6) Carolina Mammography Registry, Chapel Hill, NC.
Inclusion criteria: Postmenopausal women ages 50–79 years who underwent bilateral mammography examination for screening, between January 1996 and December 2000, identified in 6 mammography registries.
Exclusion: Premenopausal women ages 50 to 54 years having regular menstrual periods with no HT use, self-reported breast augmentation or prior diagnosis of breast cancer, missing time between mammography examinations, family history of breast cancer, or current HT use. Lobular carcinoma-in-situ was not considered as cancer.
Inclusion Age: 50–79
Sample size: 373,265
Definition: DCIS reported in breast pathology database, SEER program, or state tumor registry;
Masking of outcome assessment: Not reported
Control for bias: Stratification into three groups based on self- reported current HT use and history of hysterectomy: (1) no HT use with or without a uterus, (2) HT use and no uterus (proxy for estrogen only), and (3) HT use and uterus (proxy for estrogen and progestin use). Standardization of the rates by taking a weighted average of the rates for each covariate configuration: the same weights were used for nonusers, estrogen and progestin users, and estrogen only users.
Adjustment for age, Race, family history of breast cancer, examination year, time between mammography examinations, and mammography registry.
Patel, 200378 Country: USA
Design: Case control study
Evidence: IIB
Time Period: March 1, 1995-May 31, 1998
Length of followup/months: N/A
Data source: The Cancer Surveillance Program and the Women’s Contraceptive and Reproductive Experiences Study
Inclusion criteria: All study participants were English-speaking, U.S.-born white (including Hispanic) and black female residents of Los Angeles County between 35 and 64 years old without prior diagnosis of BCIS or invasive breast carcinoma. All had a working residential telephone at reference date. Control subjects were randomly selected (random-digit dialing) from a group of Los Angeles County control subjects participating in the Women’s Contraceptive and Reproductive Experiences (CARE) Study-multicenter, population-based, case–control study of invasive breast carcinoma among white and black women that began in mid-1994. Response rates were 80% for white patients and 75% for black patients. Response rate in Los Angeles County control subjects was 71% for blacks and 76% for whites Exclusion: Not receiving a mammogram within the 2 years before the study.
Inclusion Age: 35–64 Mean age: 51.6
Sample size: 1,183
Definition: DCIS or LCIS (the results for DCIS only did not differ) diagnosed with histologically confirmed cancer between March 1, 1995 and May 31, 1998, as identified by the University of Southern California Cancer Surveillance Program using ICD-O morphologic codes: 8500–8504, 8522, 8543, and 8573 for DCIS, 8520 for LCIS
Masking of outcome assessment: Not reported
Control for bias: Adjustment for age, race, education (< high school graduate, some college, >college graduate), income (<$15,000, $15,000–$35,000, >$35,000–$70,000, >$70,000), family history of breast carcinoma in mother, sisters, or daughters (yes, no, not known), age at menarche (younger than 12 years, ages 12–13 years, older than 13 years), smoking status (never, current, former), body mass index (BMI [kg/m2]; <25.0, 25.0 to <30.0, >30.0), oral contraceptive use (never, <2 years, 2–5 years, >5 years), number of pregnancies with gestational length greater than 26 weeks (none, 1–2, >2), menopausal status (premenopausal, perimenopausal, postmenopausal, unknown), age at menopause (younger than 50 years, ages 50–54 years, 55 years or older, unknown), postmenopausal hormone replacement therapy use (HRT) (never, ever estrogen use [unopposed or opposed], ever other hormone use), and recency of HRT use (never, <5 years from reference date, >5 years from reference date). Frequency matching within the strata of geographic site, race, and 5-year age group.
Wohlfahrt, 200479
Country: Denmark
Design: Prospective cohort study
Evidence: IIA
Time Period: January 1, 1983-December 31, 1998
Length of followup/months:
22.5 million person years
Data source: The Civil Registration System to establish a national parity database including all women born between April 1, 1935 and March 31, 1978. The Danish Breast Cancer Cooperative Group (DBCG) registry
Inclusion criteria: All Danish women born between 1935 and 1978
Exclusion: Not reported
Inclusion Age: >47 Mean age:
Sample size: 1,500,000
Definition: DCIS confirmed in the National Cancer Registry
Masking of outcome assessment: Not reported
Control for bias: Adjustment for age (quadratic splines with knots: 30, 35, 40, 45, 50, 55, 60), calendar year (1983–1987, 1988–1992, 1993–1998), age at first birth (nulliparous, 12–19, 20–24, 25–29, 30–34, >34) and parity (nulliparous, 1, 2, 3, 4+).
Anderson, 200435
Country: USA
Design: Prospective cohort study
Evidence: IIA
Time Period: 1973–2000
Length of followup/months: N/A
Data source: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute
Inclusion criteria: All women with DCIS identified in 9 original population-based registries: Connecticut, Hawaii, Iowa, Utah, and New Mexico and metropolitan areas of San Francisco, Detroit, Atlanta, and Seattle-Puget Sound.
Exclusion: Not reported
Inclusion Age: All ages; Mean age: 59
Sample size: 430,454
Definition: DCIS identified in SEER database
Masking of outcome assessment: Not reported
Control for bias: Standardization to the 2000 U.S. standard to calculated age-adjusted incidence rate ratio
Anderson, 200435
Country: USA
Design: Prospective cohort study
Evidence: IIA
Time Period: 1973–2000
Length of followup/months: N/A
Data source: The Surveillance, Epidemiology, and End Results program of the National Cancer Institute
Inclusion criteria: All women with DCIS identified in 9 original population-based registries: Connecticut, Hawaii, Iowa, Utah, and New Mexico and metropolitan areas of San Francisco, Detroit, Atlanta, and Seattle-Puget Sound.
Exclusion: Not reported
Inclusion Age: All ages
Sample size: 430,465
Definition: DCIS identified in SEER database
Masking of outcome assessment: Not reported
Control for bias: Standardization to the 2000 U.S. standard to calculated age-adjusted incidence rate ratio
Kerlikowske, 200547
Country: USA
Design: Retrospective cohort
Evidence: II-2C
Time Period: January 1986- December 2001
Length of followup/months: 12
Data source: California Cancer Registry
Inclusion criteria: Retrospective review of all women 40 years and older who were asymptomatic and underwent a bilateral mammography examination directly recorded by the radiologist as having been performed for screening in San Francisco County between January 1986 and December 2001.
Exclusion: Screening examinations that occurred after December 2001 were excluded; prior breast cancer diagnosis, breast augmentation, reduction or reconstruction, or history of mastectomy
Inclusion Age: >40; Mean age: Not specified
Sample size: 65,628
Definition: Report of medical diagnosis of DCIS
Masking of outcome assessment: Not reported
Control for bias: Race
Zeleniuch-Jacquotte, 200580
Country: USA
Design: Nested (New York University Women’s Health Study) Case control study
Evidence: II-3
Time Period: 1985–1991
Length of followup/months: 84
Data source: New York University Women’s Health Study
Inclusion criteria: 14,275 healthy women ages 34–65, participants of the NYU Women’s Health Study in breast cancer screening center in New York City between 1985 and 1991. Controls were selected at random from the appropriate risk sets in ratio 2:1. The risk set for a case consisted of all women who were postmenopausal at enrollment, were alive and free of cancer at the time of diagnosis of the case and matched the case on age at enrollment (±6 months), date of enrollment (±3 months) and number (1, 2, 3+) and dates (±3 months) of subsequent blood donations, if any.
Exclusion: Pregnancy, hormone medication use in the 6 months preceding the study
Inclusion Age: 34–65; Mean age: Median age at enrollment was 58 years
Sample size: 203
Definition: Self reported DCIS with a record linkage to the U.S. National Death Index and state cancer registries in New York, New Jersey, and Florida
Masking of outcome assessment: Laboratory personnel who measured hormones were blinded as to case/control status Control for bias: Adjusted for age
Reeves, 200681
Country: UK, Australia, New Zealand
Design: Evidence: II-2A
Time Period: 1996–2001
Length of followup/months: 32.4
Data source: UK National Health Service (NHS) Central Registers
Inclusion criteria: All UK women ages 50–64 who are registered with a general practitioner and who responded to invitations
Exclusion: Invasive cancer other than non-melanoma skin cancer (ICD10 C44) before recruitment
Inclusion Age: 50–64; Mean age: 59
Sample size: 1,031,224
Definition: ICD10-0 code 8500/2
Masking of outcome assessment: Not reported
Control for bias: Relative risk stratified by age at entry, and adjusted for region, age at birth of first child, parity, time since menopause, deprivation index, BMI, and family history of breast cancer
Chen, 200682
Country: USA
Design: Cross-sectional
Evidence: II-2B
Time Period: January 1, 1988-December 31, 2002
Length of followup/months: 48
Data source: the U.S. is the Surveillance, Epidemiology, and End Results (SEER) registry of the National Cancer Institute Inclusion criteria: Women with DCIS and Paget disease of the breast diagnosed from January 1, 1988-December 31, 2002, and identified in 9 population-based registries in the U.S. is the Surveillance, Epidemiology, and End Results (SEER) registry of the National Cancer Institute data base (November 2004 submission): 618 patients. 21,426 women with standard DCIS diagnosed at the same time period were enrolled as controls
Exclusion: Prior history of any type of cancer, positive lymph nodes
Inclusion Age: NS; Mean age: 63.8
Sample size: 21,426
Definition: DCIS and Paget disease coded with the International Classification of Disease for Oncology 2nd edition (ICD-O-2): code 8500.w (ductal carcinoma in situ) and code 8543 (Paget disease with Intraductal carcinoma).
Masking of outcome assessment: Not reported
Control for bias: Age adjustment according to the 2000 U.S. standard population (19 age groups; Census P25–1130)
Vamre, 200683
Country: Norway
Design: Cross-sectional
Evidence: IIB
Time Period: N/S
Length of followup/months: N/A
Data source: WHO Collaborative study of Neoplasia and Steroid Contraceptives: multinational study
Inclusion criteria: Retrospective review of 10 2,476 randomly selected histological materials of non-neoplastic surrounding breast tissue from women with breast cancer, participants in the WHO study who were free from invasive carcinoma but slides contained recognizable non-neoplastic epithelial tissue. Reproductive age after the introduction of steroid contraceptives
Exclusion: Missing information about oral contraceptive use
Inclusion Age: >55; Mean age: NS
Sample size: 1,503
Definition: DCIS
Masking of outcome assessment: The slide readings were performed without any knowledge of patients’ age, or other clinical data
Control for bias: Adjustment for age at diagnosis (by 5-year age groups) and country of residence
Cuzick, 200784
Country: UK, Australia, New Zealand
Design: randomized controlled clinical trial
Evidence: I
Time Period: 1992–2006
Length of followup/months: 96
Data source: IBIS (International Breast Cancer Intervention Study) center
Inclusion criteria: Women ages 35–70 years with risk factors for breast cancer indicating at least a twofold relative risk if they were 45–70 years of age, a fourfold relative risk if they were 40–44 years of age, or a 10-fold relative risk if they were 35–39 years of age. Women were eligible from age 45 years if they had 1) a mother or sister diagnosed with breast cancer before the age of 50 years, 2) two first-or second-degree relatives with breast cancer at any age, or 3) a first first-degree relative with breast cancer at any age, and either were nulliparous or had a previous hyperplastic benign lesion. Women were eligible from the age of 40 years if they had 1) atypical ductal or lobular hyperplasia, 2) a first first- degree relative with bilateral breast cancer at any age, or 3) two first- or second-degree relatives with breast cancer, one of whom was diagnosed before age 50 years. Women were eligible from the age of 35 years if they had either 1) lobular carcinoma in situ or 2) two first first-degree relatives with breast cancer, both diagnosed before the age of 50 years. Any women with an estimated 10-year risk of 5% or more were also eligible as risk equivalent after approval by the study chairman.
Exclusion: Any previous invasive cancer (excluding nonmelanoma skin cancer), previous deep-vein thrombosis or pulmonary embolism, current users of anticoagulants, or planning to become pregnant
Inclusion Age: 35–70; Mean age: 50.7
Sample size: 7,145
Definition: DCIS
Masking of outcome assessment: Double blind
Control for bias: Intention to treat, after exclusion of the 13 women found to have breast cancer at baseline The mean age was 50.8 years (SD 6.9); 54.7% of the women were between the ages of 45 and 54; 49% were postmenopausal and 41% had previously used hormone-replacement therapy.
Powles, 200785
Country: UK
Design: RCT
Evidence: I
Time Period: October 1, 1986-April 30, 1996
Length of followup/months: 158
Data source: Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial
Inclusion criteria: Healthy women between 30 and 70 years old, with no clinical or screening evidence of breast cancer and with an increased risk of breast cancer because of their family history of breast cancer with at least one first-degree relative who was younger than 50 years when diagnosed with breast cancer or one first-degree relative with bilateral breast cancer, or one first degree relative with breast cancer who was diagnosed at any age plus at least one other affected first- or second-degree relative with breast cancer.
Women with a history of a benign breast biopsy who had a first-degree relative with breast cancer were also eligible.
Exclusion: History of any cancer, deep-vein thrombosis, or pulmonary embolism; risk of pregnancy; using oral contraceptives but not hormone replacement therapy.
Inclusion Age: NS; Mean age: 7 (31–70)
Sample size: 2,471
Definition: DCIS
Masking of outcome assessment: Participants, clinicians, and data-processing staff
Control for bias: Randomized placebo controlled double blind trial with intention to treat analysis, no differences at baseline patient characteristics
Nichols, 200786
Country: USA
Design: Case control study
Evidence: IIB
Time Period: February 1997- May 2001
Length of followup/months: N/A
Data source: The Collaborative Breast Cancer Study in Wisconsin, Massachusetts, and New Hampshire
Inclusion criteria: Women 20–74 years old residing in Wisconsin, Massachusetts (excluding metropolitan Boston), and New Hampshire with a new diagnosis of breast carcinoma in situ (ICD-O version 2 C50.0–C50.9) identified in state’s cancer registry from 1997–2001, with listed telephone numbers, driver’s licenses verified by self-report (if <65 years of age), and known dates of diagnosis. 1,694 cases including 1,471 DCIS were eligible. Community controls without personal history of breast cancer, with a listed telephone number, if under 65 years of age, and self- reported driver’s license were randomly selected during 1997–2001 in each state using two sampling frames: those under 65 years of age were selected from lists of licensed drivers, and those 65–74 years of age were selected from a roster of Medicare beneficiaries compiled by the Centers for Medicare & Medicaid Services (8,041 controls)
Exclusion: Not having residential phone number Inclusion Age: >20; Mean age: 55.3 years (range, 24–74)
Sample size: 9,512
Definition: DCIS identified by ICD codes as ductal/nonlobular (8500, 8501, 8503, 8504, 8010, and 8140
Masking of outcome assessment: Not reported
Control for bias: Stratified by age of cases random selection of controls. Adjustment for age (<40,40–44, 45–49, 50–54, 55–59, 60–64, 65–69, and >70), state (Massachusetts, New Hampshire, Wisconsin), age at menarche (<12, 12, 13, z14, unknown), age at first birth (<20, 20–24, 25–29, >30, unknown), parity (≤1, 2, ≥3, unknown), menopausal status (premenopausal, postmenopausal, unknown), age at menopause (<45, 45–49, 50–54, >55, unknown), postmenopausal hormone use (never, former, current), family history of breast cancer (yes, no, unknown), education (less than high school diploma, high school diploma, some college, college diploma, unknown), smoking status (never, former, current), weight at age 18 (continuous), height (continuous), weight change since age 18 (weight loss, weight gain of 0–15, 16–30, 31–50, >50 lb, unknown), personal history of benign breast disease (yes, no, unknown), and number of mammograms within 5 years before the reference date (none, less than five, five or more, unknown).
MacKenzie, 200758
Country: USA
Design: Prospective cohort study
Evidence: IIA
Time Period: January 1994- December 2001 in VT; June 1996-July 2000 in NH
Length of followup/months: 49.2
Data source: The New Hampshire Mammography Network (NHMN) and the Vermont Breast Cancer Surveillance System (VBCSS)
Inclusion criteria: Women at least 40 years of age and had screening mammogram between January 1994 and December 2001 in VT and between June 1996 and July 2000 in NH having at least 60 days of followup in the registry
Exclusion: Personal history of breast cancer, breast implants, or breast reduction surgery
Inclusion Age: 40–98; Mean age: 52
Sample size: 154,936
Definition: DCIS identified in registry with SNOMED codes or TNM codes
Masking of outcome assessment: Not reported
Control for bias: Adjustment for age, parity, BMI, and family history in premenopausal women; adjustment for age, parity, BMI, family history, and HRT in postmenopausal women
Stacey, 200887
Country: Multinational
Design: Case-control study
Evidence: IIB
Time Period: 1993–1996
Length of followup/months: N/A
Data source: Iceland, Sweden, Holland, Spain and the United States
Inclusion criteria: Icelandic Cancer Registry (males and females) the Oncology Department of Zaragoza Hospital between March 2006 and August 2007 Swedish Familial and Consecutive patient series in the Karolinska University Hospital, Stockholm. The regional cancer registry held by the Comprehensive Cancer Centre East in Nijmegen, the Netherlands U.S. Multiethnic Cohort: predominantly of African Americans, Native Hawaiians, Japanese Americans, Latinos, and European Americans who entered the study in 1993 and 1996. Incident cancers in the MEC are identified by cohort linkage to population-based cancer Surveillance, Epidemiology and End Results (SEER) registries the Departments of Surgery and Radiotherapy, University College Hospital, Ibadan, Nigeria
Exclusion: Not reported
Inclusion Age: All ages
Sample size: 29,956
Definition: DCIS
Masking of outcome assessment: Not reported
Control for bias: Adjustment for common variants on chromosome 5p12 confer susceptibility to estrogen receptor- positive breast cancer
Gill, 200651 Country: USA
Design of the Study: Nested
Case-control study Evidence: IIB
Time Period: 1993–2000
Length of followup/months: N/A
Data source: Hawaii component of the Multiethnic Cohort
Inclusion criteria: All female members of multiethnic cohort diagnosed with primary breast cancer between cohort entry and December 2000 were identified as potential cases (n = 1,587). A similar number of randomly selected control subjects (n = 1,584) who were not known to have breast cancer were frequency matched to the distribution of ethnicity and 5-year age groups of the cases. Of the 1,396 cases eligible to participate, 52.6% responded to the mailings and gave full consent. Of the 1,500 eligible controls, 48.7% responded to the mailings and gave full consent.
After removing women who did not have suitable mammograms, the final sample consisted of 607 breast cancer cases and 667 control subjects.
Exclusion: Cases and controls with a previous diagnosis of breast cancer, a history of breast augmentation or reduction, and no mammogram.
Inclusion Age: All ages; Mean age: 62.9–63.5
Sample size: 1,268
Definition: DCIS recorded in the state-wide Hawaii Tumor Registry, a member of the National Cancer Institute's Surveillance, Epidemiology and End Results program.
Masking of outcome assessment: Not reported
Control for bias: Adjustment for the following covariates that are known to be associated with breast cancer and mammographic density: mean age of all mammograms (continuous), ethnicity, BMI (<22.5, 22.5 to <25, 25 to <30, or ≥30 kg/m2), parity (0–1, 2–3, or ≥4), age at menarche (<13, 13–14, or ≥15 years), age at first live birth (<21, 21–30, >30 years, or no children), menopausal status (pre- or postmenopausal), family history of breast cancer (breast cancer in a first-degree relative or no history), and HRT use (never, estrogen only, or estrogen + progestin).
Granström, 200888
Country: Sweden
Design of the Study: Prospective cohort study
Evidence: IIA
Time Period: 1993–2004
Length of followup/months: 11 years
Data source: Second Generation Swedish Family Register renamed to Multigeneration Register linked to the Swedish Cancer Registry (1958–2004) to make the Family-Cancer Database (MigMed2).
Inclusion criteria: Swedish-born as well as immigrant women born between years 1932 and 1953, that is, those whose minimal age at the beginning of the followup ranged from 40 to 61 years
Exclusion: Incompleteness of cancer registration was 5% in the 1970s and close to 0% in 2004. The percentage of cytologically or histologically unverified cases has been close to 0%
Inclusion Age: 40–61; Mean age: N/R
Sample size: 1,028,455
Definition: DCIS identified in registry with SNOMED codes or ICD codes
Masking of outcome assessment: Not reported
Control for bias: Adjustment for age at diagnosis (5-year bands), family history of invasive breast cancer (mother, sister, no history), parity (0, 1, 2, 3+), age at first child birth (13–20, 21–24, 25–29, 30+ years), socioeconomic status (manual worker, blue collar, professional, other) and residential area (big city, south, north)

From: Appendix F, Evidence Tables

Cover of Diagnosis and Management of Ductal Carcinoma in Situ (DCIS)
Diagnosis and Management of Ductal Carcinoma in Situ (DCIS).
Evidence Reports/Technology Assessments, No. 185.
Virnig BA, Shamliyan T, Tuttle TM, et al.

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