Clinical trial NCT02926911: Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS
Official title: Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS: A Phase III Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: DCIS
Ductal Carcinoma in Situ
Keywords: Ductal Carcinoma
Lead sponsor: Alliance Foundation Trials, LLC.
Sponsor class: OTHER
Collaborators: name: Duke University
name: Dana-Farber Cancer Institute
name: New York University
name: Washington University School of Medicine
name: Patient-Centered Outcomes Research Institute
name: The University of Texas MD Anderson Cancer Center
name: Rising Tide Foundation
name: Breast Cancer Research Foundation
First posted: 2016-10-06
Enrollment: 997
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study looks at the risks and benefits of active monitoring (AM) compared to surgery in the setting of a pragmatic prospective randomized trial for low risk DCIS. Our overarching hypothesis is that management of low-risk Ductal Carcinoma in Situ (DCIS) using an AM approach does not yield inferior cancer or quality of life outcomes compared to surgery.

Detailed description: Overdiagnosis and overtreatment resulting from mammographic screening have been estimated to be as high as 1 in 4 patients diagnosed with breast cancer although the absence of standard definitions for measuring overdiagnosis has led to much uncertainty around this estimate. The national health care expenditure resulting from false positive mammograms and breast cancer overdiagnosis has been estimated to approach $4 billion annually. There is general consensus that much of this burden derives from the treatment of DCIS; for those estimated 40,000 women per year whose DCIS may never have progressed even without treatment, medical intervention can only harm. In those women who undergo surgical management of DCIS, there is risk of developing persistent pain at the surgical site, with estimates ranging from 25-68%. Importantly, persistent pain after lumpectomy may be as prevalent as that after total mastectomy. Persistent postsurgical pain is rated by patients as the most troubling symptom, leading to disability and psychological distress, and is often resistant to management. Although prospective population-based data have demonstrated significant patient and surgical focus on pain with remarkably high levels of chronic pain 4 and 9 months after breast surgery, much of these data have been collected in women with invasive cancer, with little data directly relevant to patients with DCIS.

The overarching hypothesis of the study is that management of low-risk DCIS using an active monitoring (AM) approach does not yield inferior cancer or quality of life outcomes compared to surgery.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCIS without invasive breast cancer (date of diagnosis defined as the date of the first pathology report that diagnosed the patient with DCIS) OR: atypia verging on DCIS OR: DCIS + LCIS (mix and/or separate locations in the same breast)
* A patient who has had a lumpectomy or partial mastectomy with margins positive for DCIS (i.e. \<2mm/ink on tumor) as part of their treatment for a current DCIS diagnosis is also eligible (post-excision bilateral mammogram required at enrollment to establish a new baseline)
* No previous DCIS or invasive breast cancer in ipsilateral breast 5 years prior to current DCIS diagnosis
* 40 years of age or older at time of DCIS diagnosis
* ECOG performance status 0 or 1
* No contraindication for surgery
* Baseline imaging (must include dimensions):

  * Unilateral DCIS: contralateral normal mammogram ≤ 6 months of registration and ipsilateral breast imaging ≤ 120 days of registration (must include ipsilateral mammogram; can also include ultrasound or breast MRI)
  * Bilateral DCIS: bilateral breast imaging ≤ 120 days of registration (must include bilateral mammogram; can also include ultrasound or breast MRI)
  * DCIS s/p lumpectomy: post excision mammogram on side of excision ≤ 60 days of registration
* Pathologic criteria:

  * Any grade I DCIS (irrespective of necrosis/comedonecrosis)
  * Any grade II DCIS (irrespective of necrosis/comedonecrosis)
  * Absence of invasion or microinvasion
  * Diagnosis of DCIS confirmed on core needle biopsy, vacuum-assisted or surgery ≤ 120 days of registration
  * ER(+) and/or PR(+) by IHC (≥ 10% staining or Allred score ≥ 4) unless atypia verging on DCIS in which case biomarker criterion does not apply
  * HER2 0, 1+, or 2+ by IHC if HER2 testing is performed
* Histology slides reviewed and agreement between two clinical pathologists (not required to be at same institution) that pathology fulfills COMET eligibility criteria. In cases of disagreement between the two pathology reviews about whether or not a case fulfills the eligibility criteria, a third pathology review will be required.
* At least two sites of biopsy for those cases where individual mammographic extent of calcifications exceeds 4 cm, with second biopsy benign or both sites fulfilling pathology eligibility criteria (ER/PR testing required for second biopsy)
* Amenable to follow up examinations
* Ability to read, understand and evaluate study materials and willingness to sign a written informed consent document
* Reads and speaks Spanish or English

Exclusion Criteria:

* Male DCIS
* Grade III DCIS
* Concurrent diagnosis of invasive or microinvasive breast cancer in either breast
* Documented mass on examination or mass/hypoechoic area on imaging at site of DCIS prior to biopsy yielding diagnosis of DCIS, with exception of: subsequent lumpectomy or partial mastectomy (with positive DCIS margins i.e. \<2mm/ink on tumor) followed by a post-surgery MMG; fibroadenoma at a distinct/separate site from site of DCIS; or diagnosis of mass/hypoechoic area as a cyst or a papilloma. In cases of uncertainty about whether the mass was present on physical examination prior to biopsy, the following criteria should be applied: if mammogram noting abnormal findings is diagnostic MMG = symptomatic/if mammogram noting abnormal findings is screening MMG = asymptomatic. If a patient has a mass on imaging that is biopsied (worked-up) and does not show invasive breast cancer, they are eligible. If a patient has a mass on initial MMG that is not seen on subsequent MMG, they are eligible (if initial mass occurred due to additional work-up).
* Any color/bloody nipple discharge (ipsilateral breast)
* Mammographic finding of BIRADS 4 or greater within 6 months prior to registration at site of breast other than that of known DCIS, without pathologic assessment
* Use of investigational cancer agents within 6 weeks prior to diagnosis of DCIS
* Any serious and/or unstable pre-existing medical, psychiatric, or other existing condition that would prevent compliance with the trial or consent process
* Pregnancy. If a woman has been confirmed as pregnant, she will not be eligible to take part in the trial. If she suspects there is a chance that she may be pregnant, a pregnancy test should be undertaken, although a pregnancy test for all women of child-bearing potential is not mandatory. In addition, if a woman becomes pregnant once registered to the trial, she can continue to be followed (endocrine therapy is not a mandatory requirement of the study)
* Documented history of prior tamoxifen, aromatase inhibitor, or raloxifene use in the 6 months prior to registration
* Current use of exogenous hormones (i.e. oral progesterone)

Primary outcomes:
measure: Proportion of new diagnoses of ipsilateral invasive cancer in surgery and AM arms at 2 years of follow up
timeFrame: At 2 years follow-up
Secondary outcomes:
measure: Quality of Life (QOL)
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Psychological outcomes
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Generalized anxiety
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Generalized Depression
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Coping
timeFrame: Baseline
measure: Intolerance of uncertainty
timeFrame: Baseline and at 2 years
measure: Mastectomy rate
timeFrame: 2, 5, and 7 year follow-up
measure: Breast conservation rate
timeFrame: 2, 5, and 7 year follow-up
measure: Contralateral invasive cancer rate
timeFrame: 2, 5, and 7 year follow-up
measure: Overall survival rate
timeFrame: 2, 5, and 7 year follow-up
measure: Breast cancer specific survival rate
timeFrame: 2, 5, and 7 year follow-up
measure: Ipsilateral invasive cancer rate in surgery arm at 5 and 7 year follow-up
timeFrame: 5 and 7 year follow-up
measure: Ipsilateral invasive cancer rate in AM arm
timeFrame: 5 and 7 year follow-up
Other outcomes:
measure: Breast MRI utilization rate
timeFrame: 2, 5, and 7 year follow-up
measure: Breast biopsy rate
timeFrame: 2, 5, and 7 year follow-up
measure: Radiation rate
timeFrame: 2, 5, and 7 year follow-up
measure: Chemotherapy rate
timeFrame: 2, 5, and 7 year follow-up
measure: Self-reported co-morbidity
timeFrame: 6 months, 1 year, and once a year (years 2 through 5)
measure: Adherence to hormonal therapy
timeFrame: 6 months, 1 year, and once a year (years 2 through 5)
measure: Symptoms
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: General pain
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Breast specific pain
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Body image
timeFrame: Baseline, 6 months, 1 year, and once a year (years 2 through 5)
measure: Decisional regret
timeFrame: Years 1 through 5
measure: Knowledge
timeFrame: Baseline and 2 years
measure: Risk perceptions
timeFrame: Baseline and 2 years
measure: Communication with physicians
timeFrame: Baseline
measure: Financial burden
timeFrame: 6 months
measure: Employment status
timeFrame: Baseline, 6 months, year 1, and once a year (years 1 through 5)
measure: Concerns about future breast events
timeFrame: Baseline and 2 years
Locations:
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Denver
country: United States
facility: Colorado Cancer Research Program
state: Colorado
city: Lafayette
country: United States
facility: Saint Joseph Hospital- Cancer Centers of Colorado
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: Washington
country: United States
facility: MedStar Washington Hospital Center
state: District of Columbia
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Post Falls
country: United States
facility: Kootenai Health
state: Idaho
city: Chicago
country: United States
facility: John H Stroger Jr Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Chicago
country: United States
facility: Advocate Illinois Masonic Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care
state: Illinois
city: Rockford
country: United States
facility: OSF Saint Anthony Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates - Des Moines
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare Edgewood
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center Jefferson
state: Louisiana
city: Brewer
country: United States
facility: Eastern Maine Medical Center Cancer Care
state: Maine
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine-Scarborough
state: Maine
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Annapolis
country: United States
facility: Anne Arundel Medical Center
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland - Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer Research Consortium of West Michigan
state: Michigan
city: Royal Oak
country: United States
facility: Beaumont NCORP
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro MN Community Oncology Research Consortium (MMCORC)
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University - Siteman Cancer Center
state: Missouri
city: Anaconda
country: United States
facility: Community Hospital of Anaconda
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hooksett
country: United States
facility: New Hampshire Oncology Hematology PA
state: New Hampshire
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System / Morristown Medical Center
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Paramus
country: United States
facility: The Valley Hospital - Luckow Pavilion
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance
state: New Mexico
city: Bronx
country: United States
facility: Montefiore-Einstein Center for Cancer Care at Montefiore Medical Park
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York-Presbyterian Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Greensboro
country: United States
facility: Novant Health Breast Surgery - Greensboro
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: New Bern
country: United States
facility: Carolina East Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Belpre
country: United States
facility: Strecker Cancer Center - Belpre
state: Ohio
city: Centerville
country: United States
facility: Dayton Physicians-Miami Valley Hospital South
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel East Hospital
state: Ohio
city: Columbus
country: United States
facility: Columbus Oncology & Hematology INC
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center
state: Ohio
city: Columbus
country: United States
facility: MidOhio Oncology Hematology, Mark H. Zangmeister Center
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel West Hospital
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Physicians-Miami Valley Hospital North
state: Ohio
city: Delaware
country: United States
facility: Grady Hospital
state: Ohio
city: Delaware
country: United States
facility: OhioHealth Grady - Delaware Health Center
state: Ohio
city: Findlay
country: United States
facility: Armes Family Cancer Center
state: Ohio
city: Franklin
country: United States
facility: Dayton Physicians-Atrium
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Mansfield
country: United States
facility: OhioHealth Mansfield Hospital
state: Ohio
city: Marietta
country: United States
facility: Marietta Memorial Hospital
state: Ohio
city: Marion
country: United States
facility: OhioHealth Marion General Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Hospital
state: Ohio
city: Westerville
country: United States
facility: St. Ann's Hospital
state: Ohio
city: Youngstown
country: United States
facility: St. Elizabeth Youngstown Hospital
state: Ohio
city: Zanesville
country: United States
facility: Genesis Health Care System
state: Ohio
city: Lawton
country: United States
facility: Cancer Centers of Southwest Oklahoma
state: Oklahoma
city: Bend
country: United States
facility: Saint Charles Health System
state: Oregon
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital of UPMC
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Medical Group PC-Robert Packer Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health York Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Georgetown
country: United States
facility: Georgetown Hospital System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Memorial Hospital
state: South Carolina
city: Memphis
country: United States
facility: Baptist Cancer Care
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Laredo
country: United States
facility: Doctors Hospital of Laredo
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Morgantown
country: United States
facility: West Virginia University Medicine
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Bellevue
country: United States
facility: Overlake Hospital Medical Center
state: Washington
city: Appleton
country: United States
facility: ThedaCare Regional Cancer Center -Appleton
state: Wisconsin
city: Burlington
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Fond Du Lac
country: United States
facility: Aurora Health Center - Fond du Lac
state: Wisconsin
city: Germantown
country: United States
facility: Aurora Health Care, Germantown Health Center
state: Wisconsin
city: Grafton
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Green Bay
country: United States
facility: Saint Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: BayCare Aurora LLC, Aurora Cancer Care
state: Wisconsin
city: Kenosha
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Aurora Bay Area Medical Group - Cancer Care Clinic
state: Wisconsin
city: Marinette
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Milwaukee
country: United States
facility: Vince Lombardi Cancer Clinic of Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Oshkosh
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Racine
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Sheboygan
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Summit
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Two Rivers
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: Wauwatosa
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
city: West Allis
country: United States
facility: Aurora Health Care, Aurora Cancer Care
state: Wisconsin
Study officials:
affiliation: Duke University
name: Shelley Hwang, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Ann Partridge, MD, MPH
role: STUDY_CHAIR
affiliation: Baylor College of Medicine
name: Alastair Thompson, MD
role: STUDY_CHAIR
References:
citation: Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske K, Taplin SH, Urban N, Geller BM. Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst. 2002 Oct 16;94(20):1546-54. doi: 10.1093/jnci/94.20.1546.
citation: Erbas B, Provenzano E, Armes J, Gertig D. The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat. 2006 May;97(2):135-44. doi: 10.1007/s10549-005-9101-z. Epub 2005 Dec 1.
citation: Ozanne EM, Shieh Y, Barnes J, Bouzan C, Hwang ES, Esserman LJ. Characterizing the impact of 25 years of DCIS treatment. Breast Cancer Res Treat. 2011 Aug;129(1):165-73. doi: 10.1007/s10549-011-1430-5. Epub 2011 Mar 9.
citation: Nystrom L, Rutqvist LE, Wall S, Lindgren A, Lindqvist M, Ryden S, Andersson I, Bjurstam N, Fagerberg G, Frisell J, et al. Breast cancer screening with mammography: overview of Swedish randomised trials. Lancet. 1993 Apr 17;341(8851):973-8. doi: 10.1016/0140-6736(93)91067-v.
citation: Hwang ES, Hyslop T, Lynch T, Frank E, Pinto D, Basila D, Collyar D, Bennett A, Kaplan C, Rosenberg S, Thompson A, Weiss A, Partridge A. The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS). BMJ Open. 2019 Mar 12;9(3):e026797. doi: 10.1136/bmjopen-2018-026797.