Comparing an Operation to Monitoring, With or Without Endocrine Therapy (COMET) Trial For Low Risk DCIS

Inclusion Criteria:

• Diagnosis of unilateral, bilateral, unifocal, multifocal, or multicentric DCISwithout invasive breast cancer (date of diagnosis defined as the date of the firstpathology report that diagnosed the patient with DCIS) OR: atypia verging on DCISOR: DCIS + LCIS (mix and/or separate locations in the same breast)

• A patient who has had a lumpectomy or partial mastectomy with margins positive forDCIS (i.e. <2mm/ink on tumor) as part of their treatment for a current DCISdiagnosis is also eligible (post-excision bilateral mammogram required at enrollmentto establish a new baseline)

• No previous DCIS or invasive breast cancer in ipsilateral breast 5 years prior tocurrent 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 andipsilateral breast imaging ≤ 120 days of registration (must include ipsilateralmammogram; can also include ultrasound or breast MRI)

• Bilateral DCIS: bilateral breast imaging ≤ 120 days of registration (mustinclude bilateral mammogram; can also include ultrasound or breast MRI)

• DCIS s/p lumpectomy: post excision mammogram on side of excision ≤ 60 days ofregistration

• 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 atypiaverging 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 (notrequired to be at same institution) that pathology fulfills COMET eligibilitycriteria. In cases of disagreement between the two pathology reviews about whetheror not a case fulfills the eligibility criteria, a third pathology review will berequired.

• At least two sites of biopsy for those cases where individual mammographic extent ofcalcifications exceeds 4 cm, with second biopsy benign or both sites fulfillingpathology 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 awritten 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 DCISprior to biopsy yielding diagnosis of DCIS, with exception of: subsequent lumpectomyor partial mastectomy (with positive DCIS margins i.e. <2mm/ink on tumor) followedby 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 ofuncertainty about whether the mass was present on physical examination prior tobiopsy, the following criteria should be applied: if mammogram noting abnormalfindings is diagnostic MMG = symptomatic/if mammogram noting abnormal findings isscreening 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 apatient has a mass on initial MMG that is not seen on subsequent MMG, they areeligible (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 atsite 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 existingcondition that would prevent compliance with the trial or consent process

• Pregnancy. If a woman has been confirmed as pregnant, she will not be eligible totake 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 ofchild-bearing potential is not mandatory. In addition, if a woman becomes pregnantonce registered to the trial, she can continue to be followed (endocrine therapy isnot 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)