Clinical trial NCT01112254: Evaluation of the Diagnostic Performance of MRI±Biopsy to Optimize Resection of Ductal Carcinoma In Situ (DCIS) Breast Cancer
Official title: Evaluation of the Diagnostic Performance of MRI±Biopsy to Optimize Resection of Ductal Carcinoma In Situ (DCIS) Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Ductal Carcinoma In Situ (DCIS) breast cancer
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2010-04-28
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the diagnostic performance of MRI±biopsy to optimize resection of Ductal Carcinoma In Situ (DCIS) breast cancer.

Detailed description: Ductal carcinoma in situ (DCIS) is a frequent disease, concerning more than 15% of all breast carcinomas in France. Frequency increases due to breast screening programs. Breast conservative treatment can be done for limited lesions. Complete pathological excision with safe surgical margins is the main factor of success rate for conservative treatment. But safe surgical margins are not always obtained in the first surgery because preoperative or peroperative evaluation of the extent of the lesions is difficult. A 20 to 38% rate of involved margins is reported in the literature, implying a second surgery. MRI is not commonly performed today in the preoperative staging of DCIS, despite interesting results of breast MRI in DCIS evaluation published recently in a German study (Kuhl, Lancet 2007). Nevertheless, this retrospective study focused on a population of high-risk women (BRCA1-2 mutation carriers, family history of breast cancer...).

Additional suspicious lesions detected by MRI require MRI-guided or CT-guided biopsy as they are not detectable with mammography or ultrasound. Moreover, intraoperative pathological analysis cannot be performed in DCIS and surgical strategy will be different for a unique lesion (lumpectomy) or multiple/large lesions (mastectomy). If surgery is adapted according to MRI and biopsy results, we can assume that the entire lesion could be removed in a single operation, avoiding re-excisions, anxiety and reducing the costs.

The main objective of this protocol is to evaluate the value of MRI+biopsy in the staging of mammography-detected DCIS in an unselected population of women. It is a multicentric, randomised study including patients from France presenting a unique, limited (\< 30 mm) DCIS detected by mammography or breast ultrasound. The two compared arms are: preoperative breast MRI+biopsy versus no additional diagnostic examination. High resolution dynamic 3D images will be obtained in order to detect very small suspicious lesions, typical of DCIS. The main endpoint is the re-excision rate for involved margins. In order to show a reduction of 50% of the rate of second surgery (from 25% to 12.5% in the MRI arm), it is necessary to include 360 patients (bilateral test, alpha=5%, power=80%).

A cost-effective study will be performed. The costs likely to differ between the two arms (MRI, biopsy, outpatient visits, hospitalisations, transportation, and sick leaves) will be assessed using data collected in the trial. The endpoint of the cost-effectiveness study will be the cost by success (cost-effectiveness ratio). A success is defined as achieving margin-negative resection after initial surgery (no need for re-excision). The other secondary endpoints will be to determine the rate of initial mastectomy and to describe MRI morphologic features in the MRI+biopsy arm.

Eligibility criteria: Inclusion Criteria:

* T0 or T1 breast DCIS revealed by microcalcifications on mammography + breast ultrasound
* Histological confirmation by percutaneous biopsy : strict DCIS or micro-invasive.
* Radiological focus \< 30mm and accessible to conservative treatment.
* Single microcalcification focus
* Age : 18 to 80 years old
* Performance Status \< 2
* Patient information and signed informed consent.

Exclusion Criteria:

* Invasive carcinoma
* Non biopsiable microcalcification focus under stereotaxy
* Bilateral lesions
* Non feasible MRI (claustrophobic, serious allergy, pace-maker, etc.)
* Refusal of surgery, including mastectomy if necessary
* History of homolateral breast cancer
* patient at risk of breast cancer (BRCA1 or 2 mutation or score 5 INSERM table)
* Pregnant or possibly pregnant or breastfeeding woman
* Person deprived of freedom or under guardianship
* Inability to undergo the medical surveillance of the trial for geographical, social or psychological reasons

Primary outcomes:
measure: Re-excision rate
timeFrame: in the 6 months following randomization
Secondary outcomes:
measure: Cost-effectiveness study
timeFrame: during the 6-month period after randomization
measure: Relapse rate
timeFrame: at 30 months after randomization
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
References:
citation: Balleyguier C, Dunant A, Ceugnart L, Kandel M, Chauvet MP, Cherel P, Mazouni C, Henrot P, Rauch P, Chopier J, Zilberman S, Doutriaux-Dumoulin I, Jaffre I, Jalaguier A, Houvenaeghel G, Guerin N, Callonnec F, Chapellier C, Raoust I, Mathieu MC, Rimareix F, Bonastre J, Garbay JR. Preoperative Breast Magnetic Resonance Imaging in Women With Local Ductal Carcinoma in Situ to Optimize Surgical Outcomes: Results From the Randomized Phase III Trial IRCIS. J Clin Oncol. 2019 Apr 10;37(11):885-892. doi: 10.1200/JCO.18.00595. Epub 2019 Feb 27.