Management of low-risk ductal carcinoma in situ (low-risk DCIS): a non-randomized, multicenter, non-inferiority trial; standard therapy versus active surveillance.

Phase 3

Recruiting

Conditions: low risk ductal carcinoma in situ
pre-stage breast cancer
10006291

Registration Number: NL-OMON54716

Lead Sponsor: Antoni van Leeuwenhoek Ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 2500

Inclusion Criteria

- Written informed consent according to ICH/GCP, and national/local regulations
- Women >= 45 years old, any menopausal status
- Unilateral DCIS of any size
- American Society of Anesthesiologists (ASA) score 1 -2 and 3, only if able
to undergo surgery and yearly mammography (see Appendix E)
- Lesions of type 'calcifications only', detected by population-based or
opportunistic screening mammography
- Within twelve weeks of detection at least six 12 G biopsies (or the
equivalent of six 12 G needles) need to be taken from the area of the
calcification. This implies at least 7 cc volume irrespective of supplier, or
at least three 8G, four 9G, five 10G or five 11G biopsy needles need to be
taken to meet LORD*s eligibility criteria. Whatever needle size is applied, it
is essential to confirm that the biopsies contain representative calcifications
via biopsy radiography, microscopy, or both.
- In case of an extended lesion (> 5 cm): biopsies were taken from the center
and the periphery of the lesion, or from two peripheral parts of the lesion
- In case of multiple lesions with calcifications biopsies have been taken from
two, but not more, groups of calcifications
- Estrogen receptor >=80% positive and HER2 negative: 0 or 1+ or 2+ with
negative ISH), analysed centrally by pathology at NKI-AVL
- Marker placement at biopsy site (s) in the breast . Note: if patient prefers
surgery, marker placement is not mandatory.
- FFPE tissue blocks from the biopsy and, if applicable, from the resection
specimen, available for translational research purposes. If no FFPE tissue
blocks can be submitted, 10 unstained slides of 4-5 µm thickness from the
lesion(s) are acceptable
- Good correlation between pathological and radiological findings i.e. both
findings confirm low-risk DCIS and no suspicion high- grade DCIS or invasive
breast cancer
- The interval between histologic diagnosis of low-risk DCIS on biopsy and
randomization is <= 12 weeks

Exclusion Criteria

-Estrogen receptor negative: <80% or HER2 positive: 3+, or 2+ with positive ISH
- Presence of either mass, increased focal density or architectural distortion
around the calcifications on mammography (suspicious for invasive disease)
- Presence of Paget*s disease, invasive breast cancer, or pleomorphic LCIS;
Lobular neoplasia, referring to atypical lobular hyperplasia (ALH) and/or
classic Lobular Carcinoma In Situ according to the WHO Classification of
Tumours of the Breast, is no reason to exclude
- Symptomatic DCIS e.g. DCIS detected by palpation or bloody nipple discharge
- Synchronous invasive carcinoma in the contralateral breast
- Prior history of invasive breast cancer or DCIS, prior surgery because of
benign breast lesion (s) is allowed
- Prior history of other cancer except carcinoma in situ of the cervix or basal
carcinoma of the skin
- Serious disease that precludes definitive surgical treatment (e.g
cardiovascular/ pulmonary/ renal disease)
- Individual with a family member with a known gene mutation associated with
increased risk of breast cancer, unless study participant is a proven
non-carrier of mutation
- Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule; those conditions should be discussed with the patient before
registration in the trial
- Pregnancy or breast-feeding. Contraceptive measures during the trial are
mandatory for those patients that will participate in standard treatment arm
and adequate counselling should be provided by the treating physician. The
duration of contraception will be specified by the treating physician according
to patient and treatment characteristics, standard clinical practice and
national regulations

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Ipsilateral invasive breast cancer-free rate at 10 years.<br /><br><br /><br>The date of ipsilateral invasive breast cancer is the time of first appearance<br /><br>of a suspicious lesion in any soft tissue of the ipsilateral breast (positive<br /><br>cytology; a visible or palpable lesion), later proven to be a definite<br /><br>ipsilateral invasive breast cancer (proven by positive histology).<br /><br>Apart from ipsilateral invasive breast cancer, also regional, distant<br /><br>metastases and death from breast cancer in the absence of ipsilateral invasive<br /><br>breast cancer will be considered events. For more details see section 7.2.1.</p><br>

Secondary Outcome Measures