TARGIT-C(Consolidation) Prospective Phase IV Study of IORT in Patients With Small Breast Cancer

This prospective, multicentric single arm phase IV study is based on the protocol of the international TARGIT-A and TARGIT-E study. Patients ≥ 50 years with small, low-risk breast cancer who are operated but not irradiated show local relapse rates around 6% after 5 years. With adjuvant whole breast radiotherapy (WBRT) the local relapse rate drops to under 1% after 5 years under Tamoxifen (4). It has been demonstrated (6, 9, 10) that the efficacy of radiation of the tumor bed only in a selected group can be non-inferior to WBRT. The TARGIT C study should confirm the efficacy of a single dose of intraoperative radiotherapy (IORT) in a well selected group of patients with small breast cancer and absence of risk factors. In presence of risk factors postoperative WBRT will be added to complete the radiotherapeutic treatment according to international guidelines. Endpoints are the local relapse rate (within 2 cm of the tumor bed), ipsilateral relapse, cancer-specific and overall survival and contralateral breast cancer as well as documentation of quality of life and cosmetic outcome. The expected local relapse rates are 0.825/1.375% after 3/5 years, respectively. Discontinuation of the trial is scheduled if rates of local relapse rates rise to 1.55/2.4/4% after 1/3/5 years. Power calculations result in 387 patients with a calculated dropout and loss to follow-up rate of 10%, an alpha of 0.05 and a beta of 0.10. There will be only a pre-pathology stratum. It is a pragmatic trial in which each participating centre has the option to modify entry criteria and criteria for WBRT according to this core protocol after consultation with the steering committee and local ethics committee (e.g. size, free margins). Only centers with access to the Intrabeam® system (Carl Zeiss) can recruit patients into the trial.

Sex

Female

Minimum age

50 Years

Inclusion Criteria:

* histologically verified invasive-ductal breast cancer
* hormone receptor positive (if known)
* cT1 or small cT2 (≤ 3.5 cm) cN0 cM0
* ≥ 50 years of age
* informed consent
* compliance

Exclusion Criteria:

* extensive intraductal component (EIC)
* negative hormone receptor status
* multifocality /-centricity (mammography, breast ultrasound)
* lymph vessel invasion (L1)
* clinical signs of distant metastases or clinically suspicious lymph nodes
* other histology
* \< 50 years
* missing informed consent or non-compliance
* bilateral breast cancer at the time of diagnosis
* known BCRA1/2 gene mutations (genetic testing not required)
* any exclusion criterion in the local centre´s treatment policy

• BACKGROUNDFisher B, Anderson S, Redmond CK, Wolmark N, Wickerham DL, Cronin WM. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995 Nov 30;333(22):1456-61. doi: 10.1056/NEJM199511303332203. PMID 7477145
• BACKGROUNDVeronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989. PMID 12393819
• BACKGROUNDEarly Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 May 14-20;365(9472):1687-717. doi: 10.1016/S0140-6736(05)66544-0. PMID 15894097
• BACKGROUNDFyles AW, McCready DR, Manchul LA, Trudeau ME, Merante P, Pintilie M, Weir LM, Olivotto IA. Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):963-70. doi: 10.1056/NEJMoa040595. PMID 15342804
• BACKGROUNDHughes KS, Schnaper LA, Berry D, Cirrincione C, McCormick B, Shank B, Wheeler J, Champion LA, Smith TJ, Smith BL, Shapiro C, Muss HB, Winer E, Hudis C, Wood W, Sugarbaker D, Henderson IC, Norton L; Cancer and Leukemia Group B; Radiation Therapy Oncology Group; Eastern Cooperative Oncology Group. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004 Sep 2;351(10):971-7. doi: 10.1056/NEJMoa040587. PMID 15342805
• BACKGROUNDPolgar C, Fodor J, Major T, Nemeth G, Lovey K, Orosz Z, Sulyok Z, Takacsi-Nagy Z, Kasler M. Breast-conserving treatment with partial or whole breast irradiation for low-risk invasive breast carcinoma--5-year results of a randomized trial. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):694-702. doi: 10.1016/j.ijrobp.2007.04.022. Epub 2007 May 25.