OPTimizing Irradiation Through Molecular Assesment of Lymph Node After Primary Systemic Treatment

Breast cancer management integrating surgery, systemic therapy and radiation therapy tends to systemic treatment as the first therapeutic option, continuing afterwards by surgery and radiation therapy with the scope of decreasing the locoregional treatment. This strategy implies doubts about what should be the locoregional treatment, because many patients have remissions and a significant number of them a complete response. The responses are associated with better clinical outcome although there are doubts about they are a surrogate marker of survival. Nodal irradiation after systemic treatment in patients with breast cancer it is under discussion, particularly in the case of patients with initial clinical involvement experiencing complete remission. For this reason, some groups decide irradiation of all nodal regions and others choose no irradiation of the lymph nodes at all. To clarify this discussion the present study is proposed. The "One Step Nucleic Amplification" (OSNA) is a technique developed by Sysmex Corporation that allows a complete analysis of sentinel nodes and provides a quantification of the tumor marker Cytokeratin 19 (CK19) messenger ribonucleic acid (mRNA) in the sentinel node. The result is expressed by the Tumour Load as number of copies per microliter. This technique has shown its diagnostic ability both without primary systemic treatment and after primary systemic treatment, being more reproducible than conventional processes. In spite of this, fits to mention that the studies of validation used to obtain the European Conformity (CE) mark only included patients without previous systemic treatment to the surgery.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Infiltrating carcinoma of the breast.
* Metastatic lymph nodes (N1) at diagnosis, as determined histologically by Fine Needle Aspiration or Core Needle Biopsy.
* Primary systemic therapy (including antiestrogen or chemotherapy, and targeted therapies).
* Tumour surgery: tumorectomy, quadrantectomy or mastectomy.
* OSNA (ND) or - lymph nodes after primary systemic therapy.
* Age ≥ 18 years old.
* Karnofsky Index ≥ 70 %.
* Signed Informed Consent.

Exclusion Criteria:

* Lymphadenectomy.
* Bilateral breast cancer.
* Males.
* Previous thoracic irradiation therapy.
* Contraindications of radiotherapy (pregnancy, severe collagen diseases).
* Other neoplasms.
* Severe associated comorbidities that, according to the investigator criteria, may interfere with the study evaluations.
* Lymp nodes OSNA -(L), +, ++ after primary systemic therapy.
* Sentinel lymph node biopsy previous to the primary systemic therapy.
* Mammary internal chain affected.

• BACKGROUNDCortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14. PMID 24529560
• BACKGROUNDMamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB, Geyer CE Jr, Taghian A, Wickerham DL, Wolmark N. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012 Nov 10;30(32):3960-6. doi: 10.1200/JCO.2011.40.8369. Epub 2012 Oct 1. PMID 23032615
• BACKGROUNDNoh JM, Park W, Suh CO, Keum KC, Kim YB, Shin KH, Kim K, Chie EK, Ha SW, Kim SS, Ahn SD, Shin HS, Kim JH, Lee HS, Lee NK, Huh SJ, Choi DH. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05). Br J Cancer. 2014 Mar 18;110(6):1420-6. doi: 10.1038/bjc.2014.26. Epub 2014 Jan 30. PMID 24481403
• BACKGROUNDShim SJ, Park W, Huh SJ, Choi DH, Shin KH, Lee NK, Suh CO, Keum KC, Kim YB, Ahn SD, Kim SS, Ha SW, Chie EK, Kim K, Shin HS, Kim JH, Lee HS. The role of postmastectomy radiation therapy after neoadjuvant chemotherapy in clinical stage II-III breast cancer patients with pN0: a multicenter, retrospective study (KROG 12-05). Int J Radiat Oncol Biol Phys. 2014 Jan 1;88(1):65-72. doi: 10.1016/j.ijrobp.2013.09.021. Epub 2013 Oct 22. PMID 24161425
• BACKGROUNDNagar H, Boothe D, Ginter PS, Sison C, Vahdat L, Shin S, Smith M, Chao KS, Nori D, Hayes MK. Disease-free survival according to the use of postmastectomy radiation therapy after neoadjuvant chemotherapy. Clin Breast Cancer. 2015 Apr;15(2):128-34. doi: 10.1016/j.clbc.2014.09.012. Epub 2014 Nov 11.