OPTimizing Irradiation Through Molecular Assessment of Lymph Node (OPTIMAL)
OPTimizing Irradiation Through Molecular Assessment of Lymph Node (OPTIMAL)
The main purpose of this study is to show the non-inferiority of the incidental irradiation,
 as compared to intentional irradiation of the axillary nodes, in terms of 5-years
 disease-free survival (DFS) of early stage breast cancer patients with limited affectation of
 sentinel node assessed by OSNA (250 to 15,000 copies/uL), treated with breast-conservative
 surgery without axillary lymphadenectomy.
Since long, the standard loco-regional treatment of the early-stage breast cancer is breast
 conservative surgery (tumorectomy) followed by a selective biopsy of the sentinel lymph node
 and, if positive, lymphadenectomy of axillary levels I and II. Complementary irradiation of
 the breast and ganglionar areas has shown to reduce disease-specific mortality. Therefore,
 adjuvant radiotherapy of the whole breast is currently indicated after conservative surgery.

 The recommendation to irradiate axillary lymph nodes is clear in patients with more than
 three affected nodes. The standard volumes to irradiate after lymphadenectomy include
 supraclavicular and level III axillary regions, while axillary levels I and II, and the
 internal breast lymph node chain, are reserved for cases of cumbersome axillary affectation,
 patients who have not undergone lymphadenectomy or it was insufficient, or affectation of the
 internal breast lymph node chain.

 However, when only 1 to 3 nodes are affected, there is no unanimity on the recommendation of
 radiotherapy, despite some studies have shown that irradiation improves survival. In
 addition, the National Cancer Institute of Canada trial (NCIC-CTGMA20), high risk patients
 with negative lymph nodes and patients with positive lymph nodes (most of them with 1 to 3
 affected nodes) showed that local irradiation with or without regional lymph node irradiation
 improved disease-free survival, as well as loco-regional and distant disease control.
 Moreover, a systematic review including more than 20,000 patients from 45 studies concludes
 that the irradiation of the breast reduced the loco-regional relapse, even in patients
 without affected lymph nodes.

 One Step Nucleic Acid Amplification (OSNA) is a technique developed by Sysmex Corporation
 that allows a readily and complete analysis of sentinel lymph nodes during surgery. OSNA
 provides a quantification of the Cytokeratin 19 (CK19) tumour cell marker in the messenger
 ribonucleic acid (mRNA) of the sentinel node, the result being expressed as "total tumour
 load" (TTL), which is a discrete number of copies per microliter. This technique has shown
 ability to discriminate macrometastasis, micrometastasis or negativity, and to predict
 affectation of non-sentinel lymph nodes. According to previous results, a TTL < 15,000 is
 associated with a 85% probability of non-affectation of (non-sentinel) axillar lymph nodes.

 The therapeutic value of the axillary lymphadenectomy has been questioned since long, and the
 recent publication of the Z0011 study proposes solely a selective biopsy of the sentinel
 lymph node. This has impacted clinical practice guidelines as prestigious as those of the
 National Comprehensive Cancer Network; however, irradiation is always considered in these
 cases.

 In summary, the amount of nodal volumes to irradiate in early stages of breast cancer is
 under discussion, particularly in the case of patients not submitted to axillar
 lymphadenectomy despite affectation of sentinel lymph nodes. In most cases, the irradiation
 of the breast implies "incidental" irradiation of the axillary level I, and in some cases the
 level II. For this reason, some groups have decided not to irradiate these axillary regions
 intentionally, while others advocate irradiating these regions intentionally.
Inclusion Criteria:

 1. Infiltrating, ductal carcinoma of the breast.

 2. Treated with conservative surgery (tumorectomy or quadrantectomy) without
 lymphadenectomy.

 3. Sentinel lymph node assessed by OSNA, with TTL in the range 250 - 15,000 copies/μL.

 4. Age ≥ 18 yrs old.

 5. Karnofsky Index ≥ 70 %.

 6. Signed Informed Consent.

 Exclusion Criteria:

 1. Other types of breast cancer different from infiltrating ductal carcinoma.

 2. Bilateral breast cancer.

 3. Males.

 4. Mastectomy or axillary homolateral lymph node dissection.

 5. Previous thoracic irradiation therapy.

 6. Systemic neoadjuvant therapy previous to surgery.

 7. Contraindications of radiotherapy (pregnancy, severe collagen diseases).

 8. Other neoplasms.

 9. Severe associated comorbidities that, according to the investigator criteria, may
 interfere with the study evaluations.