A narrative review for radiation oncologists to implement preoperative partial breast irradiation.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454).

Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.

BACKGROUND: For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. METHODS: In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. FINDINGS: Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and five [corrected] regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. INTERPRETATION: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. FUNDING: None.

Can we avoid axillary dissection in the micrometastatic sentinel node in breast cancer?

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. Classical and competing risks survival analyses were performed to estimate prognostic factors for axillary recurrence, first events and overall survival. Median age was 53 years (range 26-80); median follow-up was 5 years (range 1-9). Most (91.8%) patients received conservative surgery; 209 (55.4%) had only one SN (range 1-8). Five-year overall survival was 97.3%. There were 10 local events, 2 simultaneous local and axillary events, 6 axillary recurrences and 12 distant events. The cumulative incidence of axillary recurrence was 1.6% (95% CI 0.7-3.3). By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.

Myeloid sarcoma of the breast: a pathology that should not be forgotten.

Myeloid sarcoma (MS) is a rare neoplasm, represented by a tumoural mass composed of myeloid blasts, occurring at any anatomical site other than the bone marrow. MS is considered the tissue-based equivalent of acute myeloid leukaemia (AML), requiring the same therapeutic specification, independently from the association with previous or coexisting myeloid neoplasms. Isolated breast involvement by MS is exceedingly rare, with only exceptional cases reported in the literature. This work aims to provide a pictorial essay of the main features of breast involvement by MS. Even though it is a rare condition, we should not forget this neoplasm, and its possibility of being disguised by the AML, as it requires prompt treatment.

Subareolar injection for sentinel lymph node location in breast cancer.

AIM: Several different injection techniques are currently used for sentinel node (SN) identification in patients with breast cancer. Some studies suggest that the subareolar plexus drains lymph from the whole breast to the same axillary SN. In order to test this hypothesis, we ascertained whether subareolar blue dye injection and subdermal radioisotope injection close to the tumour identify the same axillary nodes. METHODS: One day prior to surgery, 50 patients with breast cancer underwent subdermal injection of 30-40MBq of 99m-Tc colloidal albumin (Nanocoll) at the site of the cutaneous projection of the tumour. Ten minutes before surgery, each patient received a subareolar injection of 2-3cc of patent blue. All axillary radioactive nodes and blue-stained nodes were excised and a histologic examination was made. RESULTS: Radioisotope marked the SNs in 47/50 (94%) cases, and the blue dye in 43/50 cases (86%). In three cases, SNs were not identified with either method. Of the 43 cases in which both the tracers reached the axilla, in 40 (93%) the SN was hot and blue-stained, while in 3 cases the two tracers identified different nodes. CONCLUSIONS: Our findings suggest that subareolar injection and subdermal injection elsewhere in the breast usually identify the same SN. Subareolar injection appears to be particularly valuable in patients with multicentric or deep non-palpable breast tumours.