POSNOC—POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes

IntroductionACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.Methods and analysisPOSNOC is a pragmatic, multicentre, non-inferiority, international trial with participants randomised in a 1:1 ratio. Women are eligible if they have T1/T2, unifocal or multifocal invasive breast cancer, and 1 or 2 macrometastases at sentinel node biopsy, with or without extranodal extension. In the intervention group women receive adjuvant therapy alone, in the standard care group they receive ANC or axillary RT. In both groups women receive adjuvant therapy, according to local guidelines. This includes systemic therapy and, if indicated, RT to breast or chest wall. The UK Radiotherapy Trials Quality Assurance Group manages the in-built radiotherapy quality assurance programme. Primary endpoint is 5-year axillary recurrence. Secondary outcomes are arm morbidity assessed by Lymphoedema and Breast Cancer Questionnaire and QuickDASH questionnaires; quality of life and anxiety as assessed with FACT B+4 and State/Trait Anxiety Inventory questionnaires, respectively; other oncological outcomes; economic evaluation using EQ-5D-5L. Target sample size is 1900. Primary analysis is per protocol. Recruitment started on 1 August 2014 and as of 9 June 2021, 1866 participants have been randomised.Ethics and disseminationProtocol was approved by the National Research Ethics Service Committee East Midlands—Nottingham 2 (REC reference: 13/EM/0459). Results will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN54765244; NCT0240168Cite Now

Outcomes After Accelerated Partial Breast Irradiation in Women With Triple Negative Subtype and Other “High Risk” Variables Categorized as Cautionary in The ASTRO Guidelines

PurposeTo report a primary objective clinical outcome of ipsilateral breast recurrence following accelerated partial breast irradiation (APBI) in women with triple negative and other high risk breast cancer (as described in 2017 ASTRO guidelines) (i.e., age 40–49, size 2.1–3.0 cm, estrogen receptor negative and invasive lobular breast cancer). Secondary objectives of axillary and regional failure as well as overall survival are also reported.Methods and MaterialPatients from two clinical trials (NCT01185145, NCT01185132) were treated with 38.5 Gy IMRT or 3D-CRT APBI w/3.85 Gy fraction/BID fractionation for 10 fractions. Triple negative and other high risk patients (n=269) were compared to a total of 478 low risk patients which ASTRO defined as “suitable” for APBI. High risk patients, for the purpose of this study, were defined as those who possess one or more high risk criteria: triple negative (n=30), tumor size >2 cm <3 cm (n=50), HER 2+ (n=54), age range 40–50 years (n=120), ER- (n=43), and ILC histology (n=52).ResultsMedian follow up was 4.0 years for all patients. No significant difference was found for this high-risk cohort at 5 years for ipsilateral breast, or regional recurrences. Axillary recurrence was significantly adversely impacted by triple negative and ER- statuses (p=0.01, p=0.04). There were significant correlations between triple negative type and axillary recurrence on multivariate analysis (p=0.03). Overall survival for all patients was unaffected by any of the high-risk categories.ConclusionThe data from this study suggests that women possessing high risk features are at no more meaningful risk for recurrence than other patients considered to be acceptable for APBI treatment. However, the finding of axillary recurrence in patients with triple negative breast cancer does warrant a degree of caution in proceeding with accelerated partial breast irradiation technique in this patient group.

Comparison of Survival Outcomes for Axillary Surgery Extent Based on Intraoperative Sentinel Lymph Node Biopsy Result After Neoadjuvant Chemotherapy for Breast Cancer

PurposeTo investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC).MethodWe retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n=188) and ALND (n=295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups.ResultAt a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.43-2.05, p=0.876) and 5-year overall survival (97.7% vs. 97.3%, HR=1.65, 95% CI=0.58-4.65, p=0.347) between the two groups.ConclusionOur analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

“Unplanned breast-conserving surgery after systemic therapy in locally advanced breast cancer: the results of level II oncoplastic techniques”

BACKGROUND: In patients with breast cancer for whom neoadjuvant chemotherapy (NAC) is planned, it is recommended to mark the primary tumor before treatment (planned surgery). However, surgeons may have to perform breast-conserving surgery on patients whose tumors are not marked (unplanned surgery). This study focused on the results obtained with planned and unplanned level II oncoplastic surgery (OPS) techniques applied to patients after NAC. METHODS: Patient groups who underwent planned, unplanned OPS and mastectomy after NAC were compared. Surgical margin status, re-operation and re-excision requirements, ipsilateral breast tumor recurrence (IBTR) and axillary recurrence rates recorded. Long-term local recurrence-free survival (LRFS), disease-free survival and overall survival were evaluated. RESULTS: There was no significant difference between the planned and unplanned OPS groups in terms of surgical margin status, re-excision requirement, and mastectomy rates. During an average follow-up period of 43 months, 5.3% and 4% of the patients in the planned OPS group developed IBTR and axillary recurrence, respectively, whereas these rates were 6.6% and 5.3% in the unplanned OPS group. In the mastectomy group, the rates of IBTR and axillary recurrence were found to be 4.1% and 3.8%, respectively. There was no significant difference between the three groups in terms of IBTR (p: 0.06) and axillary recurrence (p: 0.08) rates. CONCLUSION: Breast conserving surgery can be applied using level II OPS techniques with the post-NAC radiological examination and marking even if primary tumor marking is not done in the pre-NAC period.