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).

Ten-year outcome results of cT4 breast cancer after neoadjuvant treatment.

BACKGROUND AND OBJECTIVES: cT4 breast cancer (BC) is classified as noninflammatory breast cancer (non-IBC) or inflammatory breast cancer (IBC). The outcome often is considered worse. The purpose of this study was to determine recurrence and outcomes in overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS) according to pathological complete response (pCR), and inflammatory status. METHODS: From 2000 to 2015 we selected 634 nonmetastatic cT4 BC patients treated with neoadjuvant therapy followed by surgery at the European Institute of Oncology. OS, IDFS, and DDFS were estimated with the Kaplan-Meier method. RESULTS: The median follow-up was 9.0 years. Twenty patients underwent only sentinel node biopsy (SNB), 13 SNB + AD, and 601 only AD. Considering the 614 patients with AD, only 2.5% of non-IBC patients reported pCR compared to 15% of IBC cases. Only two axillary recurrences were reported. Ten-year results were 52.3% (95% confidence interval [CI]: 47.8-56.5) for OS, 37.0% (95% CI: 32.6-41.3) for IDFS, and 49.8% (95% CI: 45.0-54.4) for DDFS. OS, IDFS, and DDFS were better in all BC with pCR (irrespective of inflammatory status). CONCLUSION: Our long-term results demonstrated that pCR significantly improves survival, reducing locoregional and distant recurrence risk in cT4 tumors with respect to patients with no pCR and according to inflammatory status of cT4 BC.

Is Nipple-Sparing Mastectomy Indicated after Previous Breast Surgery? A Series of 387 Institutional Cases.

BACKGROUND: Previous breast surgery does not represent an absolute contraindication for nipple-sparing mastectomy, although it may negatively interfere with surgical outcomes. The aim of the authors' study was to confirm the feasibility of nipple-sparing mastectomy after previous breast surgery, focusing on skin incisions and risk factors, complications, and oncologic outcomes. METHODS: The authors retrospectively identified 368 patients who underwent 387 nipple-sparing mastectomies and reconstruction after previous surgery (quadrantectomy, breast resection, augmentation and reduction mammaplasty, mastopexy) at the European Institute of Oncology from January of 2003 to November of 2017. Patterns of skin incisions (i.e., radial, hemiperiareolar, periareolar, vertical pattern, inframammary fold, Wise-pattern, and round-block) for primary surgery and for mastectomy, type of reconstruction, and radiotherapy have been recorded. The authors collected data regarding early and late complications and further operations (implant change, fat grafting) performed within 2 years to improve cosmetic outcomes. Oncologic follow-up has been reported for in-breast recurrences. RESULTS: Complete and partial nipple-areola complex necrosis occurred, respectively, in 2.8 percent and in 5.4 percent of cases. The authors recorded 5.4 percent failures resulting in implant removal. The analysis of risk factors for complications or for the need for further operations showed no significant association with skin incision for first surgery and mastectomy, use of the same skin incision, previous radiotherapy, or type of primary surgery. Five-year overall survival and disease-free survival were 99.1 and 93.8 percent, respectively. No nipple recurrence was recorded. CONCLUSIONS: The authors' results confirm that nipple-sparing mastectomy can be a safe surgical procedure after previous breast surgery. Surgical planning should be tailored to each patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Predictors of positive axillary non-sentinel lymph nodes in breast cancer patients with positive sentinel lymph node biopsy after neoadjuvant systemic therapy.

AIM: To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. RESULTS: Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23-56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. CONCLUSIONS: Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.

INTRODUCTION: In patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6-14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs). METHODS: This study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory. RESULTS: Axillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3-12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8-93.2) and 81.0% (95% CI, 77.2-84.2) in the whole cohort, 92.0% (95% CI, 89.0-94.2) and 81.5% (95% CI, 76.9-85.2) in those initially cN0, 89.8% (95% CI, 85.0-93.2) and 80.1% (95% CI, 72.8-85.7) in those initially cN1/2. CONCLUSION: The 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.