Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group. We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology ( www.sign.ac.uk ). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered. Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation). Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

In breast cancer, the use of a boost to the tumor bed can improve local control. The aim of this research is to evaluate the safety and efficacy of the boost with intra-operative electron radiotherapy (IOERT) in patients with early-stage breast cancer undergoing conservative surgery and postoperative whole breast irradiation (WBI). The present retrospective multicenter large data were collected between January 2011 and March 2018 in 8 Italian Radiation Oncology Departments. Acute and late toxicity, objective (obj) and subjective (subj) cosmetic outcomes, in-field local control (LC), out-field LC, disease-free survival (DFS) and overall survival (OS) were evaluated. Overall, 797 patients were enrolled. IOERT-boost was performed in all patients during surgery, followed by WBI. Acute toxicity (≥G2) occurred in 179 patients (22.46%); one patient developed surgical wound infection (G3). No patients reported late toxicity ≥ G2. Obj-cosmetic result was excellent in 45%, good in 35%, fair in 20% and poor in 0% of cases. Subj-cosmetic result was excellent in 10%, good in 20%, fair in 69% and poor in 0.3% of cases. Median follow-up was 57 months (range 12–109 months). At 5 years, in-field LC was 99.2% (95% CI: 98–99.7); out-field LC 98.9% (95% CI: 97.4–99.6); DFS 96.2% (95% CI: 94.2–97.6); OS 98.6% (95% CI: 97.2–99.3). In conclusion, IOERT-boost appears to be safe, providing excellent local control for early-stage breast cancer. The safety and long-term efficacy should encourage use of this treatment, with the potential to reduce local recurrence.

Breast cancer is one of the most frequently diagnosed malignancies and remains the leading cause of cancer-related death among women worldwide. Emerging evidence implicates the microbiota to be a potential contributor to its pathogenesis and progression. This review summarizes emerging evidence of microbial alterations across various body niches in breast cancer patients, including gut, breast tissue, nipple aspirate fluid (NAF), oral cavity, skin, urinary and reproductive tracts, and blood. Reductions in commensal taxa such as Faecalibacterium, Bifidobacterium, Lachnospira, Akkermansia, and Sphingomonas, along with an increase in pro-inflammatory genera like Prevotella, Fusobacterium, and Desulfovibrio, may promote breast tumor development and progression through multiple pathways including modulation of estrogen metabolism, production of microbial metabolites, and immunoregulation. The presence of cross-niche overlaps and possible translocation of microbiota between niches through the bloodstream suggests the existence of a complex interconnected oral–gut–breast microbiota axis. Progress in the field will depend on integrative multi-omics, translational approaches, and longitudinal studies to give a clearer mechanistic understanding of microbiota–host interactions to develop feasible microbiota-based biomarkers and therapeutic strategies in breast cancer.

Objectives: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). Methods: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Results: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Conclusions: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. Advances in knowledge: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

The applicability of RHT in the treatment and supportive care of tumors has been discussed for years in many publications. There are hundreds of articles that have reported on the good acceptance and feasibility of HT, as well as its value in terms of controlling malignant diseases, enhancing response and, in some randomized controlled trials (RCTs), clear improvements in OS. Despite this, HT has never fully been accepted as a standard treatment among radiation and medical oncologists. The increased activity that HT offers in the context of chemotherapy (CHT), radiotherapy (RT), chemoradiotherapy (CRT), and immunotherapy, thus facilitating programmed cell death (PCD), has been documented in many studies. This aspect has been demonstrated in many tumors, including soft tissue sarcoma, cancers of the cervix, esophagus, stomach, colon/rectum, pancreas, breast, head and neck, and prostate, and bone metastases. HT improves cancer cell death through many modalities, targeting both the tumor microenvironment (TME) and the cancer cells directly. Targeted HT increases the temperature of the primary tumor and surrounding tissues to 39–43 °C, causing the tumor cells to become more immune-responsive. HT can also activate the immune response of the TME through inducing heat shock proteins (HSPs), which also promote an immunological response and PCD. HT can oxygenate hypoxic tumors, facilitating RT-induced DNA damage in cancer cells. At present, it seems that the combination of HT and RT, CHT, and immunotherapy might lead to immune enhancement effects in the TME, making cancer cells more responsive to immunotherapies. This narrative review presents the novel aspects of HT reported in recent years.