Hypofractionated Radiation Therapy (HFRT) of Breast/Chest Wall and Regional Nodes in Locally Advanced Breast Cancer: Toxicity Profile and Survival Outcomes in Retrospective Monoistitutional Study.

AIM: To evaluate the efficacy and safety of hypofractionated radiation therapy (HFRT) of the breast/chest wall and regional nodes in patients with locally advanced breast cancer and positive lymph nodes. MATERIALS AND METHODS: One hundred and twenty-two patients treated between October 2016 and March 2020 with HFRT were retrospectively reviewed. A total dose of 42.4 Gy was delivered to the chest wall and lymph nodes in 16 fractions of 2.65 Gy each, using the IMRT technique. Patients treated with breast-conserving surgery received an overdose (concomitant boost of 3 Gy daily) with the SIB (Simultaneous Integrated Boost) technique. RESULTS: Median age at diagnosis was 58 years (range 34-86 years) and median follow-up was 22 months (range 6-48 months). Overall survival (OS) at 1, 2 and 3 years was 100%, 97.3% and 90%, respectively. Disease-free survival (DFS) at 1, 2, and 3 years was 91.4%, 87%, and 84.8%, respectively. Distant metastasis-free survival (MFS) at 1, 2 and 3 years was 93.1%, 88% and 85.7%, respectively. Two patients (1.6%) experienced local recurrence on the chest wall during FUP. Twenty-one patients (17%) showed a grade 2 dermal toxicity, no grade 3 acute skin toxicity was found. Sixteen patients (13%) showed early-stage arm lymphedema (grade ≤ 2). Twenty-three patients (19%) showed a grade 2 late skin toxicity. Twenty patients (16%) had grade ≤ 2 late arm lymphedema. CONCLUSION: Given the excellent local control, survival rates and the low toxicity profile demonstrated, HFRT could be considered a valid therapeutic option in patients with locally advanced breast cancer.

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Post-mastectomy immediate breast reconstruction and adjuvant radiotherapy: long term results of a mono institutional experience.

INTRODUCTION: The aim of this paper is to investigate the outcome of patients treated with mastectomy, immediate breast reconstruction (IBR) and post-mastectomy radiotherapy (PMRT) and the risk of late complications. MATERIAL AND METHOD: All patients had post-mastectomy, immediate reconstructive surgical procedure by using autologous abdominal implant; tissue expander (TE)/permanent prosthesis (PP); or even combined procedures. Adjuvant external beam radiotherapy treatment (EBRT) was delivered to the reconstructed chest wall and supraclavicular nodes, for a total dose of 50 Gy in 25 fractions. The Kaplan-Meyer analysis evaluates patients' rate of late side effects, Overall Survival (OS), Progression Free survival (PFS), Local-regional free survival (LRFS) and Metastasis Free Survival (MFS). The univariate analysis investigates the correlation between late toxicity and related factors. RESULTS: Between November 2003 and October 2016, 91 breast cancer patients were treated with IBR and PMRT. Twenty-three (25.3%) patients experimented late toxicity. Overall, 16 (17.6%) patients experienced late complications which required a surgical approach. The 1- 2- 5- years late toxicity rates were 96.6%, 87.1% and 77.9%, respectively. The type of reconstruction was not statistically related with late toxicity rate (P = 0.35). The median follow-up period was 59 months (range 6-142 months). Median OS was not reached, the 1- 2- 5-years OS rates were 100%, 95.4% and 81% respectively. CONCLUSION: This study underlines that the type of reconstruction does not influence late toxicity rate. Moreover, IBR followed by adjuvant radiotherapy, has showed acceptable late toxicity profile and no influence on OS.

Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1ß, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1ß, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Radiation therapy after breast reconstruction: outcomes, complications, and patient satisfaction.

PURPOSE: The aim of this study was to evaluate treatment-related complications, outcomes, and patient satisfaction in women with locally advanced breast cancer who received post-mastectomy radiation therapy (PMRT) after breast reconstruction (BR). MATERIALS AND METHODS: Between October 2007 and November 2010, 46 patients with locally advanced breast cancer who underwent mastectomy followed by BR received PMRT at our Department. Radiotherapy was delivered to the chest wall with a dose of 50 Gy in 25 fractions over 5 weeks. RESULTS: The median follow-up was 19 months. Skin erythema grade 1 and 2 was seen in 44 (96%) and two (4%) patients, respectively. Major complications, requiring additional corrective surgical procedure, occurred in three (7%) patients (one patient with prosthesis, one patient with tissue expander and one patient with deep inferior epigastric perforator flap). At univariate analysis, smoking, chemotherapy, hormone therapy with tamoxifen and reconstruction with implant were associated with overall complications (capsular contracture and reconstruction failure). Forty (86%) patients were very satisfied or satisfied with the cosmetic outcome of reconstruction. CONCLUSIONS: Radiotherapy can be safely delivered after BR, with a low complication rate and good patient satisfaction. Further randomised studies are needed to better define the optimal timing of breast reconstruction and post-mastectomy radiation therapy.