Anti HER2 therapy and left breast adjuvant radiation therapy (RT) can both result in cardiotoxicity. The aim of this study was to evaluate the influence of radiation dose on cardiac structures on the values of the early cardiotoxicity marker high-sensitivity cardiac troponin I (hscTnI) in patients with HER2-positive left breast cancer undergoing adjuvant concomitant antiHER2 therapy and radiotherapy, and to establish a correlation between the hscTnI values and cardiac radiation doses. Sixty-one patients underwent left breast hypofractionated radiotherapy in parallel with anti-HER2 therapy: trastuzumab, combined trastuzumab–pertuzumab or trastuzumab emtansine (T-DM1). The hscTnI values were measured prior to and upon completion of radiotherapy. A significant increase in hscTnI was defined as >30% from baseline, with the second value being 4 ng/L or higher. Dose volume histograms (DVH) were generated for the heart, left ventricle (LV) and left anterior descending artery (LAD). The hscTnI levels were corelated with radiation doses on cardiac structures. An increase in hscTnI values was observed in 17 patients (Group 1). These patients had significantly higher mean radiation doses for the heart (p = 0.02), LV (p = 0.03) and LAD (p = 0.04), and AUC for heart and LV (p = 0.01), than patients without hscTnI increase (Group 2). The patients in Group 1 also had larger volumes of heart and LV receiving 2 Gy (p = 0.01 for both) and 4 Gy (p = 0.02 for both). LAD differences were observed in volumes receiving 2 Gy (p = 0.03), 4 Gy (p = 0.02) and 5 Gy (p = 0.02). The increase in hscTnI observed in patients receiving anti-HER2 therapy after adjuvant RT was positively associated with radiation doses on the heart, LV and LAD. Full article

Objective: The liver is a critical organ at risk during right breast radiotherapy (RT). Liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) serve as biochemical markers for hepatobiliary damage. In this multicenter cross-sectional study, the effects of liver dose–volume on changes in LFTs pre- and post-RT in patients treated for right breast cancer were evaluated. Materials and Methods: Between January 2019 and November 2022, data from 100 patients who underwent adjuvant right breast RT across three centers were retrospectively assessed. Target volumes and normal structures were contoured per the RTOG atlas. Patients were treated with a total dose of 50 Gy in 25 fractions to the CTV, followed by a boost to the tumor bed where indicated. The percentage change in LFT values in the first two weeks post-RT was calculated. Statistics were analyzed with SPSS version 22 software, with significance set at p < 0.05. Statistical correlation between liver doses (in cGy) and the volume receiving specific doses (Vx in cc) on the change in LFTs were analyzed using Kolmogorov–Smirnov, Mann–Whitney U test. Results: The median age among the 100 patients was 56 (range: 29–79). Breast-conserving surgery was performed on 75% of the patients. The most common T and N stages were T1 (53%) and N0 (53%), respectively. None of the patients had distant metastasis or simultaneous systemic treatment with RT. A total of 67% of the treatments utilized the IMRT technique and 33% VMAT. The median CTV volume was 802 cc (range: 214–2724 cc). A median boost dose of 10 Gy (range: 10–16 Gy) was applied to 28% of the patients with electrons and 51% with IMRT/VMAT. The median liver volume was 1423 cc (range: 825–2312 cc). Statistical analyses were conducted on a subset of 57 patients for whom all three LFT values were available both pre- and post-RT. In this group, the median values for AST, ALT, and GGT increased up to 15% post-RT compared to pre-RT, and a median liver D_mean below 208 cGy was found significant. While many factors can influence LFT values, during RT planning, attention to liver doses and subsequent regular LFT checks are crucial. Conclusion: Due to factors such as anatomical positioning, planning technique, and breast posture, the liver can receive varying doses during right breast irradiation. Protecting patients from liver toxicity secondary to RT is valuable, especially in breast cancer patients with a long-life expectancy. Our study found that, even in the absence of any systemic treatment or risk factors, there was an average increase of nearly 15% in enzymes, indicating acute liver damage post-RT compared with pre-RT. Attention to liver doses during RT planning and regular follow-up with LFTs is essential. Full article

Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2−. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends. Full article

Introduction: The timing of contralateral symmetrisation in patients with large and ptotic breasts undergoing a unilateral skin-reducing mastectomy (SRM) is one of the most debated topics in the reconstructive field. There is no evidence to support the advantage of immediate or delayed symmetrisation to help surgeons with this decision. The aim of this study was to investigate the clinical and aesthetic outcomes of immediate symmetrisation. Methods: A randomised observational study was conducted on patients who underwent an SRM for unilateral breast cancer. Based on a simple randomisation list, patients were divided into two groups: a delayed symmetrisation group versus an immediate symmetrisation group. The postoperative complications, BREAST-Q outcomes and reoperations were compared. Results: Out of a total of 84 patients undergoing an SRM between January 2018 and January 2021, 42 patients underwent immediate symmetrisation and 42 patients had delayed symmetrisation. Three implant losses (7.2%) were observed and we reported three wound dehiscences; one of these was in a contralateral breast reconstruction in the immediate symmetrisation group. The BREAST-Q patient-reported outcome measures recorded better aesthetic outcomes and a high patient satisfaction for the immediate symmetrisation group. Conclusions: Simultaneous controlateral symmetrisation is a good alternative to achieve better satisfaction and quality of life for patients; from a surgical point of view, it does not excessively impact on the second time of reconstruction. Full article

Exposure to situations of domestic violence during the treatment for breast cancer may compromise the treatment and quality of life of women patients, so it is essential that health professionals act in tracking this phenomenon in the approach to and care of women with breast cancer. The purpose of this study was to examine experiences of violence against women by their intimate partners after mastectomy. This is an exploratory descriptive study, with a qualitative approach, carried out in the Rehabilitation Program for Mastectomized Women in a Brazilian reference hospital for oncological treatment. Semi-structured interviews were conducted with 16 mastectomized women. For data analysis, a content analysis technique was performed. The women interviewed were predominantly brown, with a minimum age of 44 years and maximum of 72 years. They presented with low education, were married, and had a mean period of five years of breast cancer diagnosis. The participants reported that after mastectomy, they experienced episodes of violence at a time when they were extremely vulnerable due to the various cancer treatments. Three major thematic categories emerged from interview data across the data collection: (1) experiences of psychological violence, (2) experiences of physical violence, and (3) experiences of sexual violence. Psychological violence took the form of humiliation and contempt for their condition. Physical violence involved assault and sexual violence in the form of forced sex by coercion. Violence was a phenomenon present after mastectomy, practiced in the domestic environment by the intimate partner. We emphasize the importance of health professionals in screening for this issue by listening to and welcoming women, recording cases, exposing this situation, and contributing to prevention. Full article

In this retrospective study we share our single-center experience using a magnetic seed for the preoperative localization of non-palpable breast lesions. Patients who underwent a preoperative localization with Magseed^® (Endomagnetics, Cambridge, UK) placement between 2020 and 2022 were enrolled. Indications to Magseed placement have been established during multidisciplinary meetings prior to surgery and all patients underwent breast-conserving surgery (BCS). 45 patients were included. Magnetic seeds have been introduced under ultrasound guidance in 40 patients (88.9%) and under stereotactic guidance in 5 patients (11.1%). We registered a highly successful placement rate (97.8%), with only one case of migration (2.2%). After BCS, all the magnetic seeds were recovered (100% retrieval rate). The re-excision rate for positive margins was 0%. Our experience, with a highly successful placement and retrieval rate and a re-excision rate equal to 0%, is consistent with the encouraging literature published on Magseed so far, suggesting this technique to be extremely effective. Moreover, our single case of seed migration supports the existing data stating that Magseed migration is rare. In conclusion, despite acknowledging Magseed limitations, we highly value the advantages linked to this technique, and we, therefore, uphold its use. Full article

The expression of estrogen receptors (ERs) in breast cancer (BC) represents a strong prognostic and predictive biomarker and directs therapeutic decisions in early and advanced stages. ER-low-positive BC, defined by the immunohistochemical (IHC) expression of ERs from 1% to 9%, constitutes a distinct subset of total BC cases. Guidelines recommend that a low expression of ERs be reported in pathology reports since the benefit of endocrine therapy in patients with ER-low-positive BC is uncertain. Recently, several cohorts, mostly of a retrospective nature, have been published, reporting the clinicopathological characteristics and outcomes of ER-low-positive BC. However, the majority of the data focus on early-stage BC and the use of (neo)adjuvant therapy, and there is a significant lack of data regarding metastatic ER-low-positive BC. Further factors, including tumor heterogeneity as well as the potential loss of ER expression due to endocrine resistance, should be considered. Including patients with ER-low-positive BC in clinical trials for triple-negative breast cancer (TNBC) might improve the understanding of this entity and allow novel therapeutic approaches. The design and conduction of randomized clinical trials regarding this subgroup of patients are greatly anticipated. Full article

Background: Risk-reducing surgeries are an option for cancer risk management in BRCA1/2 individuals. However, while adnexectomy is commonly recommended in breast cancer (BC) survivors, risk-reducing bilateral breast surgery (RRBBS) is controversial in ovarian cancer (OC) survivors due to relapse rates and mortality. Methods: We conducted a retrospective analysis of BRCA1/2-OC survivors, with OC as first cancer diagnosis. Results: Median age at OC diagnosis for the 69 BRCA1/2-OC survivors was 54 years. Median overall survival was 8 years, being significantly higher for BRCA2 patients than for BRCA1 patients (p = 0.011). Nine patients (13.2%) developed BC at a median age of 61 years. The mean overall BC-free survival was 15.5 years (median not reached). Eight patients (11.8%) underwent bilateral mastectomy (5 simultaneous with BC treatment; 3 RRBBS) at a median age of 56.5 years. The median time from OC to bilateral mastectomy/RRBBS was 5.5 years. Conclusions: This study adds evidence regarding a lower BC risk after BRCA1/2-OC and higher survival for BRCA2-OC patients. A comprehensive analysis of the competing risks of OC mortality and recurrence against the risk of BC should be individually addressed. Surgical BC risk management may be considered for longer BRCA1/2-OC disease-free survivors. Ultimately, these decisions should always be tailored to patients’ characteristics and preferences. Full article

Background: The use of preoperative breast magnetic resonance imaging (MRI) after the diagnosis of breast cancer by mammography and/or ultrasound is inconsistent. Methods: After conducting a systematic review and meta-analysis comparing preoperative breast MRI versus no MRI, we reconvened to prepare a clinical practice guideline on this topic. Results: Based on the evidence that MRI improved recurrence, decreased the rates of reoperations (re-excisions or conversion mastectomy), and increased detection of synchronous contralateral breast cancer, we recommend that preoperative breast MRI should be considered on a case-by-case basis in patients diagnosed with breast cancer for whom additional information about disease extent could influence treatment. Based on stronger evidence, preoperative breast MRI is recommended in patients diagnosed with invasive lobular carcinoma for whom additional information about disease extent could influence treatment. For both recommendations, the decision to proceed with MRI would be conditional on shared decision-making between care providers and the patient, taking into account the benefits and risks of MRI as well as patient preferences. Based on the opinion of the Working Group, preoperative breast MRI is also recommended in the following more specific situations: (a) to aid in surgical planning of breast conserving surgery in patients with suspected or known multicentric or multifocal disease; (b) to identify additional lesions in patients with dense breasts; (c) to determine the presence of pectoralis major muscle/chest wall invasion in patients with posteriorly located tumours or when invasion of the pectoralis major muscle or chest wall is suspected; (d) to aid in surgical planning for skin/nipple-sparing mastectomies, autologous reconstruction, oncoplastic surgery, and breast conserving surgery with suspected nipple/areolar involvement; and (e) in patients with familial/hereditary breast cancer but who have not had recent breast MRI as part of screening or diagnosis. Full article

Breast cancer is the most frequent neoplasm among women and the second leading cause of death by cancer. It is the most frequent cancer diagnosed during pregnancy. Pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy and/or in the postpartum period. Data about young women with metastatic HER2-positive cancer who desire a pregnancy are scarce. The medical attitude in these clinical situations is difficult and nonstandardized. We present the case of a 31-year-old premenopausal woman diagnosed in December 2016 with a stage IV Luminal HER2-positive metastatic breast cancer (pT2 N0 M1 hep). The patient was initially treated by surgery in a conservative manner. Postoperatively, the presence of liver metastases was found by CT investigation. Consequently, line I treatment (docetaxel l75 mg/m² iv; trastuzumab 600 mg/5 mL sq) and ovarian drug suppression (Goserelin 3.6 mg sq at 28 days) was administered. After nine cycles of treatment, the patient’s liver metastases had a partial response to the therapy. Despite having a favorable disease evolution and a strong desire to procreate, the patient vehemently refused to continue any oncological treatment. The psychiatric consult highlighted an anxious and depressive reaction for which individual and couple psychotherapy sessions were recommended. After 10 months from the interruption of the oncological treatment, the patient appeared with an evolving pregnancy of 15 weeks. An abdominal ultrasound revealed the presence of multiple liver metastases. Knowing all the possible effects, the patient consciously decided to postpone the proposed second-line treatment. In August 2018, the patient was admitted in the emergency department with malaise, diffuse abdominal pain and hepatic failure. Abdominal ultrasound found a 21-week-old pregnancy which had stopped in evolution, multiple liver metastases and ascites in large quantity. She was transferred to the ICU department where she perished just a few hours later. Conclusions/Discussion: From a psychological standpoint, the patient had an emotional hardship to make the transition from the status of a healthy person to the status of a sick person. Consequently, she entered a process of emotional protection of the positive cognitive distortion type, which favored the decision to abandon treatment and try to complete the pregnancy to the detriment of her own survival. The patient delayed the initiation of oncological treatment in pregnancy until it was too late. The consequence of this delay in treatment led to the death of the mother and fetus. A multidisciplinary team worked to provide this patient with the best medical care and psychological assistance throughout the course of the disease. Full article

Female BRCA1/2 pathogenic variant carriers have an increased lifetime risk for breast and ovarian cancer. Cancer-unaffected women who are newly diagnosed with this pathogenic variant may experience psychological distress because of imminent health threat. No comprehensible review on psychological morbidity in cancer-unaffected BRCA1/2 pathogenic variant carriers is currently available. This review aims to give an overview about all available the studies in which psychological outcomes have been assessed in cancer-unaffected BRCA1/2 pathogenic variant carriers, whether as a primary outcome or secondary measurement. A systematic search across four databases (Web of Science, PubMed, ScienceDirect, and EBSCO) was conducted. Studies had to report on cancer-unaffected pathogenic variant carriers (exclusively or separately) and use a validated measure of psychological morbidity to be eligible. Measures were only included if they were used in at least three studies. The final review consisted of 45 studies from 13 countries. Distress measures, including anxiety and cancer worry, were most often assessed. Most studies found a peak of distress immediately after genetic test result disclosure, with a subsequent decline over the following months. Only some studies found elevated distress in carriers compared to non-carriers in longer follow-ups. Depression was frequently investigated but largely not found to be of clinical significance. Quality of life seemed to be largely unaffected by a positive genetic test result, although there was some evidence that younger women, especially, were less satisfied with their role functioning in life. Body image has been infrequently assessed so far, but the evidence suggested that there may be a decrease in body image after genetic test result disclosure that may decrease further for women who opt for a prophylactic mastectomy. Across all the outcomes, various versions of instruments were used, often limiting the comparability among the studies. Hence, future research should consider using frequently used instruments, as outlined by this review. Finally, while many studies included cancer-unaffected carriers, they were often not reported on separately, which made it difficult to draw specific conclusions about this population. Full article