Simple Summary Left ventricular dysfunction (LVD) induced by anthracycline-based cancer chemotherapy (ACC) is becoming an urgent healthcare concern. Myocardial fibrosis (MF) may contribute to LVD after ACC. We show that elevated circulating levels of procollagen type I C-terminal propeptide (PICP, biomarker of MF) are associated with early subclinical LVD and predict later development of cardiotoxicity in patients treated with ACC. In addition, an association between PICP and LVD in patients with ACC-induced heart failure is observed. These results provide novel insights into MF as a mechanism underlying LVD after ACC, with PICP emerging as a promising tool to monitor cardiotoxicity in patients treated with ACC. Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio >= 2.95 per doubling PICP, p <= 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

The incidence of autoimmune thyroid disorders is higher among women with breast cancer (BC) than in other solid malignancies, while it has not a prognostic impact. Trastuzumab (T) is a humanized monoclonal antibody approved for human epidermal growth factor receptor 2 (HER2)-positive BC in the neoadjuvant, adjuvant, and metastatic scenarios. Since 2014, subcutaneous (SC) T has been employed with the same efficacy as the intravenous formulation together with an easier way of administration. To date, autoimmune thyroiditis has been linked rarely to the use of intravenous T, and no cases have been related to the SC presentation. We report two cases of HER2-positive early BC patients who developed hypothyroidism during maintenance therapy with SC T that required levothyroxine supplementation. SC T includes recombinant human hyaluronidase to facilitate tissue penetration of the drug. This enzyme may alter the thyroid gland stroma and facilitate the development of thyroid disorders. Thyroid function tests are recommended in patients on SC T.

Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase/phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumour cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumour cells linking inflammation to immune remodelling favouring local relapse.

Objective: The aim of this study was to assess body shape trajectories in childhood and midlife in relation to subsequent risk of breast cancer (BC) in a Mediterranean cohort. Design: The 'Seguimiento Universidad de Navarra' (SUN) Project is a dynamic prospective cohort study of university graduates initiated in 1999. With a group-based modelling approach, we assessed body shape trajectories from age 5 to 40 years. Multivariable Cox regression models were used to estimate the hazard ratio (HR) for BC after the age of 40 years according to the body shape trajectory. Setting: City of Pamplona, in the North of Spain. Participants: 6498 women with a mean age of 40 years (sd 9). Results: We identified four distinct body shape trajectories ('childhood lean-midlife increase' (19 center dot 9 %), 'childhood medium-midlife stable' (53 %), 'childhood heavy-midlife stable' (21 %) and 'childhood heavy-midlife increase' (6 center dot 1 %)). Among 54 978 women-years of follow-up, we confirmed eighty-two incident cases of BC. Women in the 'childhood lean-midlife increase' group showed a higher risk of BC (HR = 1 center dot 84, 95 % CI 1 center dot 11, 3 center dot 04) compared with women in the 'childhood medium-midlife stable' category. This association was stronger for postmenopausal BC (HR = 2 center dot 42, 95 % CI 1 center dot 07, 5 center dot 48). Conclusions: Our results suggest a role for lifetime adiposity in breast carcinogenesis.

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4 -> Dx4) followed by surgery +/- radiotherapy +/- hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade > 3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-gamma production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-beta repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome.

Evidence is still limited on the influence of sedentary lifestyles on breast cancer (BC) risk. Also, prospective information on the combined effects of both sedentariness and leisure-time physical activity (LTPA) is scarce. We aimed to assess the association of higher sedentary behavior and LTPA (separately and in combination) with the risk of BC in a middle-aged cohort of university graduates. The SUN Project is a follow-up study initiated in 1999 with recruitment permanently open. Baseline assessments included a validated questionnaire on LTPA and sedentary habits. Subsequently, participants completed biennial follow-up questionnaires. Multivariable adjusted Cox models were used to estimate the hazard ratios (HR) for incident BC according to LTPA, TV-watching, the joint classification of both, and a combined 8-item multidimensional active lifestyle score. We included 10,812 women, with 11.8 years of median follow-up of. Among 115,802 women-years of follow-up, we confirmed 101 incident cases of BC. Women in the highest category of LTPA ( 2 points) group. There was no significant supra-multiplicative interaction between TV-watching and LTPA. Both low LTPA and TV-watching 2 h/d may substantially increase BC risk, independently of each other.

Purpose To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. Materials and methods We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. Results One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and >= 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naive patients (31.5% versus 40.5% for L-pretreated versus L-naive). Grade 3/4 adverse events were reported in 19 patients (16.5%). Conclusion The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03-2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11-3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.

Introduction: We aimed to analyze the outcome in a series of women with primary advanced ovarian cancer in an Intermediate Volume Hospital where new surgical and chemotherapy treatments were implemented over a period of 14 years. Material and Methods: One hundred and twenty-seven women with stage IIIB-IV disease underwent primary (76.4%) or interval debulking surgery (23.6%). Fifty-seven were operated on from 2000 to 2005 (Group 1) and 70 from 2006 to 2014 (Group 2). Results: No gross residual disease was achieved in 51.5% and 43.3% of women who underwent primary and interval surgery, respectively. For no gross and < 1cm residual disease, median overall and progression-free survival were 94.7 vs. 60.6 months (p = 0.001) and 25.3 vs. 20.0 months, respectively (p = 0.02). The rate of no gross residual (36.8 to 60.0%) and 5-yr median overall survival (56.3 to 73.7 months) increased between 2000-2005 (Group 1) and from 2006 to 2014 (Group 2). On multivariate analysis, interval surgery, multiple peritoneal implants and residual disease were predictive of overall and progression-free survival. Conclusions: Survival after primary and interval debulking surgery progressively correlates with decrease in residual disease. Increasing rates of successful primary surgery are possible through standardization and adoption of best practices without increasing morbidity.

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARS-CoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimise pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations' and societies' recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing. Implications for Practice This work presents a set of guidelines regarding available options for breast cancer (BC) patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the suddenness of this health crisis, specialists have to make decisions with little evidence at hand. Thus, these expert guidelines may be a useful tool to facilitate medical decision making in the context of a worldwide pandemic with no resources to spare.