Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study.

BACKGROUND: Patritumab deruxtecan (HER3-DXd) is a human epidermal growth factor receptor 3 (HER3)-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [= -0.8 × tumor cellularity (in %)  + 1.3  × tumor-infiltrating lymphocytes (TILs) (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. PATIENTS AND METHODS: Patients with previously untreated hormone receptor-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 messenger RNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. RESULTS: Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P = 0.003). Among patients assessable for clinical response (n = 62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 versus +1.9). Change in CelTIL score was independent of baseline ERBB3 messenger RNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. CONCLUSIONS: A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in hormone receptor-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

Anxiety and depression in women with breast cancer: Social and clinical determinants and influence of the social network and social support (DAMA cohort).

BACKGROUND: Anxiety and depression are the most prevalent mental health pathologies among women with breast cancer. Social, clinical and contextual variables may influence emotional stress among women with breast cancer. The aim of this work is to study anxiety and depression in a cohort of women diagnosed with breast cancer between 2003 and 2013 in Barcelona. We evaluate social and clinical determinants. METHODS: We performed a mixed cohort study (prospective and retrospective) using a convenience sample of women diagnosed with breast cancer. The information sources were the Hospital Anxiety and Depression questionnaire and hospital medical records. Dependent variables were anxiety and depression; independent variables were social class, age, employment status, tumour stage at diagnosis, time since diagnosis, social network and social support. We performed a descriptive analysis, a bivariate analysis, and a multivariate logistic regression analysis. RESULTS: A total of 1086 (48.6%) women had some degree of anxiety-related problem. As for depression. In the case of depression, 225 (15%) women had some degree of depression-related problem. Low emotional support and social isolation were clear risk factors for having more anxiety and depression. Low social class was also a risk factor, and age also played a role. DISCUSSION: Our results show that women long period of cancer survival have high prevalences of anxiety than depression, and this prevalence of anxiety is higher than the general population. In addition, we found inequalities between social classes and the isolation and social support are worse too in low social class.

The superparamagnetic iron oxide is equivalent to the Tc99 radiotracer method for identifying the sentinel lymph node in breast cancer.

BACKGROUND: Preoperative injection of Tc99 is standardly performed before sentinel lymph node biopsy (SLN) for breast cancer. Multiple questions have arisen concerning appropriate technique for SLNBs including site of injection, timing and injection material. The aim of this study was to assess the concordance between a new method, superparamagnetic iron oxide (SPIO) and the Tc99 radiotracer to identify the SLN in early breast cancer. MATERIAL AND METHODS: Between July 2013 and March 2014, 120 patients with clinically node negative early breast cancer were included in the study. Patients were injected the day before the radiotracer for lymphoscintigraphy and injected the SPIO subareolar intraoperatively. SLN was excised if it was radioactive, magnetic or palpable. Patients signed an inform consent. RESULTS: There was no drainage by either technique in 2 patients, so this leaves 118 patients for further analysis. Detection rate by Tc 99 was successful in 113 (95.7%%) patients and by SPIO in 116 (98.3%). Concordance rates per patient between techniques was 98.2%. The SLN was positive in 36 (30%) patients. Of this, SLN positivity was detected by both techniques in 32 patients. Mean number of SLNs by 99Tc and SPIO were 1.9 and 2.21 respectively (p = 0.001). DISCUSSION: Detection of SLNs with SPIO allows for easy identification of axillary nodes, at a frequency not inferior to the radiotracer. It is an oncologically safe procedure, facilitates patients and operative room management and can be used to reliably identify SLNs in breast cancer.

Surgery improves survival in elderly with breast cancer. A study of 465 patients in a single institution.

INTRODUCTION: Breast cancer treatment in elderly patients is controversial. This single-centre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. METHODS: Data from all patients aged 80 years or more with primary breast cancer treated at our institution between 1995 and 2012 were included. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. RESULTS: The study population consisted of 369 patients (median age 84 years). A total of 277 (75%) patients underwent surgical treatment (PST) and 92 (25%) received primary endocrine treatment (PET). Prognostic factors (HER-2, tumour grade, lymphovascular invasion and subsequent adjuvant therapy) were homogeneously distributed in both groups. PST and PET were stratified according to stage: 273 (66%) patients with early stage disease (I, IIA, IIB) and 96 (34%) with locally advanced disease (IIIA, IIIB, IIIC). Patients were followed-up for a median of 63 months. In patients with early stage disease, the mean breast cancer-specific survival (BCSS) was 109 months (95% CI = 101-115) in PST patients, and 50 months (95% CI = 40-60) in PET patients (P < 0.01). Conversely, for patients with locally advanced breast cancer, there was no significant difference in BCSS between the surgical and non-surgical groups. In the PST group, BCSS and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those who received suboptimal treatment. There were no differences in the Charlson comorbidity index scores between the PST and PET groups. CONCLUSION: In women ≥80 years with early-stage breast cancer, standard surgical treatment was associated with a better BCSS when compared with PET.

Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay.

INTRODUCTION: The one-step nucleic acid amplification (OSNA) is a molecular procedure that yields a semiquantitative result for detection of nodal metastasis. Size of metastasis in the sentinel lymph node (SLN) by conventional histology has been described as a predictive factor for additional axillary metastasis. The objective of this study is to quantify intraoperatively the total tumoral load (TTL) in the positive SLNs assessed by OSNA and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node negative early stage breast cancer. METHODS: 306 patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation by OSNA were included. TTL was defined as the addition of CK19 mRNA copies of each positive SLN (copies/µL). RESULTS: TTL was a predictive factor of additional non-SLN metastasis in the complete axillary lymph node dissection (cALND) (OR, 1.67; 95% CI, 1.18-2.35). In the multivariate analysis, the TTL was a predictor of non-SLN metastasis in HR positive patients (OR, 1.69; 95% CI, 1.19-2.41). In our cohort of patients, with a TTL ≤1.2 × 10(5) copies/µL, there was a specificity of 85.3% and negative predictive value (NPV) of 80%. If we consider only the HR positive patients, with a TTL ≤5 × 10(5) copies/µL there was a specificity of 86.7% and NPV of 83.7%. CONCLUSIONS: TTL assessed by OSNA assay predicts for additional non-SLN metastasis and this intraoperative tool can help guiding decisions on performing a cALND in breast cancer patients.

Breast conservative surgery after neoadjuvant chemotherapy in breast cancer patients: comparison of two tumor localization methods.

AIMS: The key to surgical planning for breast conservative treatment (BCT) after neoadjuvant chemotherapy (NAC) is tumor localization. Tumor marking can be performed using either skin tattoo or metallic marker. The objective of this study is to compare both types of tumor localization markers and to assess which techniques improve BCT in achieving a complete resection without compromise margins. METHODS: 149 patients between 1999 and 2009 were eligible for the study. The skin tattoo group (TG) included 118 patients and the metallic marker group (MG) included 31 patients. Both markers were placed before starting NAC. RESULTS: Median clinical tumor volume was 10.3 cm(3) in the TG and 22.4 cm(3) in the MG (p = 0.051). After NAC treatment, there were no significant statistically differences in both groups regarding complete clinical response, partial clinical response, and complete and partial pathological response. Median pathological tumor volume was: 0.8 cm(3) in the TG and 0.69 cm(3) in the MG (p = 0.8). Lumpectomy volume was bigger in the TG (268 cm(3)) than MG (143 cm(3)); p < 0.004. There were no statistically significant differences when comparing margin status. CONCLUSIONS: Lumpectomy guided with metallic marker after NAC allows lower excision of breast tissue without compromising margins. Having similar pathologic response between groups, skin tattoo leads to excise larger volume of tissue adding no benefits to the surgery. With the increasing pathologic complete responses to NAC, patients who are candidates for BCT after NAC will benefit from marking the tumor with metallic markers.