Stressors related to the COVID-19 pandemic and their association with distress, depressive, and anxiety symptoms in cancer out-patients.

Patients with cancer might be particularly prone to stress caused by the COVID-19 pandemic. The aim of this study was to investigate the impact of pandemic-related stressors on oncological patients' psychological well-being. During the second wave of the COVID-19 pandemic in Germany 122 cancer out-patients of the Comprehensive Cancer Center Munich reported on COVID-19-related stressors (information satisfaction, threat perception, and fear of disease deterioration) and answered standardized questionnaires for psychosocial distress (DT) as well as depression and anxiety symptoms (PHQ-2, GAD-2). Multiple linear regression analyses were used to identify associations of the COVID-19-related stressors with psychological symptoms, controlling for sociodemographic, psychological (self-efficacy, ASKU) and clinical (somatic symptom burden, SSS-8) variables. Initially, satisfaction with information was significantly negatively associated with all three outcome variables. Fear of disease deterioration was associated with distress and depressive symptoms. After controlling for additional variables, only satisfaction with information remained an independent determinant of anxiety (ß = -0.35, p < 0.001). All three outcomes were most strongly determined by somatic symptom burden (ß ≥ 0.40, p < 0.001). The results of this study tentatively suggest that physical well-being overrides the relevance of some COVID-19-related stressors for oncological patients' psychological wellbeing. Physical symptoms are strongly tied to personal wellbeing as they are associated with suffering from cancer, which might be more central to personal wellbeing than the possibility of getting infected with SARS-CoV-2. However, satisfaction with the information received seems to be important beyond physical wellbeing, as this emerged as an independent determinant of anxiety.

[The views of cancer out-patients on the impact of the COVID-19 pandemic]. / Die Auswirkungen der COVID-19-Pandemie aus der Sicht ambulanter Krebspatienten.

BACKGROUND: This study investigates current needs and psychosocial burden of out-patients with cancer during the COVID-19-Pandemic. MATERIAL AND METHODS: Between 11/2020 and 02/2021 122 cancer patients who underwent out-patient treatment at the Comprehensive Cancer Center Munich participated in the study. Based on a standardized, semi-structured interview, participants were asked about their knowledge and informational needs related to COVID-19, risk perception and concerns regarding continuing out-patient treatment, COVID-19 related distress, confidence in the national health system, and their readiness to get vaccinated against COVID-19. Additionally, patients filled out the distress thermometer (DT). RESULTS: More than a third of the patients (34,2 %, n = 41/120) wanted to receive more information about the effects of the coronavirus on their cancer and their treatment. 17,2 % (n = 21/122) had faced changes concerning their current or planned treatment. 42/121 (34,7 %) of the patients were clinically distressed (DT ≥ 5). A possible overload of the health care system was the most commonly reported COVID-related concern (77,9 %, n = 95/122), followed by being concerned that their family members might be additionally worried about them (56,2 %, n = 68/121). 71,2 % (n = 74/104) of the patients are willing to be vaccinated; 60 % (n = 18/30) of those undecided or refusing at the time of the survey expressed a desire to have a consultation with an oncologist before giving their final consent to vaccination. DISCUSSION: Corona-specific distress of cancer patients relates in particular to the course of therapy, but also to a possible overload of the health care system. Oncology care teams should allow space for questions from their patients, acknowledge possible uncertainties, provide emotional support, and draw attention to reliable sources of information.

Distress in hospitalized cancer patients: Associations with personality traits, clinical and psychosocial characteristics.

OBJECTIVE: To improve allocation of psychosocial care and to provide patient-oriented support offers, identification of determinants of elevated distress is needed. So far, there is a lack of evidence investigating the interplay between individual disposition and current clinical and psychosocial determinants of distress in the inpatient setting. METHODS: In this cross-sectional study, we investigated 879 inpatients with different cancer sites treated in a German Comprehensive Cancer Center. Assessment of determinants of elevated distress included sociodemographic, clinical and psychosocial characteristics as well as dimensions of personality. Multiple linear regression was applied to identify determinants of psychosocial distress. RESULTS: Mean age of the patients was M = 61.9 (SD = 11.8), 48.1% were women. In the multiple linear regression model younger age (ß = -0.061, p = 0.033), higher neuroticism (ß = 0.178, p = <0.001), having metastases (ß = 0.091, p = 0.002), being in a worse physical condition (ß = 0.380, p = <0.001), depressive symptoms (ß = 0.270, p = <0.001), not feeling well informed about psychological support (ß = 0.054, p = 0.046) and previous uptake of psychological treatment (ß = 0.067, p = 0.020) showed significant associations with higher psychosocial distress. The adjusted R2 of the overall model was 0.464. CONCLUSION: Controlling for sociodemographic characteristics and dispositional vulnerability, that is neuroticism, current clinical and psychosocial characteristics were still associated with hospitalized patients' psychosocial distress. Psycho-oncologists should address both, the more transient emotional responses, such as depressive symptoms, as well as more enduring patient characteristics, like neuroticism.

Late Presentation at Primary Diagnosis of Breast Cancer: Patients' Personality Characteristics and Attitudes.

INTRODUCTION: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. OBJECTIVE: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. METHODS: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. RESULTS: Forty patients (20 controls, 20 late presenters) were interviewed. "Late presenters" perceived their disease as long lasting and had significantly more "positive affectivity" in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. CONCLUSION: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.

Factors associated with the decline of psychological support in hospitalized patients with cancer.

OBJECTIVE: Many distressed cancer patients do not want or, finally, do not use psychological support. This study aimed at identifying factors associated with the decline of psychological support during hospital stay. METHODS: This cross-sectional study included inpatients with different cancer diagnoses. Distress was assessed using the short form of the Questionnaire on Stress in Cancer Patients-Revised (QSC-R10) and the Distress Thermometer (DT). Multivariable logistic regression was used to identify factors associated with decline. RESULTS: Of 925 patients, 71.6% (n = 662) declined psychological support. Male sex (OR = 2.54, 95% CI = 1.69-3.80), low psychosocial distress (OR = 3.76, CI = 2.50-5.67), not feeling depressed (OR = 1.93, CI = 1.24-2.99), perceived overload (OR = 3.37, CI = 2.19-5.20), no previous psychological treatment (OR = 1.88, CI = 1.25-2.83), and feeling well informed about psychological support (OR = 1.66, CI = 1.11-2.46) were associated with decline. Among the patients who indicated clinical distress (46.2%), 53.9% declined psychological support. Male sex (OR = 2.96, CI = 1.71-5.12), not feeling depressed (OR = 1.87, CI = 1.12-3.14), perceived overload (OR = 5.37, CI = 3.07-9.37), agreeableness (OR = 0.70, CI = 0.51-0.95), and feeling well informed about psychological support (OR = 1.81, CI = 1.07-3.07) were uniquely associated with decline in this subgroup. CONCLUSIONS: Decline of psychological support is primarily due to psychological factors. Feeling well informed about support emerged as a relevant factor associated with decline. Thus, design of informational material and education about available psychological services seem crucial.

Thyronamine regulation of TAAR1 expression in breast cancer cells and investigation of its influence on viability and migration.

OBJECTIVES: A correlation exists between breast cancer and thyroid disorders, which are common in elderly women. Thyroid hormones are degraded into trace amines, which can bind to the G-protein-coupled receptor trace amine-associated receptor 1 (TAAR1) and thereby activate it. The transformation of thyroid hormones into trace amines is carried out by the ornithine decarboxylase. Previously, we showed that TAAR1 overexpression (IRS ≥6) was associated with a significantly longer OS in primary breast cancer patients during a long-term follow-up of up to 14 years. Aim of the present study was to analyze the regulation of TAAR1 in breast cancer cell lines and the influence of triiodothyronine (T3), thyronamines, and tetraiodothyroacetic acid (Tetrac) on the expression of TAAR1 in breast cancer cells. METHODS: The effect of T3, thyronamines, and Tetrac on the expression of TAAR1 in breast cancer cell lines MCF-7 and T47D was analyzed via PCR and Western blot. A MTT assay was performed to test the metabolic cell viability. A scratch assay was performed to analyze cell migration. RESULTS: Stimulation of MCF-7 cells with 10 nM 3-iodothyronamine (T1AM) significantly increased TAAR1 protein expression (P=0.008). In T47D cells, TAAR1 expression was significantly upregulated after the addition of 10 µg/mL estradiol to 10 nM T1AM (P=0.008). A significant (P=0.028) reduction in MCF-7 cell viability through the incubation with T1AM could be detected. Cell migration of MCF cells was significantly reduced through incubation with 10 nM T1AM. CONCLUSION: A significant upregulation of TAAR1 induced by stimulation with T1AM may be a sign for an increased decarboxylation of thyroid hormones in breast cancer cells. In addition, there seems to be an influence of estradiol for the T1AM-induced upregulation of TAAR1 in T47D cells. TAAR1-related cell transduction mechanisms seem to be an interesting target for endocrine treatment options of breast cancer patients.

Evaluation of Reproductive Concerns and Biographical Impact of Breast Cancer in Young Patients.

BACKGROUND: This study evaluates interventions offered to young breast cancer (BC) patients, including fertility preservation, genetic testing, and counseling for parenthood concerns, and analyzes the effect of BC on biographical issues. METHODS: Women who were diagnosed with BC at the age of 18-40 years and who underwent treatment at the Breast Center, Ludwig-Maximilian University (LMU) in Munich between 2006 and 2013, were eligible for this study. Patients received a self-developed questionnaire which covered the following topics: fertility preservation, family planning, genetic testing, parenthood concerns and children's needs, partnership status, and employment situation. RESULTS: Re-evaluating their initial decision on fertility preservation, 76.4% of patients reported satisfaction with their decision. After BC diagnosis, 45.8% reported to have maternal desire, but only 21.7% actually planned to have children. 41.7% of patients missed sufficient counseling regarding parenthood concerns. Analysis of individual employment situations showed that the time period until the return to work was longer in patients who received chemotherapy. The majority of patients (71.6%) did not report changes in their partnership status. CONCLUSION: Young BC survivors report a lack of communication related to parenthood concerns and future conception, but are satisfied with counseling regarding fertility preservation and genetics.

Dopamine synthesis and dopamine receptor expression are disturbed in recurrent miscarriages.

OBJECTIVES: l-dopa decarboxylase (DDC) is responsible for the synthesis of dopamine. Dopamine, which binds to the D2-dopamine receptor (D2R), plays an important role in the maintenance of pregnancy. Aim of our study was the analysis of DDC and D2R expression in placentas of spontaneous miscarriages (SMs) and recurrent miscarriages (RMs) in comparison to healthy controls. METHODS: Patients with SM (n = 15) and RM (n = 15) were compared with patients from healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Placental tissue has been collected from SMs and RMs from the first trimester (Department of Gynaecology and Obstetrics, LMU Munich) and from abruptions (private practice, Munich). Placental cell lines, BeWo- and JEG-3 cells, were stimulated with the trace amines T0AM and T1AM in vitro. RESULTS: Levels of DDC and D2R in trophoblasts and the decidua were lower in RMs in comparison to healthy controls. Stimulation of BeWo cells with T1AM significantly reduced DDC mRNA and protein levels. Via double-immunofluorescence, a DDC-positive cell type beneath decidual stromal cells and foetal EVT in the decidua could be detected. CONCLUSIONS: Downregulation of DDC and D2R in trophoblasts of RMs reflects a reduced signal cascade of catecholamines on the foetal side.

EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for progression-free and overall survival in sporadic breast cancer.

BACKGROUND: In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described. Our study evaluates EP3 receptor expression in sporadic breast cancer and its association with clinicopathological parameters, progression-free and overall survival. METHODS: Two hundred eighty-nine sporadic breast cancer samples without primary distant metastasis were immunohistochemically analyzed for EP3 receptor expression. Tissue was stained with primary anti-EP3-antibodies. Immunoreactivity was quantified by the immunoreactivity-score (IRS); samples with an IRS ≥ 2 scored as EP3 positive. Chi-squared and Mann-Whitney-U test were used for comparison of data; Kaplan-Meier estimates and Cox-regression were used for survival analyses. RESULTS: EP3 receptor was expressed in 205 of 289 samples analyzed (70.9%). EP3 receptor expression was not associated with clinicopathological parameters (e. g. tumor size, hormone receptors, lymph node status). Kaplan-Meier estimates showed a significant association of EP3 positivity with improved progression-free survival (p = 0.002) and improved overall survival (p = 0.001) after up to 10 years. Cox regression analysis confirmed EP3 positivity as a significant prognostic factor even when other known prognosticators were accounted for. CONCLUSIONS: In sporadic breast cancer, EP3 receptor expression is not significantly associated with clinicopathological parameters but is a significant prognostic factor for improved progression-free and overall survival. However, the functional aspects of EP3 receptor in breast cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2 elevation and COX-2 overexpression are not fully understood so far. Further studies aiming at identification of the factors regulated by EP3 are necessary to evaluate the possibility of targeting EP3 in future anti-tumor therapy in breast cancer.

TAAR1 induces a disturbed GSK3ß phosphorylation in recurrent miscarriages through the ODC.

OBJECTIVES: Thyroid hormones play an important role in the maintenance of pregnancy. Their derivates, endogenous amines, act via binding to the trace amine-associated receptor (TAAR1). The aim of our study was to analyse the regulation of TAAR1, serine/threonine kinase (pGSK3ß) and ornithine decarboxylase (ODC) in placentas of healthy pregnancies, spontaneous (SM) and recurrent miscarriages (RM) and to investigate the influence of thyroid hormone derivates on TAAR1 expression in trophoblast model cells in vitro. METHODS: Patients with SM (n = 15) and RM (n = 15) were compared with patients with healthy pregnancies (n = 15) (pregnancy weeks 7-13 each). Immunohistochemistry was applied to analyse placental TAAR1, pGSK3ß and ODC expression. Protein expression of the receptors after stimulation with T3, T1AM and RO5203548 in BeWo trophoblast model cells was determined via Western blot. Double-immunofluorescence was used to determine placental expression of TAAR1 and ODC. RESULTS: Levels of TAAR1, pGSK3ß and ODC were higher in placentas of RM in comparison to healthy controls. Stimulation of BeWo cells with T3, T1AM and RO5203548 significantly increased TAAR1 expression. ODC expression in BeWo cells was upregulated through T3. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected. CONCLUSIONS: Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T3 through an enhanced transformation of T3 into T1AM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T3 substitution plays for patients.

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

INTRODUCTION: RIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival. METHODS: Immunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in formalin-fixed paraffin-embedded tissue sections cervical cancer samples. Correlations of RIP140 and LCoR expression with histopathological variables were determined by correlation analyses. Survival rates of patients expressing low or high levels of RIP140 and LCoR were compared by Kaplan-Meier curves. RESULTS: RIP140 overexpression was associated with a significantly shorter overall survival of cervical cancer patients. This effect was significant in the squamous cell carcinoma subtype but not in adenocarcinomas. RIP140 is no longer a significant negative prognosticator for cervical cancer when LCoR expression is low. DISCUSSION: RIP140 is an independent predictor of poor survival of patients with cervical cancer. Patients with tumors expressing low levels of both RIP140 and LCoR showed a better survival compared to patients expressing high levels of RIP140. Modulation of RIP140 and LCoR may represent a novel targeting strategy for cervical cancer prevention and therapy.

Chemotherapy and Post-traumatic Stress in the Causation of Cognitive Dysfunction in Breast Cancer Patients.

Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress. Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided. Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02). Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated.

Increased trace amine-associated receptor 1 (TAAR1) expression is associated with a positive survival rate in patients with breast cancer.

PURPOSE: A correlation between breast cancer and thyroid disorders has been described in previous studies. Degraded thyroid hormones are referred to as trace amines. These endogenous amines have the ability to bind to the G-protein-coupled receptor TAAR1 (trace amine-associated receptor) and thereby activate it. TAAR1 is able to modulate the serotonergic and dopaminergic system in the brain and has so far been studied in the neurological field. The following study represents the first investigation of the regulation of TAAR1 in primary breast cancer (no metastases, M0). METHODS: Immunohistochemical analyses were carried out to detect TAAR1 expression in formalin fixed paraffin embedded breast cancer samples. Survival times of primary breast cancer patients (M0) with and without TAAR1 expression in their tumours were compared by Kaplan-Meier curves, and correlations between ordinal variables were determined with Spearman's rank correlation coefficient. RESULTS: The investigation showed a correlation between TAAR1 expression and tumour differentiation grade. A well differentiated tumour grade (G1) was associated with higher TAAR1 expression and HER2 and HER4 positivity predicted higher TAAR1 expression. A TAAR1 overexpression (IRS ≥ 6) was associated with significantly longer overall survival (OS) (p = 0.02) than that of reduced TAAR1 expression (IRS < 6) during a maximum follow-up of 14 years, demonstrating that TAAR1 has a favourable effect on OS of early breast cancer patients. CONCLUSIONS: We conclude that TAAR1 seems to be an independent predictor for breast cancer survival. Modulation of TAAR1 may represent a novel targeting strategy for breast cancer prevention and therapy.

Clinically assessed posttraumatic stress in patients with breast cancer during the first year after diagnosis in the prospective, longitudinal, controlled COGNICARES study.

OBJECTIVE: There is ongoing debate whether cancer qualifies as traumatic stressor. We investigated prevalence and course of posttraumatic stress in patients with early breast cancer (BC) during their first year after diagnosis and determined effects of mastectomy and chemotherapy. METHODS: Patients with stage 0-III BC aged ≤65 years were evaluated with the Structured Clinical Interview for DSM-IV modules for acute and posttraumatic stress disorder (ASD and PTSD, respectively) before treatment, after chemotherapy, and 1 year after diagnosis. Matched controls were assessed at matched intervals. Effects of time, mastectomy, and chemotherapy on BC-related PTSD symptom severity were tested with linear mixed model analysis. RESULTS: Stress disorder (ASD or PTSD) related to BC was diagnosed in 6 (3.6%) of 166 patients before treatment and in 3 patients (2.0%) 1 year later. The rate of patients who experienced PTSD symptoms related to BC decreased from 82.5 to 57.3% (p < 0.001), and the mean of BC-related PTSD symptoms diminished from 3.1 to 1.7 (p < 0.001). Only university education significantly predicted the course of BC-related PTSD symptom severity (p = 0.009). In 60 controls, no diagnosis of stress disorder, a rate of 18% women experiencing PTSD symptoms, and a mean of 0.4 PTSD symptoms (p vs. patients <0.001) were found. CONCLUSIONS: Most newly diagnosed patients with BC experience PTSD symptoms, whereas full diagnoses of DSM-IV stress disorder are rare. Symptoms diminish somewhat within 1 year furthered by university education but independently from mastectomy and chemotherapy. Throughout the year after diagnosis, having BC entails markedly increased PTSD symptom burden. Copyright © 2016 John Wiley & Sons, Ltd.

Chemotherapy and Cognitive Function in Breast Cancer Patients: The So-Called Chemo Brain.

Self-perceived problems of cognitive functioning after treatment for early-stage breast cancer have the potential to substantially affect the lives of patients. In the past two decades, neuropsychological studies have accumulated evidence of corresponding cognitive deficits that have mostly been attributed to neurotoxic effects of chemotherapy. Nevertheless, observations of impaired cognitive functioning already before the start of adjuvant or neoadjuvant chemotherapy question the singular role of chemotherapy for the causation of these deficits. The divergence between mostly subtle neuropsychological deficits and often dramatic subjective cognitive complaints as well as the lack of association between both in the majority of studies present an unsolved puzzle. Recent investigations that include brain imaging have begun to yield tentative answers in this regard. The present review aims at briefly summarizing and integrating the current evidence from clinical studies for purposes of patient counseling.

International Expert Consensus on Primary Systemic Therapy in the Management of Early Breast Cancer: Highlights of the Fifth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2013).

Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive than adjuvant trial, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Although pCR is an early clinical endpoint, its role as a surrogate for long-term outcomes is the key issue. New and better predictors of treatment efficacy are needed to improve treatment and outcomes. After PST, accurate management of post-treatment residual disease is mandatory. The surgery of the sentinel lymph-node could be an acceptable option to spare the axillary dissection in case of clinical negativity (N0) of the axilla at the diagnosis and/or after PST. No data exists yet to support the modulation of the extent of locoregional radiation therapy on the basis of the response attained after PST although trials are underway.