Treatment Of Primary Breast Cancer Research Articles

Improving the delivery of team-based survivorship care after primary breast cancer treatment through a multi-level intervention: a pilot randomized controlled trial.

We developed and tested a multi-level intervention, ConnectedCancerCare (CCC), which includes a tailored website and appointment reminder system for women with early-stage breast cancer and a provider summary letter sent to their medical oncologist and primary care provider to improve the delivery of team-based survivorship care. We conducted a pilot randomized controlled trial to establish the feasibility and acceptability of CCC. Women diagnosed with stages 0-II breast cancer within one year of completing primary treatment were randomized to CCC (intervention) or a static online survivorship care plan (control). Participants completed baseline and 3-month follow-up surveys online. Post-trial interviews with 5 PCPs, 6 oncology providers, and 8 intervention patients were conducted. Of the 160 eligible women invited to participate, 66 completed the baseline survey and were randomized (41%) and 54 completed a follow-up survey (83%). Participants in the intervention arm found the CCC content to be acceptable, with 82% reporting it was easy to use and 86% reporting they would recommend it to other patients. Women randomized to CCC (vs. control) more often reported scheduling a PCP follow-up visit (64% vs. 42%), communicating with their PCP about provider roles (67% vs. 18%), and higher mean team-based cancer care knowledge scores (3.7 vs. 3.4). Deploying CCC in medical oncology practices was feasible, and the intervention content was acceptable. CCC shows promise for improving patient knowledge and patient-provider communication about provider roles in team-based cancer care and encouraging patients to engage with their PCP early in the survivorship period.

Abstract 1786: Targeting the immunosuppressive microenvironment of metastatic breast cancer with viroimmunotherapy

Abstract Metastatic breast cancer is the second leading cause of cancer related death among women. Although, conventional therapies such as surgery, adjuvant and neoadjuvant therapies have shown promising outcomes in preclinical and clinical settings, long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metastases. Breast primary and metastasic niches are characterized by an immunosuppressive microenvironment. Hence, novel therapeutic regimens that modulate this challenging phenotype are desperately needed. Our group has developed and tested in preclinical models and in clinical trials for patients with recurrent glioblastoma the anti-tumor effect of oncolytic adenovirus Delta-24-RGD, also named DNX-2401, resulting with a 20% of long-term survivors, and the awaking of a antitumoral immunity after the administration of the pathogen. This paradigm shift suggests that viroimmunotherapy can be used for the treatment of metastasic cancer. Thus, here we hypothesize that viroimmunotherapy is capable of exerting abscopal effects to eradicate primary breast tumors and their metastatic niches. To test the hypothesis, 4T1 tumor bearing mice were subjected to the local administration of Delta-24-RGD and its armed derivatives, expressing expressing immune co-stimulatory ligands OX40L (Delta-24-RGDOX or DNX-2440) and GITRL (Delta-24-GREAT). We found that, the tumors treated with oncolytic adenoviruses exhibited increase of both CD8+ T cell infiltration and CD8+/CD4+ ratio. Additionally, T-cell activity measured by IFN-γ secretion of splenocytes when in co-culture with breast cancer cells was found to be increased in mice that underwent viroimmunotherapy (P<0.05, ANOVA). In addition, flow cytometry analysis of tumor-infiltrating lymphocites showed a decrease in population of exhausted T cells and MDSCs in tumor microenvironment (P<0.001, ANOVA). Most importantly, animals that underwent viroimmunotherapy showed increase in overall survival (P<0.005, logrank test) with decrease in number of metastatic niches in distant organs as compared to control group. In conclusion, immunological studies indicate that viroimmunotherapy enhances the infiltration and activation of T-cell specific anti-tumor response, stagnating primary tumor growth and metastasis leading ultimately to increase in overall survival. Therefore, we conclude that armed-oncolytic Delta-24-RGD based adenoviruses hold great potential in treatment of primary and metastatic breast cancer. Citation Format: Sagar Shashikant Sohoni, Teresa Nguyen, Dong Ho Shin, Xuejun Fan, Jiang Hong, Sumit Gupta, Ashley Ossimetha, Yanhua Yi, Chandra Bartholomeusz, Marta Alonso, Juan Fueyo, Candelaria Gomez-Manzano. Targeting the immunosuppressive microenvironment of metastatic breast cancer with viroimmunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1786.

Expert review on systemic treatment in the St. Gallen International Breast Cancer Conference 2021

: The 17th St. Gallen International Breast Cancer Consensus Conference was held in March 2021. The theme of this year’s conference was “customizing local and systemic therapies”. The conference focused on the controversies about the optimal primary treatment of early breast cancer. The St. Gallen expert panel reviewed substantial new evidences and voiced their expert opinions, hoping to provide guidance to clinicians. Despite that many randomized clinical trials provided evidence on managing breast cancer, not all the clinical scenarios can find definitive data to guide recommendations. When data from randomized clinical trials are lacking, the opinions of the St. Gallen expert panel can be used as an important reference for clinical decision making. However, the panelists’ recommendations may often be affected by the treatment availability, which vary from country to country. As a result, from Chinese experts’ perspectives, Professor Jian Zhang made an interpretation and comments of the expert opinions of the 17th St. Gallen Conference. This work focused on the field of systemic treatment, including neoadjuvant therapy (chemotherapy, HER2 targeted therapy and endocrine therapy), tailored post-neoadjuvant therapy based on neoadjuvant therapy response and adjuvant therapy. We hope this work could help clinicians understand the expert opinions of the 17th St. Gallen Conference better.

Secondary Breast Cancer Sociodemographic Characteristics and Survival by Age Group

BackgroundSecondary cancers account for 16% of all new cancer diagnoses, with breast cancer (BC) the most common secondary cancer. We have shown that secondary BC has unique characteristics and decreased survival compared with primary BC in adolescent and young adults (AYA; 15–39 years old). However, older BC populations are less well studied.MethodsFemales (age ≥ 15 years) diagnosed with primary BC during 1991–2015 (n = 377,167) and enrolled in the California Cancer Registry were compared with those with secondary BC (n = 37,625) by age (15–39, 40–64, ≥ 65 years). We examined BC-specific survival (BCSS) accounting for other causes of death as a competing risk using multivariable Cox proportional hazards regression.ResultsMost secondary BC patients were of older age (15–39, n = 777; 40–64, n = 15,848; ≥ 65, n = 21,000). Compared with primary BC treatment, secondary BCs were more often treated with mastectomy and less often with chemotherapy and/or radiation. BCSS was shorter in secondary BC patients than primary BC patients, but the survival difference between secondary and primary BC diminished with age [15–39 hazard ratio (HR): 2.09, 95% confidence interval (CI) 1.83–2.39; 40–64 HR: 1.51; 95% CI 1.44–1.58; ≥ 65 HR: 1.14; 95% CI 1.10–1.19]. Survival differences were most pronounced in women with hormone receptor positive disease and Hispanic and Asian/Pacific Islanders 40–64 years of age.ConclusionsWhen BC is diagnosed following a prior cancer of any organ site, BCSS is worse than when compared with patients for whom BC is the primary diagnosis, suggesting that we may need to tailor our treatments for women with secondary BC.

Greater Post-Surgical Pain Predicts Long-Term Depressed Affect in Breast Cancer Patients: The Role of Coping.

Depressed affect is observed during primary treatment for early-stage breast cancer and often persists into survivorship. Pain can influence the long-term emotions of women with breast cancer. Behavioral mechanisms explaining this relationship are less clear. Coping during primary treatment may play a role in the association between pain and depressed affect. Our observational study examined a longitudinal mediation model testing whether post-surgical pain intensity predicted depressed affect 5 years later via disengagement and/or engagement coping at the end of treatment. Women (N = 240) with stage 0-III breast cancer completed measures of pain, coping, and depressed affect 4-10 weeks post-surgery, and 12 months and 5 years later. Structural modeling yielded measurement models of 12-month disengagement and engagement coping. Direct effects emerged between post-surgical pain intensity and 12-month disengagement (β = .37, p < .001) and engagement coping (β = .16, p < .05). Post-surgical pain intensity was also related to 5-year depressed affect (β = .25, p < .05). Disengagement and engagement coping were not associated with depressed affect at 5-year follow-up, and there was no evidence of mediation. This is a secondary analysis of data from a trial conducted several years ago, and may not generalize due to a homogenous sample with attrition at long-term follow-up. Greater post-surgical pain intensity predicts more disengagement and engagement coping at the end of primary treatment, as well as depressed affect during survivorship. Managing post-surgical pain may influence the emotions of survivors of breast cancer up to 5 years later, possibly through coping or non-coping processes.

Doxorubicin-paclitaxel sequential treatment: insights of DNA methylation and gene expression changes of luminal A and triple negative breast cancer cell lines.

Breast cancer is one of the significant causes of death among women diagnosed with cancer worldwide. Even though several chemotherapy combinations are still the primary treatment of breast cancer, unsuccessful treatments, and poor prognostic outcomes are still being reported. DNA methylation and gene expression changes among two breast cancer cell lines representing luminal A (MCF-7) and triple-negative (MDA-MB-231) cancers were determined after sequential combination treatment of doxorubicin and paclitaxel and analyzed using Ingenuity Pathway Analysis. Promoter methylation changes were seen in different treated MCF-7 cells and accompanied by changes in the gene expression of CCNA1 and PTGS2. In MDA-MB-231 cells, the hypomethylation of ESR1 was not accompanied by an increase in its gene expression in any treated cells. The hypomethylation of GSTP1 and MGMT was accompanied by an increase in gene expression levels in the group treated with doxorubicin only. Also, significant downregulation of several genes like MUC1 and MKI67 in MCF-7 cells treated with doxorubicin showed much lower gene expression (- 37.63, - 10.88 folds) when compared with cells treated with paclitaxel (- 2.47, - 2.05 folds) or the combination treatment (- 18.99, - 2.81 folds), respectively. On the other hand, a synergistic effect on MMP9 gene expression was significantly seen in MDA-MB-231 cells treated with the combination (- 9.99 folds) in comparison with the cells treated with doxorubicin (- 3.62 folds) or paclitaxel (1.75 folds) alone. Chemotherapy combinations do not always augment the molecular changes seen in each drug alone, and these changes could be utilized as treatment response markers.

Heterogeneity between core needle biopsy and synchronous axillary lymph node metastases in early breast cancer patients: Comparison of HER2, estrogen and progesterone receptor expression profiles during primary treatment regime.

e12565 Background: Therapeutic decisions for the primary treatment of breast cancer is commonly based on the expression profiles of estrogen (ER), progesterone (PR) and the human epidermal growth factor 2 (HER2) receptors. However, breast cancer is a very heterogeneous disease, and receptor changes were manifold reported during progression. Little is known about receptor discordance in the primary setting. Here, we compared receptor expression profiles between core needle biopsy (CNB) of the breast tumor tissue and synchronous axillary lymph node metastases (LNM) not at recurrence, but at the primary treatment. Methods: In a German single center study, we retrospectively analyzed 175 breast cancer patients with axillary synchronous LNM. 69,7% of our patients were without any upfront therapy. Profiles of ER, PR and HER2 were immunohistochemically analyzed using the common cut-off at 10% positive tumor cells vs. the controversially discussed low-positive cut-off at 1%. Receptor status was compared between CNB specimens of the primary tumor tissue and axillary LNM. Further, clinicopathological characteristics were correlated to receptor changes. Results: The discordance rates between CNB and axillary LNM were 12.7% for HER2, 6.9% for ER and 22.6% for PR using the ≥1% cut-off, respective 7.5% for ER and 25.6% for PR when using the ≥10% cut-off-level. The most frequently occurring change was a PR loss. Analysis of clinical parameters revealed a significant association of ER change between CNB and LNM in younger patients (p &lt; 0.01) with increased proliferation marker Ki-67 (p = 0.04). Conclusions: Receptor discordance between CNB and synchronous axillary LNM appears to exist at the primary setting already. Hence, receptor profiles of the tumor tissue and the synchronous axillary LNM should be considered for treatment decision.

A Novel Technique to Identify the Latissimus Dorsi Muscle During Modified Radical Mastectomy

Breast cancer is the most common cancer affecting women in India and worldwide. Surgery is the primary treatment of nonmetastatic breast cancer. Modified radical mastectomy (MRM) is a very important aspect of the surgical training in general surgery and surgical oncology. The lateral limit of the dissection is the latissimus dorsi (LD) muscle. In the early part of the learning curve, many trainees tend to overshoot the border of the LD muscle and enter into the posterior plane. The technique described is a simple anatomical method of identifying the anterior border of the LD during MRM.

The effectiveness of mammography surveillance after treatment of primary breast cancer: A single centre retrospective cohort study

IntroductionThere is a little evidence that routine follow-up of patients treated for early breast cancer (BC) to detect ibsilateral breast tumour recurrence (IBTR), or contralateral breast cancer (CBC), is either effective or offers any mortality benefits. We report our experience of following patients with early BC for recurrences and new primaries in order to determine the role of mammogram surveillance.MethodsSingle centre, retrospective primary observational study was designed. Patients who had BC during year 2001–2006 were included and followed for a minimum of ten years. Patients were divided based on the modalities of detecting BC in to screen detected group and clinically detected one i.e. symptomatic BC. These two groups were compared.ResultsTotal number of patients considered for analysis was 2530 (screen detected BC - 703 patients and symptomatic BC - 1827 patients). The rate of recurrence including regional and distant metastasis in screen detected BC group was 8% (57/703) and 2% (43/1827) in symptomatic one. However, the prevalence of IBTR/CBC in the whole cohort was 2% (62/2530). Mammography surveillance identified 60% (37/62) of patients who had IBTRs/CBCs.Mammography surveillance detected 85% (29/34) of all IBTRs/CBCs in the screen detected BC group. In contrast, it picked up only 29% (8/28) in the other group (Chi squared 20.5 p < 0.005).ConclusionsMammography surveillance is efficient for the screen detected BC group but not for the symptomatic one. Hence, it is worth suggesting different follow-up strategies for both groups. Further studies are therefore recommended.

Clinicopathological Study and Management of Carcinoma of The Breast

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death in women. In India, breast cancer accounts for 19% of all cancers in women and is second only to lung cancer as a cause of cancer deaths. Many early breast carcinomas are asymptomatic; pain or discomfort is not usually a symptom of breast cancer. Breast cancer is often first detected as an abnormality on a mammogram before it is felt by the patient or healthcare provider. Surgery and radiation therapy, along with adjuvant hormone or chemotherapy when indicated, are now considered the primary treatment for breast cancer. For many patients with low-risk early-stage breast cancer, surgery with local radiation is curative. In India, Breast cancer is the second most common malignancy among women next to the Ca cervix. Since it presents as a painless lump, patients neglect and come to the hospital often late. This study is an attempt has been made to study the various risk factors, the natural history of the disease, clinical features, and mode of spread, pathological types, staging and management of breast cancer. Since most cases presented to us either in the Early or Locally Advanced stage, they were included in the study. For the diagnosis of breast lesions, Triple Assessment should be involved to characterize the lesions, which include clinical examination, imaging and FNAC/ Biopsy for histopathological correlation.

Predictors of the Utilization and Waiting Period Before Starting an Oncological Rehabilitation after Breast Cancer

This study explores the sociodemographic, medical and work-related factors leading to a participation in an in-house rehabilitation measure after primary treatment for breast cancer. The prospective multi-center study is based on a written survey with employed breast cancer patients who were recruited at 11 breast cancer centers in Lower Saxony, Germany. Predictors of participation were examined by logistic regression, predictors of the time period before starting the rehabilitation by linear regression. 409 patients returned their questionnaires at all three time-points. Response rates were 80,1% 3 weeks after surgery (t0), 95,2% 6 months after surgery (t1) and 89,9% one year after surgery (t2). Altogether, 294 patients (72%) participated in the rehabilitation measure. Respondents, 90% of whom participated in rehabilitation before returning to work, began their rehabilitation on average 21 weeks after primary surgery. They showed an increased probability of participation if they had indicated the need to clarify their job situation (OR=2,74, p<0,01), or if their answers displayed a detrimental relation between effort and reward at work (OR=3,89, p<0,05). At the same time, higher age, a higher level of school education (OR=4,23) and reduced physical health (OR=0,94, p<0,01) increased the chance for breast cancer patients to take part in oncological rehabilitation. The starting point of rehabilitation was only predictable by medical treatments: adjuvant chemotherapy (β=0,492, p≤0,001), additional surgery (β=0,112, p<0,05), and radiation therapy within the second half year after primary surgery (β=0,20; p<0,001) led to a postponement. This study shows that an increased need of breast cancer patients for medical and socio-psychological support leads to their participation in an in-house rehabilitation and thus underlines the necessity of these institutions. Women with an impaired psychological health should be given extra attention.

Epidemiology and Predictive Factors for Persistent Breast Pain Following Breast-Conserving Surgery.

BackgroundIn general, breast pain is one of the most common causes for referral to breast units; treatment-related breast pain is frequently seen in clinical practice but not well addressed in the literature. While our primary objective was to identify the incidence of persistent breast pain following breast-conserving surgery and possible risk factors, our secondary aim was to assess the possibility of using a breast ultrasound scan to detect parenchymal changes that can contribute to breast pain.MethodsWe have conducted a prospective study including patients who had wide local excision for primary breast cancer treatment between January 2017 and January 2019. Patients’ demographics, including age, BMI, breast volume, and tumour characteristics, were noted. All patients had a clinical assessment and were asked standard questions about their breast pain each visit; they also had an ultrasound scan of the breast and axilla 6 and 12 months after surgery to look for parenchymal changes.ResultsA total of 239 female breast cancer patients were included in our analysis. The mean age was 43.9 years, mean weight was 72.8 kg, mean BMI was 27.4 and mean breast volume was 1173 ml. In total, 38.5% had standard wide local excision, and 61.5% had oncoplastic resection; the mean specimen weight was 74.6 grams. All patients had adjuvant whole breast radiotherapy. We found that patients with younger age, larger breast size, high BMI, oncoplastic resections, and persistent parenchymal changes are associated with an increased incidence of postoperative breast pain while the type of axillary procedure and adjuvant chemotherapy had no significant effect.ConclusionPersistent postoperative breast pain was noted in 33% of our patients. We have also indicated that younger patients, patients with larger breast, those with high BMI, with preoperative breast pain, who had oncoplastic resections, and patients with persistent parenchymal changes, as fat necrosis and scarring, are associated more with persistent breast pain.

Clinical Perspectives in Addressing Unsolved Issues in (Neo)Adjuvant Therapy for Primary Breast Cancer.

Simple SummaryThe development of adjuvant and neoadjuvant therapies, and breast cancer surgery for primary breast cancer has led to the dramatic improvements in the survival rates of breast cancer patients over the past 50 years. However, recurrence with distant metastasis during the 10 years after surgical treatment is still seen, although not often. Current clinical perspectives are summarized to address unsolved issues in (neo)adjuvant therapy for primary breast cancer. It is necessary to elucidate the gain of antitumor immunity via anticancer agents, the enhancement of drug sensitivity by overcoming drug resistance, and the targeting of therapy based on genomic profiles, which will lead to the complete curing of primary breast cancer.The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.

Abstract PS18-24: Impact of protein corona formation on Fn14-targeted DART nanoparticle selectivity, uptake, and cytotoxicity on TNBC cells

Abstract Despite dramatic improvements in the treatment of primary breast cancers, there currently are no effective targeted therapeutics for women diagnosed with metastatic triple negative breast cancer (mTNBC), resulting in an overall survival of just ~13 months in these patients. Drug-loaded nanoparticles (NPs) offer the potential to improve the therapeutic efficacy and pharmacokinetic profile of drugs through use of passive and active targeting to metastatic tumors. However, effective and active targeting of nanodrug formulations to tumor cells is complicated by the adsorption of proteins to NP surfaces upon exposure to the systemic circulation. Termed ‘protein coronas’, this protein coat can drastically reduce the blood circulation time and targeting capability of NPs in vivo. We have developed paclitaxel (PTX)-loaded NPs that are engineered for decreased non-specific adhesivity and receptor-targeting (‘DART’) characteristics, which balance minimal recognition by circulating immune cells and low non-specific binding to tumor extracellular matrix proteins with maximal targeting to tumor tissues. These DARTs selectively bind the fibroblast growth factor-inducible 14 (Fn14) cell surface receptor, which is overexpressed in over a dozen solid cancers and their metastases, including mTNBC tumors. We recently demonstrated the enhanced therapeutic efficacy of Fn14-targeted DARTs in comparison to a non-targeted nanoformulation and Abraxane, an FDA-approved nanoformulation for mTNBC, in xenograft models of primary and intracranial TNBC. In addition, we found that these DARTs retain targeting capability and traffic to Fn14+ tumors in the presence of an endogenous protein corona in vitro and in vivo. This encouraged further investigation into the specific mechanisms of DART NP uptake in tumor cells in both the presence and absence of protein coronas using surface plasmon resonance, flow cytometry, total internal reflection fluorescence and confocal microscopy, and cytotoxicity assays. Understanding the role of protein coronas on this drug delivery platform is crucial for its clinical development and these results provide valuable new information pertaining to the optimization of NP surface properties for minimizing the impact of protein coronas and improving mTNBC tumor targeting in vivo. Citation Format: Christine P Carney, Anshika Kapur, Nikhil Pandey, Jimena G Dancy, Aniket S Wadajkar, Graeme F Woodworth, Jeffrey A Winkles, Anthony J Kim. Impact of protein corona formation on Fn14-targeted DART nanoparticle selectivity, uptake, and cytotoxicity on TNBC cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-24.

Abstract OT-38-01: MEDEA: A randomized trial of weight loss to reduce cancer-related fatigue (CRF) among overweight and obese breast cancer (BC) patients

Abstract Rationale: Overweight and obesity are highly prevalent among BC patients and are linked to poorer prognosis and worse patient-reported outcomes (PROs). Weight loss interventions, based on caloric restriction, increased physical activity (PA) and behavioral counselling, are safe and feasible among BC survivors and hold the promise to improve BC-specific outcomes. MEDEA: Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (ClinicalTrials.gov NCT04304924) will evaluate the impact of weight loss on CRF. Trial design: French multi-center 1:1 randomized controlled trial comparing a 12-month personalized, telephone-based weight loss program + health education intervention vs health education alone in overweight or obese BC patients. Endpoints and measures: Primary endpoint: difference in self-reported CRF 12 months post-randomization between arms, measured using the EORTC QLQ-C30 CRF subscale. Secondary endpoints: 1) PROs (EORTC QLQ-C30, -B45, -FA12), anxiety and depression (Hospital Anxiety and Depression Scale); 2) weight and body mass index (BMI), diet habits and quality, PA, sleep; 3) cost-effectiveness (number and length of hospital-admissions, all-drug consumption, number and duration of sick leaves). Accelerometer data will be collected to track PA and sleep measures. Qualitative analyses will evaluate patient motivation and satisfaction. Main eligibility criteria: stage I-II-III BC, primary BC treatment completed within the prior 12 months (definitive surgery, adjuvant chemo-, and/or radio-therapy, if administered), BMI ≥25 kg/m2, ability to walk at least 400 meters at any pace, ECOG PS 0-1, not participating in another weight loss, dietary or PA intervention clinical trial. Intervention and Control arms: The intervention and health education program are adapted from the BWEL: Breast Cancer WEight Loss study (ClinicalTrials.gov NCT02750826; PI Ligibel JA). The behavior change program is based on the Social Cognitive Theory. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls of 30-60 minutes, supplemented by a detailed participant workbook and scheduled as follows: 1) intensive phase (weeks 1-12), 12 weekly calls; 2) consolidation phase (weeks 13-24), 6 bi-weekly calls; 3) maintenance phase (weeks 25-52), 1 monthly call. Coaches were hired and trained specifically for MEDEA, they are located at a centralized call center and receive support from coordinating nutrition, PA, and behavioral experts. Regular meetings with study team and investigators assure standardized delivery of the intervention and troubleshooting. Intervention goals include weight loss ≥10% of baseline weight, caloric restriction of 500-1000 Kcal/day, increased PA to 150 minutes/week in the initial phase and 225-300 minutes/week in the maintenance phase. Toolbox solutions are offered to tailor the intervention and meet the needs of specific ethnic, socioeconomic or other patient populations with difficulties in achieving intervention goals. All participants in both arms receive a health education program focusing on healthy living. Accrual: MEDEA will enroll 220 patients overall. Recruitment started in June 2020. Statistical considerations: The primary analysis of MEDEA will compare the primary endpoint of CRF scores at the 12-month post-randomization time point between arms. The study has 90.0% power at two-sided α=0.05 to detect a standardized effect size of 0.40 (sample size inflated for drop outs). For interpreting the clinical significance of effects, 0.2, 0.5 and 0.8 standard deviation effects will be considered as small, moderate, and large (Cohen, 1988). All other measures, time points and analyses will be considered secondary or exploratory. Citation Format: Antonio Di Meglio, Elise Martin, Stefan Michiels, Cecile Charles, Tracy E. Crane, Aude Barbier, Bruno Raynard, Anthony Mangin, Olivier Tredan, Paul H. Cottu, Laurence Vanlemmens, Carine Segura-Djezzar, Anne Lesur, Barbara Pistilli, Florence Joly, Thomas Ginsbourger, Bernadette Coquet, Guillemette Jacob, Aude Sirven, Julia Bonastre, Jennifer A. Ligibel, Ines Vaz-Luis. MEDEA: A randomized trial of weight loss to reduce cancer-related fatigue (CRF) among overweight and obese breast cancer (BC) patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-38-01.

Effects of brief stress management interventions on distress and leukocyte nuclear factor kappa B expression during primary treatment for breast cancer: A randomized trial

BackgroundA randomized controlled trial (RCT) of 5-week stress management interventions teaching cognitive behavioral therapy (CBT) or relaxation training (RT) techniques showed decreases in stress and serum inflammatory markers over 12 months in women undergoing treatment for breast cancer (BCa). To understand the molecular mechanisms involved, we examined the effects of these interventions on the transcription factor NF-κB DNA binding activity in leukocytes in parallel with circulating inflammatory markers, stress management skill efficacy and multiple distress indicators. MethodsThis is a secondary analysis using blood samples of 51 BCa patients (Stage 0–III) with high cancer-specific distress selected from a completed RCT (NCT02103387). Women were randomized to one of three conditions, CBT, RT or health education control (HE). Blood samples and self-reported distress measures (Affects Balance Scale-Negative Affect [ABS-NA], Impact of Events Scale-hyperarousal [IES-H] and intrusive thoughts [IES-I]) were collected at baseline (T0) and 12-month follow-up (T2). Self-reported distress measures and perceived stress management skills (PSMS) were also measured immediately post-intervention (baseline + 2 months: T1). Repeated measures analyses compared changes in distress and NF-κB expression among conditions, controlling for age, stage of cancer, days from surgery to baseline, and receipt of chemotherapy and radiation. Regression analyses related T0 to T2 change in NF-κB expression with T0 to T1 changes in self-reported PSMS and distress measures. Exploratory regression analyses also associated change in NF-κB expression with change in serum cytokines (IL-1β, IL-6 and TNF-α); and s100A8/A9, a circulating inflammatory marker important in breast cancer progression. ResultsThere was a significant condition (CBT/RT, HE)xtime (T0, T2) effect on NF-κB, F(1, 39)= 5.267, p = 0.036, wherein NF-κB expression significantly increased over time for HE but did not change for RT or CBT. Greater increases in PSMS from T0 to T1 were associated with less increase in NF-κB expression over 12 months (β = −0.426, t(36) = −2.637, p = 0.048). We found that women assigned to active intervention (CBT/RT) had significant decreases in ABS-NA (F(1, 40)= 6.537, p = 0.028) and IES-I (F(1, 40)= 4.391, p = 0.043) from T0 to T1 compared to women assigned to HE, who showed no change over time (p’s > 0.10). For women assigned to CBT or RT, lower NF-κB expression at T2 was related to less ABS-NA, IES-H, and IES-I, all p’s < 0.05, although T0–T1 change in distress was not related to T0–T2 change in NF-κB expression for those in an active intervention. ConclusionsBrief CBT or RT stress management interventions can mitigate increases in pro-inflammatory leukocyte NF-κB binding over 12 months of primary treatment in highly distressed BCa patients. These effects are likely brought about by improved stress management skills.

Clinicopathologic features of single bone metastasis in breast cancer.

The most common site for metastasis in patients with breast cancer is the bone. In this case series, we investigated patients whose surgical and medical treatment for primary breast cancer was conducted at our center and first disease recurrence was limited to only 1 bone.We analyzed 910 breast cancer patients, 863 had no metastasis and 47 cases had a single bone metastasis ≥ 6 months after their first diagnosis. Demographic, epidemiological, histopathological and intrinsic tumor subtype differences between the non-metastatic group and the group with solitary bone metastases and their statistical significance were examined. Among established breast cancer risk factors, we studied twenty-nine variables.Three variables (Type of tumor surgery, TNM Stage III tumors and mixed type (invasive ductalcarsinoma + invasive lobular carcinoma) histology) were significant in multivariate logistic regression analysis. Accordingly, the risk of developing single bone metastasis was approximately 15 times higher in patients who underwent mastectomy and 4.8 and 2.8 times higher in those with TNM Stage III tumors and with mixed type (invasive ductal carcinoma + invasive lobular carcinoma) histology, respectively.In conclusion, the risk of developing single bone metastasis is likely in non-metastatic patients with Stage III tumors and possibly in mixed type tumors. Knowing this risk, especially in patients with mixed type tumors, may be instrumental in taking measures with different adjuvant therapies in future studies. Among these, treatment modalities such as prolonged hormone therapy and addition of bisphosphonates to the adjuvant treatments of stage III and mixed breast cancer patients may be considered.

Potentially Modifiable Factors Associated with Adherence to Adjuvant Endocrine Therapy among Breast Cancer Survivors: A Systematic Review.

Simple SummaryEndocrine therapy taken after primary breast cancer treatment helps prevent breast cancer recurrence. However, many women are unable to adhere to endocrine therapy. This review examines potentially modifiable factors that are associated with endocrine therapy adherence, which might help future efforts to improve endocrine therapy use. Six categories of factors were identified: side effects, attitudes toward endocrine therapy, psychological factors, healthcare provider-related factors, sociocultural factors, and general or quality of life factors. Overall, self-efficacy (i.e., one’s belief in their ability to do something) and positive decisional balance (i.e., one’s belief that the benefits of endocrine therapy outweigh the risks) were the most consistently associated with adherence. They might represent factors worth investigating in future studies seeking to support the adherence of breast cancer survivors.Adjuvant endocrine therapy (AET) reduces risk of breast cancer recurrence. However, suboptimal adherence and persistence to AET remain important clinical issues. Understanding factors associated with adherence may help inform efforts to improve use of AET as prescribed. The present systematic review examined potentially modifiable factors associated with adherence to AET in accordance with PRISMA guidelines (PROSPERO registration ID: CRD42019124200). All studies were included, whether factors were significantly associated with adherence or results were null. This review also accounted for the frequency with which a potentially modifiable factor was examined and whether univariate or multivariate models were used. This review also examined whether methodological or sample characteristics were associated with the likelihood of a factor being associated with AET adherence. A total of 68 articles were included. Potentially modifiable factors were grouped into six categories: side effects, attitudes toward AET, psychological factors, healthcare provider-related factors, sociocultural factors, and general/quality of life factors. Side effects were less likely to be associated with adherence in studies with retrospective or cross-sectional than prospective designs. Self-efficacy (psychological factor) and positive decisional balance (attitude toward AET) were the only potentially modifiable factors examined ≥10 times and associated with adherence or persistence ≥75% of the time in both univariate and multivariate models. Self-efficacy and decisional balance (i.e., weight of pros vs. cons) were the potentially modifiable factors most consistently associated with adherence, and hence may be worth focusing on as targets for interventions to improve AET adherence among breast cancer survivors.

The role of the neoadjuvant approach in the treatment of primary operable HER2 positive breast cancer

Neoadjuvant systemic therapy is an essential component of the comprehensive treatment of primary operable HER2‑positive breast cancer. Therefore, it is extremely important to search for treatment efficacy predictors and optimal system for assessing tumor response to treatment. The study analyzed factors predicting pathological complete response (pCR) in patients with luminal and non‑luminal HER2‑positive tumor subtypes. The morphological assessment of the tumor response to treatment was carried out using the RCB system; additional characteristics of the residual tumor were studied as well. It was shown that a comprehensive assessment involving the use of the RCB system and determination of the Ki ‑ 67 level helps to divide patients into prognostic groups and individualize the adjuvant therapy plan.

Comprehensive trends in incidence, treatment, survival and mortality of first primary invasive breast cancer stratified by age, stage and receptor subtype in the Netherlands between 1989 and 2017.

Our study aimed to provide a comprehensive overview of trends in incidence, survival, mortality and treatment of first primary invasive breast cancer (BC), according to age, stage and receptor subtype in the Netherlands between 1989 and 2017. Data from all women diagnosed with first primary stage I to IV BC (N = 320 249) were obtained from the Netherlands Cancer Registry. BC mortality and general population data were retrieved from Statistics Netherlands. Age‐standardised incidence and mortality rates were calculated with annual percentage change (APC) and average annual percentage change (AAPC) statistics. The relative survival (RS) was used as estimator for disease‐specific survival. The BC incidence for all BC patients combined significantly increased until 2013 from 126 to 158 per 100 000 person‐years, after which a declining trend was observed. Surgery became less extensive, but (neo‐)adjuvant systemic treatments and their combinations were given more frequently. The RS improved for all age groups and for most stages and receptor subtypes, but remained stable for all subtypes since 2012 to 2013 and since 2000 to 2009 for Stage IV BC at 15 years of follow‐up. Overall, the 5‐ and 10‐year RS increased from 76.8% (95% confidence interval [CI]: 76.1, 77.4) and 55.9% (95% CI: 54.7, 57.1) in 1989 to 1999 to 91.0% (95% CI: 90.5, 91.5) and 82.9% (95% CI: 82.2, 83.5), respectively, in 2010 to 2016. BC mortality improved regardless of age and overall decreased from 57 to 35 per 100 000 person‐years between 1989 and 2017. In conclusion, the BC incidence in the Netherlands has steadily increased since 1989, but the latest trends show promising declines. Survival improved markedly for most patients and the mortality decreased regardless of age.