Outcomes In Breast Cancer Survivors Research Articles

Survival Outcomes of Early-Stage Hormone Receptor-Positive Breast Cancer in Elderly Women.

Elderly women (≥ 70years old) form a significant proportion of patients affected by breast cancer (BC); however, the treatment decisions for this patient population are complicated, owing to the presence of comorbidities, limited life expectancy, reduced tolerability of therapy, and limited enrollment in clinical trials. A growing body of evidence suggests equivalent outcomes in elderly patients with hormone receptor-positive early-stage breast cancer receiving primary endocrine therapy only or surgery with subsequent endocrine therapy. Whether these results are reproduced in the larger BC population outside of a clinical trial currently remains unclear. Women ≥ 70years old diagnosed with early-stage invasive breast cancer between January 2008 and December 2013 with tumor size T1 or T2, minimal nodal involvement (N0 and N1), and estrogen and/or progesterone receptor positivity who started endocrine therapy within a year of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked datasets. Endocrine therapy was identified using outpatient prescription fills for anastrozole, exemestane, fulvestrant, letrozole, raloxifene, tamoxifen, and toremifene; the first fill date was used as the treatment initiation date. Surgical intervention included either breast-conserving surgery or mastectomy. Women who received chemotherapy were excluded. Trends in the use of primary endocrine therapy only were assessed using Poisson regression. Multivariable Cox proportional hazard regression was used to estimate the association between undergoing surgery within a year of diagnosis and 5-year all-cause mortality, after adjusting for patient demographics, comorbidities, and clinical cancer characteristics. Similar methods were used to assess 5-year cancer-specific mortality, where noncancer mortality was treated as a competing risk. Overall, 8784 women were included in the analysis: 8006 (91%) received surgery with endocrine therapy and 778 (9%) received primary endocrine therapy alone. The proportion of women not receiving surgery remained consistent between 2008 and 2013 (p = 0.10). The 5-year mortality was 11% (n = 619), and 19% of all deaths were due to cancer causes (n = 117). After adjustment, 5-year mortality was lower among women undergoing surgery (HR 0.59, 95% CI 0.47-0.74, p < 0.0001). Similar results were found when looking at 5-year cancer-specific mortality (HR 0.52, 95% CI 0.30-0.90, p < 0.0001). Elderly breast cancer patients with early-stage hormone-receptor-positive disease receiving primary surgical intervention plus endocrine therapy may have significantly improved survival than those receiving primary endocrine therapy alone. This study suggests the importance of surgical intervention for elderly breast cancer patients and warrants further investigation and comprehensive geriatric assessment to identify subsets of elderly breast cancer patients who may benefit significantly from surgical intervention.

Predictors of Response and Survival Outcomes of Triple Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

Background: In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. Methods: We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. Results: Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). Conclusions: Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.

Breast cancer survival among Japanese individuals and US residents of Japanese and other origins: a comparative registry-based study.

Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO). Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status. We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45-0.47 for Japanese and 0.66 [95% CI 0.59-0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51-0.55] for Japanese and 0.53 [95% CI 0.52-0.74] for USJ). In stage I-III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.

Eight immune-related genes predict survival outcomes and immune characteristics in breast cancer.

Advancements in immunotherapy have improved our understanding of the immune characteristics of breast cancer. Here, we analyzed gene expression profiles and clinical data obtained from The Cancer Genome Atlas database to identify genes that were differentially expressed between breast tumor tissues and normal breast tissues. Comparisons with the Immunology Database and Analysis Portal (ImmPort) indicated that many of the identified differentially expressed genes were immune-related. Risk scores calculated based on an eight-gene signature constructed from these immune-related genes predicted both overall survival and relapse-free survival outcomes in breast cancer patients. The predictive value of the eight-gene signature was validated in different breast cancer subtypes using external datasets. Associations between risk score and breast cancer immune characteristics were also identified; in vitro experiments using breast cancer cell lines confirmed those associations. Thus, the novel eight-gene signature described here accurately predicts breast cancer survival outcomes as well as immune checkpoint expression and immune cell infiltration processes.

Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer

Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41-0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01-0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

The Influence of Pre-Existing Beta-Blockers Use on Survival Outcomes in HER2 Positive Advanced Breast Cancer: Pooled Analysis of Clinical Trial Data.

Introduction: Beta-blockers (BB) are commonly used to manage cardiovascular disease and may have benefits in controlling complications of anti-HER2 therapies. This study aimed to evaluate the association of pre-existing BB use with survival outcomes in patients initiating anti-HER2 therapy for advanced breast cancer (ABC).Materials and Methods: Data from clinical trials EMILIA, TH3RESA, MARIANNE, and CLEOPATRA was pooled. Cox proportional analysis was used to assess the association between pre-existing BB use with survival outcomes in patients initiating anti-HER2 therapies.Results: Of the 2,777 patients with HER2 positive ABC, 266 were using a BB at the time of anti-HER2 therapy initiation. BB use was associated with worse overall survival (OS) (adjusted HR = 1.27, 95% CI: 1.04–1.55). Sensitivity analysis in patients with pre-existing cardiovascular disease (CVD) also indicated that BB use was associated with worse OS (1.29, 1.02–1.63).Conclusion: In large high-quality data, BB use at the time of anti-HER2 therapy initiation for ABC was independently associated with worse OS, regardless of CVD status. The finding is contrary to pre-study hypotheses and findings in other BC subtypes. Future research should aim to gain a deeper understanding of the effects of BBs on specific BC subtypes, cancer types, and cancer treatments.

Association of Independent Prognostic Factors and Treatment Modality With Survival and Recurrence Outcomes in Breast Cancer

It is not well understood whether prognostic factors in breast cancer are affected by specific treatment and vary by clinical outcome type compared with untreated patients. To identify independent clinical and molecular measurements associated with overall survival (OS) and recurrence-free survival (RFS) by homogeneous treatment in women with breast cancer. This prognostic study included 956 patients diagnosed with invasive breast cancer from hospital centers across 4 geographical regions of the United States who participated in the accreditation program of the Commission on Cancer of the American College of Surgeons from 1985 to 1997. The duration of follow-up ranged from 1 to 282 months. The study analysis was conducted from June 10, 2019, to March 18, 2020. Analysis of OS and RFS in patients who underwent chemotherapy, radiotherapy, or endocrine therapy alone compared with no systemic or locoregional therapy. Cox proportional hazards regression models were used to estimate independent performance and 95% CI of age, tumor size, number of positive nodes (nodal status), tumor grades 2 and 3, p53 status, estrogen receptor (ER) status, and ERBB2 (formerly HER2) status. Among 956 participants, median age was 61 (range, 25-96) years. Age (adjusted hazard ratio [AHR], 2.24; 95% CI, 1.27-3.94; P = .01) and high grade (AHR, 2.05; 95% CI, 1.09-3.86; P = .02), in addition to nodal status and tumor size, were independently associated with OS and RFS, respectively, in untreated patients. p53 status (AHR, 2.11; 95% CI, 1.07-4.18; P = .03) and ER status (AHR, 0.46; 95% CI, 0.23-0.92; P = .03) were associated with higher and lower risks of death, respectively, whereas nodal status (AHR, 1.13; 95% CI, 1.06-1.20; P < .005), high grade (AHR, 4.01; 95% CI, 1.51-10.70; P = .01), and ERBB2 positivity (AHR, 2.67; 95% CI, 1.25-5.70; P = .01) were associated with the risk of recurrence after endocrine therapy. Tumor size (AHR for OS, 2.76 [95% CI, 1.79-4.31; P < .005]; AHR for RFS, 2.27 [95% CI, 1.23-4.18; P = .01]) and ERBB2 status (AHR for OS, 5.35 [95% CI, 1.31-21.98; P = .02]; AHR for RFS, 6.05 [95% CI, 1.48-24.78; P = .01]) were independently associated with radiotherapy outcomes, and nodal status was significantly associated with chemotherapy outcomes (AHR for OS, 1.06 [95% CI, 1.02-1.09; P < .005]; AHR for RFS, 1.05 [95% CI, 1.01-1.09; P = .01]). In this study, independent prognostic factors were associated with specific treatment and weighted by the outcome category with reference to untreated patients within biological and clinical contexts.

Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer

BackgroundObesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses.MethodsAmong 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression.ResultsStudy participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HRadj = 0.52, 95% CI 0.31–0.88) and OS (HRadj = 0.64, 95% CI 0.44–0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease.ConclusionsLow CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making.

Reducing Cardiac Radiation Dose From Breast Cancer Radiation Therapy With Breath Hold Training and Cognitive Behavioral Therapy.

The delivery of radiation therapy shares many of the challenges encountered in imaging procedures. As in imaging, such as MRI, organ motion must be reduced to a minimum, often for lengthy time periods, to effectively target the tumor during imaging-guided therapy while reducing radiation dose to nearby normal tissues. For patients, radiation therapy is frequently a stress- and anxiety-provoking medical procedure, evoking fear from negative perceptions about irradiation, confinement from immobilization devices, claustrophobia, unease with equipment, physical discomfort, and overall cancer fear. Such stress can be a profound challenge for cancer patients' emotional coping and tolerance to treatment, and particularly interferes with advanced radiation therapy procedures where active, complex and repetitive high-level cooperation is often required from the patient.In breast cancer, the most common cancer in women worldwide, radiation therapy is an indispensable component of treatment to improve tumor control and outcome in both breast-conserving therapy for early-stage disease and in advanced-stage patients. High technological complexity and high patient cooperation is required to mitigate the known cardiac toxicity and mortality from breast cancer radiation by reducing the unintended radiation dose to the heart from left breast or left chest wall irradiation. To address this, radiation treatment in daily deep inspiration breath hold (DIBH), to create greater distance between the treatment target and the heart, is increasingly practiced. While holding the promise to decrease cardiac toxicity, DIBH procedures often augment patients' baseline stress and anxiety reaction toward radiation treatment. Patients are often overwhelmed by the physical and mental demands of daily DIBH, including the nonintuitive timed and sustained coordination of abdominal thoracic muscles for prolonged breath holding.While technologies, such as DIBH, have advanced to millimeter-precision in treatment delivery and motion tracking, the "human factor" of patients' ability to cooperate and perform has been addressed much less. Both are needed to optimally deliver advanced radiation therapy with minimized normal tissue effects, while alleviating physical and cognitive distress during this challenging phase of breast cancer therapy.This article discusses physical training and psychotherapeutic integrative health approaches, applied to radiation oncology, to leverage and augment the gains enabled by advanced technology-based high-precision radiation treatment in breast cancer. Such combinations of advanced technologies with training and cognitive integrative health interventions hold the promise to provide simple feasible and low-cost means to improve patient experience, emotional outcomes and quality of life, while optimizing patient performance for advanced imaging-guided treatment procedures - paving the way to improve cardiac outcomes in breast cancer survivors.

Prior Treatment Time Affects Survival Outcomes in Metastatic Breast Cancer.

PURPOSESequential drug treatments in metastatic breast cancer (MBC) are disparate. Clinical trial data includes limited reporting of treatment context, primarily including the number of prior therapies. This study evaluates the relationship between prior treatment time, prior lines of treatment, and survival using a novel visualization technique coupled with statistical analyses.PATIENTS AND METHODSThis retrospective cohort study used a nationwide, de-identified electronic health record–derived database to identify women with hormone receptor–positive, human epidermal growth factor receptor 2–negative MBC diagnosed in 2014 who subsequently received paclitaxel. Images were created, with individual patients represented on the y-axis and time, on the x-axis. Specific treatments were represented by colored bars, with Kaplan-Meier curves overlaying the image. Separate images assessed progression-free survival and overall survival (OS). Hazard ratios (HRs) and 95% CIs from Cox proportional hazards models evaluated the association between prior treatment time and OS.RESULTSOf 234 patients, median survival from first paclitaxel administration was 20 months (interquartile range, 8-53 months). An inverse relationship was observed between OS after paclitaxel and timing of administration. In adjusted models, each year on treatment prior to paclitaxel was associated with a 16% increased hazard of death after paclitaxel (HR, 1.16; 95% CI, 1.05 to 1.29).CONCLUSIONOS after a specific treatment is dependent on when a drug is given in the disease context, highlighting the potential for an overall OS benefit to be observed on the basis of treatment timing. Prior time on treatment should be considered as a stratifying factor in randomized trials and a confounding factor when examining survival in observational data.

Correlation of hormonal receptor level and survival outcome in HER2-positive nonmetastatic breast cancer.

e12568 Background: In human epidermal growth factor 2 (HER2)-positive breast cancer, emerging evidences imply that clinical behavior and prognosis differ according to hormone receptor (HR) status. However, there is no conclusion about the relevance between estrogen receptor (ER) or progesterone receptor (PR) expression and clinical outcome of HER2-positive breast cancer. Our study is designed to determine the effect of different ER/PR levels on survival benefit of HER2-positive early breast cancer. Methods: 984 non-metastatic HER2-positive breast cancer patients between January 2009 and December 2016 were retrospectively reviewed and HR+/HER2+ patients were further classified into several subgroups based on ER expression level (Low/L: 1-9%; Median/M: 10-74%; High/H: 75-100%) and PR expression level (Low/L: 0-19%; High/H: 20%-100%). Clinical features and survival outcomes were evaluated. Results: A total of 461 HR+/HER2+ and 523 HR-/HER2+ breast cancer patients were included in our study and 69.8% of them received target therapy (HR+ 67.5%, HR- 71.9%). While HR+/HER2+ breast cancer showed better survival than HR-/HER2+ subtype in 5-year disease free survival (DFS, 92.6% vs 87.6%, p = 0.002), no significant difference was observed between 5-year DFS rates in ER+/PR+ and ER+/PR- subgroup (94.3% vs 89.7%, p = 0.150). However, a possible correlation was found between ER/PR levels and DFS both in HR+/HER2+ (p = 0.057) and all HER2+ (p &lt; 0.001) breast cancer. In HR+/HER2+ breast cancer, all subgroups showed DFS improvement trend versus M-ER/L-PR patients and hazard ratio of H-ER/H-PR subtype had a statistical difference (0.36, 95%CI 0.13-0.99, p = 0.047). In all HER2+ patients, hazard ratio of H-ER/H-PR compared with HR- subtype was 0.32 (95% CI, 0.13-0.80, p = 0.015). M-ER/L-PR presented similar DFS outcome with HR- subtype in our study. Conclusions: ER/PR expression may become a predictor of survival benefit in HER2-positive non-metastatic breast cancer and a higher ER/PR expression level might be associated with better DFS.

Survival outcomes in post-menopausal patients with underlying cardiovascular disease receiving endocrine therapy for the treatment of breast cancer.

e12549 Background: Breast cancer remains the number one threat to women’s health while cardiovascular disease (CVD) continues to be the leading cause of mortality in women worldwide. Adjuvant therapy with endocrine therapies (selective estrogen receptor modulators (SERM), estrogen receptor blockers (ERB), and aromatase inhibitors (AI) although known to reduce the recurrence of breast cancer in hormone receptor positive breast cancer patients, raise a concern for increased risk of cardiovascular disease. Our study aims to examine breast cancer survival outcomes on patients receiving endocrine therapy who have pre-existing CVD including heart failure. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Preexisting CVD included coronary artery disease (CAD), history of myocardial infarction (MI), and prior diagnosis of heart failure (HF). Patients were divided in groups depending on treatment with endocrine therapy and underlying CVD. Statistical analysis was performed with SAS v9.4. software. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance was assumed at the p &lt; 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Out of those 336 patients, 62.2 % (n = 209) received at least one of the endocrine therapies consisting of AI, SERM or an ERB. Of these patients, 2.9 % (n = 6), 9.6% (n = 20) and 5.7% (n = 12) had a significant medical history of underlying MI, HF and CAD, respectively. Survival analysis was performed on 80% (n = 168) patients of the 209 patients with 2.3% (n = 4), 8.9% (n = 15) and 5.2% (n = 11) with underlying MI, HF and CAD respectively. There was no statistically significant difference in survival in these postmenopausal women who received endocrine therapy despite preexisting cardiovascular disease (HR 3; 95% CI, 0.5-16, p &gt; 0.05). Conclusions: A commonly known toxicity related to the adjuvant therapy including endocrine therapy of breast cancer is cardiac toxicity. Patients with history of CVD might be at the highest risk for such toxicity. Our finding is reassuring that endocrine therapy in patients with preexisting CVD including heart failure did not result in reduced survival for our patient cohort.

The PAPHIO study protocol: a randomised controlled trial with a 2 x 2 crossover design of physical activity adherence, psychological health and immunological outcomes in breast cancer survivors

BackgroundThe PAPHIO study; a randomized controlled trial with 2X2 crossover design will implement a self-directed physical activity program in which participants will engage in self-monitoring and receive motivational interviewing to enhance physical activity adherence. The study aims to determine the effects of 24 weeks self-directed activity combined with motivational interviewing (MI) on (i) psychological health, (ii) quality of life (QoL) and (iii) immune function in female breast cancer survivors.MethodsThe study will recruit 64 female breast cancer survivors within 3 years of diagnosis and at least 6 months post primary treatments at Western Health Sunshine Hospital, Melbourne, Australia. They will be randomly allocated to immediate intervention (IIG group) or delayed intervention groups (DIG group) in a 1:1 ratio. All participants will be given a wearable device (Fitbit Alta HR) and undertake self-directed physical activity for 24 weeks and will receive MI for 12 weeks (IIG; during week 0 to week 12 and DIG; during week 13 to week 24). Participants’ daily step count and the changes of immune cell functionality will be assessed at the beginning (week 1: T1), week 12 (T2) and week 24 (T3) of the program. Physical activity adherence will be assessed at T2 and T3. Participants will also complete four questionnaires assessing exercise self-regulation (BREQ2), exercise barrier and task self-efficacy, mental health (DASS-21) and QoL (FACT-B) at three time points (T1 to T3). Linear-mixed models will be used to assess the relationship between physical activity volume by step counting and mental health (DASS-21), QoL (FACT-B), immune biomarkers, self-regulation (BREQ2) and self-efficacy at T1, T2 and T3;between 2 groups.DiscussionWe expect this physical activity intervention to be acceptable and beneficial to the participants in terms of psychological and immunological well-being with the potential outcomes to be implemented more widely at relatively low cost to these or other patient populations.Trial registrationAustralian New Zealand Clinical trials Registry- ACTRN12619001271190. Prospectively registered on 13 September 2019.

Relationships of hepatitis B virus infection with clinicopathological features in breast cancer and survival outcomes in central China.

BackgroundThe purpose of this study was to determine the effect of hepatitis B virus (HBV) infection on the clinicopathological features and survival outcomes of breast cancer (BC) patients.MethodsPatients diagnosed with BC at the Breast and Thyroid Center, Renmin Hospital, Wuhan University between January 2013 and December 2017 were included in the study. Among these patients, 100 (8.4%) were infected with HBV (case group), while 237 (19.9%) had never come into contact with HBV (control group). Chi-square tests for analyses of clinicopathological features, Kaplan-Meier survival analyses, the log-rank test for disease-free survival (DFS) between the case and control group, along with the factors correlated with prognosis, were evaluated using univariate and multivariate analyses.ResultsThe median follow-up of the patients in the case and control groups was 34.5 months. The clinicopathological features revealed that patients with HBV tended to have smaller tumors compared with the control group (case vs. control: 53.0% vs. 65.8%, P<0.05). In addition, more grade 3 tumors were observed in patients with HBV (case vs. control: 55.0% vs. 37.6%, P<0.01). The 3-year DFS was 94.3% in the case group and 89.4% in the control group patients (P=0.212). In multivariate analysis, nodal status [hazard ratio (HR) =5.033, P=0.003] and estrogen receptor (ER) status (HR =0.216, P=0.023) were both independent prognostic risk factors for DFS. However, HBV infection had no association with the DFS of BC.ConclusionsBC patients in central China have a higher incidence rate of HBV infection than the general population does. BC patients with chronic HBV infection tend to have an earlier tumor stage and higher histological grade, but there is no association with the DFS of BC.

A Pilot Intervention Study to Improve Sexuality Outcomes in Breast Cancer Survivors

Objective:The main objective of the study is to assess the efficacy of the Permission, Limited information, Specific Suggestion, and sexual therapy (PLISSIT) model directly with breast cancer survivor (BCS) on sexual function and quality of life (QOL) domains.Methods:A pilot control trial was conducted comparing the PLISSIT model intervention to usual care. The intervention was delivered by two health professionals (nurse and professional sexual therapist) consisted of five sessions on counseling, genitalia anatomy, human sexual response, and sexual function. Data were collected before and 3 months after the intervention using the Female Sexual Function Index and the World Health Organization QOL-BREF questionnaire.Results:The sample consisted of 19 BCS (11 intervention, 8 controls) with a mean age of 54.5 8 years (standard deviation = 7.14) and the majority were married, Black or mixed Brazilian, received chemotherapy, radiation and/or hormonal therapy, and education varied from high school to college. There was significant improvement in physical health (P = 0.031), social relationships (P = 0.046), orgasm (P = 0.055), and pain (P = 0.049) over time and the intervention resulted in improved arousal (P = 0.038).Conclusions:The results suggest that the PLISSIT model may be an effective intervention for BCS in coping with and managing changes in sexuality and sexual function after treatment. It is important that nurses are aware of sexual intimacy concerns for BCS and integrate assessment into their nursing care.

Abstract GS5-01: Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis

Abstract Background: Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer (BC) to better inform on patient outcomes. Also, a pooled subject-level analysis allows more detailed analyses of generalizability of the prognostic meaning of RCB assessments in a broader experience of practice settings. Method: Subject-level RCB results, with relevant clinical and pathologic stage, tumor subtype and grade, demographic, treatment and follow-up data from 11 institutes/trials are being collected for combined analysis. The association between the continuous RCB index and event-free survival (EFS), and distant recurrence free survival (DRFS) were assessed using mixed effect Cox models with the incorporation of random RCB coefficients to account for between-study heterogeneity. We will also allow for differences in baseline hazard across biological BC subtypes and, if needed, across studies as well. In addition to this stratified mixed effect model, a multivariate analysis adjusting for age, T-category, nodal status and grade was performed within each subtype. In addition, mixed effect Cox models will be employed to evaluate association between RCB index with EFS and DRFS within each HR/HER2 subtype. Kaplan Meier estimates of EFS and DRFS at 5 and 10 years were computed for each RCB class within subtype. Results: We analyzed subject-level data from 9 institutes/trials representing 4077 patients currently available from an anticipated final total of 4,800 patients (to be presented at the meeting). There were 950 EFS and 876 DRFS events during follow up (median 65 months, IQR: 70 months). RCB index (continuous) was independently prognostic within each subtype: HR+/HER2- (EFS HR (per unit increase in RCB index) =1.64, 95%CI 1.48-1.82; DRFS HR=1.68, 1.51-1.87), HR+/HER2+ (EFS HR=1.80, 1.57-2.05; DRFS HR=1.93, 1.67-2.24), HR-/HER2+ (EFS HR=2.15, 1.76-2.62; DRFS HR=2.10, 1.77-2.50), and HR-/HER2- (EFS HR=2.05, 1.89-2.22; DRFS HR=2.16, 1.90-2.46); and remained prognostic in multivariate models adjusting for age, grade, and clinical T and N stage at diagnosis. Table 1 contains the response rate and estimated EFS at 5 years and 10 years for each RCB class within each HR/HER2 phenotype (DRFS results were similar). Conclusions: Long-term prognosis after pCR was similarly excellent in all phenotypic subtypes. RCB index and classification was independently and strongly prognostic in all subtypes, and generalizable to multiple practice settings. Prognostic differences by RCB class occurred within 5 years in HR- BC, but extended to 10 years in HR+ BC. RCB-I had slightly worse EFS than pCR in HR- BC and HR+/HER2+ BC (after 5 years), but the same EFS as pCR in HR+/HER2- BC. Complete analysis of all subjects, including neoadjuvant treatments, will be presented at the meeting. PhenotypeOutcomepCRRCB-IRCB-IIRCB-IIIHR+/HER2-Frequency (%)11%10%52%27%(N=1467)5 yr EFS (95% CI)91% (86-96)93% (89-98)82% (79-85)70% (65-75)10 yr EFS (95% CI)84% (75-93)88% (82-95)71% (67-75)52% (46-58)HR+/HER2+Frequency (%)38%18%35%9%(N=762)5 yr EFS (95% CI)94% (91-97)93% (88-98)78% (73-84)49% (37-65)10 yr EFS (95% CI)91% (86-96)79% (70-90)65% (59-73)42% (29-60)HR-/HER2+Frequency (%)66%11%18%5%(N=550)5 yr EFS (95% CI)93% (90-96)88% (79-97)60% (50-71)45% (30-69)10 yr EFS (95% CI)90% (86-94)84% (74-95)56% (46-68)45% (30-69)HR-/HER2-Frequency (%)41%13%33%13%(N=1293)5 yr EFS (95% CI)92% (90-94)85% (79-91)68% (63-72)28% (21-36)10 yr EFS (95% CI)87% (82-91)80% (72-88)63% (58-68)24% (18-33) Citation Format: Christina Yau, Marieke van der Noordaa, Jane Wei, Marie Osdoit, Fabien Reyal, Anne-Sophie Hamy, Marick Lae, Miguel Martin, Maria del Monte, I-SPY 2 TRIAL Consortium, Judy C Boughey, Rebekah Gould, Jelle Wesseling, Tessa Steenbruggen, Maartje van Seijen, Gabe Sonke, Stephen Edge, Stephen-John Sammut, Elena Provenzano, Jean Abraham, Peter Hall, Ashley Graham, Lorna Mackintosh, David Cameron, Alice Wang, Priyanka Sharma, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura van ‘t Veer, Laura Esserman, W. Fraser Symmans. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-01.

Abstract P3-08-51: Association between BRCA mutational status and survival in patients with breast cancer: A meta-analysis

Abstract Background: BRCA mutated breast cancer is associated with an aggressive phenotype with marked differences in histological grade and distant metastases and sensitive to PARPi and platinum therapy. Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results due to the differences in clinical and pathological status among study population. Therefore, we assessed the impact of BRCA mutations on survival of BC patients, based on their baseline characteristics and follow-up durations. Methods: Using PICO framework, articles comparing survival outcomes of BC patients having BRCA mutations against sporadic BRCA phenotype were retrieved from PubMed, EMBASE and Cochrane Library. Overall survival (OS) was the primary outcome, with disease free survival (DFS), distant metastasis free survival (DMFS) and breast cancer specific survival (BCCS) as the secondary outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Sub-group analysis was performed for survival based on age, tumor stage, estrogen receptor status, triple negative breast cancer (TNBC) status, tumor stage (Stage I-III vs I-IV) and follow-up durations. Results: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included in the analysis. In BRCA1/2+ group, no significant difference in OS and DFS than BRCA- group were observed (HR: 0.98, 1.36, respectively),have a better DMFS in BRCA- patients than that in BRCA1/2+ patients (HR: 1.32; 95% CI: 0.71, 2.44). However, the difference observed between the groups was insignificant (P = 0.3825). BRCA1+ patients had significantly lower OS (HR [95%CI]: 1.2 [1.08, 1.33]; P&amp;lt;0.001),poor BCSS at 10 years follow-up. DMFS was significantly poor in BRCA1+ patients compared with BRCA- patients both at 5 years follow-up (HR [95%CI]: 1.07 [1.04, 1.10]; P&amp;lt;0.0001) and 10 years follow-up (HR [95%CI]: 1.21 [1.13, 1.29]; P&amp;lt;0.0001).BRCA2+ patients had significantly lower DFS (HR [95%CI]: 1.35 [1.1, 1.67]; P = 0.0049) and BCSS (HR [95%CI]: 1.46 [1.26, 1.7]; P&amp;lt;0.0001) than BRCA2- patients. Among TNBC patients, OS was non-significantly better in BRCA1/2+ patients (HR 0.96, P = 0.803) than in BRCA- patients. However, DFS was significantly poor in BRCA1+ TNBC patients than BRCA1-/TNBC patients (HR [95% CI]:1.65 [1.08, 2.54]; P = 0.0216).Conclusion: BRCA1/2 mutation is associated with poor prognosis in patient with breast cancer. Hence, BRCA testing might help assess patient prognosis and treatment such as PARPi and platinum. Citation Format: Miao Liu, Shu Wang. Association between BRCA mutational status and survival in patients with breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-51.

Associations between amygdala reactivity to social threat, perceived stress and C-reactive protein in breast cancer survivors.

Chronic inflammation in women diagnosed with breast cancer is critically linked with tumor progression, metastasis and survival. C-reactive protein (CRP)—a circulating marker of inflammation—is an important prognostic marker for cancer-related outcomes in breast cancer survivors (e.g. recurrence, fatigue). Psychological stress, which increases circulating markers of inflammation following sympathetic nervous system (SNS) activation, may modulate tumor-relevant inflammatory processes. However, little is known about neural mechanisms that might link stress and downstream SNS-initiated proinflammatory processes, such as elevated CRP. Past work suggests that threat-related neural regions, such as the amygdala, may be key in translating psychological stress into SNS activity and subsequent peripheral inflammation. Thus, we examined amygdala reactivity to socially threatening stimuli in association with perceived stress and plasma CRP levels to further elucidate neuro-immune pathways of social threat processing within breast cancer survivors (N = 37). Significant positive correlations were found between left amygdala reactivity in response to socially threatening stimuli (e.g. angry/fearful faces vs happy faces) and perceived stress in the previous month (r = 0.32, P = 0.025) and between left amygdala reactivity and CRP (r = 0.33, P = 0.025). This work builds on prior research implicating the amygdala as a key structure in crosstalk between threat-related neural circuitries and peripheral inflammation, particularly within cancer survivors.

Effects of an Evidence-based Exercise Intervention on Clinical Outcomes in Breast Cancer Survivors: A Randomized Controlled Trial

OBJECTIVES The number of breast cancer survivors throughout the world has increased. Breast cancer survivors need to know how to exercise to improve their clinical outcomes. The purpose of this study was to find the effects of an evidence-based combined exercise intervention on the fitness levels of breast cancer survivors.METHODS A total of 38 female breast cancer survivors were randomly assigned to an exercise group (n=19) or a control group who did usual care (n=19). Subjects in the exercise group participated eight weeks of moderate intensity aerobic exercise and bodyweight strength exercise three times per week. Weight, body mass index (BMI), cardiorespiratory fitness, handgrip strength, and flexibility were measured to assess the effects of the exercise intervention.RESULTS Women who completed the exercise intervention had decreased weight and BMI and increased cardiorespiratory fitness, handgrip strength, and flexibility.CONCLUSIONS Breast cancer survivors had improved health outcomes. A combined exercise intervention of moderate intensity three times per week for eight weeks can help breast cancer survivors improve their health. Participating in aerobic exercise and bodyweight strength exercise, which provide dynamic movements and use large muscle groups with no equipment, can help increase physical fitness levels of breast cancer survivors.

Age-related mutational signature negatively associated with immune activity and survival outcome in triple-negative breast cancer

ABSTRACT Triple-negative breast cancer (TNBC) is characterized by broad genomic and transcriptional heterogeneity and results in a worse prognosis than other breast cancer types. Here, we integrated genomic and transcriptomic data combined with clinicopathologic information from 538 patients with TNBC and identified four novel significantly mutated genes (SMGs), namely, KDM6A, CD86, RBM47, and IFNGR1. A mutational signature (known as age-related signature 1) featured by enrichment of C > T mutations at NpCpG trinucleotides was associated with worse survival in TNBC (HR, 1.76 [95% CI, 1.07–2.90]; P = .025). We also analyzed gene transcriptomic profiles of TNBC samples and identified immune regulation-related gene pathways (e.g., antigen processing presentation and interferon signaling), and the cell cycle was significantly altered in samples with different signature 1 activity groups. The analysis further revealed that signature 1 was associated with decreased tumor immunogenicity and immunocyte infiltration in TNBC. This negative correlation was also observed in lung adenocarcinoma and prostate cancer samples. Furthermore, we found that patients with mutational signature 1 were markedly associated with decreased tumor mutation burden, even after controlling for age, grade, histological type, lymph node status, mutations in BRCA1/2 and ATR, and APOBEC and homologous recombination repair deficiency signatures (OR, 0.19 [95% CI, 0.11–0.32]; P < .001). Overall, this study identified previously unreported SMGs and re-annotated that age-related signature 1 was associated with a weakened immune microenvironment and predictive of poor survival in TNBC, offering opportunities to stratify patients into optimal treatment plans based on genomic subtyping.