On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. METHODS: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. RESULTS: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. CONCLUSIONS: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.

Effects of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors: A randomized controlled trial.

OBJECTIVE: To examine the effectiveness of partnErship-based, needs-tailored self-Management support Program fOr Women with breast cancER (EMPOWER), a partnership-based, needs-tailored, self-management (SM) support intervention designed to empower post-treatment breast cancer survivors (BCSs) and ultimately improve their health outcomes. METHODS: This multi-center, two-armed, randomized controlled trial comprised 94 female BCSs who had completed primary cancer treatment in South Korea. Participants were randomly assigned (1:1) to the intervention group or the wait-list control group. The intervention group received a 7-week EMPOWER intervention via telephone counseling. The primary outcome was empowerment. Secondary outcomes included self-efficacy for post-treatment SM behaviors, mental adjustment, anxiety, depression, and health-related quality of life. Data were collected via a self-reported questionnaire at baseline (T0) and at 8 (T1) and 20 weeks (T2) of follow-up. Linear mixed models were used to assess group differences over time. Effective sizes were calculated using Cohen's d. RESULTS: Retention rates were excellent (95.7% at T1; 94.7% at T2). Linear mixed model analyses revealed that the EMPOWER group showed significantly improved empowerment (mean difference 2.24, 95% CI = 0.18 to 4.29; p = 0.016) and general health perception (mean difference 3.68, 95% CI = 0.67 to 6.72; p = 0.037) compared with the control group. Time point analysis showed that several secondary outcomes significantly improved at T1, but the effects were not sustained. CONCLUSION: EMPOWER was effective in improving empowerment and general health perception among post-treatment BCS. Further studies are needed to determine the effectiveness of the EMPOWER intervention in other cancer populations.

Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer.

PURPOSE: Neutropenia is the most common toxicity of CDK4/6 inhibitors, causing frequent dose interruptions. However, CDK4/6 inhibitor-induced neutropenia shows a benign clinical course in contrast to that caused by chemotherapy. Here, we investigated the safety of a new dose scheme for palbociclib, which avoids dose delays or reductions due to afebrile grade 3 neutropenia. METHODS: A consecutive cohort of ER( +)/HER2( -) advanced breast cancer patients who received palbociclib between 2017 and 2018 was analyzed. The patients were classified into Group 1 (patients who maintained palbociclib dose with afebrile grade 3 neutropenia), Group 2 (patients who experienced any dose modification with afebrile grade 3 neutropenia), and Group 3 (patients without afebrile grade 3 neutropenia). The primary endpoint was febrile neutropenia incidence; other toxicities were compared with those of the PALOMA-2 trial. RESULTS: Among the 107 patients, 54.2%, 22.4%, and 23.4% were classified into Groups 1, 2, and 3, respectively. There was no febrile neutropenia in Groups 1 and 2 during palbociclib treatment. Group 1 showed higher incidence of thrombocytopenia (all-grade, 32.8%; grade 3-4, 8.6%) than Group 2 and the PALOMA-2 data, but there was no bleeding related to thrombocytopenia. Group 1 showed higher incidence of all-grade non-hematologic adverse events than Group 2; only one grade 3 non-hematologic toxicity was observed in Group 1. There were no treatment-related hospitalizations or deaths in Group 1. CONCLUSIONS: Thus, omitting palbociclib dose modification with afebrile grade 3 neutropenia is safe and tolerable without febrile neutropenia events. This scheme could be useful to avoid unnecessary reductions in palbociclib doses in future practice.

Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older.

PURPOSE: An antibody-drug conjugate targeting HER2, DS8201, has shown clinical activity against breast cancer with low-level HER2 expression. We aimed to evaluate the prognostic impact of intermediate HER2 expression in estrogen receptor (ER)+ early breast cancer (EBC) and metastatic breast cancer (MBC) cohorts. METHODS: We analyzed prospectively collected data from EBC and MBC cohorts at Yonsei Cancer Center. Patients with HER2 immunohistochemistry (IHC) 0 ~ 1+ were assigned to the HER2-negative group, and patients with IHC 2+ and in situ hybridization (ISH)-negativity were assigned to the HER2-intermediate group. After the exclusion of HER2 IHC 3+ or ISH+ patients, a total of 2657 EBC and 535 MBC patients were analyzed. RESULTS: In total, 654 (24.6%) EBC and 166 (31.0%) MBC patients were classified in the HER2-intermediate group. The HER2-intermediate patients more frequently tended to have progesterone receptor (PR)-negativity and higher nuclear grade in the EBC cohort, and showed a higher proportion of patients aged ≥ 55 years compared with the HER2-negative group in the MBC cohort. The HER2-intermediate patients showed significantly poorer recurrence-free survival (RFS) compared to the HER2-negative patients in the EBC cohort (p = 0.044). Notably, intermediate HER2 expression predicted poorer RFS in EBC patients aged ≥ 55 years (hazard ratio 1.95; p = 0.042) in multivariate Cox analysis but did not affect RFS in those aged < 55 years. In line with the EBC cohort results, intermediate HER2 expression predicted poorer overall survival (OS) in MBC patients aged ≥ 55 (hazard ratio 1.45; p = 0.044) without affecting OS of those aged < 55 years. CONCLUSION: Intermediate HER2 expression is an independent predictor of poor prognosis in both ER+ EBC and MBC patients aged ≥ 55 years. The clinical efficacy of new HER2-targeting antibody-drug conjugates needs to be validated in this high-risk subset of ER+ breast cancer patients.

Correction to: Palbociclib use with grade 3 neutropenia in hormone receptor-positive metastatic breast cancer.

In the original publication of the article, under the Results section, subheading "Patient survival", the second sentence that reads as "The 6-month PFS was 92.4%, 81.8%, and 93.3% and the one-year PFS was 72.0%, 88.9%, and 78.9% in Groups 1-3, respectively." should read as "The 6-month PFS was 82.8%, 75.0%, and 68.0% and the one-year PFS was 77.0%, 62.0%, and 63.8% in Groups 1-3, respectively.".

Design of a randomized controlled trial of a partnership-based, needs-tailored self-management support intervention for post-treatment breast cancer survivors.

BACKGROUND: Self-management is becoming essential for breast cancer survivors, but evidence about the effectiveness of self-management support (SMS) intervention is lacking. To address this issue, we developed a theory-based SMS intervention, the 'EMPOWER', aimed at empowering breast cancer survivors. Here we describe the rationale of the intervention and its development. METHODS: The conceptual framework of this study is the Chronic Care Model, which posits that SMS can influence patient-provider relationships and ultimately improve health outcomes. We will conduct a multi-center, 2-armed randomized controlled trial to assess the effectiveness of EMPOWER among post-treatment breast cancer survivors in South Korea. The trial will include 94 women who completed primary breast cancer treatment within the last 6 months. Participants will be randomly assigned to the intervention group or the wait-list control group (1:1). The intervention group will receive a 7-week partnership-based and needs-tailored SMS intervention via telephone counseling. The primary outcome is empowerment. The secondary outcomes include self-efficacy for post-treatment self-management behaviors, mental adjustment, psychological distress, and health-related quality of life (HRQOL). Data will be collected by self-reported questionnaire at baseline, post-intervention, and 3-month follow-up. DISCUSSION: We believe that the EMPOWER intervention could improve HRQOL of post-treatment breast cancer survivors by enhancing their empowerment. If found successful, it could aid clinicians engaged in the long-term care of breast cancer survivors. TRIAL REGISTRATION: Clinical Research Information Service, KCT0004794. Registered 5 March 2020.

Pre-post analysis of a social capital-based exercise adherence intervention for breast cancer survivors with moderate fatigue: a randomized controlled trial.

PURPOSE: This study assessed the effectiveness of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), regarding cancer-related fatigue (CRF), quality of life (QOL), physical activity, and psychosocial characteristics. METHODS: Forty-eight BCS with moderate or high (≥ 4) CRF participated in this randomized control trial (intervention group n = 23, control group n = 25). The intervention group participated in small group sessions to activate social capital while targeting CRF in supervised physical exercises supplemented by home-based physical exercises. The control group was only given written information on exercise. A questionnaire was used to assess CRF, QOL, physical activity, depression, anxiety, sleep quality, and social capital. RESULTS: The majority of participants had undergone surgery less than 2 years ago. After participating in BLESS, the CRF behavioral/severity domain significantly decreased (t = 2.642, p = 0.011) and physical activity significantly increased (t = - 2.049, p = 0.046) in the intervention group, in comparison with the control group; there were no significant post-intervention differences in the control group. Both groups showed improvements in sleep quality, depression, anxiety, and QOL. CONCLUSION: The BLESS program decreased behavioral/severity in the CRF and increased physical activity after 12 weeks among BCS. Future research needs to evaluate whether the promising results on physical activity and behavioral fatigue observed in the short term will persist over time. Also, longer-term effects should be examined.

Adjuvant chemotherapy and survival among patients 70 years of age and younger with node-negative breast cancer and the 21-gene recurrence score of 26-30.

BACKGROUND: The benefits of chemotherapy in node-negative, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with the 21-gene recurrence score (RS) of 18-30, particularly those with RS 26-30, are not known. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) data, we retrospectively identified 29,137 breast cancer patients with the 21-gene RS of 18-30 diagnosed between 2004 and 2015. Mortality risks according to the RS and chemotherapy use were compared by the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: Among the breast cancer patients with the RS 18-30, 21% of them had RS 26-30. Compared to breast cancer patients with RS 18-25, patients with RS 26-30 had more aggressive tumor characteristics and chemotherapy use and increased risk of breast cancer-specific mortality and overall mortality. In breast cancer patients who were aged ≤ 70 years and had RS of 26-30, chemotherapy administration was associated with a 32% lower risk of breast cancer-specific mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.47-0.99) and a 42% lower risk of overall mortality (HR, 0.58; 95% CI, 0.44-0.76). Survival benefits were most pronounced in breast cancer patients who were younger or had grade III tumor. CONCLUSIONS: The 21-gene RS of 18-30 showed heterogeneous outcomes, and the RS 26-30 was a significant prognostic factor for an increased risk of mortality. Adjuvant chemotherapy could improve the survival of node-negative, hormone receptor-positive, and HER2-negative breast cancer patients with the 21-gene RS 26-30 and should be considered for patients, especially younger patients or patients with high-grade tumors.

Prevalence of breast cancer-related risk factors in underweight premenopausal women: the Korea National Health and Nutrition Examination Survey IV-VI.

PURPOSE: This study aimed to examine the prevalence and trends of breast cancer-related risk factors and characteristics in premenopausal underweight Korean women according to birth year cohort. METHODS: Socioeconomic and breast cancer-related risk factors were investigated in 13,415 premenopausal women using nationwide cross-sectional surveys performed between 2007 and 2015. Underweight was defined as body mass index < 18.5 kg/m2. Multivariable models were created using complex sample procedures. RESULTS: Underweight women comprised 9.5% of the sample. Compared with those who were obese or of normal weight, underweight women were characterized by younger age, higher rate of metropolitan residence, higher economic status, more education, higher rates of non-manual employment and unmarried status, lower rate of early menarche, higher rates of nulliparity, lower parity, alcohol consumption, and never having breastfed, and lower levels of high physical activity. Multivariable analysis showed that underweight women had a significantly lower rate of early menarche, lower parity, higher nulliparity, older age at first delivery, and lower levels of high physical activity compared to premenopausal women with normal weight. These trends were more apparent among women born in recent years. CONCLUSIONS: Underweight Korean premenopausal women exhibit distinctive features associated with an increased risk of breast cancer, except for a lower rate of early menarche. These associations were prominent in recent generations. Assessment of the association between underweight and premenopausal breast cancer risk should focus on promoting healthy lifestyles to reduce breast cancer risk.

Retrospectively validating the results of the ACOSOG Z0011 trial in a large Asian Z0011-eligible cohort.

PURPOSE: The Z0011 trial demonstrated that axillary dissection (ALND) could be omitted during breast-conserving therapy for cT1-2N0 breast cancers with 1-2 metastatic SLNs. However, that result has not been validated in a larger cohort and the significance of the small number of SLNs remains unclear. This study aimed to validate the Z0011 results within an Asian Z0011-eligible cohort and determine whether the number of sentinel lymph nodes (SLNs) influenced the Z0011-based outcomes. METHODS: Data from Asian patients who fulfilled the Z0011 criteria were collected from five hospitals. Disease recurrence (DR) was compared between patients who underwent ALND or SLN dissection (SLND) alone. Propensity-score matching was performed to reduce the effects of potential selection biases. RESULTS: During 2010-2016, 1750 Asian patients had 1-2 SLN metastases and fulfilled the Z0011 criteria. These patients included 707 cases treated using SLND alone (40%) and 967 patients with ≤ 2 SLNs (55%). Ninety-five patients (5.4%) experienced DR at a median interval of 50 months, although the rates of DR were similar in the ALND and SLND groups. The adjusted hazard ratios for DR after ALND omission were 0.95 (95% CI 0.55-1.64) among the entire cohort and 0.83 (95% CI 0.34-2.03) among patients with ≤ 2 SLNs. CONCLUSIONS: In this Asian Z0011-eligible cohort, ALND omission did not increase risk of DR, even among patients with ≤ 2 SLNs. Therefore, the Z0011 strategy might be safely applied in Asia, and a small number of SLNs did not significantly influence this strategy.

Development of an exercise adherence program for breast cancer survivors with cancer-related fatigue-an intervention mapping approach.

PURPOSE: Cancer-related fatigue (CRF) is the most common and distressing symptom in breast cancer survivors (BCS), with severe impact on quality of life. CRF can be reduced through exercise, but conversely, is also a barrier to exercising. The aim of this article was to apply the intervention mapping protocol (IMP) to develop an exercise adherence intervention for BCS with CRF. METHOD: The program was developed using the IMP, which consists of six steps. Based on the data from focus group interviews and literature review, we produced a logic model of change. RESULTS: Two performance objectives (survivors adopt and maintain exercise and survivors cope with fatigue) and 17 change objectives were generated. Also, we designed theory-based methods of change, and strategies for practical application. A structured program plan that includes intervention content and methods, ranges, and program data was proposed. Finally, an implementation and evaluation plan was developed. CONCLUSION: The IMP provided a useful framework to systematically plan an exercise adherence program. This study resulted in a theory and practice-based exercise adherence program, based on behavioral change theories, and practice-based knowledge that fits the needs of BCS with CRF.

Impact of Micrometastatic Axillary Nodes on Survival of Breast Cancer Patients with Tumors ≤2 cm.

BACKGROUND: This study investigated the impact of pN1mi disease on the survival of T1 breast cancer patients and examined the clinical usefulness of the online PREDICT tool and updated staging system. METHODS: The node stages of 2344 patients were divided into pN0, pN1mi, and pN1a. Clinicopathological parameters and survival outcomes were retrospectively analyzed. Data for 111 micrometastatic diseases were applied to the PREDICT version 2.0 and re-classified using the 8th edition of the cancer staging manual. RESULTS: Univariable analyses demonstrated worse disease-free and overall survival rates for patients with node-positive cancer; however, the significance was not maintained in multivariable analyses. Chemotherapy improved outcomes in patients with node-positive and non-luminal A-like subtype cancers. The PREDICT tool demonstrated good performance when estimating the 5-year overall survival for pN1mi disease (area under the receiver operating characteristic curve, 0.834). According to the updated staging system, 74% of cases were down-staged to IA, and clearly splitting survival curves were identified. CONCLUSION: pN1mi disease alone did not adversely affect survival outcomes. Biologic and treatment factors determined outcomes in cases of small-volume node micrometastasis. The PREDICT tool or new staging classification could help predict the survival of patients with micrometastatic sentinel nodes.

Factors predictive of occult nipple-areolar complex involvement in patients with carcinoma in situ of the breast.

OBJECTIVES: To investigate predictors of occult nipple-areolar complex (NAC) involvement in patients with carcinoma in situ (CIS) and to validate an online probability calculator (CancerMath; www.lifemath.net/cancer/breastcancer/nipplecalc/index.php). METHODS: Mastectomized patients with CIS (n = 104) were retrospectively selected. Clinicopathology and preoperative mammography, ultrasound, and magnetic resonance imaging (MRI) findings were analyzed. RESULTS: Histopathological NAC-positivity was confirmed in 20 (19.2%) patients. Short nipple-tumor distance and suspicious extension to the nipple by mammography were significant but ultrasound was not significant to predict NAC involvement. NAC-positive cases had MRI findings of shorter nipple-tumor distance in both the early and delayed phases. Multivariable regression model showed age >50 years and shorter tumor-nipple distance on the delay phase of MRI were statistically significant predictors of NAC involvement. Area under the receiver operating characteristics curve (AUC) was 0.618 when calculated by CancerMath; however, an AUC of 0.954 was achieved when distance and age were applied together as predictor. CONCLUSIONS: Mammographic and MRI findings were significant for predicting NAC involvement, with distance of the tumor from the nipple in delay phase MRI the most significant predictor of NAC involvement. Therefore, breast MRI could be beneficial for planning nipple-sparing mastectomy in patients with CIS.

A proposal for a new classification of T4 breast cancer as stage IIIC: a report from the Korean Breast Cancer Society.

The objective of this study is to investigate staging system of the stage IIIB and stage IIIC Breast cancer and determine the criteria for an update of the classification system. Since AJCC 6th edition, it is pointed out that stage IIIB showed a worse outcome compared with stage IIIC. Using information from two databases, including the nationwide Korean Breast Cancer Registry (KBCR), three cohorts composed of patients from the Asan Medical Center from 1989 to 2002 (cohort I), from 2003 to 2008 (cohort II), and KBCR from 2003 to 2005 (cohort III) were assembled. New classifications were suggested that rearranged stage IIIB as T1-3N3 disease and stage IIIC as T4 any N disease. From the joint analysis of 9640, invasive breast cancer patients from cohorts I and II showed the stage IIIB group showed a significantly worse DFS (HR 10.4, 95% CI 6.9-15.7) compared with the stage IIIC group (HR 7.2, 95% CI 5.9-8.7). T4d breast cancer showed worse DFS than T4 abc breast cancer but not significant (p = 0.505). The survival of patients with T1N3 and T2N3 tumors was higher than the other groups, and patients with T4N3 tumors showed the worst survival outcomes in terms of DFS, CSS. Using new suggested classification, in cohort III, the stage IIIB HR for CSS was changed from 15.4 (95% CI 10.6-22.1) in the AJCC 6th edition to 12.6 (95% CI 10.1-15.6) in the proposed new staging system. The stage IIIC HR for CSS was changed from 13.3 (95% CI 10.7-16.4) in the AJCC 6th edition to 18.9 (95% CI 14.0-25.6) in the proposed new staging using stage I as a reference. Reclassification of T4 any N disease as stage IIIC and T1-3N3 disease as stage IIIB is appropriate.

Giant mixed hemangioma of the breast: A case report with imaging findings.

Hemangioma of the breast is an uncommon tumor type that is usually small, superficially located, and impalpable. The majority of cases are cavernous hemangiomas. We describe a rare case of a large, palpable mixed hemangioma of the breast which was located in the parenchymal layer, studied with magnetic resonance imaging, mammography, and sonography. Magnetic resonance imaging findings of slow and persistent enhancement from the center to periphery are useful in characterizing benign breast hemangiomas, where even the lesion presents with a suspicious shape and margin on sonography.

Long Term Effects of a Social Capital-Based Exercise Adherence Intervention for Breast Cancer Survivors With Moderate Fatigue: A Randomized Controlled Trial.

OBJECTIVES: This study reports on the long-term effects of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), implemented using a randomized controlled trial design. The study investigated outcomes related to cancer-related fatigue (CRF), quality of life (QOL), physical activity, depression, anxiety, sleep quality, and social capital. METHODS: Participants who had moderate or greater CRF were randomly assigned to the intervention (n = 24), consisting of supervised and home-based exercise, or the control (n = 26), who received exercise leaflets. Generalized estimating equations models were fitted for the outcome variables. The assessment points were baseline (M1), immediately after completing the intervention at 12 weeks (M2), 1 month (M3), and 6 months post-intervention (M4). RESULTS: A significant reduction in the total CRF score was found for both groups. We observed a significant time by group effect at M2, indicating a reduction of behavioral/severity CRF scores and a higher increase of physical activity. Also, there was an increase in the QOL score of both groups at M2, M3, and M4, compared to M1. Both groups had reduced anxiety at M3 and M4 compared to M1. The time by group effect for depression, sleep quality and social capital was not statistically significant. CONCLUSION: This 12-week exercise adherence program improved behavioral/severity CRF and physical activity post-intervention. Both the experimental group and control group showed significant improvements in CRF, QOL, and anxiety domains compared to the baseline, which extended to 6 months post-intervention. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0005763).

The radiosensitivity of endothelial cells isolated from human breast cancer and normal tissue in vitro.

We developed a novel method for harvesting endothelial cells from blood vessels of freshly obtained cancer and adjacent normal tissue of human breast, and compared the response of the cancer-derived endothelial cells (CECs) and normal tissue-derived endothelial cells (NECs) to ionizing radiation. In brief, when tissues were embedded in Matrigel and cultured in endothelial cell culture medium (ECM) containing growth factors, endothelial cells grew out of the tissues. The endothelial cells were harvested and cultured as monolayer cells in plates coated with gelatin, and the cells of 2nd-5th passages were used for experiments. Both CECs and NECs expressed almost the same levels of surface markers CD31, CD105 and TEM-8 (tumor endothelial marker-8), which are known to be expressed in angiogenic endothelial cells, i.e., mitotically active endothelial cells. Furthermore, both CECs and NECs were able to migrate into experimental wound in the monolayer culture, and also to form capillary-like tubes on Matrigel-coated plates. However, the radiation-induced suppressions of migration and capillary-like tube formations were greater for CECs than NECs from the same patients. In addition, in vitro clonogenic survival assays demonstrated that CECs were far more radiosensitive than NECs. In summary, we have developed a simple and efficient new method for isolating endothelial cells from cancer and normal tissue, and demonstrated for the first time that endothelial cells of human breast cancer are significantly more radiosensitive than their normal counterparts from the same patients.