Low physical activity, fatigue and depression in breast cancer survivors: Moderation by levels of IL-6 and IL-8.

BACKGROUND AND AIMS: Although previous studies suggested that depressed mood and fatigue among cancer survivors are associated with chronic inflammation, the effect of cytokines on the relation between physical activity and fatigue and depressed mood is characterized by inconsistent results. The aim was to examine levels of pro-inflammatory (IL-6, IL-8, TNFα, IL-12) and anti-inflammatory (IL-10) cytokines in relation to the effects of physical activity on fatigue and depressed mood. METHODS: Breast cancer survivors (n = 108; stages I-III), aged >20 and who were 1-6 months postchemotherapy were recruited consecutively. Participants completed the Fatigue Symptom Inventory and Center for Epidemiologic Studies Depression Scale and reported physical activity details; 10 cc of blood were drawn for assessment of levels of IL-6, IL-8, IL-10, Il-12, and TNFα in serum. RESULTS: Only IL-6 and IL-8 were associated with fatigue and depressed mood. Controlling for background variables, physical activity and IL-6 were significantly associated with fatigue, but only physical activity was significantly associated with depressed mood. A moderated effect of IL-6 and IL-8 was found in the association of physical activity and fatigue, indicating that this association is significant only in individuals with lower levels of IL-6 or IL-8. CONCLUSIONS: Fatigue and depressed mood are differently associated with pro-inflammatory cytokines. In addition, IL-6 and IL-8 are main cytokines affected by physical activity. The study stresses the need to provide information and tailored guidance for cancer survivors for maintaining an active lifestyle into survivorship and the importance of allocating resources for programs to encourage active lifestyles among cancer survivors. Caution should be exercised in the interpretation of the results due to the cross-sectional design and possibility of bidirectional associations between the study variables.

Safety and tolerability of subcutaneous trastuzumab at home administration, results of the phase IIIb open-label BELIS study in HER2-positive early breast cancer.

PURPOSE: The subcutaneous (SC) administration of trastuzumab is highly preferred by patients. At home, administration of trastuzumab SC might further improve patient benefit. The aims of the BELIS study are to evaluate the safety and tolerability of trastuzumab SC when administered at home by a healthcare professional (HCP) and to evaluate patient-reported outcomes for treatment experience of at home cancer therapy. METHODS: This open-label phase IIIb study enrolled HER2-positive early breast cancer patients in Belgium and Israel who completed the first six cycles of trastuzumab IV (neo)adjuvant therapy. The study consisted of three consecutive treatment periods: three cycles of trastuzumab IV and SC each at the hospital and six cycles of trastuzumab SC at home. RESULTS: Between November 2013 and December 2014, 23 centres enrolled 102 patients in the intent-to-treat population of which 101 patients entered the safety population. No new safety signals were detected with as expected, more mild administration site events with trastuzumab SC when compared to IV treatment. All patients agreed that they had benefit from at home administration to a large (18/81; 22%) or very large (63/81; 78%) extent. All HCPs (21/21) agreed that SC is the quickest method from start of preparation to finish of administration and that less resource use is needed. CONCLUSION: The results of the BELIS study support that trastuzumab SC can be safely administered at home by a HCP and all patients considered this setting as beneficial. HCPs consider the SC formulation as the quickest method to administer trastuzumab. TRIAL REGISTRATION: EudraCT Identifier: 2013-000123-13. ClinicalTrials.gov Identifier: NCT01926886.

Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Stability and change of postchemotherapy symptoms in relation to optimism and subjective stress: A prospective study of breast cancer survivors.

OBJECTIVES: Inconsistent findings were reported about the course of postchemotherapy symptoms; specifically, the effect of changes in optimism and perception of subjective stress on the evolution of symptoms remains understudied. This prospective study aimed (a) to examine the course of postchemotherapy symptoms of emotional distress, fatigue, and cognitive difficulties among breast cancer survivors and (2) to assess the effect of changes in optimism and subjective stress on the trajectory of these symptoms. METHODS: Ninety-eight breast cancer survivors, diagnosed at stages I to III, aged 30 to 74, recruited consecutively (response rate 84.7%) completed fatigue, emotional distress, self-reported cognitive difficulties, optimism, and subjective stress questionnaires at three points in time: upon enrollment (1-6 months after completing treatment, Time 1) posttreatment, 6 months (Time 2), and 12 months (Time 3). A linear mixed-effects model was used to analyze the data. RESULTS: Emotional distress decreased between time-points, level of cognitive difficulties remained stable, and a marginal decrease in fatigue was evident. Optimism or subjective stress predicted changes in each of the symptoms (P<.01), except for the effect of optimism on cognitive difficulties (P=.06). The interactions between time and optimism and between time and subjective stress were only significant regarding their effect on emotional distress (P<.05), showing that the strongest effect of these variables was at Time 2. CONCLUSION: The course of postchemotherapy symptoms shows patterns of stability and change over a 1-year period. Optimism and subjective perceptions of stress were shown to affect the decrease of symptoms. Therefore, these two factors should be specifically targeted in psycho-social interventions.

Symptom cluster of emotional distress, fatigue and cognitive difficulties among young and older breast cancer survivors: The mediating role of subjective stress.

OBJECTIVES: To examine the nature of the symptom cluster of emotional distress, fatigue, and cognitive difficulties in young and older breast cancer survivors (BCS); To assess the mediating role of subjective stress and coping strategies (emotional control and meaning-focused coping) in the association between age and symptom cluster. MATERIALS AND METHODS: Participants were 170 BCS, stages I-III, 1-12 months post-chemotherapy, filled-out the Fatigue, Emotional Control, Meaning-focused Coping, Emotional Distress and the Cognitive Difficulties Questionnaires. Statistical analyses included tests for difference between-groups Pearson correlations and Structural Equation Modeling for the assessment of the study model. RESULTS: Older BCS (aged 60-82) reported lower levels of emotional distress (M = 0.87, SD = 0.87), fatigue (M = 3.85, SD = 2.38), and cognitive difficulties (M = 1.17, SD = 1.07) compared to the younger BCS (aged 24-59) (emotional distress M = 1.17, SD = 0.85, fatigue M = 5.02, SD = 2.32, and cognitive difficulties M = 1.66, SD = 1.23, p < .01-,05). The older survivors reported lower levels of subjective stress and used more emotional control strategies compared to the younger BCS. The empirical model had good fit indices (χ2 = 27.60, p = 0.20, χ2/df = 1.26; CFI = 0.98; TLI = 0.98; NFI = 0.95; RMSEA = 0.04 (90% CI = 0.00, 10) and showed that subjective stress, but not coping strategies, mediated the effect of age on symptom cluster severity. CONCLUSIONS: Lower levels of subjective stress, but not coping strategies, mediated the association of age with the symptom cluster of emotional distress, fatigue and cognitive difficulties. Further research is needed to explore differences in subjective stress by age.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 (N = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated (n = 27) and 2.9% in chemotherapy-untreated patients (n = 352); P = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients (n = 102) was significantly lower than in untreated patients (n = 156) (1.0% vs. 9.7% P = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated (n = 89) and 4.4% in chemotherapy-untreated patients (n = 488); P = 0.521. In conclusion, our findings support using endocrine therapy alone in ER+ HER2-negative breast cancer patients with micrometastases/1-3 positive nodes and Recurrence Score < 18.

Clinical outcomes in patients with node-negative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry.

The 21-gene Recurrence Score® (RS) assay is a validated prognostic/predictive tool in ER + early-stage breast cancer. However, clinical outcome data from prospective studies in RS ≥ 11 patients are lacking, as are relevant real-life clinical practice data. In this retrospective analysis of a prospectively designed registry, we evaluated treatments/clinical outcomes in patients undergoing RS-testing through Clalit Health Services. The analysis included N0 ER + HER2-negative breast cancer patients who were RS-tested from 1/2006 through 12/2010. Medical records were reviewed to verify treatments/recurrences/survival. The cohort included 1801 patients (median follow-up, 6.2 years). Median age was 60 years, 50.4% were grade 2 and 81.1% had invasive ductal carcinoma; 48.9% had RS < 18, 40.7% RS 18-30, and 10.4% RS ≥ 31, with chemotherapy use of 1.4, 23.7, and 87.2%, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 0.8, 3.0, and 8.6%, for patients with RS < 18, RS 18-30 and RS ≥ 31, respectively; the corresponding 5-year Kaplan-Meier estimates for breast cancer death were 0.0, 0.9, and 6.2%. Chemotherapy-untreated patients with RS < 11 (n = 304) and 11-25 (n = 1037) (TAILORx categorization) had 5-year Kaplan-Meier estimates for distant recurrence risk/breast cancer death of 1.0%/0.0% and 1.3%/0.4%, respectively. Our results extend those of the prospective TAILORx trial: the 5-year Kaplan-Meier estimates for distant recurrence and breast cancer death rate for the RS < 18 patients were very low supporting the use of endocrine therapy alone. Furthermore, in chemotherapy-untreated patients with RS 11-25 (where TAILORx patients were randomized to chemoendocrine or endocrine therapy alone), 5-year distant recurrence rates were also very low, suggesting that chemotherapy would not have conferred clinically meaningful benefit.

Biopsy of breast cancer metastases: patient characteristics and survival.

BACKGROUND: Discordance in hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) status between primary tumors and metastatic sites for breast cancer is well established. However, it is uncertain which patient-related factors lead to biopsy when metastases are suspected and whether having a biopsy impacts survival. METHODS: The medical charts of metastatic breast cancer (MBC) patients diagnosed January 2000-August 2014 were retrospectively reviewed. A biopsy was defined as a procedure where tissue was obtained and assessed for both HR and HER2. Both bivariate and multivariate analyses were performed to assess patient characteristics related to biopsy and whether having a biopsy was associated with improved survival. RESULTS: Of 409 patients suspected of having MBC, 165 (40%) had a biopsy, and 34% of these had discordant HR or HER2 status when compared to the initial diagnosis. In multivariate analysis, having a biopsy was associated with: recurrence in years 2010-2014, disease-free interval of > =3 years, stage 0-IIA at presentation, suspected locoregional recurrence, being HR+/HER2-, or missing HR/HER2 at diagnosis. A similar multivariate analysis revealed that having a biopsy was associated with improved survival (HR = 0.67, p = 0.002). The association of biopsy and improved survival was noted in specific subgroups: patients with missing HR and HER2 data at initial diagnosis (p = 0.001), those without metastases in liver, lung or brain (p = 0.001), and being younger than 70 years old at recurrence (p < 0.001). CONCLUSIONS: Specific clinical factors were associated with biopsy at the time of suspected recurrence. Having a biopsy was associated with reduced mortality.

Oral Bisphosphonates and Improved Survival of Breast Cancer.

Purpose: Bisphosphonates are used for treatment or prevention of osteoporosis and of bone metastases. The use of oral bisphosphonates was suggested to be associated with reduced risk of developing breast cancer, and their positive influence on breast cancer survival was only demonstrated with third-generation bisphosphonates. We studied the association of use of oral bisphosphonates after breast cancer diagnosis on overall and breast cancer survival.Experimental Design: A nested case-control analysis was performed using data from the population-based Breast Cancer in Northern Israel Study (BCINIS). Participants were postmenopausal women with newly diagnosed breast cancer insured by Clalit. Use of second-generation bisphosphonates (alendronate and/or risedronate) was identified using computerized prescription records. The analysis was restricted to women who did not use bisphosphonates prior to diagnosis.Results: In a cohort of 3,731 postmenopausal women with breast cancer, followed up for an average of 70 months, there were 799 cases of death which were matched to 15,915 control periods of living breast cancer cases. Use of bisphosphonates after diagnosis for at least 18 months was significantly more common among survivors than among their matched controls who died, adjusted for tumor stage/grade (overall survival: OR = 0.63, 0.41-0.96, P = 0.03; breast cancer-specific survival: OR = 0.28, 0.09-0.91, P = 0.035). A similar advantageous effect, but statistically underpowered, was found in estrogen receptor (ER)-positive, ER-negative, and HER2neu-positive tumors.Conclusions: The use of oral bisphosphonates, by postmenopausal, probably osteoporotic, women initiated after diagnosis of breast cancer was associated with a significant improvement in overall and breast-specific odds of survival. Clin Cancer Res; 23(7); 1684-9. ©2016 AACR.

Prospective comparison of whole-body bone SPECT and sodium 18F-fluoride PET in the detection of bone metastases from breast cancer.

OBJECTIVE: The superiority of sodium F-fluoride PET (F-PET)/computed tomography (CT) over planar and single field-of-view single-photon emission computed tomography (SPECT) bone scintigraphy with Tc-methylene diphosphonate in bone metastases detection has been established. The present study prospectively compares whole-body Tc-methylene diphosphonate SPECT (WB-SPECT) and F-PET performance indices for the detection of bone metastases in breast cancer. METHODS: A total of 41 pairs of studies in female breast cancer patients (average age 58 years, range 30-75) were included. Half-time WB-SPECT and F-PET/CT were performed at a 4-day average interval (range 0-36 days), with subsequent fusion of CT to WB-SPECT. Two readers independently interpreted the studies, with differences resolved by consensus. Composite gold standard included the CT component of the F-PET/CT study with follow-up CT, MRI, F-fluoro-deoxyglucose-PET/CT, and bone scans. RESULTS: On patient-based analysis, metastases were diagnosed in 21 patients, with 19 patients detected by WB-SPECT and 21 with F-PET, the latter being the only modality to detect a single metastasis in two patients. The sensitivity of WB-SPECT and F-PET was 90 and 100% (P=NS), and the specificity were 95 and 85%, respectively (P=NS). On lesion-based analysis, 284 total sites of increased uptake were found. WB-SPECT detected 171/284 (60%) and F-PET 268/284 (94%) lesions, with good interobserver agreement for WB-SPECT (κ=0.679) and excellent agreement for F-PET (κ=0.798). The final analysis classified 204 lesions as benign and 80 as metastases. WB-SPECT identified 121 benign and 50 malignant sites compared with 192 and 76, respectively, for F-PET. WB-SPECT and F-PET had a sensitivity of 63 vs. 95%, P-value of less than 0.001, and a specificity of 97 vs. 96% (P=NS), respectively, on lesion-based analysis. CONCLUSION: F-PET had higher sensitivity for the diagnosis of bone metastases from breast cancer compared with WB-SPECT, showing a statistically significant 32% increase on lesion-based analysis.

Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy.

OBJECTIVE: The efficacy and safety of olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, was investigated in a subgroup of patients with germline BRCA1/2 mutated (gBRCA1/2m) advanced ovarian cancer who had received ≥3 prior lines of chemotherapy. Primary data from this Phase II study (Study 42, ClinicalTrials.govNCT01078662) have been reported previously. METHODS: Eligible patients were treated with oral olaparib 400mg bid capsule monotherapy until disease progression according to RECIST v1.1. Objective response rate (ORR) and duration of response (DoR) were assessed for patients with measurable disease at baseline. Safety and tolerability were assessed for all patients by adverse event (AE) incidence and changes in laboratory parameters. Platinum resistance status was obtained retrospectively, and responses to olaparib evaluated. RESULTS: In patients with gBRCA1/2m ovarian cancer, 154/193 (80%) had received ≥3 prior lines of chemotherapy, of whom 137/154 (89%) had measurable disease at baseline. ORR was 34% (46/137; 95% confidence interval [CI] 26-42) and median DoR was 7.9 (95% CI 5.6-9.6) months. ORR in platinum-resistant tumors was 30%. Median DoR for platinum-sensitive and platinum-resistant disease was similar: 8.2months (95% CI 5.6-13.5) compared with 8.0months (4.8-14.8), respectively. Six of the 193 (3%) patients had an AE with an outcome of death. None of these AEs at time of occurrence was considered causally related to olaparib. CONCLUSION: Following ≥3 prior lines of chemotherapy, olaparib 400mg bid (capsule form) monotherapy demonstrated notable antitumor activity in patients with gBRCA1/2m advanced ovarian cancer. No new safety signals were identified.

Physicians' Considerations for Repeat Biopsy in Patients With Recurrent Metastatic Breast Cancer.

BACKGROUND: A strong recommendation has been made to perform repeat biopsy for recurrent metastatic breast cancer (RMBC), to reconfirm the histologic features, and to assess for possible changes in hormone receptors (HRs) or human epidermal growth factor receptor 2 (HER2) status. The present study was undertaken to assess the documented and nondocumented factors affecting physicians' decisions to perform a repeat biopsy in patients with RMBC. PATIENTS AND METHODS: We reviewed the medical records of 410 patients with RMBC for whom recurrence had developed between January 2000 and August 2014. The demographic data and characteristics regarding early and metastatic disease were recorded. The written follow-up records were examined, seeking considerations for or against repeat biopsy. Multivariate analysis was performed using logistic regression to determine the nondocumented reasons for repeat biopsy. RESULTS: A new biopsy was performed in 295 of 410 patients (72%). However, only 88 of the 295 patients (30%) had a documented reason for rebiopsy. The reason for not performing repeat biopsy was documented for only 1 of the 115 patients. The main documented consideration for rebiopsy was to obtain a new receptor status (recorded in 47 of 88 patients; 53%). The other recorded reasons were suspicion of a second primary, differential diagnosis of metastasis from a second primary, the time from early diagnosis, and patient desire. Significant, but undocumented, considerations for repeat biopsy were low stage at early diagnosis, year of recurrence, interval to recurrence, and site of recurrence. Only for 165 of 295 patients (56%) was the full HR and HER2 status from the new biopsy specimen obtained. CONCLUSION: Nondocumented factors influence physicians' decisions for referring patients for rebiopsy. This might reflect a low rate of patient involvement in their disease management and decision making.

Post-irradiation angiosarcoma of the breast: clinical presentation and outcome in a series of six cases.

Angiosarcoma of the breast represents 1% of all soft tissue breast tumors. With breast-conserving therapy (BCT) as standard in the last three decades, a new type of angiosarcoma has been reported: post-irradiation angiosarcoma (PIAS). A recent study based on the SEER database found an absolute risk for PIAS of seven per 100,000 person-years for BCT patients. We present a retrospective analysis of the clinical characteristics, treatment, and outcome of six cases of PIAS treated in our institution from 1995 to 2010. Mean age at diagnosis of breast cancer was 68 years (range 54-76 years). All patients underwent BCT. Adjuvant radiotherapy was given to all patients at doses of 45-50 Gy. Mean time from adjuvant radiotherapy to PIAS was 9.2 years (range 5.3-13.8 years); median follow-up from diagnosis of PIAS was 41.8 months (range 11-102 months). At diagnosis of PIAS, mean age of patients was 78 years (range 63-87 years). All patients underwent simple mastectomy, following which one patient received chemotherapy with doxorubicin and three patients received radiation therapy. Two patients developed local recurrence, one concurrent with metastatic disease. Another patient was diagnosed after 24 months with extensive small cell lung cancer and died of disease without recurrence of PIAS. Four patients are alive without evidence of recurrence. PIAS is a very rare sarcoma occurring after BCT. Careful observation after adjuvant radiotherapy is required. Standard treatment is the surgery with simple mastectomy and adjuvant radiotherapy; chemotherapy may be considered for more advanced cases.

Clinical and molecular characteristics of triple-negative breast cancer patients in Northern Israel: single center experience.

INTRODUCTION: Triple-negative breast cancer (TNBC) lacks estrogen and progesterone receptors and does not overexpress HER2. It displays a distinct clinical behavior. This study aims to assess the clinical, molecular and prognostic characteristics of TNBC patients. PATIENTS/METHODS: TNBC patients, referred to a tertiary medical center, 1/1/2000 - 31/12/2005, were included. Clinical, molecular and prognostic characteristics were retrospectively collected from patients' records. RESULTS: Overall, 122 consecutive TNBC patients were included with a median age of 54 years. Among the TNBC patients, 101 (82.8%) were Jews and 21 (17.2%) were Arabs. Family history for breast cancer was reported in 30 patients (24.6%). Genetic counseling was conducted in 30 patients (24.6%); 22/30 (73.3%) had BRCA1/2 mutations. Median tumor size was 2 cm and positive lymph nodes were detected in pathological examination in 40 patients (34%). At the time of data analysis, 21/118 patients (17.8%), who initially presented with early disease, had developed metastasis. Local recurrence was detected in four patients (3.4%). The overall survival (OS) was significantly longer for patients younger than 60 years compared to those ≥ 60 years, (Hazard ratio (HR) =2.1, p=0.046). Nulliparous patients had significantly higher OS than patients with a reproductive history of ≥ 4 children. (HR=0.31, p= 0.041). Mortality rate was higher for Arabs versus Jews but did not reach significance, (HR=1.33; P=0.64). CONCLUSIONS: TNBC represents an exclusive clinical behavior. Older age and parity were found to be poor prognostic factors. Further larger studies are needed to reaffirm our findings and explore the genetics among non-BRCA1/2 TNBC patients.

Cancer-related fatigue and depression in breast cancer patients postchemotherapy: Different associations with optimism and stress appraisals.

OBJECTIVE: Symptoms of depression and cancer-related fatigue (CRF) are common among breast cancer patients postchemotherapy and may seriously impair quality of life (QoL). This study aimed to assess the relationship between depression and CRF in breast cancer patients postchemotherapy and to examine their relationships to optimism and to threat and challenge appraisals. METHOD: Participants included 95 breast cancer patients (stages 1-3) 1 to 6 months after completion of chemotherapy. Patients submitted personal and medical details and completed the following: physical symptom questionnaires (EORTC QLQ-C30, and QLQ-BR23), a symptoms of depression questionnaire (CES-D), the Fatigue Symptom Inventory (FSI), the Life Orientation Test (LOT-R), and a stress appraisals questionnaire. RESULTS: We found levels of depression, CRF, and appraisals of cancer as a threat to bemoderate and levels of optimism and appraisals of cancer as a challenge to be high. Depression and CRF were positively associated. A multivariate regression analysis revealed that 51% of the CRF variancewas explained; physical symptoms and threat appraisal were significantly associated with CRF. A 67% of the CRF variance of depression was explained; challenge and threat appraisals were significantly associated with depression [corrected]. SIGNIFICANCE OF RESULTS: Although CRF and depression were often experienced simultaneously and both were found to be higher among individuals who gave higher appraisals of cancer as a threat, only depression was related to optimism and challenge appraisals, while CRF was related mainly to intensity of physical symptoms. The different pattern of associations between optimism and appraisals warrants further clinical attention as well as future study.

Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation.

PURPOSE: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers. PATIENTS AND METHODS: This multicenter phase II study enrolled individuals with a germline BRCA1/2 mutation and recurrent cancer. Eligibility included ovarian cancer resistant to prior platinum; breast cancer with ≥ three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. Olaparib was administered at 400 mg twice per day. The primary efficacy end point was tumor response rate. RESULTS: A total of 298 patients received treatment and were evaluable. The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. Stable disease ≥ 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade ≥ 3 AEs were reported for 54% of patients; anemia was the most common (17%). CONCLUSION: Responses to olaparib were observed across different tumor types associated with germline BRCA1/2 mutations. Olaparib warrants further investigation in confirmatory studies.

"I do not want my baby to suffer as I did"; prenatal and preimplantation genetic diagnosis for BRCA1/2 mutations: a case report and genetic counseling considerations.

This article presents the complexity of prenatal genetic diagnosis and preimplantation genetic diagnosis for hereditary breast-ovarian cancer syndrome. These issues are discussed using a case report to highlight the genetic counseling process, together with decision-making considerations, in light of the clinical, psychological, and ethical perspectives, of both the mutation carriers and health professionals; and the health policy regarding these procedures in Israel compared to several European countries.