Cognitive function in postmenopausal breast cancer patients one year after completing adjuvant endocrine therapy with letrozole and/or tamoxifen in the BIG 1-98 trial

Endocrine therapy for breast cancer may affect cognition. The purpose of this study was to examine whether cognitive function improves after cessation of adjuvant endocrine therapy. Change in cognitive function was assessed in 100 postmenopausal breast cancer patients in the BIG 1-98 trial, who were randomized to receive 5 years of adjuvant tamoxifen or letrozole alone or in sequence. Cognitive function was evaluated by computerized tests during the fifth year of trial treatment (Y5) and 1 year after treatment completion (Y6). Cognitive test scores were standardized according to age-specific norms and the change assessed using the Wilcoxon signed-rank test. There was significant improvement in the composite cognitive function score from Y5 to Y6 (median of change = 0.22, effect size = 0.53, P < 0.0001). This improvement was consistent in women taking either tamoxifen or letrozole at Y5 (P = 0.0006 and P = 0.0002, respectively). For postmenopausal patients who received either adjuvant letrozole or tamoxifen alone or in sequence, cognitive function improved after cessation of treatment.

Suicide in breast cancer patients: an individual-centered approach provides insight beyond epidemiology

Epidemiologic studies have identified increased suicide rates among breast cancer (BC) patients. The population-based approach, however, has considerable methodic shortcomings. None of the studies have been carried out in a prospective manner and none reported suicide rates from a country in which physician-assisted suicide (PAS) is legal.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients

High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia.

Sentinel lymph node biopsy in early-stage breast cancer patients: improved survival through better staging?

The objective of this review is to summarize the evidence demonstrating that the sentinel lymph node (SLN) procedure is not only associated with significantly less morbidity compared to the axillary dissection, but may also result in better staging and improved patient outcomes.

Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

BACKGROUND: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients

OBJECTIVE: The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96-98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I ; II axillary lymph node dissection (ALND). METHODS: Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2< or =3 cm, pN0/pN(SN)0) were assessed from our prospective database. Patients underwent either ALND (n=178) in 1990-1997 or SLN biopsy (n=177) in 1998-2004. All SLN were examined by step sectioning, stained with H;E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H;E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen. RESULTS: The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p=0.008) and overall survival (p=0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10-0.73, p=0.009) and overall survival (HR: 0.34, 95% CI: 0.14-0.84, p=0.019). CONCLUSIONS: This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.

Fertility preservation options in breast cancer patients.

The purpose of this review is to analyse current options for fertility preservation in young women with breast cancer (BC). Considering an increasing number of BC survivors, owing to improvements in cancer treatment and delaying of childbearing, fertility preservation appears to be an important issue. Current fertility preservation options in BC survivors range from well-established standard techniques to experimental or investigational interventions. Among the standard options, random-start ovarian stimulation protocol represents a new technique, which significantly decreases the total time of the in vitro fertilisation cycle. However, in patients with oestrogen-sensitive tumours, stimulation protocols using aromatase inhibitors are currently preferred over tamoxifen regimens. Cryopreservation of embryos and oocytes are nowadays deemed the most successful techniques for fertility preservation in BC patients. GnRH agonists during chemotherapy represent an experimental method for fertility preservation due to conflicting long-term outcome results regarding its safety and efficacy. Cryopreservation of ovarian tissue, in vitro maturation of immature oocytes and other strategies are considered experimental and should only be offered within the context of a clinical trial. An early pretreatment referral to reproductive endocrinologists and oncologists should be suggested to young BC women at risk of infertility, concerning the risks and benefits of fertility preservation options.

Laparoscopic Indocyanine Green Sentinel Lymph Node Mapping in Pregnant Cervical Cancer Patients.

We present cases of 2 pregnant patients with early-stage cervical cancer who have undergone indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by laparoscopic SLN biopsy, pelvic lymphadenectomy, and cervical conization. Eight milliliters of ICG were injected in the 4 quadrants of the cervix after having obtained an adequate pneumoperitoneum and having inspected the abdominal cavity. SLNs were identified in both hemipelvises in both patients. In the final pathologic analysis, both SLNs and non-SLNs were negative for metastatic disease. No adverse events from ICG injection were recorded. ICG SLN mapping seems to be feasible in pregnant cervical cancer patients.

The effect of yoga on cardiovascular health as measured by heart rate variability in a sample of breast cancer patients

The study is a three-armed randomized controlled trial comparing values for heart rate variability (HRV), a measure of cardiovascular health, throughout a yoga intervention of breast cancer patients undergoing radiotherapy. Patients attended either a yoga (n=45), stretch, (n=46), or control (n=42) condition 3 times per week for 6 weeks of radiation. Electrocardiograms (ECGs) were conducted on each participant to provide the values necessary for HRV analysis. Analyses focused on examining scores for those participants with HRV baseline values considered to be below the cutoff point for healthy HRV levels, defined by the authors as below the cutpoint of 68 ms. From the entire sample of 133 with available baselines, 26 yogis, 26 stretchers, and 23 controls were determined to be “pathologic” in terms of HRV, and selected for follow-up analysis at 3 weeks and then again at 6 weeks. Though no statistically significant differences were found between either group means at each timepoint or group change score means, the yoga group had consistently higher mean score and mean change scores. These findings are suggestive and indicate the need to refine the use of ECGs and HRV analysis programs to more accurately and comprehensively assess the effects of yoga on cardiovascular health in cancer patients.^

Trastuzumab use and risk of congestive heart failure in older breast cancer patients

Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^

Running away from side effects: physical exercise as a complementary intervention for breast cancer patients

The number of breast cancer survivors increases every year, thanks to the development of new treatments and screening techniques. However, patients present with numerous side effects that may affect their quality of life. Exercise has been demostrated to reduce some of these side effects, but in spite of this, few breast cancer patientes know and follow the exercise recommendations needed to remain healthy. In this review, we describe the differente breast cancer treatments and the related side effects and implications of exercise in relation to these. We propose that exercise could be and integrative complementary intervention to improve physiological, physical and psychological factors that affect survival and quality of life of these patients. For that reason, the main objective of this review is to provide a general overview of exercise benefits in breast cancer patients and recommendations of how to design exercise interventions in patients with different side effects.

Influencia de un programa de ejercicio aeróbico en la calidad de vida de pacientes afectadas por cáncer de mama = Influence of an aerobic exercise program on breast cancer patients’ quality of life

INTRODUCCIÓN Actualmente las supervivientes de cáncer de mama viven durante más tiempo. Sin embargo, los tratamientos utilizados presentan importantes efectos secundarios que afectan y marcan su calidad de vida. Numerosos estudios han mostrado que el ejercicio es una herramienta apta, segura y efectiva reduciendo algunos de estos efectos secundarios y, en suma, mejorando la calidad de vida de estas pacientes, aspecto que presenta al ejercicio físico como una intervención integral para ellas. Por el contrario, se ha observado que las supervivientes de cáncer de mama reducen la cantidad de ejercicio que realizan después de dichos tratamientos. Por ello, el objetivo de este proyecto es examinar los efectos de un programa integral de ejercicio en la calidad de vida y la cantidad de ejercicio físico que realizan las pacientes con cáncer de mama en su tiempo, tras finalizar sus tratamientos. MATERIAL Y MÉTODOS Se diseñó un Ensayo Clínico Aleatorizado. Noventa pacientes diagnosticadas de cáncer de mama en estadios tempranos que habían terminado sus tratamientos de radioterapia y quimioterapia recientemente, fueron reclutadas por la Universidad Politécnica de Madrid, desde enero de 2013 hasta junio de 2014. Las pacientes fueron aleatorizadas tras las mediciones iniciales al grupo control (tratamientos habituales) o grupo intervención, durante tres meses. La intervención consistió en 24 clases de ejercicio combinando práctica aeróbica y de fuerza con el fin de reducir los efectos secundarios de dichos tratamientos. La calidad de vida, la cantidad de ejercicio físico realizado en tiempo de ocio, VO2max, la fuerza, la movilidad articular del hombro, la fatiga, la depresión y la ansiedad fueron medidos al inicio y después de los tres meses en todos los pacientes. RESULTADOS Un total de 89 pacientes con una media de 49.06±8.75 de edad fueron finalmente analizadas. El grupo intervención (n=44) mostraron significativamente mejores resultados en calidad de vida (p=0.0001; d=0.85), cantidad de ejercicio en tiempo de ocio (p=0.0001; d=2.77), en variables de la composición corporal, en variables físicas y en variables psicológicas comparado con el grupo control (n=45). Además, se observó una correlación significativa entre la calidad de vida y el ejercicio realizado en tiempo de ocio en el grupo intervención (r= 0.58; p=0.001), que no fue patente en el grupo control. Se observaron cambios significativos en el grupo de intervención relativos a la composición corporal, con aumento de la masa muscular (p=0.001) y reducción de la masa grasa (p=0.0001). Tanto las variables físicas como psicológicas también mostraron diferencias significativas a favor al grupo de intervención en las comparaciones entre grupos. CONCLUSIONES Según estos resultados, un programa de ejercicio físico específico es una intervención integral que mejora los hábitos y la calidad de vida de las supervivientes de cáncer de mama, lo que reduce determinados efectos secundarios de los tratamientos y aumenta la salud física y psicológica general de estas mujeres. Este tipo de intervenciones pude ser una herramienta barata y efectiva para ofrecer a los pacientes, integrada en los tratamientos habituales. ABSTRACT INTRODUCTION It is well known that breast cancer survivors are living longer. However, breast cancer treatments present serious side effects, which could affect breast cancer survivors’ (BCS) health and quality of life (QoL). Exercise has been presented as a feasible, safe and effective tool in reducing some of these side effects and to improve survivors’ QoL, acting as an integrative treatment for them, although it has been observed that BCS reduce their leisure time exercise (LTE) levels. Therefore, the aim of this study was to examine the effects of an integrative exercise program in QoL and LTE in BCS after the completion of their adjuvant treatment. MATERIAL AND METHODS A randomized controlled trial (RCT) was designed. Ninety patients diagnosed with an early stage of breast cancer and who recently finished chemotherapy and radiotherapy treatments were recruited by the Technical University of Madrid from January 2013 to June 2014. Patients were randomized after baseline assessments to the intervention group (IG) or to the control group (CG) (usual care) for three months. The Intervention consisted in 24 supervised exercise classes, combining aerobic and resistance exercises in order to reduce the most common side effects of the treatments. QoL, LTE, body composition, VO2max, strength, shoulder range of motion, fatigue, depression and self-esteem were measured in all the patients at baseline and after three months. RESULTS A total of 89 patients aged 49.06±8.75 years were finally assessed. IG (n=44) showed significant better results in QoL (p=0.0001; d=0.85), LTE (p=0.0001; d=2.77), in body composition, in the physical variable and in psychological outcomes, compared with the CG (n=45). In addition, a correlation between QoL and LTE (r= 0.58; p=0.001) was found in the IG, while CG did not show this correlation. Significant changes in body composition were observed in the group comparisons, especially in lean mass (p=0.001) and body fat mass (p= 0.0001). Positive changes were also observed in the physical and psychological variables in comparisons between groups. CONCLUSIONS These results suggest that this exercise program may be an integrative intervention, which is able to improve QoL and LTE levels in breast cancer survivors, reducing breast cancer side effects of treatments and improving their physical and psychological general health. Exercise may be an effective and inexpensive strategy to be included in patients integrative care.

Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: A phase I trial

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each. The vaccine was well tolerated, and no definite differences were observed among the three formulations. Serologic analyses demonstrated the generation of IgM antibody titers in most patients, with minimal IgG antibody stimulation. There was significant binding of IgM antibodies to MCF-7 tumor cells in 16 patients, whereas IgG antibody reactivity was observed in a few patients. There was evidence of complement-dependent cytotoxicity in several patients. Affinity column purification supported the specificity of IgM antibodies for globo H. On the basis of these data, globo H will constitute one component of a polyvalent vaccine for evaluation in high-risk breast cancer patients.

Confirming the Association Between Affective Disturbance and Perceived Cognitive Dysfunction Among Breast Cancer Patients: A Meta-Analysis of Available Literature

Purpose: Breast cancer is the most frequently diagnosed cancer among women worldwide. While undergoing chemotherapy treatment for breast cancer, patients often report experiencing "chemobrain." Previous literature reports correlations between psychological distress and these perceived cognitive problems. The aim of the present study was to examine the strength of the association between affective disturbance and subjective cognitive dysfunction.Methods: This study included a meta-analysis of the literature reporting a correlation between mood and subjective cognitive dysfunction. Eight studies with 1344 breast cancer patients treated with chemotherapy were selected based on stringent study inclusion criteria. Studies reporting a correlation coefficient between mood and subjective cognitive dysfunction were included.Results: In these data, there was no significant correlation between affective disturbance and subjective cognitive dysfunction. A random effects model yielded an overall weighted mean effect size of 0.12.Conclusion: Although this meta-analysis did not confirm the correlation between mood and subjective cognitive dysfunction, there was a clear association between these factors in the original disaggregated analyses, and they are clearly impactful from the time of diagnosis through long-term after care. The clinical implications of the present study and future directions for research are discussed.