Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

BACKGROUND: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. METHODS: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. RESULTS: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. CONCLUSION: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

Design and implementation of a standard care programme of therapeutic exercise and education for breast cancer survivors.

BACKGROUND: Breast cancer survivors (BCS) face several symptoms and are at higher risk of weight gain following diagnosis. Current literature shows that both exercise and diet play a key role in recovery of BCS. However, there is a gap between current guidelines and the real-world context. The aim of this article is to describe the process behind a free, not-for-profit community-based therapeutic exercise and education programme (TEEP) for BCS in the clinical setting. METHODS: The "Onco-Health Club" (OHC) consists of therapeutic exercise (TE) intervention aimed at ameliorating cancer-related fatigue (CRF) and improving QoL and physical function. TE is supplemented with nutritional education, providing information about the Mediterranean diet. To this end, patients are recruited from an oncologist and are referred to a physiotherapist and a nutritionist for baseline assessment. TEEP consists of a 3-month intervention, delivered twice a week in a group format with 1 h of TE and 30 min of nutritional education. BCS then have a final assessment and are advised to continue with a healthy lifestyle. Data about referral, compliance and assessment were collected. RESULTS: From May 2017 to February of 2020, a total of 158 patients were recruited from 8 cohorts and 142 initially started the OHC. From 119 that joined the program, 96 patients were considered to have finished it with good adherence (assistance > 80%). BCS significantly improved their QoL, as well as upper and lower limb's function, and increased their level of physical activity. CRF tended to decrease (p = 0.005). CONCLUSIONS: This study obtained data on recruitment, compliance, and possible limitations of these kinds of programmes in a real-world context. Further research is needed in order to optimize patient engagement and compliance, as well as to determine the transferability of these programmes in the clinical setting. TRIAL REGISTRATION: NCT03879096, Registered 18th March 2019. Retrospectively registered.

Validation of pain catastrophizing scale on breast cancer survivor.

INTRODUCTION: Pain catastrophizing scale (PCS) is the most used scale to measure pain catastrophizing. In breast cancer survivors (BCS), pain catastrophizing is related to upper-limbs dysfunction and disability. This study aimed to assess the internal consistency, internal structure, and convergent validity of the Spanish version of the PCS in Spanish BCS. MATERIAL AND METHODS: Breast cancer survivors were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The psychometric properties were evaluated with analysis factor structure by maximum likelihood extraction (MLE), internal consistency, and construct validity by confirmatory factor analysis (CFA). RESULTS: Factor structure was three-dimensional, and one item was removed due to cross-loading. The new 12-item PCS showed a high internal consistency for the total score (α = 0.91) and a good homogeneity, and CFA revealed a satisfactory fit. PCS showed an acceptable correlation with FACS (r = 0.53, p < 0.01). CONCLUSION: Pain catastrophizing scale is a valid and reliable instrument to evaluate pain catastrophizing in Spanish BCS. This tool may help clinicians in the management of pain by assessing pain and by measuring the effect of interventions.

Validity and reliability of the Spanish fear-avoidance components scale in breast cancer survivors.

OBJECTIVE: The aim of this study was to carry out a psychometric analysis of the Fear-Avoidance Components Scale (FACS-Sp) in Spanish breast cancer survivors (BCS). METHODS: A validation study was carried out in 154 BCS. Participants were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). A psychometric analysis of internal consistency, internal structure and convergent validity of the FACS-Sp was performed. Cronbach's alpha was calculated for internal consistency. Exploratory Factor Analysis was used to determine the internal structure of the FACS-Sp. Convergent validity with the Tampa Scale of Kinesiophobia (TSK) and the Pain Catastrophizing Scale (PCS) was determined using the Pearson correlation coefficient. RESULTS: The internal consistency was high (McDonald's ω = 0.91). The Exploratory Factor Analysis yielded one factor explaining the 40.80% of total variance. Convergent validity with the TSK and the PCS was demonstrated. CONCLUSIONS: The FACS-Sp has demonstrated to be a valid and reliable measure for assessing pain-related fear avoidance in BCS based on internal consistency, structural validity and convergent validity. Further studies that analyse other measurement properties in different Spanish cancer populations are needed.

Structural validity and reliability of the Spanish Central Sensitization Inventory in breast cancer survivors.

INTRODUCTION: One of the most widely used instruments to identify symptoms that may be related to central sensitization is the Central Sensitization Inventory (CSI). Although this instrument has been translated and validated in Spanish patients with chronic musculoskeletal pain, no psychometric analysis has been carried out in breast cancer survivors. The aim of this study was to perform a psychometric analysis of the Spanish version of the Central Sensitization Inventory (CSI-Sp) in Spanish breast cancer survivors. MATERIALS AND METHODS: A validation study was carried out in 183 breast cancer survivors. A psychometric analysis of internal consistency, factor structure, and test-retest reliability of the CSI-Sp was performed. Internal consistency was determined using Cronbach's alpha. Test-retest reliability was evaluated using the Intraclass Correlation Coefficient (ICC) Type 2.1. Exploratory factor analysis was used to determine the internal structure of the questionnaire. RESULTS: The internal consistency was high (α = 0.91). The test-retest reliability was satisfactory with excellent values (ICC 2.1 = 0.95). The exploratory factor analysis yielded a one factor structure explaining the 33.88% of total variance. CONCLUSIONS: The CSI-Sp has demonstrated to be a psychometrically strong measure for assessing central sensitization symptoms in breast cancer survivors based on internal consistency, test-retest reliability, and structural validity. Further studies that analyze other measurement properties in different Spanish clinical populations are needed.

Hereditary breast and ovarian cancer in Andalusian families: a genetic population study.

BACKGROUND: The BRCA1/2 mutation profile varies in Spain according to the geographical area studied. The mutational profile of BRCA1/2 in families at risk for hereditary breast and ovarian cancer has not so far been reported in Andalusia (southern Spain). METHODS: We analysed BRCA1/2 germline mutations in 562 high-risk cases with breast and/or ovarian cancer from Andalusian families from 2010 to 2015. RESULTS: Among the 562 cases, 120 (21.4%) carried a germline pathogenic mutation in BRCA1/2; 50 in BRCA1 (41.7%) and 70 in BRCA2 (58.3%). We detected 67 distinct mutations (29 in BRCA1 and 38 in BRCA2), of which 3 in BRCA1 (c.845C > A, c.1222_1223delAC, c.2527delA) and 5 in BRCA2 (c.293 T > G, c.5558_5559delGT, c.6034delT, c.6650_6654delAAGAT, c.6652delG) had not been previously described. The most frequent mutations in BRCA1 were c.5078_5080delCTG (10%) and c.5123C > A (10%), and in BRCA2 they were c.9018C > A (14%) and c.5720_5723delCTCT (8%). We identified 5 variants of unknown significance (VUS), all in BRCA2 (c.5836 T > C, c.6323G > T, c.9501 + 3A > T, c.8022_8030delGATAATGGA, c.10186A > C). We detected 76 polymorphisms (31 in BRCA1, 45 in BRCA2) not associated with breast cancer risk. CONCLUSIONS: This is the first study reporting the mutational profile of BRCA1/2 in Andalusia. We identified 21.4% of patients harbouring BRCA1/2 mutations, 58.3% of them in BRCA2. We also characterized the clinical data, mutational profile, VUS and haplotype profile.

Effect of neuromuscular taping on musculoskeletal disorders secondary to the use of aromatase inhibitors in breast cancer survivors: a pragmatic randomised clinical trial.

BACKGROUND: Aromatase inhibitors reduce breast cancer recurrence rates in postmenopausal women by about 30% compared with tamoxifen while treatments differ. Unfortunately, nearly half of women taking AIs report AI-associated arthralgia (AIA), leading to therapy abandon in on third of patients, which could lead to cancer recurrence. The purpose of the current study was to evaluate the effectiveness of Neuromuscular Taping (NMT) in the treatment of AIA in women who have been treated of BC. METHODS: This study included 40 BC survivors receiving endocrine therapy (either AIs or TMX) from Hospital Universitario Virgen de la Victoria (Málaga, Spain) suffered from AIA. Patients were randomized to one of the two groups that made this pilot study: A. Placebo intervention B. Real NMT. Clinical data were collected from medical history, grip strength, algometry measured, questionnaires and VAS scale. There have been three interventions prior to the completion of the study, 5 weeks later. The primary objective of this pilot study was to achieve an improvement of pain by 20% decrease of VAS. RESULTS: Significant differences in measures of VAS (p = 0.009), global health status/QoL (p = 0.005), fatigue (p = 0.01) and pain (p = 0.04) were observed post intervention with NMT. CONCLUSIONS: An intervention by NMT to MSCM under treatment with AIs improves their subjective sensation of pain. In addition, this taping had an impact on variables related to the quality of life. This pilot study may be the basis for others to support the use of NMT for the treatment of AIAs, thereby improving their well-being and reducing the dropout rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02406794 . Registered on 2 April 2015 Retrospectively registered.

Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index.

INTRODUCTION: Recurrence risk in breast cancer varies throughout the follow-up time. We examined if these changes are related to the level of expression of the proliferation pathway and intrinsic subtypes. METHODS: Expression of estrogen and progesterone receptor, Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) and cytokeratin 5/6 (CK 5/6) was performed on tissue-microarrays constructed from a large and uniformly managed series of early breast cancer patients (N = 1,249). Subtype definitions by four biomarkers were as follows: luminal A (ER + and/or PR+, HER2−, Ki-67 <14), luminal B (ER + and/or PR+, HER2−, Ki-67 ≥14), HER2-enriched (any ER, any PR, HER2+, any Ki-67), triple-negative (ER−, PR−, HER2−, any Ki-67). Subtype definitions by six biomarkers were as follows: luminal A (ER + and/or PR+, HER2−, Ki-67 <14, any CK 5/6, any EGFR), luminal B (ER + and/or PR+, HER2−, Ki-67 ≥14, any CK 5/6, any EGFR), HER2-enriched (ER−, PR−, HER2+, any Ki-67, any CK 5/6, any EGFR), Luminal-HER2 (ER + and/or PR+, HER2+, any Ki-67, any CK 5/6, any EGFR), Basal-like (ER−, PR−, HER2−, any Ki-67, CK5/6+ and/or EGFR+), triple-negative nonbasal (ER−, PR−, HER2−, any Ki-67, CK 5/6−, EGFR−). Each four- or six-marker defined intrinsic subtype was divided in two groups, with Ki-67 <14% or with Ki-67 ≥14%. Recurrence hazard rate function was determined for each intrinsic subtype as a whole and according to Ki-67 value. RESULTS: Luminal A displayed a slow risk increase, reaching its maximum after three years and then remained steady. Luminal B presented most of its relapses during the first five years. HER2-enriched tumors show a peak of recurrence nearly twenty months post-surgery, with a greater risk in Ki-67 ≥14%. However a second peak occurred at 72 months but the risk magnitude was greater in Ki-67 <14%. Triple negative tumors with low proliferation rate display a smooth risk curve, but with Ki-67 ≥14% show sharp peak at nearly 18 months. CONCLUSIONS: Each intrinsic subtype has a particular pattern of relapses over time which change depending on the level of activation of the proliferation pathway assessed by Ki-67. These findings could have clinical implications both on adjuvant treatment trial design and on the recommendations concerning the surveillance of patients.

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis.

INTRODUCTION: Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. METHODS: We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003-02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. RESULTS: Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. CONCLUSIONS: Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.

Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer.

BACKGROUND: Human papillomavirus (HPV)-related head and neck cancer has been associated with an improved prognosis in patients treated with radiotherapy (RT) +/- chemotherapy (CT); however, RT combined with epidermal growth factor receptor (EGFR) inhibitors has not been fully studied in this group of patients. METHODS: Immunohistochemical expression of p16 and PCR of HPV16 DNA were retrospectively analyzed in tumor blocks from 108 stage III/IV head and neck cancer patients treated with RT+CT (56) or RT+EGFR inhibitors (52). Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. RESULTS: DNA of HPV16 was found in 12 of 108 tumors (11%) and p16 positivity in 18 tumors (17%), with similar rates in both arms of treatment. After a median follow-up time of 35 months (range 6-135), p16-positive patients treated with RT+EGFR inhibitors showed improved survival compared with those treated with RT+CT (2-year OS 88% vs. 60%, HR 0.18; 95% CI 0.04 to 0.88; p = 0.01; and 2-year DFS 75% vs. 47%, HR 0.17; 95% CI 0.03 to 0.8; p = 0.01). However, no differences were observed in p16-negative patients (2-year OS 56% vs. 53%, HR 0.97; 95% CI 0.55 to 1.7; p = 0.9; and 2-year DFS 43% vs. 45%, HR 0.99; 95% CI 0.57 to 1.7; p = 0.9). CONCLUSIONS: This is the first study to show that p16-positive patients may benefit more from RT+EGFR inhibitors than conventional RT+CT. These results are hypothesis-generating and should be confirmed in prospective trials.

Development of a functional assessment task in metastatic breast cancer patients: the 30-second lie-to-sit test.

PURPOSE: To develop a physical function test based on lie-to-sit transition and to study its feasibility in patients suffering from metastatic breast cancer (MBC). MATERIALS AND METHODS: This cross-sectional study recruited 90 women diagnosed with MBC. Patients were asked to transfer from lying to sitting position as fast as possible during 30 s, performing the 30-second lie-to-sit test (30-LTS). Heart rate (HR), rate of perceived exertion (RPE) and number of repetitions were measured. An assessment included the 30-second sit-to-stand test (30-STS), handgrip strength, Upper Limb Functional Index (ULFI) and Lower Limb Functional Index (LLFI). Pearson correlation was calculated between 30-LTS and independent outcomes. A linear regression model explaining the 30-LTS results was further constructed with variables that had a significant correlation. RESULTS: About 72 patients were measured, of which 65 were able to perform 30-LTS. Subjects performed 8.13 repetitions on average, with a mean RPE of 4.78 (0-10), reaching 63.08% of maximal HR. 30-LTS was significantly correlated with 30-STS (r = 0.567), handgrip (p = 0.26) and LLFI (r = 0.348). The regression model was significant (F = 4.742; p = 0.00), and these variables explained 32% of the variance of the 30-LTS. CONCLUSION: The 30-LTS showed to be a feasible functional and submaximal test in a sample of MBC. IMPLICATIONS FOR REHABILITATIONThe 30-second lie-to-sit (30-LTS) developed does not require the patient to acquire a standing position and therefore it is an alternative to other more biomechanically demanding tests such as a 30 second sit-to-stand test or Timed up-and-go.30-LTS involves both a functional and energy system assessment tool that can be implemented by allied health professionals in oncology rehabilitation to individualize exercise prescription, as well as for functional screening purposes.The present study adds value to current research focused on individualizing exercise prescription in the oncology field and provides reference values of function in metastatic breast cancer patients.

Development and psychometric properties of the Stressors in Breast Cancer Scale.

Background: A diagnosis of breast cancer generates psychological stress, due not only to treatment and its side effects but also to the impact on different areas of the patient's daily life. Although there are instruments for measuring psychological stress in the cancer context, there is currently no tool for assessing stressors specific to breast cancer. Aims: The aim of this study was to develop the Stressors in Breast Cancer Scale (SBCS). Method: A panel of experts evaluated the clarity and relevance of scale items, providing validity evidence based on test content. Psychometric properties of the scale were then analyzed. Results: Validity evidence based on the internal structure of the SBCS was obtained through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), following a cross-validation strategy. The CFA supported a second-order factor model with five dimensions: physical appearance and sex strains, health and daily difficulties, interpersonal relationship strains, healthcare strains, and worries and concerns about the future. This structure was invariant across two groups distinguished by time from cancer diagnosis (less than 3 and 3 years or more from diagnosis). Reliability, based on McDonald's omega and Cronbach's alpha coefficients, ranged from 0.83 to 0.89 for factor scores, and reached 0.95 for total scores. Validity evidence was also provided by correlations with depression, anxiety, perceived stress, and perceived health and quality of life. Discussion: The results support the use of the SBCS for measuring stress as a stimulus in the breast cancer context. Implications for clinical practice and research are discussed.

Factors associated with upper limb function in breast cancer survivors.

BACKGROUND: Breast cancer survivors may have side effects from treatment, such as impaired upper limb function after surgery, which may be affected by a range of factors. OBJECTIVE: To analyze the association between upper limb function and strength, fear avoidance, and central sensitization symptoms among breast cancer survivors, and to explore how these variables are associated with upper limb function. DESIGN: Validation cohort. SETTING: Institutional practice at a public hospital. PATIENTS: One hundred seventy-four breast cancer survivors who had been undergone surgery for a primary tumor. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Upper limb function was measured by the Upper Limb Functional Index (ULFI-Sp). Independent outcomes were: handgrip strength, which was measured using a Jamar dynamometer on the dominant side; fear avoidance, measured using the Fear-Avoidance Components Scale (FACS-Sp); and central sensitization symptoms, which were measured using the Central Sensitisation Inventory (CSI-Sp). A linear regression model explaining the ULFI-Sp results was constructed with the variables. RESULTS: The regression model was significant (F = 46.826; p < .0001), and explained 45% of the variance of the ULFI values. All variables showed strong associations with upper limb function. CONCLUSIONS: Greater upper limb function is associated with higher grip strength, lower fear-avoidance behavior and fewer central sensitization symptoms among breast cancer survivors. These variables explained 45% of the upper limb function in the regression model, and concur with earlier research showing that factors such as central sensitization symptoms and kinesiophobia negatively affect upper limb function in such patients. Clinicians should therefore take into account strength, fear avoidance, and central sensitization symptoms when considering interventions aimed at improving upper limb function among breast cancer survivors.

Rucaparib for PARP inhibitor-pretreated ovarian cancer: A GEICO retrospective subgroup analysis from the Spanish Rucaparib Access Program.

The poly(ADP-ribose) polymerase inhibitor (PARPi) rucaparib is approved as maintenance therapy for patients with platinum-sensitive recurrent high-grade ovarian cancer (HGOC). The efficacy and safety of rucaparib after PARPi therapy are largely unknown; therefore, we analyzed outcomes in the subgroup of PARPi-pretreated patients from Spanish hospitals participating in the Rucaparib Access Program. This post hoc subgroup analysis explored baseline characteristics, treatment exposure, safety, effectiveness, and subsequent therapy among women receiving rucaparib 600 mg twice daily after at least one prior PARPi for HGOC. Of 14 women eligible for the analysis, 11 (79%) had tumors harboring BRCA1/2 mutations. Patients had received a median of 5 (range 3-8) treatment lines before rucaparib. Twelve patients (86%) had previously received olaparib and two (14%) niraparib; 12 patients received rucaparib as treatment for platinum-resistant HGOC, one as treatment for platinum-sensitive HGOC, and one as maintenance therapy. Progression-free survival was 0.2-9.1 months. One of seven patients assessable for response by RECIST achieved stable disease. Adverse events occurred in 11 patients (79%; grade 3 in 29%), leading to treatment interruption in eight patients (57%), dose reduction in six (43%), but treatment discontinuation in only one (7%). No new safety signals were observed. This is one of the first reported series of real-world data on rucaparib after prior PARPi for HGOC. In this heavily pretreated population, rucaparib demonstrated meaningful activity in some patients and tolerability consistent with previous prospective trials. Future investigation should focus on identifying patients who may benefit from rucaparib after prior PARPi exposure.

Implementation of a Standard Care Program of Therapeutic Exercise in Metastatic Breast Cancer Patients.

BACKGROUND: There is little information on the feasibility and benefit of therapeutic exercise (TE) in women with metastatic breast cancer (MBC). The aim of this article is to describe the implementation of a TE intervention in MBC patients, and to determine the recruitment, compliance and improvement in outcomes after its completion. METHODS: The "Therapeutic Exercise program in MBC" (TEP-MBC) consists of 1 h of individualized TE supervised by a physiotherapist in a group format, consisting of four groups of seven to eight participants. TEP-MBC was delivered twice a week, lasting 12 weeks (22 sessions), with patients considered to have completed the program when attending at least 17 sessions (>75% attendance). After referral, patients underwent a clinical interview and a physical and functional assessment. This information was complemented with patient-reported outcomes. Data about referral, compliance and assessment were collected. RESULTS: Only 11 of the 30 patients completed the program. Drop-out was mainly related to personal issues and symptoms arising from the disease or treatment. All patients who completed the program improved cancer-related fatigue and increased their functional parameters. CONCLUSIONS: The TEP-MBC was safe and feasible in patients with MBC, although with low compliance. The high variability in baseline measures reflects the heterogeneous level of function.

Responsiveness of the new index muscular echotexture in women with metastatic breast cancer: an exercise intervention study.

Ultrasound imaging texture analyses may provide information on tissue homogeneity changes in metastatic breast cancer (MBC) through second-order analyzes based on the gray-level co-occurrence matrix. This study aimed to analyze the responsiveness and correlations of biomarkers of muscular and fat echotexture after an exercise intervention in women with MBC. A 12-week exercise intervention was conducted in 2019, including aerobic and strength training. Echotexture variables were obtained at baseline and after intervention from the quadriceps (Q) and biceps brachii and brachialis. Mean differences were calculated using the T-Student parametric test for dependent samples of the differences in the means (P = 0.05; 95% CI). Data obtained from 13 MBC women showed significant differences in some echotexture variables after the intervention. QLQ-BR23 questionnaire correlated with several echotexture variables from muscle and subcutaneous fat. PFS-R scale correlated positively with the Q Subcutaneous Fat Non-Contraction Homogeneity (R = 0.43, P < 0.05). Q Muscle Non-Contraction Energy and Q Muscle Non-Contraction Textural Correlation explained 90% of the variance of QLQ-BR23. Some muscle and subcutaneous fat echotexture biomarkers showed good responsiveness after the exercise intervention. Additionally, some muscle and subcutaneous fat variables correlated with QLQ-BR23 and cancer-related fatigue measured by PFS-R scale in MBC patients.Trial registration: NCT03879096.

Role of germline variants in the metastasis of breast carcinomas.

Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumour cells, tumour microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumour characteristics but the host's genetic makeup. However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. In this work, we leveraged the extreme discordant phenotypes approach and the epistasis networks to analyse the genotypes of 97 breast cancer patients. We found that the host's genetic makeup facilitates metastases by the dysregulation of gene expression that can promote the dispersion of metastatic seeds and help establish the metastatic niche-providing a congenial soil for the metastatic seeds.

Outcome of small invasive breast cancer with no axillary lymph node involvement.

The prognosis and need or not for adjuvant therapy in patients with small breast tumors (≤1cm N0) is the subject of controversy as regards the clinical benefit obtained, toxicity, and the economical costs generated. A retrospective analysis was made of 238 patients with early-stage breast cancer (pT1≤1 cm N0M0) diagnosed between January 1993 and May 2008. As regards the systemic adjuvant treatments provided, (a) 122 (51%) received no treatment, (b) 102 (43%) received hormone therapy, (c) 9 (4%) chemotherapy, and (d) 5 (2%) received both hormone therapy and chemotherapy. An analysis was made of disease-free survival (DFS) and breast cancer-specific survival in our series of patients, and of their correlation to clinicopathological factors (age, tumor size, histological grade, estrogen receptor (ER) expression, HER-2 overexpression, and systemic adjuvant therapy). The median follow-up of this cohort was 63months (range 5-145). Some type of relapse was recorded in 4.2% of the patients (six patients presented local recurrence in all cases subjected to rescue treatment with surgery and/or radiotherapy, three patients developed distant metastases, and one patient presented a resected local recurrence followed by systemic relapse). The 5year DFS was 96%, and the 5year breast cancer-specific survival was 99.6%. A univariate analysis was made of the clinicopathological variables and their association to DFS. None of the variables was seen to be significantly correlated to shorter DSF except for an association between HER-2 overexpression and poor outcome borderline significance (p=0.07). The prognosis of our pT1≤1cm N0M0 tumors was excellent, although the absence of systemic adjuvant therapy in one-half of the patients.

Ultrasound use in metastatic breast cancer to measure body composition changes following an exercise intervention.

Changes in body composition and muscle dysfunction are common in metastatic breast cancer (MBC). Ultrasound imaging (US) offers reliable information about muscle and fat tissue architecture (thickness) and quality (echo-intensity). This study aimed to analyze the responsiveness of thickness and echo-intensity and its possible relationship with functional and patient reported-outcomes (PRO) in MBC patients after an exercise intervention. A prospective study was conducted in 2019. A 12-week exercise program was performed, including aerobic exercise and strength training. Measurements were made at baseline and after intervention. Thickness and echo-intensity were obtained from the quadriceps and biceps brachii and brachialis (BB). Mean differences were calculated using the T-Student parametric test for dependent samples of the differences in the means before and after the intervention (p = 0.05; 95% CI). Data from 13 MBC patients showed that some US muscle variables had significant differences after intervention. Best correlations were found between the quality of life questionnaire (QLQ-BR23) PRO and variables from BB muscle thickness in contraction (r = 0.61, p < 0.01), and Non-contraction (r = 0.55, p < 0.01). BB Muscle Non-contraction Thickness also explained 70% of QLQ-BR23 variance. In conclusion, muscle architecture biomarkers showed great responsiveness and are correlated with PRO after an exercise intervention in MBC patients.

Machine learning and natural language processing (NLP) approach to predict early progression to first-line treatment in real-world hormone receptor-positive (HR+)/HER2-negative advanced breast cancer patients.

BACKGROUND: CDK4/6 inhibitors plus endocrine therapies are the current standard of care in the first-line treatment of HR+/HER2-negative metastatic breast cancer, but there are no well-established clinical or molecular predictive factors for patient response. In the era of personalised oncology, new approaches for developing predictive models of response are needed. MATERIALS AND METHODS: Data derived from the electronic health records (EHRs) of real-world patients with HR+/HER2-negative advanced breast cancer were used to develop predictive models for early and late progression to first-line treatment. Two machine learning approaches were used: a classic approach using a data set of manually extracted features from reviewed (EHR) patients, and a second approach using natural language processing (NLP) of free-text clinical notes recorded during medical visits. RESULTS: Of the 610 patients included, there were 473 (77.5%) progressions to first-line treatment, of which 126 (20.6%) occurred within the first 6 months. There were 152 patients (24.9%) who showed no disease progression before 28 months from the onset of first-line treatment. The best predictive model for early progression using the manually extracted dataset achieved an area under the curve (AUC) of 0.734 (95% CI 0.687-0.782). Using the NLP free-text processing approach, the best model obtained an AUC of 0.758 (95% CI 0.714-0.800). The best model to predict long responders using manually extracted data obtained an AUC of 0.669 (95% CI 0.608-0.730). With NLP free-text processing, the best model attained an AUC of 0.752 (95% CI 0.705-0.799). CONCLUSIONS: Using machine learning methods, we developed predictive models for early and late progression to first-line treatment of HR+/HER2-negative metastatic breast cancer, also finding that NLP-based machine learning models are slightly better than predictive models based on manually obtained data.