Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer ...patients receiving EM as second, third and fourth line in a national real‐life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression‐free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti‐HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth‐line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth‐line). No significant difference was reported in second‐line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd‐line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real‐world database, HER2‐negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2‐targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti‐HER2 therapies addition in this setting still needs to be defined.
What's new?
An emerging therapy for metastatic breast cancer may extend survival over other chemotherapies. Eribulin mesylate (EM), a microtubule‐dynamics inhibitor, was approved by the FDA in 2010 as a later‐line therapy for metastatic breast cancer. Here, the authors evaluated EM effectiveness by analyzing data from 16,703 MBC patients. Treatment with EM as a third or fourth line therapy improved survival compared to other chemotherapy, but as a second line therapy, EM only benefited patients with HER2‐ disease. Since this trial was retrospective, not randomized, different proportions of patients in the two treatment groups received HER‐targeting therapies, which may have influenced the result.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Guidelines for the management of elderly patients with early breast cancer are scarce. Additional adjuvant systemic treatment to surgery for early breast cancer in elderly populations is challenged ...by increasing comorbidities with age. In non-metastatic settings, treatment decisions are often made under considerable uncertainty; this commonly leads to undertreatment and, consequently, poorer outcomes. This study aimed to develop a decision support tool that can help to identify candidate adjuvant post-surgery treatment schemes for elderly breast cancer patients based on tumor and patient characteristics. Our approach was to generate predictions of patient outcomes for different courses of action; these predictions can, in turn, be used to inform clinical decisions for new patients. We used a cohort of elderly patients (≥ 70 years) who underwent surgery with curative intent for early breast cancer to train the models. We tested seven classification algorithms using 5-fold cross-validation, with 80% of the data being randomly selected for training and the remaining 20% for testing. We assessed model performance using accuracy, precision, recall, F1-score, and AUC score. We used an autoencoder to perform dimensionality reduction prior to classification. We observed consistently better performance using logistic regression and linear discriminant analysis models when compared to the other models we tested. Classification performance generally improved when an autoencoder was used, except for when we predicted the need for adjuvant treatment. We obtained overall best results using a logistic regression model without autoencoding to predict the need for adjuvant treatment (F1-score = 0.869).
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Sarcopenia has been identified as an important prognostic factor for patients with cancer. This study aimed at exploring the potential associations between a 6-month physical activity ...intervention and muscle characteristics, sarcopenia, oxidative stress and toxicities in patients with metastatic breast cancer.
Methods
Women newly diagnosed with metastatic breast cancer (
N
= 49) participated in an unsupervised, personalized, 6-month physical activity intervention with activity tracker. Computerized tomography images at the third lumbar vertebra were analysed at baseline, three months and six months to assess sarcopenia (muscle mass index < 40 cm
2
/m
2
) and muscle quality (poor if muscle attenuation < 37.8 Hounsfield Units). Oxidative markers included plasma antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase activities), prooxidant enzymes (NADPH oxidase and myeloperoxidase activities) and oxidative stress damage markers (advanced oxidation protein products, malondialdehyde (MDA) and DNA oxidation.
Results
At baseline 53% (mean age 55 years (SD 10.41)) were sarcopenic and 75% had poor muscle quality. Muscle cross sectional area, skeletal muscle radiodensity, lean body mass remained constant over the six months (
p
= 0.75,
p
= 0.07 and
p
= 0.75 respectively), but differed significantly between sarcopenic and non-sarcopenic patients at baseline and 6-months. Sarcopenic patients at baseline were more likely to have an increase of MDA (
p
= 0.02) at 6 months. Being sarcopenic during at least one moment during the 6-month study was associated with a higher risk of developing severe toxicities (grade > 2) (
p
= 0.02).
Conclusions
This study suggests potential benefits of physical activity for maintenance of muscle mass. Sarcopenia can alter many parameters and disturb the pro and antioxidant balance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose
Lack of physical activity (PA), weight gain, and overweight have been associated with increased risk of recurrence and mortality after breast cancer diagnosis. We evaluated the feasibility of ...implementing an individualized exercise program and nutritional counseling during adjuvant treatment of localized invasive breast cancer.
Methods
Sixty-one patients eligible for adjuvant chemotherapy were randomized 2:1 to receive a 6-month program of weekly aerobic exercises associated with nutritional counseling (
n
= 41) or usual care with nutritional counseling (
n
= 20, one withdrawal). The primary endpoints were the proportion of patients compliant with two weekly supervised sessions and their overall adherence (i.e., proportion of supervised and unsupervised sessions completed versus planned sessions).
Results
Ten percent of patients in the intervention group were compliant with the two weekly supervised sessions for 6 months, but the overall median adherence rate was 85% of supervised and non-supervised sessions completed. Non-adherence was mainly due to intrinsic reasons (medical, organizational, psychological barriers). Adherence was positively associated with education and baseline PA level and inversely associated with baseline weight and tumor grade. No statistically significant benefits were observed in the intervention group, even if overall PA level and body composition improved and anthropometrics were maintained over time (
p
< 0.05).
Conclusions
Overall, there was good adherence with the 6-month exercise program during adjuvant treatment for breast cancer, despite poor compliance to twice-weekly supervised sessions. This study highlights the need for flexible exercise modalities and innovative experimental design to reach patients who would most adhere and benefit from intervention.
Trial registration:
ClinicalTrials.gov
Identifier: NCT01331772. Registered 8 April 2011,
https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1
Objective
This secondary analysis of the ABLE Trial (ClinicalTrials.gov NCT03148886) aimed to assess physical activity preferences before and after a 6‐month physical activity intervention for women ...recently diagnosed with metastatic breast cancer and to investigate demographic and clinical correlates of these preferences.
Methods
Forty‐nine patients participated in the ABLE Trial, a single‐arm, unsupervised 6‐month physical activity intervention with activity trackers. At baseline and 6 months, physical activity preferences, physical activity level, clinical variables, demographics and social vulnerability were assessed.
Results
At baseline, 49 participants were included, among whom 85% were interested in receiving physical activity counselling and 89% were interested in following a physical activity programme designed for metastatic breast cancer. At the end of the study, more participants preferred practising in a community fitness centre (66%) rather than at home (19% vs. 44% at baseline, p = .03). A higher social vulnerability score and not being treated by chemotherapy at baseline were significantly associated with lower desire to receive physical activity counselling (p = .01 and p = .04 respectively).
Conclusions
This study will help design future studies within patients with metastatic breast cancer in accordance with their preferences. Designing tailored physical activity interventions according to the participant's preferences may be one key to success for adherence.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain ...(RAD51-BD; exon 11) of
gene affects the clinical outcome of ovarian cancer patients.
A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for
and
genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer (
= 316) was used as a validation cohort.
In the study cohort, 78 patients were carriers of germline mutations of
After adjustment for FIGO stage and macroscopic residual disease,
carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS 58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64;
= 0.001 and prolonged PFI (29.7 vs. 15.5 months,
= 0.011), compared with noncarriers.
carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07;
= 0.094) or PFI (19 vs. 15.5 months,
= 0.146). In the TCGA cohort, only
carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68;
= 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38;
= 0.001).
Among ovarian cancer patients,
carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS.
.
Background
Additional systemic treatment for early breast cancer in elderly is challenged by increasing comorbidities with age. We aimed to examine the effect of additional chemotherapy on overall ...survival in patients aged 70 years or older and the impact of comorbidities on chemotherapy benefit.
Methods
This retrospective monocentric cohort study includes data from all patients aged 70 years and older who underwent surgery for an early breast cancer from 1997 to 2016. A propensity score analysis allowed adjustment for chemotherapy prescription preferences based on tumour characteristics.
Results
Of 15,599 patients who had surgery for an early breast cancer, 1743 (11.2%) over 70 years old were included, of whom 269 (15.4%) had received additional chemotherapy. Median follow-up was 5.3 years. Multivariate analyses on the propensity-score weighted cohort (
n
= 1 354) identified improved overall survival in patients with chemotherapy
versus
without (HR 0.54, 95% CI 0.31–0.92). Chronic obstructive pulmonary disease (HR, 2.16, 95% CI 1.40–3.34) and polypharmacy (HR 1.40, 95%CI 1.07–1.84) were associated with worse overall survival. No statistically significant interactions were identified between these comorbidities and chemotherapy prescription.
Conclusion
Additional chemotherapy in elderly with early breast cancer is feasible and associated with overall survival benefit, supporting the importance of chemotherapy considerations in this population, and of avoiding undertreatment based on chronological age considerations alone.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Glucocorticoids could theoretically decrease breast cancer risk through their anti-inflammatory effects or increase risk through immunosuppression. However, epidemiological evidence is limited ...regarding the associations between glucocorticoid use and breast cancer risk.
We investigated the association between systemic glucocorticoid use and breast cancer incidence in the E3N cohort, which includes 98,995 women with information on various characteristics collected from repeated questionnaires complemented with drug reimbursement data available from 2004. Women with at least two reimbursements of systemic glucocorticoids in any previous 3-month period since January 1, 2004, were defined as exposed. We considered exposure as a time-varying parameter, and we used multivariable Cox regression models to estimate hazard ratios (HRs) of breast cancer. We performed a competing risk analysis using a cause-specific hazard approach to study the heterogeneity by tumour subtype/stage/grade.
Among 62,512 postmenopausal women (median age at inclusion of 63 years old), 2864 developed breast cancer during a median follow-up of 9 years (between years 2004 and 2014). Compared with non-exposure, glucocorticoid exposure was not associated with overall breast cancer risk HR = 0.94 (0.85-1.05); however, it was associated with a higher risk of in situ breast cancer and a lower risk of invasive breast cancer HR
= 1.34 (1.01-1.78); HR
= 0.86 (0.76-0.97); P
= 0.01. Regarding the risk of invasive breast cancer, glucocorticoid exposure was inversely associated with oestrogen receptor (ER)-positive breast cancer HR
= 0.82 (0.72-0.94); HR
= 1.21 (0.88-1.66); P
= 0.03; it was also inversely associated with the risk of stage 1 or stage 2 tumours but positively associated with the risk of stage 3/4 breast cancers HR
= 0.87 (0.75-1.01); HR
= 0.67 (0.52-0.86); HR
= 1.49 (1.02-2.20); P
= 0.01.
This study suggests that the association between systemic glucocorticoid use and breast cancer risk may differ by tumour subtype and stage.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Resistance of advanced hormone‐dependent endometrial carcinoma to endocrine therapy remains a worldwide clinical issue. We recently reported that the combination of Vistusertib (V, mTOR inhibitor) ...and Anastrozole (A, aromatase inhibitor) improves the progression‐free rate compared to Anastrozole alone. However, a better patient selection based on biomarkers would improve patient outcome. We evaluate for the first time the usage of ribosome biogenesis (RiBi) factors as a source of innovative markers. Using 47 FFPE tumours (A n = 18; V + A n = 29), 32 blood samples (A n = 13; V + A n = 19) and 30 samples of total RNAs (A n = 12; V + A n = 18) from the VICTORIA clinical trial, we observed an association between RiBi‐associated markers and drug activity or prediction of treatment response. NOP10 and NHP2 mRNA levels were significantly higher in non‐responders compared to responders in the Vistusertib + Anastrozole arm (P = 0.0194 and P = 0.0002 respectively; i.e. 8 weeks progression‐free survival as endpoint). This study provides RiBi‐based markers relevant for a better selection of patients with advanced endometrial carcinoma by predicting the response of endocrine therapy combined with mTOR inhibitor.
Schematic workflow of the first ancillary research associated to the randomized phase I/II VICTORIA trial (NCT02730923, Anastrozole + Vistusertib in advanced endometrial cancer, Heudel et al. JAMA Oncol 2022) that investigates the ribosome biogenesis factors as predictive markers of combined aromatase/mTOR inhibitors. Distinct expression patterns of two RiBi genes (NHP2 and NOP10) were observed in responders and non‐responders of Vistusertib + Anastrozole combination therapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose
Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a ...negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF).
Methods
In this multicenter randomized double-blind placebo-controlled phase III study (
ClinicalTrials.gov
NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization.
Results
Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, − 2.9; P, − 2.5 points,
p
= 0.756) and relative decrease (A, − 17%; P, − 15%,
p
= 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (
p
= 0.470).
Conclusions
The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.
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