Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary ...epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the ...cancer recur locally in the breast or in other areas of the body. We explore the use of clinical history, immunohistochemical markers, and multiparametric magnetic resonance imaging (DCE, ADC, Dixon) to predict the risk of post-treatment recurrence within five years. We performed a retrospective study on a cohort of 1738 patients from Institut Curie and analyzed the data using classical machine learning, image processing, and deep learning. Our results demonstrate the ability to predict recurrence prior to NAC treatment initiation using each modality alone, and the possible improvement achieved by combining the modalities. When evaluated on holdout data, the multimodal model achieved an AUC of 0.75 (CI: 0.70, 0.80) and 0.57 specificity at 0.90 sensitivity. We then stratified the data based on known prognostic biomarkers. We found that our models can provide accurate recurrence predictions (AUC > 0.89) for specific groups of women under 50 years old with poor prognoses. A version of our method won second place at the BMMR2 Challenge, with a very small margin from being first, and was a standout from the other challenge entries.
Breast cancer (BC) is the most frequent cancer and the leading cause of cancer-related death in women. The French National Cancer Institute has created a national cancer cohort to promote cancer ...research and improve our understanding of cancer using the National Health Data System (SNDS) and amalgamating all cancer sites. So far, no detailed separate data are available for early BC.
To describe the creation of the French Early Breast Cancer Cohort (FRESH).
All French women aged 18 years or over, with early-stage BC newly diagnosed between 1 January 2011 and 31 December 2017, treated by surgery, and registered in the general health insurance coverage plan were included in the cohort. Patients with suspected locoregional or distant metastases at diagnosis were excluded. BC treatments (surgery, chemotherapy, targeted therapy, radiotherapy, and endocrine therapy), and diagnostic procedures (biopsy, cytology, and imaging) were extracted from hospital discharge reports, outpatient care notes, or pharmacy drug delivery data. The BC subtype was inferred from the treatments received.
We included 235,368 patients with early BC in the cohort (median age: 60 years). The BC subtype distribution was as follows: luminal (80.2%), triple-negative (TNBC, 9.5%);
(10.3%), or unidentifiable (
= 44,388, 18.9% of the cohort). Most patients underwent radiotherapy (
= 200,685, 85.3%) and endocrine therapy (
= 165,655, 70.4%), and 38.3% (
= 90,252) received chemotherapy. Treatments and care pathways are described.
The FRESH Cohort is an unprecedented population-based resource facilitating future large-scale real-life studies aiming to improve care pathways and quality of care for BC patients.
Survival disparities persist in ovarian cancer and may be linked to the environments in which patients live. The main objective of this study was to analyze the global impact of the area of residence ...of ovarian cancer patients on overall survival. The data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We included all the patients with epithelial ovarian cancers diagnosed between 2010 and 2016. The areas of residence were analyzed by the hierarchical clustering of the principal components to group similar counties. A multivariable Cox proportional hazards model was then fitted to evaluate the independent effect of each predictor on overall survival. We included a total of 16,806 patients. The clustering algorithm assigned the 607 counties to four clusters, with cluster 1 being the most disadvantaged and cluster 4 having the highest socioeconomic status and best access to care. The area of residence cluster remained a statistically significant independent predictor of overall survival in the multivariable analysis. The patients living in cluster 1 had a risk of death more than 25% higher than that of the patients living in cluster 4. This study highlights the importance of considering the sociodemographic factors within the patient's area of residence when developing a care plan and follow-up.
The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker ...for immune checkpoint inhibitors' (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (
= 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC,
= 0.25, and PD-L1-IC,
= 0.95) or overall survival (OS) (PD-L1-TC,
= 0.48, and PD-L1-IC,
= 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS,
= 0.0014, and OS,
= 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.
Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly
pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant ...chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to
status.
Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline
pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses.
Among 1199 BC patients: 46 were
-deficient and 221
proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in
deficient BC (
0.001), and this association remained statistically significant only in the luminal BC subtype (
0.006). The interaction test between BC subtype and
status was nearly significant (
= 0.056). Pre and post-NAC TILs were not significantly different between
deficient and
proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in
deficient BC. Survival analysis were not different between
carriers and non-carriers.
mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC.
-carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC.
Breast cancer (BC) is the most common cancer in women worldwide. Neoadjuvant chemotherapy (NAC) makes it possible to monitor in vivo response to treatment. Several studies have investigated the ...impact of the seasons on the incidence and detection of BC, on tumor composition, and on the prognosis of BC. However, no evidence is available on their association with immune infiltration and the response to treatment. The objective of this study was to analyze pre- and post-NAC immune infiltration as assessed by TIL levels, the response to treatment as assessed by pathological complete response (pCR) rates, and oncological outcomes as assessed by relapse-free survival (RFS) or overall survival (OS) according to the seasonality of BC diagnoses in a clinical cohort of patients treated with neoadjuvant chemotherapy. Out of 1199 patients, the repartition of the season at BC diagnosis showed that 27.2% were diagnosed in fall, 25.4% in winter, 24% in spring, and 23.4% in summer. Baseline patient and tumor characteristics, including notable pre-NAC TIL levels, were not significantly different in terms of the season of BC diagnosis. Similarly, the pCR rates were not different. No association for oncological outcome was identified. Our data do not support the idea that the seasonality of diagnoses has a major impact on the natural history of BC treated with NAC.
No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against
-positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the ...prognosis of
-positive BC patients treated with NAC to that of patients treated with adjuvant chemotherapy (AC).
We retrospectively analyzed disease-free (DFS) and overall survival (OS) in 202
-positive patients treated with NAC and 701 patients treated with AC. All patients received trastuzumab in addition to chemotherapy. Patient data were weighted by a propensity score to overcome selection bias.
After inverse probability of treatment weights (IPTW) adjustment, no difference in DFS (
= 0.3) was found between treatments for the total population. However, after multivariate analysis, an interaction was found between cN status and chemotherapy strategy (IPTW-corrected corrected Hazard ratio cHR = 0.52, 95% CI (0.3-0.9),
= 0.08) and between menopausal status and chemotherapy (CT) strategy (cHR = 0.35, 95%CI (0.18-0.7))
< 0.01). NAC was more beneficial than AC strategy in cN-positive patients and in postmenopausal patients. Moreover, after IPTW adjustment, the multivariate analysis showed that the neoadjuvant strategy conferred a significant OS benefit (cHR = 0.09, 95%CI 0.02-0.35,
< 0.001).
In patients with
-positive BC, the NAC strategy is more beneficial than the AC strategy, particularly in cN-positive and postmenopausal patients. NAC should be used as a first-line treatment for
-positive tumors.
The three different breast cancer subtypes (Luminal,
positive, and triple negative (TNBCs) display different natural history and sensitivity to treatment, but little is known about whether residual ...axillary disease after neoadjuvant chemotherapy (NAC) carries a different prognostic value by BC subtype.
We retrospectively evaluated the axillary involvement (0, 1 to 3 positive nodes, ≥4 positive nodes) on surgical specimens from a cohort of T1-T3NxM0 BC patients treated with NAC between 2002 and 2012. We analyzed the association between nodal involvement (ypN) binned into three classes (0; 1 to 3; 4 or more), relapse-free survival (RFS) and overall survival (OS) among the global population, and according to BC subtypes.
1197 patients were included in the analysis (luminal (
= 526, 43.9%), TNBCs (
= 376, 31.4%),
-positive BCs (
= 295, 24.6%)). After a median follow-up of 110.5 months, ypN was significantly associated with RFS, but this effect was different by BC subtype (
= 0.004), and this effect was nonlinear. In the luminal subgroup, RFS was impaired in patients with 4 or more nodes involved (HR 2.8; 95% CI 1.93; 4.06,
< 0.001) when compared with ypN0, while it was not in patients with 1 to 3 nodes (HR = 1.24, 95% CI = 0.86; 1.79). In patients with TNBC, both 1-3N+ and ≥4 N+ classes were associated with a decreased RFS (HR = 3.19, 95% CI = 2.05; 4.98 and HR = 4.83, 95% CI = 3.06; 7.63, respectively
ypN0,
< 0.001). Similar decreased prognosis were observed among patients with
-positive BC (1-3N +: HR = 2.7, 95% CI = 1.64; 4.43 and ≥4 N +: HR = 2.69, 95% CI = 1.24; 5.8 respectively,
= 0.003).
The prognostic value of residual axillary disease should be considered differently in the 3 BC subtypes to accurately stratify patients with a high risk of recurrence after NAC who should be offered second line therapies.
Breast cancer (BC) is the most commonly diagnosed type of cancer and the leading cause of cancer deaths in women. Smoking is the principal modifiable risk factor for cancers and has a negative ...influence on long-term survival. We conducted a retrospective study on consecutive BC survivors seen at follow-up consultations between 3 June and 30 October 2019 at Institut Curie, Paris, France. Smoking behaviors were evaluated prospectively via interviewer-administered questionnaires. The aim of this study was to describe smoking-related patient care at diagnosis and smoking cessation patterns in women with a history of BC. A total of 1234 patients were included in the study. Smoking status at diagnosis was missing from electronic health records in 32% of cases, including 13% of patients who smoke. Only 20% of the 197 patients currently smoking at diagnosis recalled having a discussion about smoking with a healthcare professional. Radiotherapists and surgeons were more likely to talk about complications than other practitioners. The main type of information provided was general advice to stop smoking (n = 110), followed by treatment complications (n = 48), while only five patients were referred to tobaccologists. Since diagnosis, 33% (n = 65) of the patients currently smoking had quit. Patients who quit had a lower alcohol consumption, but no other factor was associated with smoking cessation. The main motivation for tobacco withdrawal was the fear of BC relapse (63%). This study highlights room for improvement in the assessment of smoking behavior. Our data raise important perspectives for considering BC treatment and follow-up as a window of opportunity for smoking cessation.
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