Leveraging G-CSF prescribing in the outpatient setting: considerations beyond clinical factors-a questionnaire study.

PURPOSE: This study aims to delineate G-CSF treatment practices, assess decision criteria, and measure their implementation in ambulatory settings for patients with breast (BC), lung (LC), or gastrointestinal cancers (GIC), beyond standard recommendations. METHODS: In this non-interventional, cross-sectional, multicenter study, clinical cases were presented using conversational interfaces (chatbots), simulating a conversation with one or more virtual interlocutors through voice or text exchange. The clinical simulations were configured by four parameters: types of cancer, risk of FN related to chemotherapy and comorbidities, access to care, and therapy setting (adjuvant/neoadjuvant/metastatic). RESULTS: The questionnaire was completed by 102 physicians. Most practitioners (84.5%) reported prescribing G-CSF, regardless of tumor type. G-CSF was prescribed more frequently for adjuvant/neoadjuvant therapy than for metastatic cases. The type of chemotherapy was cited as the first reason for prescribing G-CSF, with access to care being the second. Regarding the type of chemotherapy, physicians do not consider this factor alone, but combined with comorbidities and age (56.7% of cases). Pegfilgrastim long-acting was prescribed in most cases of BC and LC (70.1% and 86%, respectively), while filgrastim short-acting was named in the majority of cases of GIC (61.7%); 76.3% of physicians prescribed G-CSF as primary prophylaxis. CONCLUSIONS: Our findings suggest that recommended practices are broadly followed. In the majority of cases, G-CSF is prescribed as primary prophylaxis. In addition, physicians seem more inclined to prescribe G-CSF to adjuvant/neoadjuvant patients rather than metastatic patients. Finally, the type of chemotherapy tends to be a more significant determining factor than the patient's background.

Real-World Impact of Adjuvant Anti-HER2 Treatment on Characteristics and Outcomes of Women With HER2-Positive Metastatic Breast Cancer in the ESME Program.

BACKGROUND: Although adjuvant cancer treatments increase cure rates, they may induce clonal selection and tumor resistance. Information still lacks as whether (neo)adjuvant anti-HER2 treatments impact the patterns of recurrence and outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC). We aimed to assess this in the large multicenter ESME real-world database. PATIENTS AND METHODS: We examined the characteristics and outcomes (overall survival (OS) and progression-free survival under first-line treatment (PFS1)) of HER2+ patients with MBC from the French ESME program with recurrent disease, as a function of the previous receipt of adjuvant trastuzumab. Multivariable analyses used Cox models adjusted for baseline demographic, prognostic factors, adjuvant treatment received, and disease-free interval. RESULTS: Two thousand one hundred and forty-three patients who entered the ESME cohort between 2008 and 2017 had a recurrent HER2+ MBC. Among them, 56% had received (neo)adjuvant trastuzumab and 2.5% another anti-HER2 in this setting. Patients pre-exposed to trastuzumab were younger, had a lower disease-free interval, more HR-negative disease and more metastatic sites. While the crude median OS appeared inferior in patients exposed to adjuvant trastuzumab, as compared to those who did not (37.2 (95%CI 34.4-40.3) versus 53.5 months (95% CI: 47.6-60.1)), this difference disappeared in the multivariable model (HR = 1.05, 95%CI 0.91-1.22). The same figures were observed for PFS1. CONCLUSIONS: Among patients with relapsed HER2+ MBC, the receipt of adjuvant trastuzumab did not independently predict for worse outcomes when adjusted to other prognostic factors.

Feasibility of personalized screening and prevention recommendations in the general population through breast cancer risk assessment: results from a dedicated risk clinic.

PURPOSE: A personalized approach to prevention and early detection based on known risk factors should contribute to early diagnosis and treatment of breast cancer. We initiated a risk assessment clinic for all women wishing to undergo an individual breast cancer risk assessment. METHODS: Women underwent a complete breast cancer assessment including a questionnaire, mammogram with evaluation of breast density, collection of saliva sample, consultation with a radiologist, and a breast cancer specialist. Women aged 40 or older, with 0 or 1 first-degree relative with breast cancer diagnosed after the age of 40 were eligible for risk assessment using MammoRisk, a machine learning-based tool that provides an individual 5-year estimated risk of developing breast cancer based on the patient's clinical data and breast density, with or without polygenic risk scores (PRSs). DNA was extracted from saliva samples for genotyping of 76 single-nucleotide polymorphisms. The individual risk was communicated to the patient, with individualized screening and prevention recommendations. RESULTS: A total of 290 women underwent breast cancer assessment, among which 196 women (68%) were eligible for risk assessment using MammoRisk (median age 52, range 40-72). When PRS was added to MammoRisk, 40% (n = 78) of patients were assigned a different risk category, with 28% (n = 55) of patients changing from intermediate to moderate or high risk. CONCLUSION: Individual risk assessment is feasible in the general population. Screening recommendations could be given based on individual risk. The use of PRS changed the risk score and screening recommendations in 40% of women.

BEAUTY and the breast: is adjuvant chemotherapy the right time for a beauty boost? Lessons learned from a large randomized controlled trial.

PURPOSE: Beauty care (BTC) is offered at many cancer hospitals having a great uptake among patients. Nevertheless, its benefits in the Quality of life (QoL) of cancer survivors have not been assessed so far. METHODS: Our study aims to determine whether BTC improves patients' QoL related to their body image measured by the BRBI scale of the QLQ-BR23 questionnaire at the end of adjuvant chemotherapy, after breast cancer (BC) surgery. The BEAUTY study is a prospective, randomized, controlled intervention trial. The following patient-reported outcomes were filled before initiation of chemotherapy (T1) and after their last cycle (T2): EORTC QLQ-C30, QLQ-BR23, and Body Image Scale (BIS). Primary objective was improvement in the BIS of BR23 (BRBI). A qualitative assessment of patients' experience was performed at each cycle through a relevant questionnaire. RESULTS: In total, 269 (67%) patients filled BRBI at T1 and T2. Mean BRBI scores substantially decreased between T1 and T2 and were not different with or without BTC (p = 0.88). Qualitative assessment suggests impact of BTC in physical well-being and avoids thoughts related to the disease. CONCLUSION: A substantial proportion of patients have a poor body image and chemotherapy induced a substantial degradation of BRBI scores. Although BTC does not seem to impact BRBI scores, the qualitative assessment suggests some benefit of BTC in other domains. Our study highlights the need to assess patients-perceived body image and build tailored interventions at this critical phase of their disease and generates hypothesis for the impact of BTC among BC patients. Clinical trial registration The study is registered at ClinicalTrials.gov under the NCT01459003 number since October 25, 2011.

Creation of a tool to evaluate supportive care.

RATIONAL: The absence of a specific tool to evaluate the impact of supportive care in general and socioesthetics (SE) in particular is undoubtedly at the origin of the lack of published research based on scientific standards. OBJECTIVE: We developed a supportive-care, patient-reported outcome questionnaire using the multistep methods, following COSMIN recommendations. METHODS: The Patient Centricity Questionnaire (PCQ) was developed using the standardized methodology for designing patient-reported outcome (PRO) questionnaires according to the following steps: elaboration of the questionnaire, measurement properties of the questionnaire, internal and external validation, test-retest validation and translation, cross-cultural adaptation, and cognitive debriefing. A multidisciplinary work group was designed including professionals, such as physicians, public health experts, sociologists, supportive-care experts, and socioestheticians. RESULTS: Our questionnaire includes 11 items. It is scored by adding each Visual Analogue Scale [VAS], making it range from 0 to 110, with a higher benefit when the score is higher. The Cronbach's α coefficient is 0.88 for the entire questionnaire. As the questionnaire is a reflection of the patient's feelings, it is quite natural that the name "Patient Centricity Questionnaire" (PCQ) was retained and validated by the Scientific Committee. The PCQ correlated negatively and moderately with the Perceived Stress Scale [PSS], positively and moderately with the mental dimension of the Short Form-12, and poorly with the Well Beng 12 [WB12], the physical dimension of the SF-12, and the satisfaction VAS. CONCLUSION: Constructed according to the recommendations, the PCQ meets the prerequisite for this type of questionnaire. Its short format and simplicity of use allow it to be used by a large number of people. The PCQ is a simple, reliable, easy-to-use, and validated tool for research teams, making it possible for randomized studies to prove the impact of supportive care in general and SE in particular, on the patient's quality of life.

Multicenter evaluation of breast cancer patients' satisfaction and experience with oncology telemedicine visits during the COVID-19 pandemic.

INTRODUCTION: During the COVID-19 pandemic, teleconsultation was implemented in clinical practice to limit patient exposure to COVID-19 while monitoring their treatment and follow-up. We sought to examine the satisfaction of patients with breast cancer (BC) who underwent teleconsultations during this period. METHODS: Eighteen centres in France and Italy invited patients with BC who had at least one teleconsultation during the first wave of the COVID-19 pandemic to participate in a web-based survey that evaluated their satisfaction (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) with teleconsultation. RESULTS: Among the 1299 participants eligible for this analysis, 53% of participants were undergoing standard post-treatment follow-up while 22 and 17% were currently receiving active anticancer therapy for metastatic and localised cancers, respectively. The mean satisfaction scores were 77.4 and 73.3 for the EORTC OUT-PATSAT 35 and TSQ scores, respectively. In all, 52.6% of participants had low/no anxiety. Multivariable analysis showed that the EORTC OUT-PATSAT 35 score correlated to age, anxiety score and teleconsultation modality. The TSQ score correlated to disease status and anxiety score. CONCLUSION: Patients with BC were satisfied with oncology teleconsultations during the COVID-19 pandemic. Teleconsultation may be an acceptable alternative follow-up modality in specific circumstances.

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

BACKGROUND: The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. METHODS: In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. RESULTS: A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. CONCLUSIONS: Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.).

Uncovering Professional Attitudes Toward Treatment of Rare Carcinomas of the Breast: An International Practice e-Survey Involving 32 Countries.

World Health Organization classification has identified a dozen rare subtypes accounting for less than 10% of all breast cancers (BC), generally not taken into account in treatment guidelines. We evaluated professionals' attitudes toward decision-making regarding rare BC and consensus guidelines needs. In this international e-survey, 236 BC experts from all specialties were contacted through email to fill an online questionnaire about their practices. Eighty-six experts from 32 countries participated (36%); 50% medical oncologists, 21% surgeons, 17% pathologists, and 12% radiation oncologists. General BC care decisions were based on consensus guidelines in 77% of expert, whereas routine individual treatment decisions for BC were made by multi-disciplinary boards in 76%. Only 10% strongly considered rare BC should be treated following existing standard guidelines. Interestingly, 50-80% described individualizing treatment for rare BC according to pathologic subtype. More than 90% of experts would welcome international recommendations for rare BC. This large scale international multi-disciplinary survey revealed overarching concerns centered on several key themes: the lack of resources and data to address these less common BC; the heterogeneous management of rare BC depending on geographical location and specialist training; the demand for international consensus guidelines regarding their diagnosis and treatment.

Identifying potential indicators to measure the outcome of translational cancer research: a mixed methods approach.

BACKGROUND: In a context where there is an increasing demand to evaluate the outcome of bio-medical research, our work aims to develop a set of indicators to measure the impact of translational cancer research. The objective of our study was to explore the scope and issues of translational research relevant to evaluation, explore the views of researchers on the evaluation of oncological translational research, and select indicators measuring the outcomes and outputs of translational research in oncology by consensus. METHODS: Semi-structured interviews amongst 23 researchers involved in translational cancer research were conducted and analysed using thematic analysis. A two-round modified Delphi survey of 35 participants with similar characteristics was then performed followed by a physical meeting. Participants rated the feasibility and validity of 60 indicators. The physical meeting was held to discuss the methodology of the new indicators. RESULTS: The main themes emerging from the interviews included a common definition for translational research but disagreements about the exact scope and limits of this research, the importance of multidisciplinarity and collaboration for the success of translational research, the disadvantages that translational research faces in current evaluation systems, the relative lack of pertinence of existing indicators, and propositions to measure translational cancer research in terms of clinical applications and patient outcomes. A total of 35 participants took part in the first round survey and 12 in the second round. The two-round survey helped us select a set of 18 indicators, including four that seemed to be particularly adapted to measure translational cancer research impact on health service research (number of biomarkers identified, generation of clinical guidelines, citation of research in clinical guidelines, and citation of research in public health guidelines). The feedback from participants helped refine the methodology and definition of indicators not commonly used. CONCLUSION: Indicators need to be accepted by stakeholders under evaluation. This study helped the selection and refinement of indicators considered as the most relevant by researchers in translational cancer research. The feasibility and validity of those indicators will be tested in a scientometric study.

Trastuzumab deruxtecan in previously treated HER2-positive metastatic or unresectable breast cancer: Real-life data from the temporary use authorization program in France.

BACKGROUND: Early access program (formerly cohort Temporary Authorization for Use) was granted for trastuzumab deruxtecan (T-DXd) in France based on DESTINY-Breast01 trial which demonstrated its efficacy and safety in HER2-positive metastatic/unresectable breast cancer after ≥2 anti-HER2-based regimens received at metastatic stage. METHODS: This multicenter real-world early access program included HER2-positive metastatic/unresectable breast patients pretreated with at least two lines of anti-HER2 regimens who received T-DXd 5.4 mg/kg intravenously in monotherapy every 3 weeks. RESULTS: Four hundred and fifty-nine patients (median age, 58 years; hormone receptor-positive, 67%; brain metastases, 28.1%) received T-DXd. Before inclusion, 81.7% of patients had radiation therapy and 76.5% had undergone surgery. Median number of prior metastatic treatment lines was four (range, 2-22); 99.8% patients had received trastuzumab, 94.8% trastuzumab emtansine and 79.3% pertuzumab. Follow-up was performed from September 30, 2020 to March 30, 2021; when the early access program stopped, the median duration of T-DXd treatment was 3.4 (range, 0-7.8) months. In 160 patients with available tumor assessment, objective response rate was 56.7% and 12.1% had progression. In 57 patients with available brain tumor assessment, complete or partial intracranial response was reported for 35.7% patients and 5.4% had progression. A total of 17 (3.7%) patients with interstitial lung disease (ILD) was reported with no cases of ILD-related death. CONCLUSIONS: In this early access program in patients with heavily pretreated HER2-positive metastatic/unresectable breast cancer, T-DXd had antitumor activity with a similar response to that reported in previous clinical studies. T-DXd was well tolerated and no new safety signals were observed.

Assessing excellence in translational cancer research: a consensus based framework.

BACKGROUND: It takes several years on average to translate basic research findings into clinical research and eventually deliver patient benefits. An expert-based excellence assessment can help improve this process by: identifying high performing Comprehensive Cancer Centres; best practices in translational cancer research; improving the quality and efficiency of the translational cancer research process. This can help build networks of excellent Centres by aiding focused partnerships. In this paper we report on a consensus building exercise that was undertaken to construct an excellence assessment framework for translational cancer research in Europe. METHODS: We used mixed methods to reach consensus: a systematic review of existing translational research models critically appraised for suitability in performance assessment of Cancer Centres; a survey among European stakeholders (researchers, clinicians, patient representatives and managers) to score a list of potential excellence criteria, a focus group with selected representatives of survey participants to review and rescore the excellence criteria; an expert group meeting to refine the list; an open validation round with stakeholders and a critical review of the emerging framework by an independent body: a committee formed by the European Academy of Cancer Sciences. RESULTS: The resulting excellence assessment framework has 18 criteria categorized in 6 themes. Each criterion has a number of questions/sub-criteria. Stakeholders favoured using qualitative excellence criteria to evaluate the translational research "process" rather than quantitative criteria or judging only the outputs. Examples of criteria include checking if the Centre has mechanisms that can be rated as excellent for: involvement of basic researchers and clinicians in translational research (quality of supervision and incentives provided to clinicians to do a PhD in translational research) and well designed clinical trials based on ground-breaking concepts (innovative patient stratification, substantial fraction of phase I/II trials, investigator-initiated trials). Critically, the framework supports reduced bureaucracy by building on existing European evaluation systems. CONCLUSIONS: The excellence framework is the product of an intense stakeholder consensus building exercise. It will be piloted during an expert peer review/site visit of at least three European Comprehensive Cancer Centres. The findings regarding content, governance and implementation can have relevance for other clinical and research fields.

[Adapted physical activity and metastatic cancer: What needs and expectations?] / Activité Physique Adaptée et cancer métastatique : quels besoins et quelles attentes ?

This French study aimed to evaluate oncologists' and patients' perception of physical activity, particularly adapted physical activity, in order to identify the obstacles and levers to its practice in patients with metastatic cancer. METHOD: Between October 2019 and March 2020, 60 medical oncologists and 305 patients with metastatic cancer were asked to fill in a self-completed questionnaire. RESULTS: The benefits of physical activity are recognised by most oncologists and patients. These benefits were perceived more by oncologists in prevention (78%) or in the early stage (72%) of the disease than in the metastatic stage (55%) (P=0.01). Patient's physical condition (45%) and age (37%) but also the lack of time during the consultation to explain supportive care (35%) are the main obstacles identified by the oncologist to the integration of physical activity into patient care. Furthermore, lack of knowledge of adapted programmes is the main reason given by the physicians who have never prescribed physical activity (51%). On the patient side, while 88% of them had heard of the benefits of physical activity, only 11% had received a prescription. Most oncologists and patients were very interested in receiving information on where and what types of activities to practice, as well as what to avoid. CONCLUSION: Efforts in terms of information for both oncologists and patients seem necessary to increase the level of physical activity prescription and practice for patients followed for metastatic cancer.

Use of mHealth to Increase Physical Activity Among Breast Cancer Survivors With Fatigue: Qualitative Exploration.

BACKGROUND: Physical activity has shown beneficial effects in the treatment of breast cancer fatigue; nevertheless, a significant portion of patients remain insufficiently physically active after breast cancer. Currently most patients have a smartphone, and therefore mobile health (mHealth) holds the promise of promoting health behavior uptake for many of them. OBJECTIVE: In this study, we explored representations, levers, and barriers to physical activity and mHealth interventions among inactive breast cancer patients with fatigue. METHODS: This was an exploratory, qualitative study including breast cancer patients from a French cancer center. A total of 4 focus groups were conducted with 9 patients; 2 independent groups of patients (groups A and B) were interviewed at 2 consecutive times (sessions 1 to 4), before and after their participation in a 2-week mHealth group experience consisting of (1) a competitive virtual exercise group activity (a fictitious world tour), (2) participation in a daily chat network, and (3) access to physical activity information and world tour classification feedback. We used a thematic content analysis. RESULTS: Several physical activity levers emerged including (1) physical factors such as perception of physical benefit and previous practice, (2) psychological factors such as motivation increased by provider recommendations, (3) social factors such as group practice, and (4) organizational factors including preplanning physical activity sessions. The main barriers to physical activity identified included late effects of cancer treatment, lack of motivation, and lack of time. The lack of familiarity with connected devices was perceived as the main barrier to the use of mHealth as a means to promote physical activity. The tested mHealth group challenge was associated with several positive representations including well-being and good habit promotion and being a motivational catalyzer. Following feedback, modifications were implemented into the mHealth challenge. CONCLUSIONS: mHealth-based, easily accessed group challenges were perceived as levers for the practice of physical activity in this population. mHealth-based group challenges should be explored as options to promote physical activity in a population with fatigue after breast cancer.

Analysing the attributes of Comprehensive Cancer Centres and Cancer Centres across Europe to identify key hallmarks.

There is a persistent variation in cancer outcomes among and within European countries suggesting (among other causes) inequalities in access to or delivery of high-quality cancer care. European policy (EU Cancer Mission and Europe's Beating Cancer Plan) is currently moving towards a mission-oriented approach addressing these inequalities. In this study, we used the quantitative and qualitative data of the Organisation of European Cancer Institutes' Accreditation and Designation Programme, relating to 40 large European cancer centres, to describe their current compliance with quality standards, to identify the hallmarks common to all centres and to show the distinctive features of Comprehensive Cancer Centres. All Comprehensive Cancer Centres and Cancer Centres accredited by the Organisation of European Cancer Institutes show good compliance with quality standards related to care, multidisciplinarity and patient centredness. However, Comprehensive Cancer Centres on average showed significantly better scores on indicators related to the volume, quality and integration of translational research, such as high-impact publications, clinical trial activity (especially in phase I and phase IIa trials) and filing more patents as early indicators of innovation. However, irrespective of their size, centres show significant variability regarding effective governance when functioning as entities within larger hospitals.

Molecular features of untreated breast cancer and initial metastatic event inform clinical decision-making and predict outcome: long-term results of ESOPE, a single-arm prospective multicenter study.

BACKGROUND: Prognosis evaluation of advanced breast cancer and therapeutic strategy are mostly based on clinical features of advanced disease and molecular profiling of the primary tumor. Very few studies have evaluated the impact of metastatic subtyping during the initial metastatic event in a prospective study. The genomic landscape of metastatic breast cancer has mostly been described in very advanced, pretreated disease, limiting the findings transferability to clinical use. METHODS: We developed a multicenter, single-arm, prospective clinical trial in order to address these issues. Between November 2010 and September 2013, 123 eligible patients were included. Patients at the first, untreated metastatic event were eligible. All matched primary tumors and metastatic samples were centrally reviewed for pathological typing. Targeted and whole-exome sequencing was applied to matched pairs of frozen tissue. A multivariate overall survival analysis was performed (median follow-up 64 months). RESULTS: Per central review in 84 patients (out of 130), we show that luminal A breast tumors are more prone to subtype switching. By combining targeted sequencing of a 91 gene panel (n = 67) and whole-exome sequencing (n = 30), a slight excess of mutations is observed in the metastases. Luminal A breast cancer has the most heterogeneous mutational profile and the highest number of mutational signatures, when comparing primary tumor and the matched metastatic tissue. Tumors with a subtype change have more mutations that are private. The metastasis-specific mutation load is significantly higher in late than in de novo metastases. The most frequently mutated genes were TP53 and PIK3CA. The most frequent metastasis-specific druggable genes were PIK3CA, PTEN, KDR, ALK, CDKN2A, NOTCH4, POLE, SETD2, SF3B1, and TSC2. Long-term outcome is driven by a combination of tumor load and metastasis biology. CONCLUSIONS: Profiling of the first, untreated, metastatic event of breast cancer reveals a profound heterogeneity mostly in luminal A tumors and in late metastases. Based on this profiling, we can derive information relevant to prognosis and therapeutic intervention, which support current guidelines recommending a biopsy at the first metastatic relapse. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov ( NCT01956552 ).

[Real-life study of 7-year survival in patients treated with trastuzumab for HER2+ early breast cancer]. / Étude en vie réelle de la survie à 7 ans des patientes traitées avec trastuzumab pour un cancer du sein précoce HER2.

BACKGROUND AND RATIONALE: Despite improved prognosis of HER2 since the introduction of trastuzumab in the adjuvant setting of early breast cancer, disease recurrences still occur, particularly in certain patient subgroups. The objective of this real-life study conducted in France is to evaluate after 7 years, disease-free survival (DFS) and distant metastatic-free survival (MFS). METHODS: This was a multi-center, retrospective, observational study assessing early HER2+ breast cancer patients diagnosed between January 1st, 2009 and December 31st, 2010 treated with adjuvant trastuzumab. DFS and MFS were evaluated within subgroups according to hormonal and nodal status. RESULTS: Based on 2311 patients documented, according to nodal status, the 7-year DFS rate was significantly higher for N- than for N+ patients [87.2% vs. 66.8%; P<0.001], and the 7-year MFS rate [94.7% for N- vs. 74.9% for N+; P<0.001]. According to hormonal status, the 7-year DFS rate was significantly higher for HR+ than for HR- patients [80.5% vs. 69.2%; P<0.001], and the 7-year MFS rate [88.0% for HR+ vs. 77.7% HR-]. CONCLUSIONS: Despite the overall improvement in the prognosis of early HER2+ breast cancers, patients in the N+ and RH- subgroups have a high risk of metastatic recurrence at seven years, justifying the search for more effective treatment alternatives.

Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial.

PURPOSE: MINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen. PATIENTS AND METHODS: R-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety. RESULTS: Of 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]). CONCLUSION: Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.

[Management of side effects related to adjuvant hormone therapy in young women with breast cancer]. / Gestion des effets secondaires de l'hormonothérapie du cancer du sein chez la femme jeune.

Despite proven survival benefits after breast cancer, long-trem compliance with adjuvant hormone therapy remains a major issue, partly due to the side effects of treatment. In young women treated for breast cancer, these treatments include tamoxifen, anti-aromatase and LH-RH analogues, with even more side effects when these treatments are combined, especially for younger patients with more aggressive disease. The management of the potential side effects requires first of all detailed and precise information at initiation of treatment, and preventive measures including patient education. Once the treatment has been initiated, clinicians should be able to propose to their patients appropriate measures to alleviate the potential of the side effects, which can be of various types: biological (dyslipidemia), physical (weight gain, hot flushes, vaginal dryness, sexual disorders with low libido, musculoskeletal symptoms…) or psychosocial (anxio-depressive disorders, poor body image, difficulties of professional reintegration). Management of these effects can combine various modalities: drugs (switching hormone therapy, anti-depressants, hormonal treatments of vaginal dryness in some cases, gabapentin), physical treatments (CO2 laser for vulvovaginal atrophy) or psycho-physical techniques (physical activity, mindfulness, acupuncture…). Eventually, the lenghth of these adjuvant hormonal treatments requires supportive measures to help young patients engage in new lifestyle measures, in particular in term of physical activity and diet. This will help them mitigate the symptoms related to these side-effects while reducing the long-term risks related to their disease and treatments.