Impact of web application support versus standard management on adherence with adjuvant hormone therapy in patients treated for breast cancer: the WEBAPPAC study.

BACKGROUND: Non-metastatic breast cancer treatment is mainly based on surgery, with or without chemotherapy, radiotherapy and/or hormone therapy. To reduce the risk of hormone receptor positive (HR+) disease recurrence, hormone therapy is prescribed for at least 5 years. It may induce adverse drug reactions (ADRs) as joint pain, sexual dysfunction, weight increase, fatigue, mood disorders and vasomotor symptoms. Around 30-40% of patients withhold hormone therapy within 5 years after initiation. Based on encouraging results of mobile health in patient follow-up, we developed a web-application addressed for breast cancer patients initiating adjuvant hormonal therapy and aimed to assess its impact on hormone therapy adherence, ADRs management, and health-related quality of life. METHODS: The WEBAPPAC trial is a randomized, open-label, prospective, single-center phase 3 study aiming to assess the interest of a web-application support as compared to standard management among breast cancer patients initiating hormone therapy. The main endpoint is the proportion of patients with hormone therapy adherence failure within 18 months after treatment start, in each arm. Eligible patients will be 1:1 randomized between the WEBAPPAC web-application support (experimental arm,) or standard support (control arm), with stratification on type of hormone therapy (Aromatase inhibitor or Tamoxifen). We plan to enroll 438 patients overall. Failure to hormone therapy will be assessed using the Morisky 8-item self-questionnaire (MMSA8), patient adherence logbook, and medical consultations. Secondary outcomes include hormone therapy adherence at 6 months, pain (Visual Analogue Scale and Brief Pain Inventory), quality of life (EORTC QLQ-C30 and BR23 self-questionnaires), anxiety and depression (Hospital and Depression Scale), and return to work and/or daily activities. The user experience with the WEBAPPAC web-application will be assessed using the System Usability Scale (SUS) questionnaire. DISCUSSION: Hormone therapy discontinuation or adherence failure in breast cancer patients may be indirectly related to an increased risk of recurrence. A better control of medication adherence, through the detection of side effects and some proposed actions trying to reduce them, appears therefore essential to limit the risk of disease recurrence. The WEBAPPAC web-application thus aims better monitoring and allowing higher level of responsiveness in case of ADRs, thus improving treatment adherence. TRIAL REGISTRATION: NCT04554927, registered September 18, 2020. PROTOCOL VERSION: Version 2.1 dated from December 21, 2021.

HELENA: HER2-Low as a prEdictive factor of response to Neoadjuvant chemotherapy in eArly breast cancer.

BACKGROUND: HER2 expression has a prognostic and predictive impact in early-stage breast cancer (BC). HER2 positive BC (immunohistochemistry (IHC) score 3 + or 2 + with in situ hybridization (ISH) amplification) are treated with HER2 targeted therapies. The concept of HER2-low BC (IHC score 1 + or 2 + without ISH amplification) is drawing attention as anti-HER2 treatment has recently shown efficacy in this subgroup. We aimed to explore the response to neoadjuvant chemotherapy (NAC) in HER2-low early BC according to the HER2 score (1 + or 2 + without amplification). METHODS: We conducted a retrospective study in two French comprehensive cancer centers. All patients with HER2-low BC treated with NAC from January 2014 to December 2020 were included. The primary objective was to analyze the pathological complete response (pCR) rate to NAC using the Sataloff or RCB system, according to the HER2 score. Secondary objectives were to assess disease free survival (DFS), overall survival (OS) and to explore the immune environment through the Neutrophil-to-Lymphocyte Ratio (NLR), according to HER2 expression. Univariate and multivariate analyses were performed. RESULTS: We included 237 tumors for 229 patients. Of these, 160 (67.5%) tumors were HER2 1 + , 77 (32.5%) were HER2 2 + , and 152 (64.1%) were hormone receptor (HR) positive. The median age was 53.9 years. No differences in tumor characteristics were observed between HER2 1 + and HER2 2 + subgroups. pCR was achieved in 38 tumors (17%), without any difference between HER2 1 + and HER2 2 + subgroups (p = 0.77). DFS and OS were significantly different between HER2 1 + and HER2 2 + patients (HR = 0.41,CI95%[0.17;0.97] p = 0.037 and HR = 0.31,CI95%[0.09;1.02] p = 0.042, respectively). HER2 status was still associated with DFS and OS after adjustment for age, HR status and NLR, with better outcomes in favor of HER2 score 2 + (HR = 0.35 [0.15-0.84] and HR = 0.24 [0.07-0.81], respectively). NLR was not associated with worse DFS or OS. CONCLUSION: In HER2-low early BC, no differences in pCR were observed between HER2 1 + and HER2 2 + tumors, however patients with HER2 2 + tumors had a better DFS and OS than those with HER2 1 + . Further investigations are needed to describe the intrinsic differences in the spectrum of HER2-low BC.

Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer.

PURPOSE: Everolimus, an oral inhibitor of the mammalian target of rapamycin, improves progression-free survival in combination with endocrine therapy (ET) in postmenopausal women with aromatase inhibitor-resistant metastatic breast cancer. However, the benefit of adding everolimus to ET in the adjuvant setting in early breast cancer is unknown. PATIENTS AND METHODS: In this randomized double-blind phase III study, women with high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer were randomly assigned to everolimus or placebo for 2 years combined with standard ET. Stratification factors included ET agent, receipt of neoadjuvant versus adjuvant chemotherapy, progesterone receptor status, duration of ET before random assignment, and lymph node involvement. The primary end point was disease-free survival (DFS). The trial is registered with ClinicalTrials.gov (identifier: NCT01805271). RESULTS: Between June 2013 and March 2020, 1,278 patients were randomly allocated to receive everolimus or placebo. At the first interim analysis, the trial was stopped for futility and a full analysis undertaken once data snapshot complete. One hundred forty-seven patients have had a DFS event reported and at 3 years, DFS did not differ between patients who received ET plus everolimus (88% [95% CI, 85 to 91]) or ET plus placebo (89% [95% CI, 86 to 91; hazard ratio, 0.95; 95% CI, 0.69 to 1.32; P = .77]). Grade ≥ 3 adverse events were reported in 22.9% of patients (29.9% with everolimus v 15.9% with placebo, P < .001). 53.4% everolimus-treated patients permanently discontinued experimental treatment early compared with placebo-treated 22.3%. CONCLUSION: Among high-risk patients, everolimus added to adjuvant ET did not improve DFS. Tolerability was a concern, with more than half of patients stopping everolimus before study completion. Everolimus cannot be recommended in the adjuvant setting.

Self-referential processes and resting-state connectivity in breast cancer patients before and 1 year after chemotherapy.

Modifications in the processing of information relevant to oneself have been reported in breast cancer (BC) patients. Here, we characterize the longitudinal changes to self-representations in BC patients and how they are related to intrinsic functional brain connectivity. We tested 16 BC patients before (T1) and 1 year after the end of chemotherapy (T2) along with 24 healthy control participants (HC) at similar time points. Participants underwent resting-state fMRI and completed the Questionnaire of Self-Representation (QSR), which evaluates self-assertion and self-esteem. Resting-state functional connectivity (RSFC) was calculated for regions implicated in self-referential processes (dorsomedial prefrontal cortex [dmPFC], posterior cingulate cortex [PCC], and dorsal anterior cingulate cortex [dACC]) and correlated with QSR scores. QSR scores were on average larger in patients compared with HC and did not vary over time. RSFC between the dACC and regions supporting body awareness (precentral/postcentral and supramarginal gyri, superior parietal lobule) decreased more between T1 and T2 in BC patients than in HC. BC patients had lower RSFC than HC between the dmPFC and the PCC, and regions supporting mental imagery (precuneus, lingual gyrus), at each time point, and a greater decrease from T1 and T2. QSR scores negatively correlated with RSFC. Patients described themselves as having greater self-awareness and positive self-image, reflecting a fighting spirit. In parallel, patients presented a decrease in cortical activity related to body awareness and mental imagery of self-representations over time that may be related to the positive self-image patients have and could reflect a temporary adaptive strategy.

Baseline lymphopenia as prognostic factor in patients with metastatic breast cancer treated with palbociclib.

Cyclin-dependent-kinase 4-6 inhibitors (CDK4/6i) have improved the management of hormone receptor (HR)+/human epidermal growth factor receptor (HER)2- metastatic breast cancer (mBC). Currently, there are no valid prognostic factors for response to CDK4/6i. Baseline lymphopenia is reported as a prognostic factor in several types of cancer. The present retrospective study aimed to evaluate the effect of baseline absolute lymphocyte count (ALC) on response to palbociclib. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival (OS), best response and safety. A total of 114 patients treated for mBC between 2016 and 2019 were included. Median baseline ALC was 1.4 g/l (range, 0.2-4.3 g/l). A total of 65 (57%) and 49 (43%) patients had baseline ALC values of <1.5 and ≥1.5 g/l, respectively. Patients with baseline lymphopenia exhibited significantly shorter PFS (6 vs. 10 months; P=0.004) and OS (20 vs. 33 months; P=0.02). ALC <1.5 g/l independently predicted worse survival, as indicated by multivariate analysis (P=0.04; hazard ratio, 1.76; 95% confidence interval, 1.02-3.02). Patients with baseline ALC <1.5 g/l had significantly less partial response (14 vs. 22%; P=0.016) and more disease progression (46 vs. 20%; P=0.016) than those with ALC ≥1.5 g/l. ALC is a strong and easy-to-use dosage with prognostic factor for patients with HR+/HER2- mBC treated with palbociclib and endocrine therapy. Lymphopenia may also be a predictive factor of early progression. These data need to be verified in a larger prospective study.

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors.

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis. Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9-57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI95% = [0.32-0.79]) and worse OS (HR=0.45, [CI95%: 0.23-0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively). Conclusion: High NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A 3-arm randomized trial.

BACKGROUND: There is no treatment for cancer-related cognitive impairment, an important adverse effect that negatively impacts quality of life (QOL). We conducted a 3-arm randomized controlled trial to evaluate the impact of computer-assisted cognitive rehabilitation (CR) on cognition, QOL, anxiety, and depression among cancer patients treated with chemotherapy. METHODS: Patients who reported cognitive complaints during or after completing chemotherapy were randomly assigned to 1 of 3 12-week CR programs: computer-assisted CR with a neuropsychologist (experimental group A), home cognitive self-exercises (active control group B), or phone follow-up (active control group C). Subjective cognition was assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), objective cognition was assessed by neuropsychological tests, QOL was assessed by the FACT-General, and depression and anxiety were assessed by psychological tests. The primary endpoint was the proportion of patients with a 7-point improvement in the FACT-Cog perceived cognitive impairment (PCI) score. RESULTS: Among the 167 enrolled patients (median age, 51 years), group A had the highest proportion of patients with a 7-point PCI improvement (75%), followed by groups B (59%) and C (57%), but the difference was not statistically significant (P = .13). Compared with groups B and C, the mean difference in PCI score was significantly higher in group A (P = .02), with better perceived cognitive abilities (P < .01) and a significant improvement in working memory (P = .03). Group A reported higher QOL related to cognition (FACT-Cog QOL) (P = .01) and improvement in depression symptoms (P = .03). CONCLUSIONS: These results suggest a benefit of a computer-based CR program in the management of cancer-related cognitive impairment and complaints.

Efficacy and Safety of Weekly Paclitaxel in Breast Cancer With Symptomatic Bone Marrow Infiltration.

BACKGROUND/AIM: Currently, there is no recommendation for the treatment of breast cancer (BC) with bone-marrow cell infiltration (BMI). We evaluated the efficacy and safety of weekly-paclitaxel in this population. PATIENTS AND METHODS: This retrospective study included all BC patients with BMI receiving weekly-paclitaxel between January 2014 and May 2018. Overall-survival (OS) was the primary endpoint. Secondary endpoints were progression-free-survival (PFS) and safety. RESULTS: BMI was diagnosed in 26 patients. This infiltration was suggested by peripheral blood smear in 73% of cases. All patients had anemia, and 77% had thrombocytopenia. OS and PFS were 7.2 months [95% confidence interval (CI)=2.6-20.7] and 3.3 months (95%CI=1.6-7.2), respectively. Good performance-status, absence of thrombocytopenia and presence of less than 5% of circulating erythroblasts at BMI diagnosis, were associated with better survival. One patient presented grade 5 febrile neutropenia but no episodes of bleeding were reported. CONCLUSION: Weekly-paclitaxel is an effective therapeutic option with limited toxicity for BC with BMI.

Longitudinal investigation of cognitive deficits in breast cancer patients and their gray matter correlates: impact of education level.

Cognitive deficits are a major complaint in breast cancer patients, even before chemotherapy. Comprehension of the cerebral mechanisms related to cognitive impairment in breast cancer patients remains difficult due to the scarcity of studies investigating both cognitive and anatomical imaging changes. Furthermore, only some of the patients experienced cognitive decline following chemotherapy, yet few studies have identified risk factors for cognitive deficits in these patients. It has been shown that education level could impact cognitive abilities during the recovery phase following chemotherapy. Our main aim was to longitudinally evaluate cognitive and anatomical changes associated with cancer and chemotherapy in breast cancer patients. Our secondary aim was to assess the impact of education level on cognitive performances and gray matter (GM) atrophy in these patients. Twenty patients were included before chemotherapy (T1), 1 month (T2) and 1 year (T3) after chemotherapy. Twenty-seven controls without a history of cancer were assessed at T1 and T3 only. Cluster groups based on education level were defined for both groups and were further compared. Comparison between patients and controls revealed deficits in patients on verbal episodic memory retrieval at T1 and T3 and on executive functions at T3. After chemotherapy, breast cancer patients had GM atrophy that persisted or recovered 1 year after chemotherapy depending on the cortical areas. Increase in GM volumes from T1 to T3 were also found in both groups. At T2, patients with a higher level of education compared to lower level exhibited higher episodic memory retrieval and state anxiety scores, both correlating with cerebellar volume. This higher level of education group exhibited hippocampal atrophy. Our results suggest that, before chemotherapy, cancer-related processes impact cognitive functioning and that this impact seems exacerbated by the effect of chemotherapy on certain brain regions. Increase in GM volumes after chemotherapy were unexpected and warrant further investigations. Higher education level was associated, 1 month after the end of chemotherapy, with greater anxiety and hippocampal atrophy despite a lack of cognitive deficits. These results suggest, for the first time, the occurrence of compensation mechanisms that may be linked to cognitive reserve in relationship to state anxiety. This identification of factors, which may compensate cognitive impairment following chemotherapy, is critical for patient care and quality of life.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

BACKGROUND: Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. PATIENTS AND METHODS: Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. RESULTS: The sample consisted of women newly diagnosed with EBC (n = 118) and healthy controls (n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant (p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. CONCLUSION: This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy.

Decline in Cognitive Function in Older Adults With Early-Stage Breast Cancer After Adjuvant Treatment.

BACKGROUND: The impact of chemotherapy on cognition among elderly patients has received little attention, although such patients are more prone to presenting with age-related cognitive deficits and/or cognitive decline during chemotherapy. The present study assessed the cognitive function in older adults treated for early-stage breast cancer (EBC). PATIENTS AND METHODS: The participants were newly diagnosed EBC patients aged ≥65 years without previous systemic treatment or neurological or psychiatric disease and matched healthy controls. They underwent two assessments: before starting adjuvant therapy and after the end of chemotherapy (including doxorubicin ± docetaxel [CT+ group], n = 58) or radiotherapy for patients who did not receive chemotherapy (CT- group, n = 61), and at the same interval for the healthy controls (n = 62). Neuropsychological and geriatric assessments were performed. Neuropsychological data were analyzed using the Reliable Change Index. RESULTS: Forty-nine percent of the patients (mean age, 70 ± 4 years) had objective cognitive decline after adjuvant treatment that mainly concerned working memory. Among these patients, 64% developed a cognitive impairment after adjuvant treatment. Comorbidity was not associated with cognitive decline. No significant difference in objective cognitive decline was found between the two groups of patients; however, the CT+ group had more subjective cognitive complaints after treatment (p = .008). The oldest patients (aged 70-81 years) tended to have more objective decline with docetaxel (p = .05). CONCLUSION: This is the largest published study assessing cognitive function in older adults with EBC that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. IMPLICATIONS FOR PRACTICE: This is the largest published study assessing cognitive function in older adults with early-stage breast cancer that included a group of patients treated with modern chemotherapy regimens. Approximately half the patients had objective cognitive decline after adjuvant treatment. The oldest patients were more likely to have cognitive decline with chemotherapy, particularly with docetaxel. Cognitive deficits could affect patients' quality of life and their compliance to treatment. Assessing cognitive dysfunctions in the elderly cancer population is a challenge in clinical practice, but it could influence the choice of the most appropriate therapy, including the use of oral drugs.

How to improve the prevention of chemotherapy-induced nausea and vomiting? The French NAVI study.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) still remain frequent. The procedure for announcing the diagnosis (PAD) was an emblematic measure of the first French Plan Cancer aiming at providing patients with time to listen, information after cancer diagnosis, and discussion on treatments and their side effects. We aimed at assessing the risk factors of CINV, focusing on patients' satisfaction with the PAD. METHODS: This prospective multicentre study assessed the frequency and intensity of CINV among chemonaïve patients during the first cycle of treatment. CINV was defined by ≥1 emetic episode or reported nausea intensity ≥3 on a 0-10 scale. Multivariate analysis was used to identify factors related to global CINV onset including satisfaction with the PAD (satisfaction score ≥the median on a 0-10 scale). RESULTS: Data from 291 patients (women, 85.2%; mean age, 57 years) were analyzed. Most patients (69.4%) received highly emetogenic chemotherapy regimens and 77.7% received antiemetic drugs consistent with international guidelines. Acute, delayed and overall CINV were experienced by 40.4, 34.8 and 52.4% of patients, respectively. Sixty-seven per cent of patients were satisfied with the PAD. No relation was noted between PAD satisfaction and CINV onset. The nausea and vomiting dimension of the QLQ-C30 questionnaire before chemotherapy (OR 3.62), motion sickness history (OR 2.73), highly emetogenic CT (OR 2.73), anxiety (OR 1.99) and younger age (OR 1.96) were independent predictive factors. CONCLUSIONS: Although patients were mostly satisfied with the PAD, half of them experienced CINV. A state of anxiety could be identified during the PAD to be managed.

Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial.

BACKGROUND: The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first-line treatment of patients with carcinoma of unknown primary site (CUP). METHODS: In this randomized phase 2 trial, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re-evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients in group A then continued receiving single-agent belinostat, whereas patients in group B stopped treatment. The primary endpoint was progression-free survival (PFS): The authors postulated that the addition of belinostat would improve PFS from 5 months (expected with paclitaxel/carboplatin) to 8 months. RESULTS: In total, 89 patients were randomized (group A, n = 44; group B, n = 45), and the demographics and disease characteristics were balanced between the 2 groups. The addition of belinostat to paclitaxel/carboplatin did not improve PFS (group A, 5.4 months [95% confidence interval, 3.0-6.0 months]; group B, 5.3 months [95% confidence interval, 2.8-6.6 months]; P = .85). Overall survival was 12.4 months for group A versus 9.1 months for group B (P = .20). The response rate favored the belinostat group (45% vs 21%; P = .02). Belinostat resulted in a modest increase in treatment toxicity. CONCLUSIONS: The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first-line therapy, although the patients who received belinostat had a higher investigator-assessed response rate. Future trials in CUP should focus on specific subsets, defined either by the predicted tissue of origin or by the identification of targetable molecular abnormalities.

Baseline cognitive functions among elderly patients with localised breast cancer.

PURPOSE: Cognitive deficits (CD) are reported among cancer patients receiving chemotherapy, but may also be observed before treatment. Though elderly patients are expected to be more prone to present age-related CD, poor information is available regarding the impact of cancer and chemotherapy on this population. This study assessed baseline cognitive functions (before adjuvant treatment) in elderly early stage breast cancer (EBC) patients. METHODS: Women >65years-old with newly diagnosed EBC were included in this prospective study. Episodic memory, working memory, executive functions and information processing speed were assessed by neuropsychological tests. Questionnaires were used to assess subjective CD, anxiety, depression, fatigue, quality of life and geriatric profile. Objective CD were defined using International Cognition and Cancer Task Force criteria. A group of elderly women without cancer coupled with published data related to healthy women were used for comparison (respectively to subjective and objective CD). RESULTS: Among the 123 elderly EBC patients (70±4years) included, 41% presented objective CD, which is greater than expected in healthy population norms (binomial test P<.0001). Verbal episodic memory was mainly impaired (21% of patients). No correlation was observed between objective CD and cancer stage or geriatric assessment. Subjective CD only correlated with verbal episodic memory (P=.01). CONCLUSIONS: This is the first large series assessing baseline cognitive functions in elderly EBC patients. More than 40% presented objective CD before any adjuvant therapy, which is higher than what is reported among younger patients. Our results reinforce the hypothesis that age is a risk factor for CD in EBC patients.

Staging the axilla in breast cancer patients with ¹8F-FDG PET: how small are the metastases that we can detect with new generation clinical PET systems?

PURPOSE: Point spread function (PSF) reconstruction improves spatial resolution throughout the entire field of view of a PET system and can detect smaller metastatic deposits than conventional algorithms such as OSEM. We assessed the impact of PSF reconstruction on quantitative values and diagnostic accuracy for axillary staging of breast cancer patients, compared with an OSEM reconstruction, with emphasis on the size of nodal metastases. METHODS: This was a prospective study in a single referral centre in which 50 patients underwent an (18)F-FDG PET examination before axillary lymph node dissection. PET data were reconstructed with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by a pathologist who measured the largest nodal metastasis per axilla. This size was used to evaluate PET diagnostic performance. RESULTS: On pathology, 34 patients (68%) had nodal involvement. Overall, the median size of the largest nodal metastasis per axilla was 7 mm (range 0.5 - 40 mm). PSF reconstruction detected more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM SUVmax ratio was 1.66 (95 % CI 1.01 - 2.32). The sensitivities of PSF and OSEM reconstructions were, respectively, 96% and 92% in patients with a largest nodal metastasis of >7 mm, 60% and 40% in patients with a largest nodal metastasis of ≤7 mm, and 92% and 69% in patients with a primary tumour ≤30 mm. Biggerstaff graphical comparison showed that globally PSF reconstruction was superior to OSEM reconstruction. The median sizes of the largest nodal metastasis in patients with nodal involvement not detected by either PSF or OSEM reconstruction, detected by PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6 and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected by PSF reconstruction but not by OSEM reconstruction, the smallest detectable metastasis was 1.8 mm. CONCLUSION: As a result of better activity recovery, PET with PSF reconstruction performed better than PET with OSEM reconstruction in detecting nodal metastases ≤7 mm. However, its sensitivity is still insufficient for it to replace surgical approaches for axillary staging. PET with PSF reconstruction could be used to perform sentinel node biopsy more safely in patients with a primary tumour ≤30 mm and with unremarkable PET results in the axilla.

Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study.

PURPOSE: Cross-talk between signal transduction pathways likely contributes to hormone resistance in metastatic breast cancer (mBC). Everolimus, an oral inhibitor of the mammalian target of rapamycin, has restored sensitivity in endocrine-resistance models and shown anticancer activity in early-phase mBC clinical trials. This analysis evaluated efficacy and safety of everolimus in combination with tamoxifen in patients with mBC resistant to aromatase inhibitors (AIs). PATIENTS AND METHODS: This open-label, phase II study randomly assigned postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, AI-resistant mBC to tamoxifen 20 mg/d plus everolimus 10 mg/d (n = 54) or tamoxifen 20 mg/d alone (n = 57). Randomization was stratified by primary and secondary hormone resistance. Primary end point was clinical benefit rate (CBR), defined as the percentage of all patients with a complete or partial response or stable disease at 6 months. No formal statistical comparison between groups was planned. RESULTS: The 6-month CBR was 61% (95% CI, 47 to 74) with tamoxifen plus everolimus and 42% (95% CI, 29 to 56) with tamoxifen alone. Time to progression (TTP) increased from 4.5 months with tamoxifen alone to 8.6 months with tamoxifen plus everolimus, corresponding to a 46% reduction in risk of progression with the combination (hazard ratio [HR], 0.54; 95% CI, 0.36 to 0.81). Risk of death was reduced by 55% with tamoxifen plus everolimus versus tamoxifen alone (HR, 0.45; 95% CI, 0.24 to 0.81). The main toxicities associated with tamoxifen plus everolimus were fatigue (72% v 53% with tamoxifen alone), stomatitis (56% v 7%), rash (44% v 7%), anorexia (43% v 18%), and diarrhea (39% v 11%). CONCLUSION: This study suggests that tamoxifen plus everolimus increased CBR, TTP, and overall survival compared with tamoxifen alone in postmenopausal women with AI-resistant mBC.

One-year longitudinal study of fatigue, cognitive functions, and quality of life after adjuvant radiotherapy for breast cancer.

PURPOSE: Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life. METHODS AND MATERIALS: Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules. RESULTS: At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio [OR] = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment. CONCLUSIONS: Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.

Early 2'-deoxy-2'-[18F]fluoro-D-glucose PET metabolic response after corticosteroid therapy to differentiate cancer from sarcoidosis and sarcoid-like lesions.

PURPOSE: We aimed at investigating whether early metabolic response to corticosteroid therapy may be used as a diagnostic tool to discriminate between cancer and sarcoidosis, a well-known cause of false-positive 2-deoxy-2-[F-18]fluoro-D: -glucose-positron emission tomography (FDG-PET) findings in oncology. PROCEDURE: Two cancer patients with biopsy-proven sarcoidosis or sarcoid-like reaction had multiple thoracic FDG foci. After infectious disease had been excluded, patients received oral corticosteroids for 16 and 14 days, respectively, and underwent posttherapeutic FDG-PET examination. RESULTS: Posttreatment PET revealed a complete metabolic response in both patients, and clinical and imaging follow-up showed no sign of cancer progression. CONCLUSION: Early metabolic response to systemic corticosteroid treatment may be used as a tool in the establishment of final diagnosis when sarcoidosis is suspected in a cancer patient and could be capable of differentiating cancer from sarcoidosis in the case of coexisting diseases.

HER2 status in ovarian carcinomas: a multicenter GINECO study of 320 patients.

BACKGROUND: Despite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemoresistance. The use of targeted therapies such as trastuzumab may potentially improve outcomes for patients with ovarian cancer. HER2 overexpression/amplification has been reported in ovarian cancer, but the exact percentage of HER2-positive tumors varies widely in the literature. In this study, HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: The HER2 status of primary tumors and metastases was evaluated by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue on conventional slides. The prognostic impact of HER2 expression was analyzed. HER2 gene was overexpressed and amplified in 6.6% of analyzed tumors. Despite frequent intratumoral heterogeneity, no statistically significant difference was detected between primary tumors and corresponding metastases. CONCLUSIONS/SIGNIFICANCE: Our results show that the decision algorithm usually used in breast cancer (IHC as a screening test, with equivocal results confirmed by FISH) is appropriate in ovarian cancer. In contrast to previous series, HER2-positive status did not influence outcome in the present study, possibly due to the fact that patients in our study received paclitaxel/carboplatin-based chemotherapy. This raises the question of whether HER2 status and paclitaxel sensitively are linked.

First-line therapy with gemcitabine and paclitaxel in locally, recurrent or metastatic breast cancer: a phase II study.

BACKGROUND: This phase II study evaluated the efficacy and safety of gemcitabine (G) plus paclitaxel (T) as first-line therapy in recurrent or metastatic breast cancer. METHODS: Patients with locally, recurrent or metastatic breast cancer and no prior chemotherapy for metastatic disease received G 1200 mg/m2 on days 1 and 8, and T 175 mg/m2 on day 1 (before G) every 21 days for a maximum of 10 cycles. RESULTS: Forty patients, 39 metastatic breast cancer and 1 locally-advanced disease, were enrolled. Their median age was 61.5 years, and 85% had a World Health Organization performance status (PS) of 0 or 1. Poor prognostic factors at baseline included visceral involvement (87.5%) and > or =2 metastatic sites (70%). Also, 27 (67.5%) patients had prior adjuvant chemotherapy, 25 of which had prior anthracyclines. A total of 220 cycles (median 6; range, 1-10) were administered. Of the 40 enrolled patients, 2 had complete response and 12 partial response, for an overall response rate of 35.0% for intent-to-treat population. Among 35 patients evaluable for efficacy the response rate was 40%. Additional 14 patients had stable disease, and 7 had progressive disease. The median duration of response was 12 months; median time to progression, 7.2 months; median survival, 25.7 months. Common grade 3/4 toxicities were neutropenia in 17 (42.5%) patients each, grade 3 leukopenia in 19 (47.5%), and grade 3 alopecia in 30 (75.0%) patients; 1 (2.5%) patient had grade 4 thrombocytopenia. CONCLUSION: GT exhibited encouraging activity and tolerable toxicity as first-line therapy in metastatic breast cancer. Phase III trials for further evaluation are ongoing.