Good versus bad news consultations in advanced breast cancer: the role of empathy in information recall - an observational study.

OBJECTIVE: We explored, in advanced breast cancer, whether: (1) patients recall less information following bad versus good news consultations; (2) empathy has a greater effect on recalled information following bad versus good news consultations. METHODS: Observational study using audio-recorded consultations. Participants' recall of provided information about treatment options, aims/positive effects and side-effects was assessed. Clinician-expressed empathy and consultation type were determined. Regression analyses assessed associations between consultation type and recall, exploring moderating influences of clinician-expressed empathy. RESULTS: For 41 consultations (18 bad news, 23 good news), recall data were completed; total recall (47% vs 73%, p=0.03) and recall about treatment options (67% vs 85%, p=0.08, trend) were significantly worse following bad news compared with good news consultations. Recall about treatment aims/positive effects (53% vs 70%, p=0.30) and side-effects (28% vs 49%, p=0.20) was not significantly worse following bad news. Empathy moderated the relationship between consultation type and total recall (p<0.01), recall about treatment options (p=0.03) and about aims/positive effects (p<0.01) but not about side-effects (p=0.10). Only following good news consultations empathy influenced recall favourably. CONCLUSIONS: This explorative study suggests that in advanced cancer, information recall is especially impaired following bad news consultations, for which empathy does not improve remembered information.

Mind your words: Oncologists' communication that potentially harms patients with advanced cancer: A survey on patient perspectives.

BACKGROUND: Many complaints in medicine and in advanced illnesses are about communication. Little is known about which specific communications harm. This study explored the perspectives of patients with advanced cancer about potentially harmful communication behaviors by oncologists and helpful alternatives. METHODS: An online survey design was used that was based on literature scoping and patient/clinician/researcher input. Patients with advanced cancer (n = 74) reflected on the potential harmfulness of 19 communication situations. They were asked whether they perceived the situation as one in which communication could be harmful (yes/no). If they answered "yes," they were asked whether they perceived the examples as harmful (yes/no) or helpful (yes/no) and to provide open comments. Results were analyzed quantitatively and qualitatively (content analysis). RESULTS: Communication regarding information provision, prognosis discussion, decision-making, and empathy could be unnecessarily potentially harmful, and this occurred in various ways, such as making vague promises instead of concrete ones (92%), being too directive in decision-making (qualitative), and not listening to the patient (88%). Not all patients considered other situations potentially harmful (eg, introducing the option of refraining from anticancer therapy [49%] and giving too much [prognostic] information [60%]). Exploring each individual patients' needs/preferences seemed to be a precondition for helpful communication. CONCLUSIONS: This article provides patient perspectives on oncologists' unnecessarily potentially harmful communication behaviors and offers practical tools to improve communication in advanced cancer care. Both preventable pitfalls and delicate challenges requiring an individualized approach, where exploration might help, are described. Although providing difficult and unwelcome news is a core task for clinicians, this study might help them to do so while preventing potentially unnecessary harm.

Oncologists' Communication About Uncertain Information in Second Opinion Consultations: A Focused Qualitative Analysis.

Introduction: Uncertainty is omnipresent in cancer care, including the ambiguity of diagnostic tests, efficacy and side effects of treatments, and/or patients' long-term prognosis. During second opinion consultations, uncertainty may be particularly tangible: doubts and uncertainty may drive patients to seek more information and request a second opinion, whereas the second opinion in turn may also affect patients' level of uncertainty. Providers are tasked to clearly discuss all of these uncertainties with patients who may feel overwhelmed by it. The aim of this study was to explore how oncologists communicate about uncertainty during second opinion consultations in medical oncology. Methods: We performed a secondary qualitative analysis of audio-recorded consultations collected in a prospective study among cancer patients (N = 69) who sought a second opinion in medical oncology. We purposively selected 12 audio-recorded second opinion consultations. Any communication about uncertainty by the oncologist was double coded by two researchers and an inductive analytic approach was chosen to allow for novel insights to arise. Results: Seven approaches in which oncologists conveyed or addressed uncertainty were identified: (1) specifying the degree of uncertainty, (2) explaining reasons of uncertainty, (3) providing personalized estimates of uncertainty to patients, (4) downplaying or magnifying uncertainty, (5) reducing or counterbalancing uncertainty, and (6) providing support to facilitate patients in coping with uncertainty. Moreover, oncologists varied in their (7) choice of words/language to convey uncertainty (i.e., "I" vs. "we"; level of explicitness). Discussion: This study identified various approaches of how oncologists communicated uncertain issues during second opinion consultations. These different approaches could affect patients' perception of uncertainty, emotions provoked by it, and possibly even patients' behavior. For example, by minimizing uncertainty, oncologists may (un)consciously steer patients toward specific medical decisions). Future research is needed to examine how these different ways of communicating about uncertainty affect patients. This could also facilitate a discussion about the desirability of certain communication strategies. Eventually, practical and evidence-based guidance needs to be developed for clinicians to optimally inform patients about uncertain issues and support patients in dealing with these.

Patient-provider communication during second opinion consultations in oncology.

OBJECTIVE: Providing a second opinion (SO) in oncology is complex, and communication during SOs remains poorly understood. This study aimed to systematically observe how patients and oncologists communicate about SO-specific topics (i.e., patient motivation, the referring oncologist, treatment transfer/back-referral), and how such communication affects patient satisfaction. METHODS: A prospective mixed-methods study of cancer patients seeking a SO (N = 69) and consulting oncologists was conducted. Before the SO, patients reported their expected place of future treatment. Following the SO, patients' and oncologists' satisfaction was assessed. All SOs were audio-recorded. Absolute and relative duration of SO-specific talk were calculated and specific events (e.g., questions/utterances) were coded (incl. valence, explicitness). RESULTS: SOs lasted 19-73 min, of which 3.7% was spent discussing motivations. Oncologists rarely explored patients' motivations. Talk about referring oncologists (12.5% of consultation) was mostly critical by patients (M = 43.0%), but positive/confirming by consulting oncologists (M = 73.5%). Although 22.2% of patients expected a treatment transfer, this topic (3.3% of consultation time) was rarely explicitly discussed. Patients who were referred back were significantly less satisfied (d = 0.85). CONCLUSION: Patient-provider communication in oncological SOs appears insufficiently aligned. PRACTICE IMPLICATIONS: Patients and oncologists need support to explicitly and productively communicate about SO-specific topics and to better manage expectations. Recommendations are provided.

Surgical Complications of Skin-Sparing Mastectomy and Immediate Implant-Based Breast Reconstruction in Women Concurrently Treated With Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND AND AIM: To date, studies on adjuvant chemotherapy as a risk factor for the surgical outcome of combined mastectomy and breast reconstruction were hampered by the inclusion of mixed reconstructive cohorts of both delayed and immediate timing and of both autologous and implant-based techniques. Consequently, there is a paucity of data on the impact of adjuvant chemotherapy on surgical complication rates after combined skin-sparing mastectomy and immediate implant-based breast reconstruction. METHODOLOGY: We compared the postoperative complications that occurred within 16 weeks after this combined procedure in 131 women (139 breasts) treated with adjuvant chemotherapy with those in a control group of 491 women (517 breasts) not receiving any adjuvant therapy within 16 weeks. RESULTS: In line with the clinically indicated selection of women to undergo adjuvant chemotherapy, the interventional group differed significantly from the control group in 7 of the 12 patient- and procedure-related characteristics. The prevalence of minor complications (13.7% and 12.4%, respectively, P = 0.68) and major complications (31.7% and 29.4%, respectively, P = 0.60) did not differ significantly between the interventional group and the controls. The fraction of breasts that needed unscheduled surgery (0.29 and 0.24, respectively, P = 0.20), the fraction of total number of interventions (0.34 and 0.33, respectively, P = 0.24), and the fraction of implants lost (0.72 and 0.67, respectively, P = 0.86) did not differ significantly between both groups. The onset of chemotherapy, furthermore, seemed not to influence the occurrence or severity of complications. CONCLUSIONS: Like other women who have to undergo mastectomy, women who need to undergo adjuvant chemotherapy can potentially benefit from combined skin-sparing mastectomy and immediate implant-based breast reconstruction.

Reducing uncertainty: motivations and consequences of seeking a second opinion in oncology.

BACKGROUND: Cancer patients increasingly seek second opinion (SO) consultations, but there is scarce empirical evidence to substantiate medical and psychological benefits for patients. This is the first study to examine patient- and oncologist-reported (1) motivations and expectations of patients to seek a SO, (2) the perceived medical outcome, and (3) psychological consequences of SOs over time (i.e. patients' uncertainty and anxiety). MATERIAL AND METHODS: This multi-informant longitudinal cohort study (SO-COM) included consecutive cancer patients referred for a SO (N = 70; age 28-85), as well as their referring and consulting oncologists. Outcome measures were completed at three time points: Patients and referring oncologists reported motivations and expectations before the SO (T0), patients and consulting oncologists reported the medical outcome of the SO (i.e. discrepancy between first and second opinion) immediately following the SO (T1), and patients reported their uncertainty and anxiety at T0, T1, and two months following the SO (T2). RESULTS: Cancer patients most frequently reported wanting expert advice, exhausting all options, and/or needing more information as motivations for SOs. Referring oncologists rather accurately anticipated these motivations, except most did not recognize patients' information needs. The vast majority of patients (90.0%) received a medical advice similar to the first opinion, although 65.7% had expected to receive a different opinion. Patients' uncertainty (F = 6.82, p=.002; η2 =.22), but not anxiety (F = 3.074, p=.055, η2 =.11) was significantly reduced after the SO. CONCLUSIONS: SOs can yield psychological benefits by reducing patients' uncertainty, but the added medical value remains debatable. Referring oncologists may not be fully aware of their patients' information needs. Patients should be better informed about goals and benefits of SOs to better manage their expectations. More cost-effective ways of optimally providing medically and psychologically valuable SOs need to be explored.

Neutrophil Recovery in Breast Cancer Patients Receiving Docetaxel-Containing Chemotherapy with and without Granulocyte Colony-Stimulating Factor Prophylaxis.

OBJECTIVE: The primary outcome of the current study is, whether there is a protective effect of prior chemotherapy or of prior granulocyte colony-stimulating factor (G-CSF) on the next cycle blood cell counts. METHODS: Hematologic toxicity was evaluated, based on a randomized phase III study in breast cancer patients (n = 167) with >20% risk of febrile neutropenia. The primary endpoint was the nadir blood cell counts for patients treated with G-CSF given during all 6 chemotherapy cycles or limited to the first 2 chemotherapy cycles only. RESULTS: For the present analyses, 47 patients were eligible. In the G-CSF 1-6 arm, the median white blood cell count (WBC) and absolute neutrophil count (ANC) nadir slowly decreased from 10.8 × 109/L in cycle 1 to 7.5 × 109/L in cycle 6 and from 7.1 × 109/L to 5.5 × 109/L, respectively. The median WBC nadir in the G-CSF 1-2 arm decreased from 1.2 × 109/L in cycle 3 to 0.9 × 109/L in cycle 6 and the ANC nadir showed a grade 4 neutropenia of 0.1 × 109/L in cycles 3-6. All patients had ANC recovery to normal levels (≥1.5 × 109/L) without delay on day 1 of the next cycle. CONCLUSION: We conclude that there is no protective effect of prior G-CSF or prior chemotherapy use on nadir blood cell counts in subsequent cycles.

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study.

BACKGROUND: The addition of pertuzumab to neoadjuvant trastuzumab-based chemotherapy improves pathologic complete response rates in HER2-positive breast cancer. However, increased toxicity has been reported with the addition of pertuzumab, and this may differ between various chemotherapy backbone regimens. We evaluated toxicities of pertuzumab when added to either FEC-T (5-fluorouracil, epirubicin, cyclophosphamide, trastuzumab) or weekly paclitaxel, trastuzumab, carboplatin (PTC). METHODS: The TRAIN-2 study is a neoadjuvant randomized controlled trial in stage II and III HER2-positive breast cancer (NCT01996267). Patients are randomly assigned to receive either three cycles of FEC-T plus pertuzumab or three cycles of PTC plus pertuzumab, followed by six cycles of PTC plus pertuzumab in both arms. Toxicities are described per treatment arm according to the Common Toxicity Criteria for Adverse Events version 4.03. RESULTS: This analysis includes 110 patients balanced over both treatment arms. Neutropenia was the most common hematologic toxicity, with grade 3-4 occurring in 53% in the FEC-T-arm and in 51% in the PTC-arm. Febrile neutropenia occurred in 9% in the FEC-T arm and did not occur in the PTC-arm. Secondary G-CSF prophylaxis was used in 35-40% of patients. Asymptomatic ejection fraction decrease grade 2 was observed in 24% in the FEC-T-arm and 11% in the PTC-arm. The most common grade 3-4 non-hematologic toxicity was diarrhea (5% in the FEC-T-arm and 18% in the PTC-arm). CONCLUSIONS: Pertuzumab in combination with FEC-T mostly causes neutropenia, and when added to PTC mostly causes diarrhea. Significant cardiac toxicity is rare with both regimens, and toxicity is overall well manageable.

Cost effectiveness of primary pegfilgrastim prophylaxis in patients with breast cancer at risk of febrile neutropenia.

PURPOSE: Guidelines advise primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during chemotherapy if risk of febrile neutropenia (FN) is more than 20%, but this comes with considerable costs. We investigated the incremental costs and effects between two treatment strategies of primary pegfilgrastim prophylaxis. METHODS: Our economic evaluation used a health care perspective and was based on a randomized study in patients with breast cancer with increased risk of FN, comparing primary G-CSF prophylaxis throughout all chemotherapy cycles (G-CSF 1-6 cycles) with prophylaxis during the first two cycles only (G-CSF 1-2 cycles). Primary outcome was cost effectiveness expressed as costs per patient with episodes of FN prevented. RESULTS: The incidence of FN increased from 10% in the G-CSF 1 to 6 cycles study arm (eight of 84 patients) to 36% in the G-CSF 1 to 2 cycles study arm (30 of 83 patients), whereas the mean total costs decreased from € 20,658 (95% CI, € 20,049 to € 21,247) to € 17,168 (95% CI € 16,239 to € 18,029) per patient, respectively. Chemotherapy and G-CSF determined 80% of the total costs. As expected, FN-related costs were higher in the G-CSF 1 to 2 cycles arm. The incremental cost effectiveness ratio for the G-CSF 1 to 6 cycles arm compared with the G-CSF 1 to 2 cycles arm was € 13,112 per patient with episodes of FN prevented. CONCLUSION: We conclude that G-CSF prophylaxis throughout all chemotherapy cycles is more effective, but more costly, compared with prophylaxis limited to the first two cycles. Whether G-CSF prophylaxis throughout all chemotherapy cycles is considered cost effective depends on the willingness to pay per patient with episodes of FN prevented.

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia.

PURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. PATIENTS AND METHODS: In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. RESULTS: After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). CONCLUSION: In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned.

Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial.

BACKGROUND: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. METHODS: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. RESULTS: For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). CONCLUSION: First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.

mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients.

PURPOSE: Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer. EXPERIMENTAL DESIGN: CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors. RESULTS: We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels. CONCLUSIONS: Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs.

Weekly docetaxel in metastatic breast cancer patients: no superior benefits compared to three-weekly docetaxel.

BACKGROUND: In anthracycline-pretreated metastatic breast cancer (MBC) patients, it is unknown whether weekly single-agent docetaxel is preferable to 3-weekly docetaxel regarding its toxicity and efficacy profile. PATIENTS AND METHODS: In this multicenter, randomised, open-label phase III trial, 162 patients were randomised to weekly docetaxel (group A) or 3-weekly docetaxel (group B). The primary end-point was tolerability; secondary end-points were efficacy and quality of life (QoL). RESULTS: Group A (weekly docetaxel, n=79) experienced less haematological toxicity, with just 1.3% versus 16.9% febrile neutropenia in group B (3-weekly docetaxel, n=77) (p=0.001). Not this difference, but fatigue and general malaise foremost led to more patient withdrawals in group A (24 versus 12 patients, p=0.032), less patients completing treatment (29 versus 43 patients, p=0.014) and reduced dose-intensity (15.6 versus 26mg/m(2)/week, 58% versus 70% of projected dose, p=0.017). As a result, 3-weekly docetaxel was related to better overall survival in multivariate analysis (hazard ratio 0.70, p=0.036), although in univariate analysis efficacy was similar in both groups. Reported QoL was similar in both groups, but less effective treatment with more general toxicity led to less completed QoL forms in group A (65.4% versus 50%, p=0.049). CONCLUSION: Weekly docetaxel is less well tolerated than a 3-weekly schedule, due to more non-haematological toxicity, despite less febrile neutropenia. Also, no efficacy benefits can be demonstrated for weekly docetaxel, which may even be inferior based on multivariate analysis. Therefore, a 3-weekly schedule should be preferred in the setting of MBC.