• metastatic breast cancer;
  • survival;
  • group therapy;
  • randomized clinical trial;
  • estrogen receptor status;
  • stress;
  • distress;
  • psychosocial support


  1. Top of page
  2. Abstract
  6. Acknowledgements


This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed.


One hundred twenty-five women with confirmed metastatic (n = 122) or locally recurrent (n = 3) breast cancer were randomly assigned either to the supportive-expressive group therapy condition (n = 64), where they received educational materials plus weekly supportive-expressive group therapy, or to the control condition (n = 61), where they received only educational materials for a minimum of 1 year. The treatment, 90 minutes once a week, was designed to build new bonds of social support, encourage expression of emotion, deal with fears of dying and death, help restructure life priorities, improve communication with family members and healthcare professionals, and enhance control of pain and anxiety.


Overall mortality after 14 years was 86%; median survival time was 32.8 months. No overall statistically significant effect of treatment on survival was found for treatment (median, 30.7 months) compared with control (median, 33.3 months) patients, but there was a statistically significant intervention site-by-condition interaction. Exploratory moderator analysis to explain that interaction revealed a significant overall interaction between estrogen-receptor (ER) status and treatment condition (P = .002) such that among the 25 ER-negative participants, those randomized to treatment survived longer (median, 29.8 months) than ER-negative controls (median, 9.3 months), whereas the ER-positive participants showed no treatment effect.


The earlier finding that longer survival was associated with supportive-expressive group therapy was not replicated. Although it is possible that psychosocial effects on survival are relevant to a small subsample of women who are more refractory to current hormonal treatments, further research is required to investigate subgroup differences. Cancer 2007. © 2007 American Cancer Society.

Does living better mean living longer with cancer? Considerable interest in this topic has been generated since the possibility was raised that intensive group psychotherapy may result not only in improved mood,1 better coping,1 and reduced pain,2 but also in longer survival.3 Our original study, begun in the 1970s, was a randomized trial in which we had initially hypothesized better emotional outcome but not longer survival. The treatment and control groups were well balanced on prognostic variables, and we found a mean 18-month survival advantage that was not accounted for by differences in medical treatment.4 Since then, 3 other published randomized trials5–8 and 1 matched cohort trial9 also found that psychosocial treatment for patients with a variety of cancers produced both psychological and survival benefits. However, 6 other published studies,10, 11 4 involving breast cancer patients,12–15 found no survival benefit for those treated with psychotherapy. Three of these studies reported only transient12 or no psychological benefit of any kind.11, 13 The quality of the psychosocial intervention may be 1 variable that is critical to medical outcome.16 An intervention that does not help emotionally is not likely to provide physical benefit. However, 3 other studies10, 14, 15 showed a positive psychological effect but no survival advantage. The quality of the group therapy in the Goodwin et al. study14 was attested to by reductions in distress and pain, with even greater psychological benefit found among those who were more anxious and depressed initially. Likewise, Kissane et al.15 reported reduced anxiety, a trend toward improved family functioning, and greater satisfaction with treatment among women with primary breast cancer offered Cognitive-Existential Group Therapy, but neither found a survival advantage.

One systematic review17 and 2 meta-analyses18, 19 that examined survival at specific time points after intervention found no effect of psychotherapy on cancer survival time. However, another meta-analysis reported an overall survival advantage for individual, but not group, interventions,20 although the small number of studies and diversity of treatments and cancers makes this a difficult distinction to sustain.21 Other systematic reviews have found the evidence to be divided but the results to be not random, with some studies showing a survival advantage for psychosocial intervention, others showing no difference, but none showing a survival disadvantage for those given psychosocial support.16, 22, 23 This study was designed as a replication trial of our original finding.


  1. Top of page
  2. Abstract
  6. Acknowledgements

Research Participants

Patients were eligible for study if they had a very high risk for death from breast cancer and were selected on the basis of having metastatic and/or recurrent breast cancer. Other inclusion criteria included an ability to speak English, the absence of a second cancer or other life-threatening illness, and willingness to participate in group treatment if randomized to that condition. Enrolling 125 women into this study was determined to have better than 90% power to detect effects of the treatment condition on survival corresponding to a standardized mean difference between average survival times of approximately .64, based upon results from our prior study,3 indicating a 67% probability (area-under-the-curve [AUC]) that a treatment subject would live longer than a control subject and a 34% probability that a control subject would outlive a treatment subject.

A total of 155 women were screened between 1991 and 1996, but 30 were not randomized; 12 dropped out because of disease progression, 7 were found to be ineligible after medical record review; and 11 decided they did not want to continue in the study (see Fig. 1).

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Figure 1. Consort diagram.

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The 125 participants were enrolled at 1 of 3 treatment intervention sites by location. Twenty-eight women were recruited through the Oncology Day Care Center at Stanford University Medical Center, 37 through letters sent to community oncologists (including Kaiser Permanente patients), 6 were referred by oncology social workers, and 54 were self-referred from brochures distributed in the community and notices in local newspapers and breast cancer newsletters. All continued to receive standard cancer treatment throughout the study. Only 1 patient in the present trial was treated with trastuzumab (Herceptin).24 Analysis is by intention-to-treat (N = 125), with the characteristics of the final sample presented in Tables 1 and 2. All participants gave written informed consent for participation in a protocol approved by the Stanford University School of Medicine Human Subjects Committee.

Table 1. Demographic Variables at Baseline (Mean [SD] or Number of Cases [% of Total Sample])
Demographic variables at baselineTotal sampleSan Francisco n = 36 (%)Stanford n = 58 (%)San Jose n = 31 (%)
Control n = 61 (%)Treatment n = 64 (%)
  • *

    Significant main effect for site, P < .05.

Age at randomization*53.3 (10.8)53.1 (10.6)54.8 (10.48)54.8 (11.4)48.4 (7.9)
Education, y*15.9 (2.4)16.1 (2.7)17.1 (2.7)15.6 (2.4)15.5 (2.4)
Ethnicity (% white)50 (82.0)59 (92.2)32 (88.9)51 (87.9)26 (83.9)
 Below $39,99921 (34.4)14 (21.9)10 (27.8)19 (32.8)6 (19.4)
 $40,000–$79,99922 (36.1)24 (37.5)13 (36.1)18 (31.0)15 (48.4)
 Above $80,00018 (29.5)25 (39.1)13 (36.1)20 (34.5)10 (32.3)
 Did not respond01 (1.6)01 (1.7)0
Currently employed (% yes)33 (54.1)37 (57.8)24 (66.7)21 (36.2)25 (80.6)
Hours worked per wk*31.6 (13.3)32.2 (11.7)33.5 (10.7)25.4 (16.5)34.8 (9.2)
No. of children2.1 (1.5)2.6 (2.4)2.3 (2.4)2.7 (2.0)1.9 (1.2)
No. of people in household2.2 (1.0)2.4 (1.2)2.2 (1.1)2.2 (1.0)2.4 (1.1)
Table 2. Prognostic Variables at Baseline (Mean [SD] or Number of Cases [% of Total Sample])
Prognostic variables at baselineTotal sampleSan Francisco n = 36Stanford n = 58San Jose n = 31
Control n = 61Treatment n = 64
  • *

    Significant main effect for site, P < .05.

  • Significant site-by-condition interaction, P < .05.

Age at initial diagnosis, y47.2 (10.3)47.2 (10.2)48.6 (10.2)48.7 (10.5)42.8 (8.5)
Age at recurrence, y*50.9 (10.1)51.3 (10.5)52.5 (10.0)52.7 (10.9)46.5 (8.0)
Premenopausal at randomization <50 y* (%)26 (42.6)25 (39.1)15 (41.7)18 (31.0)18 (58.1)
Disease free interval, mo from initial diagnosis to metastasis44.5 (34.7)47.7 (36.4)46.6 (38.9)48.0 (33.8)42.1 (35.3)
Months from recurrence/metastasis to study randomization28.7 (48.2)22.2 (27.0)29.0 (47.9)24.9 (35.7)22.1 (33.1)
Dominant location of metastasis or recurrence
 Chest wall or regional lymph nodes (%)20 (32.8)18 (28.1)10 (27.8)16 (27.6)12 (38.7)
 Bone (%)22 (36.1)28 (43.8)13 (36.1)21 (36.2)16 (51.6)
 Viscera (%)19 (31.1)18 (28.1)13 (36.1)21 (36.2)3 (9.7)
Estrogen receptor status
 Negative (%)12 (21.4)13 (21.0)6 (17.1)13 (24.1)6 (20.7)
 Positive (%)44 (78.6)49 (79.0)29 (82.9)41 (75.9)23 (79.3)
Chemotherapy (%)31 (50.8)29 (45.3)17 (47.2)33 (56.9)10 (32.3)
Hormone therapy (%)47 (77.0)50 (78.1)28 (77.8)44 (75.9)25 (80.6)


Participants were randomized by the project director, a research nurse, who used computer-assisted adaptive randomization based on a biased coin-design method to promote comparability of medical status in treatment and control conditions25 of the following variables: 1) dominant location of metastasis (chest wall/regional lymph nodes, bone, viscera), 2) estrogen-receptor status (positive, negative, unknown), 3) disease-free interval (time from initial diagnosis of breast cancer to first metastasis and/or recurrence at <1 year, 1–3 years, >3 years), 4) age (<50 years, ≥50 years), 5) systemic treatment received since metastasis and/or recurrence (none, chemotherapy only, hormonal therapy only, chemotherapy and hormonal therapy), and 6) institution (Stanford Oncology Day Care, Kaiser Medical Center, community oncologist). Randomization was conducted for overall assignment to treatment versus control condition. On average, participants had been initially diagnosed with primary breast cancer 6 years (71.5 months) before study entry (standard deviation [SD] = 55.6) and with metastasis for an average of 2 years (25.4 months, SD = 38.8).


Participant survival or death was determined for all participants by research staff communication with participants, family members, and/or physicians, or by consulting the Social Security Death Index, and then all reported deaths were confirmed by death certificate.

Intervention Condition

The weekly 90-minute therapy sessions involved 3–15 participants (patients only, not family members) and were led by 2 therapists; study therapists included a psychiatrist, psychologists, and social workers. Different therapists led the groups at each site, but 1 (D.S.) led the Stanford group, attended groups at the other 2 sites, and supervised all therapists. The supportive-expressive therapy model involved the creation of a supportive environment where participants were encouraged to confront their problems, strengthen their relationships, and find enhanced meaning in their lives. The intervention was semistructured, with therapists trained to facilitate discussion of the themes listed, as material emerged in an emotionally expressive rather than didactic format. The themes included 1) building new bonds of social support, 2) facilitating the expression of emotion, 3) confronting fears of dying and death including dealing with the deaths of group members, 4) reordering life priorities, 5) improving support from and communication with family and friends, 6) enhancing communication with physicians, and 7) learning to use self-hypnosis for anxiety and pain control.24, 26–28 There were 3 treatment groups, 1 at each site, and they met weekly for 90-minute sessions. Although the basic treatment period was 1 year, participants were invited to remain in the groups for as long as they wished, and most continued to participate as long as their health permitted, up to 12.5 years. The psychological efficacy of the intervention in this trial was demonstrated by previously reported significant reductions in mood disturbance, traumatic stress symptoms,24 and pain, and improvements in emotion regulation.28 None of these significant psychosocial treatment outcomes differed by site.24, 28

Control Condition

To ensure full participation and cooperation, we offered a self-directed education intervention to all women in the study, so the experimental comparison was group therapy plus education versus education alone. All participants were given a form from which to select materials to take home on loan. The selection of 30 books, 15 pamphlets, 5 videotapes, and 7 audio tapes covered a wide range of topics related to medical and emotional aspects of breast cancer. Participants were also given a 1-year membership to a consumer health library in their community. Thirty-two (53%) control patients and 35 (55%) treatment patients used these resources.

Data Analysis

The primary hypothesis of the current study was that randomization to group psychotherapy would result in longer subsequent survival. Overall mortality was 86%, close enough to our a priori level of 90% that no subsequent change would affect our conclusions. Survival analysis was by intent-to-treat, and all 125 women who were randomized were included in analyses. One treatment participant never attended group, 2 dropped out after 1 or 2 sessions, and 2 began attending only a year or more after randomization. Demographic and medical variables are described in Table 1.

In the primary a priori analysis, Cox proportional hazards analysis was used to test for effects of the condition (group therapy plus education or education only), site, and the site-by-condition interaction, (site was included to test whether or not treatment effects on survival generalized across sites).29 A preliminary analysis examined potential imbalance in assignment to condition and site, with baseline continuous demographic and medical status variables tested by 2-way analysis of variance, including site, condition, and the site-by-condition interaction (with independent variables and the interaction term all centered).30 The significance of baseline categorical variables was, likewise, tested by logistic regression with site, condition, and the site-by-condition interaction (centered).

Whereas the a priori hypothesis was unidirectional, all tests of statistical significance were 2-tailed. After the primary survival analysis was completed, which included tests of site as a moderator of treatment outcome, 3 additional exploratory analyses were conducted to examine possible sources of treatment-effect differences across sites as follows: location of metastatic spread, disease-free interval, and estrogen-receptor status. The first 2 variables were chosen because of significant baseline site-by-condition effects, and analyses were conducted to examine possible sources of survival differences across sites. Estrogen-receptor status was chosen because the most important medical treatment difference between our original study and the current one is the advent of hormonal therapies for women with estrogen-receptor positive tumors.31, 32 For each of these analyses, Cox proportional hazards analysis was used to test for effects of the moderator, condition, site, and all interactions of site with the moderator and with condition (all centered) on survival. As exploratory analyses, these are not definitive tests but hypotheses for future research.


  1. Top of page
  2. Abstract
  6. Acknowledgements

Overall median survival time was 32.8 months from study entry, 33.3 months for the educational control sample and 30.7 months for the treatment group. Cox proportional hazards analysis of survival with condition (treatment, control), site (San Francisco, San Jose, or Stanford), and site-by-condition interactions (all centered) indicated that there was no overall significant effect of treatment on survival, hazard ratio = 0.93 (95% confidence interval [CI], 0.62 to 1.40; P = .73; see Table 3). There was a statistically significant site-by-condition interaction, specifically a difference between the treatment effects at the San Francisco and San Jose sites. At the San Francisco site, control group median survival was 18.4 months (95% CI, 6.8–30.0), and treatment group median survival was 51.0 months (95% CI, 2.6–99.3). At the San Jose site, control group median survival was 70.6 months (95% CI, 13.9–127.2), and treatment group median survival 29.8 months (95% CI, 26.0–33.5). Whereas at Stanford, control group median survival was 32.8 months (95% CI, 13.2–52.4), and treatment group median survival was 28.4 months (95% CI, 18.8–38.0).

Table 3. Cox Regression on Survival for Treatment Versus Control by Site for Women with Metastatic Breast Cancer (N = 125)
 BSEWalddfPHazard ratio95% CI lower-upper
  1. Cox regression analysis included condition, dummy variables for N-1 Sites. (Stanford and San Francisco) and the interaction between Condition and Sites. All variables were centered.

  2. B indicates Cox regression; SE, standard error of the mean; df, degrees of freedom; P, probability; CI, confidence interval.

Stanford site0.450.253.1210.0781.560.95–2.56
San Francisco site0.440.282.4810.1151.550.90–2.67
Condition × Stanford−0.620.511.5210.2180.540.20–1.45
Condition × San Francisco−1.410.566.3810.0120.240.08–0.73

When we examined baseline differences in site and site-by-condition interaction, we found the following results and used these to guide subsequent analyses. There were significant differences across sites (but not between treatment and control samples) in age at randomization, education, and hours worked per week. There was a significant site-by-condition interaction for disease-free interval and dominant location of recurrence or metastasis (chest wall or regional lymph nodes vs bone or viscera).

Because we found them to be unbalanced across sites, we examined location of metastatic spread (bone and viscera vs chest wall) and disease-free interval at baseline in exploratory moderator analyses30, 33–35 to identify possible sources of the significant site-by-condition differences in survival. However, in these moderator analyses, the site differences in treatment effects on survival persisted, indicating that location of metastatic spread and disease-free interval could not account for site differences in treatment effects on survival. Estrogen-receptor (ER) status was selected for the third post hoc moderator analysis because ER status identified those patients who were refractory to the major medical treatment advance, which was the advent of hormonal therapies for women with ER-positive tumors, between the first study conducted in the 1970s and the current trial.31 There was a significant interaction between ER status and condition (Cox proportional hazards interaction B = −1.84, Wald = 9.76, P = .002) within the entire sample, as well as the expected significant effect of ER status on survival (Cox proportional hazards B = .63, Wald = 4.53, P = .033). Also, the statistically significant site-by-condition interaction disappeared (P = .66) when ER status was included in the analysis. Figure 2 presents the survival curves for ER-positive and ER-negative status by treatment and control group. It can be seen that although there are no significant treatment effects in the ER-positive group (control-group median survival, 42.5 months; treatment-group median survival, 30.7 months), the treatment versus control differences in the ER-negative group (control-group median survival, 9.3 months; treatment-group median survival, 29.8 months) are similar to those reported in our earlier study.3 That study was conducted at a time when hormonal treatments were less widely used and when overall survival was shorter.31 Furthermore, the treatment-control differences among ER-negative patients were consistent across all 3 treatment sites.

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Figure 2. Kaplan-Meier survival curves for treatment and control groups by ER-negative and ER-positive status. Cox proportional hazards interaction B = −1.84 (Wald = 9.76, P = .002) for overall interaction between ER status and group condition.

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Since our earlier study,3 the availability of community cancer support groups has increased. We examined participation by women in both control and treatment conditions in additional support groups (both cancer and noncancer groups), volunteer activities, and individual or couple's therapy (Table 4). As would be expected, women in the control condition participated in significantly more cancer groups outside the study (control: 26 of 61 [42.6%]; treatment: 14 of 64 [21.9%], chi-square = 5.90, P = .02, logistic regression with site, condition, and the site-by-condition interaction, all centered). However, they did not differ in the total number of additional support groups in which they participated (control: mean = 1.0, standard deviation = 1.1; treatment: mean = 0.8, standard deviation = 0.9, 2-way analysis of variance, site, condition, and the site-by-condition interaction, all centered). A similar number of women in each condition participated in individual, couple's, and family therapy outside the study (control: 12 of 61 [19.7%]; treatment 16 of 64 [25.4%], chi-square = .58, P = .45).

Table 4. Outside Group and Other Therapy Participation Assessed During the First Year of the Study
Participation During Study PeriodControl n = 61 (%)Treatment n = 64 (%)
No. of groups attended1.0 (1.11)0.8 (0.91)
Participation in groups outside study38 (62.3)37 (57.8)
Participation in cancer groups26 (42.6)14 (21.9)
Participation in therapy outside study12 (19.7)16 (25.4)


  1. Top of page
  2. Abstract
  6. Acknowledgements

Although this study failed to replicate our original finding of enhanced survival among women randomly assigned to a year of supportive-expressive group psychotherapy in the overall sample, it did replicate the inconsistency of results found since then between different studies. The median survival of 32.8 months in this study is substantially longer than the 17.6 months reported by Goodwin et al. in the BEST trial (who analyzed her results earlier than we did)14 and the 17 months in our earlier trial,36 suggesting sample differences. The control participants in the present study had much longer survival, a median of 33 months. This is particularly notable given similarities in the disease-free interval and time from metastasis to study entry of the current participants (mean = 46.1 months and mean = 25.4 months, respectively) compared with those of the original study participants (mean = 37.0 months and mean = 22.9 months, respectively). Thus, the current sample had far longer overall survival, likely reflecting both sample differences and recent improvements in breast cancer treatment.31, 32 Our earlier study3 had been criticized by Fox37 because survival in the control arm was not consistent with Surveillance, Epidemiology, and End Results [SEER] registry survival data, although it was noted that the internal comparison between treatment and control groups in a randomized trial is more telling than matching to an external comparison group.38 Nonetheless, the overall finding of this study is consistent with that of Goodwin et al.14 and Kissane et al.39 in finding no effect of group psychotherapy on survival time of women with metastatic breast cancer.

The source of the statistically significant differential effects of treatments across sites cannot be definitively determined, but it does not affect the overall finding. The reduction in distress and improvement in emotion regulation provided by group therapy obtained at all 3 sites,24, 28 so differences in adherence to the treatment model are not likely to account for differences in survival outcome. Moderator analysis is useful to search for subpopulations that may be differentially responsive to treatments.33 In an exploratory moderator analysis, we found a significant treatment effect by ER status on survival suggesting that, among ER-negative patients (21% of our sample), random assignment to group psychotherapeutic treatment was associated with significantly longer survival, whereas the same is not true for those with ER-positive status. Furthermore, when ER status was included in the analysis, site-by-treatment interactions seen in the primary analysis disappeared, and ER-negative treatment patients lived longer than ER-negative controls at each of the 3 sites. Although this was exploratory, there are several reasons to believe that differences in estrogen-receptor status may be crucial to breast cancer prognosis and treatment response. Significant advances have been made in improving hormonal therapies that use selective estrogen response modifiers and aromatase inhibitors, as well as in improving risk:benefit ratios of targeted chemotherapies.40, 41 Indeed, survival with metastatic breast cancer has improved substantially since the mid-1980s.31, 32 Recent studies have shown that among ER-positive patients, hormonal treatments are sufficiently effective that chemotherapy adds relatively little to survival, whereas improved chemotherapy treatment regimens make a considerable difference among ER-negative women.42 Similarly, a diet intervention has been found to reduce risk of recurrence more among ER-negative than ER-positive women.43 Breast cancer is coming to be understood as a family of diseases, as gene array analysis of mRNA expression is showing considerable heterogeneity of breast cancer subtypes44, 45 with wide variability in prognosis and treatment response. In particular, ER-positive and ER-negative tumors come from different cell lineages (luminal vs basal), further explaining resistance to hormone-related treatments among ER-negative patients,46 who have poorer overall prognosis.47 Thus, it is possible that any putative effect of psychosocial support on survival among ER-positive women has been superseded by highly effective hormonal treatments, which may also have effects on hypothalamic-pituitary-adrenal (HPA) functioning that is affected by stress management. Outcome among ER-negative women is less affected by hormonal treatments, leaving room for the impact of other treatments such as chemotherapy, specific oncogene-targeted monoclonal antibodies, or effects of psychosocial intervention on stress response systems in the body. However, conclusions about the effect of group therapy in this subgroup of patients awaits further study and replication.

Recognition of the need for psychosocial support for cancer patients has increased substantially over the past few decades as has the availability of support groups for cancer patients.48 When we started our original trial in the late 1970s, our main problem was convincing patients randomized to group therapy to participate in this novel intervention. In the current study that started in the 1990s, the recruitment challenge had changed. Control patients who were not assigned to group treatment were disappointed. Indeed, 1 control patient demanded a list of names of other control patients in the study so that she could start a support group (we did not comply with this request). Also, breast cancer patients are now far less likely to be alone emotionally with their illness because there is greater public understanding, acceptance, and support.49


As noted above, there are several limitations to the present study, including significant baseline differences across sites in age at randomization, education, and hours worked per week. There was also a significant site-by-condition interaction for disease-free interval and dominant location of recurrence or metastasis, leading to apparent differences in treatment effects across sites that were likely driven by imbalances in the prognostic variables. These imbalances might have been produced by our efforts to stratify for prognostic variables in a sample of modest size. In addition, randomization was determined by computer program, but it was conducted by the project director rather than someone independent of the project, and patients were randomized for the study as a whole, not by site.


Although the present study failed to replicate earlier findings of psychotherapy treatment effects on survival, it is clear that group psychotherapy is emotionally beneficial for metastatic breast cancer patients. Being confronted with their worst fears as they see others die of the same illness, with help in managing the strong emotions that understandably arise, is emotionally helpful for patients and not physically harmful. Picturing and even watching the manner of one's own death does not hasten it. As both medical treatment and psychosocial support have improved and our understanding of breast cancer has become more sophisticated, more targeted treatments of both types may enhance overall effectiveness.


  1. Top of page
  2. Abstract
  6. Acknowledgements

The authors acknowledge the contributions of Irvin Yalom, Jane Benson, Xin-Hua Chen, Karin Calde, Leslie Kinder, Lynne LoPresto, Julie Seplaki, Krista Thorne Yocam, Thai Nguyen, Trina Kurek, Rita Halbach, Christopher Biggs, Susan Diamond Moore, Susan Weisberg, Meg Marnell, Frank Stockdale, Eric Neri, Sandie Sephton, Amanda Kovattana, Catherine Byers, Christine Blasey, Bill Moyers, referring community physicians, the Stanford Oncology Day Care Center, and the patients and their spouses and families who participated in the study.


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  2. Abstract
  6. Acknowledgements
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