Randomized trial of a shared decision-making intervention consisting of trade-offs and individualized treatment information for BRCA1/2 mutation carriers.

PURPOSE: To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries. PATIENTS AND METHODS: The SDMI consisted of two value assessment sessions, using the time trade-off method, followed by individualized treatment information based on (quality-adjusted) life expectancy. After the baseline assessment (2 weeks after a positive DNA test result), women were randomly assigned to the SDMI group (n = 44), receiving the SDMI 2 months after the test result, or to the control group (n = 44). The short- and long-term effects, 3 and 9 months after the test result, were assessed using questionnaires. Data were collected on well-being, treatment choice, and decision-related outcomes. RESULTS: In the short term, the SDMI had no effect. In the long term, with respect to well-being, patients in the SDMI group had less intrusive thoughts (P =.05) and better general health (P =.01) and tended to be less depressed (P =.07). With respect to decision-related outcomes for the breasts, the SDMI group held stronger preferences (P =.02) and agreed more strongly to having weighed the pros and cons (P =.01). No effect was found on treatment choice. In the long term, interaction effects between the SDMI and cancer history were found. The SDMI showed an overall beneficial effect for unaffected women, whereas affected women tended to experience detrimental effects. CONCLUSION: We conclude that the SDMI improved decision making in unaffected BRCA1/2 mutation carriers. Supporting decision making in a systematic way using trade-offs is beneficial for these women.

Impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with breast or ovarian cancer.

To evaluate the impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with cancer. Longitudinal cohort study including women affected and unaffected with breast or ovarian cancer testing for a BRCA1/2 mutation. Data on well-being (anxiety, depression, cancer related distress, general health), treatment choice, and decision making about cancer prevention were collected at baseline (1 week after blood sampling; affected n = 192, unaffected n = 176) and at follow-up (2 weeks after disclosure of a positive test result; affected n = 23, unaffected n = 66). Women affected and unaffected with breast or ovarian cancer were compared using univariate statistics. Change over time was examined using repeated measures analysis of variance. With respect to well-being, affected women scored worse at baseline. At follow-up, both affected and unaffected women experienced a decline in well-being, which tended to be stronger in affected women. Women diagnosed with cancer less than 1 year previously tended to report a worse well-being than those diagnosed longer ago. With respect to treatment choice, more affected women intended to obtain prophylactic surgery and valued it higher at both time points. With respect to decision making, affected women had a lower preference for participation in decision making at baseline; no differences were found at follow-up. At follow-up, both affected and unaffected women showed an increase in strength of treatment preference and a decrease in decision uncertainty. Disclosure of a positive test result had a negative impact on well-being. Affected women, especially those who have been recently diagnosed with cancer, experienced the worst well-being and could benefit from psychosocial support.

Randomised trial of a decision aid and its timing for women being tested for a BRCA1/2 mutation.

The aim of the study was to evaluate the impact of a decision aid (DA) and its timing in women being tested for a BRCA1/2 mutation. Women with and without a previous history of cancer were included after blood sampling for genetic testing. The DA consisted of a brochure and video providing information on screening and prophylactic surgery. To evaluate the impact of the DA, women were randomised to the DA group (n=184), receiving the DA 2 weeks after blood sampling, or to the control group (n=184). To evaluate the impact of timing, mutation carriers who had received the DA before the test result (n=47) were compared to mutation carriers who received the DA after the test result (n=42). Data were collected on well-being, treatment choice, decision and information related outcomes. The impact of the DA was measured 4 weeks after blood sampling. The impact of timing was measured 2 weeks after a positive test result. The DA had no impact on well-being. Regarding decision related outcomes, the DA group more frequently considered prophylactic surgery (P=0.02) corroborated with higher valuations (P=0.04). No differences were found for the other decision related outcomes. Regarding information related outcomes, the DA group felt better informed (P=0.00), was more satisfied with the information (P=0.00), and showed more accurate risk perceptions. Timing of the DA had no effect on any of the outcomes. No interactions were found between the DA and history of cancer. In conclusion, women being tested for a BRCA1/2 mutation benefit from the DA on information related outcomes. Because timing had no effect, the DA is considered useful either before or after the test result.

Post-radiotherapy contrast enhancement changes in fast dynamic MRI of cervical carcinoma.

This pilot study determines fast dynamic gadolinium enhanced MRI contrast enhancement parameters (onset of enhancement and time to peak enhancement) before and after radiotherapy in 10 cervical carcinoma patients. Before radiotherapy, onset of enhancement and time to peak enhancement were early, with a median of 4.5 and 5.2 seconds, respectively. High-grade tumors showed early enhancement, compared with low-grade. After radiotherapy, contrast enhancement patterns differed. In survivors, onset of enhancement after radiotherapy was later than before radiotherapy. In non-survivors, onset of enhancement after radiotherapy was still early. The median difference in onset of enhancement before and after radiotherapy in survivors and non-survivors was an increase of 3.2 and a decrease of 1.1 seconds, respectively. Early onset of enhancement after radiotherapy was a better predictor for survival than a high-signal intensity zone on post radiotherapy unenhanced T1/T2-weighted MRI. It is concluded that enhancement parameters from fast dynamic Gd-enhanced MR images can provide additional functional information with regard to tumor vascularization, and may have prognostic significance. It complements clinical examination and unenhanced MRI in determining the effectiveness of radiotherapy treatment in cervical carcinoma. Future studies will focus on the clinical utility and improvements of the estimation of contrast-enhanced parameters with this new technique.

Prophylactic mastectomy or screening in women suspected to have the BRCA1/2 mutation: a prospective pilot study of women's treatment choices and medical and decision-analytic recommendations.

BACKGROUND: Women suspected to have the BRCA1/2 mutation may choose between two management options: breast cancer screening and prophylactic mastectomy (PM). OBJECTIVES: To compare women's treatment choices with medical and decision-analytic recommendations and to explore variables related to the women's choices. METHODS: After provision of information, individual time-tradeoff values for the health outcome "living after PM" were assessed and incorporated into a decision-analytic model, which compared the management options PM and screening with respect to their effects on quality-adjusted life expectancy. RESULTS: Of the 54 women suspected to have the mutation, 51 completed the shared-decision-making procedure. Quality-adjusted life expectancy after PM management was longer for 67% of proven carriers and for 58% of women awaiting the DNA-test result. Twelve proven carriers made definitive treatment choices: eight (67%) chose PM and four (33%) chose screening. All carriers' treatment choices agreed with the normative decision-analytic recommendations. Four (33%) disagreed with the medical recommendations. Of the 36 women awaiting DNA-test results, 32 made hypothetical treatment choices. The agreement between these hypothetical treatment choices and the decision-analytic recommendations was good (78%). Combining data from all 48 women, being married (OR = 14.00, p = 0.006), having children (OR = 4.71, p = 0.02), low desire to participate (OR = 0.14, p = 0.004), high decisional stress (OR = 5.22, p = 0.01), a lower estimate of the "probability of cure for screen-detected breast cancer" (OR = 0.13, p = 0.004), and higher time-tradeoff values for PM (OR = 182, p < 0.0001) made a choice for PM more likely. CONCLUSIONS: The complete agreement between the decision-analytic recommendations and the carriers' choices suggests that women act in accordance with normative decision theory. The disagreement between the carriers' choices and the medical recommendations suggests that women's choices and physicians' recommendations were guided by different arguments. The strong association between time-tradeoff value and treatment choice suggests that the time-tradeoff is a valid method to assess preferences.

Evaluation of a shared decision making program for women suspected to have a genetic predisposition to breast cancer: preliminary results.

BACKGROUND: Women suspected to have a genetic predisposition to breast cancer face the difficult choice between regular breast cancer screening and prophylactic mastectomy. The authors developed a shared decision making program (SDMP) to support this decision. OBJECTIVES: To evaluate the SDMP in terms of practicality, beneficial effects, and patient satisfaction. DESIGN: A one-group pretest-posttest design was used. MEASURES: Decision uncertainty, decision burden, subjective knowledge, and risk comprehension were assessed before and after the SDMP. Additional measures were obtained for concepts related to breast cancer concern, desire to participate in the program, satisfaction, program acceptability, and emotional reaction to the program information. RESULTS: Seventy-two women, most of whom were awaiting the genetic test results, participated. Decision uncertainty (effect size d = 0.37) and decision burden (d = 0.41) were reduced by the SDMP. Subjective knowledge (averaged d = 0.94) and risk comprehension were improved. The women were satisfied with the SDMP and found its rationale acceptable. Women who had strong emotional reactions to the information benefited less from the SDMP, whereas women with strong desires to participate in the decision benefited more. CONCLUSIONS: There is a need to give patients more information, especially about prophylactic mastectomy and among gene carriers. Beneficial effects were observed irrespective of whether genetic status was known, suggesting that information concerning treatment options should be made available as soon as DNA testing begins. The better psychological outcomes of women with stronger desires to participate may arise because the desire to participate is characteristic of emotional stability.

Assessment of the time-tradeoff values for prophylactic mastectomy of women with a suspected genetic predisposition to breast cancer.

BACKGROUND: Female carriers of the breast-cancer-susceptibility genes BRCA1 and BRCA2 are at high risk for breast cancer (85%). They face the choice between prophylactic mastectomy (PM) and breast cancer screening. For this treatment choice, a shared-decision-making program was developed. In this program, the time tradeoff (TTO) was used to assess preferences for PM. PURPOSE: Assessment of the feasibility, constant proportional tradeoff, and reliability of using the TTO for this purpose. METHODS: Fifty-four women suspected to carry the BRCA1/2 mutation were provided with comprehensive relevant information. Their preferences for PM were assessed on two occasions. Discrepancies between preferences indicated by the two tests were resolved by testing a third time. The preferences assessed on the last occasion were used for individual decision analyses. In order to test constant proportional tradeoff, the TTO consisted of four items with different numbers of life years. RESULTS: Forty-two women (78%) completed the TTO twice and nine women (17%) performed the test a third time. Three women (5%) completed the TTO only once. The mean TTO value for PM at the last replication was 0.69 (SD=0.30). Violations of constant proportional tradeoff were significant: the largest tradeoffs were recorded for the shortest durations. Pearson's correlation coefficient between the TTO values for the two last sessions was 0.96. CONCLUSION: Assessment of individual preferences by the TTO in this patient group is feasible and reliable. Therefore, the TTO can be used in clinical settings to elicit treatment preferences of women proven or suspected to have a genetic predisposition to breast cancer.

Risk attitude in gambles with years of life: empirical support for prospect theory.

According to prospect theory, risk attitude changes depending on whether a prospect is perceived as a gain or a loss relative to a reference or aspiration level. To investigate risk attitude with respect to years of life, the authors elicited utilities at two occasions by the certainty equivalent method from 30 women from the general population. The respondents gave certainty equivalents to gambles with years of life. The gambles were two-outcome gambles with equal probabilities to experience each outcome. A shift from a risk-seeking towards a risk-averse attitude was observed with increasing expected value of the gambles. For each individual, the averaged responses over the two replications were fitted with an s-shaped logistic curve that showed an excellent fit (r2 > or = 0.97) for all respondents. The aspiration level of survival can be derived from this function and was negatively correlated with age (r = -0.43, p < 0.025). The data are consistent with prospect theory and may explain why patients opt for risky treatments, since most of the respondents were risk-seeking in the short term.

Tamoxifen as sole therapy for primary breast cancer in the elderly patient.

In a retrospective study the data concerning 40 patients, with primary operable breast cancer were analysed. The mean follow-up of the patient group was 29 months. All patients received tamoxifen only. 17 (43%) reached remission and there was stable disease in 16 (40%). 7 (18%) showed progression, although they have had stable disease for at least 18 months. There were 1 local, 1 distant and 5 local plus distant progressions. 3 patients required salvage mastectomy. The mean progression-free interval was 33 months. Death was attributable to breast carcinoma in only 6 patients (15%). The 3-year survival was 47.2%. We conclude that primary treatment with tamoxifen as a sole therapy is acceptable in operable breast carcinoma for those patients for whom surgery is contraindicated or who refuse surgery.

Breast-conserving treatment or mastectomy in early breast cancer: a clinical decision analysis with special reference to the risk of local recurrence.

A clinical decision analysis was performed to judge the impact of local recurrences after breast-conserving treatment (BCT) on the (quality-adjusted) life expectancy of breast cancer patients. A life-long follow-up of two patient groups, one of which had undergone mastectomy and one BCT, was simulated by a Markov model of medical prognosis. Data used in the model originated from the literature. Since results in the source papers were not split according to stage, we performed two analyses: one with data from all source studies (T1 and T2) and one with data from source studies, concerning only T1 patients. In both analyses, the conclusion was that BCT yields better quality-adjusted life expectancy than mastectomy. Sensitivity analysis, however, identified subgroups of patients who should preferably undergo mastectomy. These subgroups are: patients preferring mastectomy to BCT, patients with a high risk of local recurrence, young patients and patients at high age, if they also have a high local recurrence risk. For these groups, patient preferences should play a major role in recommending treatment.