Generosa Grana

The interpersonal process model of intimacy: The role of self-disclosure, partner disclosure, and partner responsiveness in interactions between breast cancer patients and their partners

This study evaluated H. Reis and P. Shavers (1988) interpersonal process model of intimacy in a sample of 98 women with breast cancer and their partners. Couples engaged in two discussions and rated self- and partner disclosure, perceived partner responsiveness, and intimacy experienced. A mediational model was tested in which partner responsiveness mediated the association between disclosure and intimacy. For patients, perceived responsiveness partially mediated the association between partner disclosure and intimacy, but self-disclosure was not significantly associated with responsiveness or intimacy. For partners, perceived responsiveness mediated the association between self-disclosure and perceived partner disclosure and intimacy. For breast cancer patients, partner disclosure predicted patient feelings of intimacy, because this type of disclosure was associated with greater feelings of acceptance, understanding, and caring. These findings may have implications for interventions to improve relationship closeness among couples coping with breast cancer.

Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility

Purpose:Multiplex genetic testing, including both moderate- and high-penetrance genes for cancer susceptibility, is associated with greater uncertainty than traditional testing, presenting challenges to informed consent and genetic counseling. We sought to develop a new model for informed consent and genetic counseling for four ongoing studies. Methods:Drawing from professional guidelines, literature, conceptual frameworks, and clinical experience, a multidisciplinary group developed a tiered-binned genetic counseling approach proposed to facilitate informed consent and improve outcomes of cancer susceptibility multiplex testing.Results:In this model, tier 1 “indispensable” information is presented to all patients. More specific tier 2 information is provided to support variable informational needs among diverse patient populations. Clinically relevant information is “binned” into groups to minimize information overload, support informed decision making, and facilitate adaptive responses to testing. Seven essential elements of informed consent are provided to address the unique limitations, risks, and uncertainties of multiplex testing.Conclusion:A tiered-binned model for informed consent and genetic counseling has the potential to address the challenges of multiplex testing for cancer susceptibility and to support informed decision making and adaptive responses to testing. Future prospective studies including patient-reported outcomes are needed to inform how to best incorporate multiplex testing for cancer susceptibility into clinical practice.Genet Med 17 6, 485–492.

Acceptability and pilot efficacy trial of a web‐based breast reconstruction decision support aid for women considering mastectomy

The study aim was to test the acceptability and preliminary efficacy of a novel interactive web‐based breast reconstruction decision support aid (BRAID) for newly diagnosed breast cancer patients considering mastectomy.

Initial Development of the Mental Health Assessment and Dynamic Referral for Oncology (MHADRO)

The Mental Health Assessment and Dynamic Referral for Oncology (MHADRO) is a program that conducts a computerized assessment of physical, psychological, and social functioning related to oncology treatment, prints personalized summary reports for both the patient and the provider, and for those who provide consent, faxes a referral and assessment summary report to a matched mental health treatment provider (i.e., dynamic referral). The functionality, feasibility, and end user satisfaction of the MHADRO were tested in a comprehensive care center. Of the 101 participants enrolled, 61 (60%) exhibited elevated distress on at least one of the mental health indices, and, of these, 12 (20%) chose a dynamic referral for mental health services. Patients and health care providers exhibited high levels of satisfaction with the program. The MHADRO has potential for assisting in meeting the psychosocial needs faced by individuals with cancer and should be tested further for its facilitation of mental health treatment initiation.

A roundtable discussion of aromatase inhibitors as therapy for breast cancer

Abstract:  This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second‐line therapy in postmenopausal women with hormone‐responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first‐line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone‐responsive disease.

Screening for BRCA1 Mutations in Patients with Triple Negative Breast Cancer and Basal Phenotype.

Introduction: Most models estimating risk of carrying germline BRCA mutations are based on family history and age of cancer onset. Additional histologic criteria may be useful to identify patients at risk for harboring BRCA1 mutations. BRCA1 positive breast tumors are significantly more often estrogen receptor, progesterone receptor, and erbB-2 (HER2-neu) negative (“triple negative” (TN)) and are strongly associated with a basal phenotype confirmed by DNA microarray. Basal-like tumors express cytokeratins 5,6, and 14 or 17 by immunohistochemistry (IHC). It is unknown whether testing for BRCA1 mutations in TN basal-like breast cancer patients will identify additional carriers of mutations in this gene.Methods: A retrospective evaluation of patients with triple negative breast cancer seen at Cooper Cancer Center between 2004 and 2006 was performed after IRB approval. IHC was performed to identify the subset of basal-like breast cancers.Results: A total of 89 women were identified as diagnosed with TN breast cancer, while 53 had pathology available for review. 21 patients were identified as basal phenotype, whereas 32 were non-basal. Of the 21 patients who had basal-phenotype tumors, six underwent genetic testing and 3 were found to have a deleterious BRCA1 mutation. Of 32 non-basal patients, 9 patients underwent genetic testing and 2 were found to have a deleterious BRCA1 mutation. There was no difference between basal subtype and BRCA1 postivity [Fisher9s Exact Test p=0.32]. Of note, 1of 5 (20%) patients with basal phenotype had no family history but tested positive for BRCA1 mutation and would have been missed by relying on conventional methods.Conclusion: Although there is a trend towards a higher percentage of TN breast cancer patients with basal subtype having BRCA 1 mutations (50 vs 22%), this was not found to be statistically significant (Fisher9s exact p=0.32). However, this dataset is limited by a small sample size. Only 40% of TN breast cancer patients had a basal phenotype by IHC in this study, while other studies have shown 70- to 85% rate. Ongoing evaluation of patients with basal-like subtype and triple negative tumors should continue to investigate this relationship, especially in light of newer therapeutics that may impact this population. This data also suggests that patients with basal phenotype and triple negative disease should be considered for referral for genetic testing even in the absence of family history. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4075.

Randomized Noninferiority Trial of Telephone vs In-Person Disclosure of Germline Cancer Genetic Test Results

Background Germline genetic testing is standard practice in oncology. Outcomes of telephone disclosure of a wide range of cancer genetic test results, including multigene panel testing (MGPT) are unknown. Methods Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone disclosure (TD) of genetic test results with usual care, in-person disclosure (IPD) after tiered-binned in-person pretest counseling. Primary noninferiority outcomes included change in knowledge, state anxiety, and general anxiety. Secondary outcomes included cancer-specific distress, depression, uncertainty, satisfaction, and screening and risk-reducing surgery intentions. To declare noninferiority, we calculated the 98.3% one-sided confidence interval of the standardized effect; t tests were used for secondary subgroup analyses. Only noninferiority tests were one-sided, others were two-sided. Results A total of 1178 patients enrolled in the study. Two hundred eight (17.7%) participants declined random assignment due to a preference for in-person disclosure; 473 participants were randomly assigned to TD and 497 to IPD; 291 (30.0%) had MGPT. TD was noninferior to IPD for general and state anxiety and all secondary outcomes immediately postdisclosure. TD did not meet the noninferiority threshold for knowledge in the primary analysis, but it did meet the threshold in the multiple imputation analysis. In secondary analyses, there were no statistically significant differences between arms in screening and risk-reducing surgery intentions, and no statistically significant differences in outcomes by arm among those who had MGPT. In subgroup analyses, patients with a positive result had statistically significantly greater decreases in general anxiety with telephone disclosure (TD -0.37 vs IPD +0.87, P = .02). Conclusions Even in the era of multigene panel testing, these data suggest that telephone disclosure of cancer genetic test results is as an alternative to in-person disclosure for interested patients after in-person pretest counseling with a genetic counselor.

Phase I Study of Sequential Administration of Topotecan and 5-Fluorouracil in Patients with Advanced Malignancies

Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an antimetabolite that interferes with DNA synthesis. Preclinical studies using human cancer cell line models have shown potential therapeutic synergy between these two drugs by showing the maximum cytolytic effect using sequential 5FU followed by topotecan. In the current study, 5FU was used at a fixed dose of 375 mg/m2 given intravenously for five consecutive days on a 28 day cycle. Topotecan was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m2 given intravenously for 5 days after the 5FU dose. Eleven patients were entered at different dose levels. Both hematological and gastrointestinal toxicity were dose limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m2 of topotecan. Two cases of grade 4 neutropenia were also observed at this dose level. One patient with small cell lung cancer had a complete response, while one patient with metastatic colorectal cancer had a partial remission. Three other patients had stable disease, lasting between 6 and 8 months. Overall, the regimen was well tolerated. A phase II study using a dose of 5FU at 375 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously over 5 days every 28 days is recommended.