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Use of surveillance mammography and magnetic resonance imaging (MRI) has been understudied among women with variant of uncertain significance (VUS) compared to pathogenic and likely pathogenic variants (P/LP).Using data from two cancer settings, we calculated use of risk-reducing mastectomy (RRM) and surveillance during each 13-month span after genetic testing up to 6 years afterwards for a cohort of genetically elevated risk women.Of 889 women, VUS carriers were less likely to undergo RRM compared to those with P/LP (hazard ratio [HR], 0.17; p = .001) and high-risk women were more likely to undergo RRM than average-risk women (HR, 3.91; p = .005). Longitudinally, surveillance use among unaffected women decreased from 49.8% in the first year to 31.2% in the sixth year after genetic testing. In comparison, a greater proportion of women with a personal history of breast cancer underwent surveillance, which increased from 59.3% in the first year to 63.6% in the sixth year after genetic testing. Mammography rates did not differ between women with P/LP and VUS within the first 13 months after genetic testing and up to 4 years afterward. Over the first 4 years after genetic testing, women with VUS were less likely to undergo annual MRIs compared to P/LP.The authors found that VUS, whether in high or moderate penetrance breast cancer susceptibility genes, was associated with lower use of annual breast MRI compared to P/LP variants and equivalent use of annual mammography. These results add important evidence regarding VUS-related breast surveillance.

Purpose To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multi-gene panel testing. Patients and Methods Adults who were proceeding with germline cancer genetic testing were randomized to telephone disclosure (TD) with a genetic counselor or in-person disclosure (IPD) of test results (i.e., usual care). All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations. Results 473 participants were randomized to TD and 497 to IPD. There were no differences between arms for any cognitive, affective or behavioral outcomes at 6 and 12 months. Only 50% of participants in the TD arm returned for the medical follow-up appointment. Returning was associated with site (p

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

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.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.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.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.

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.

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 Mental Health Assessment and Dynamic Referral for Oncology (MHADRO) were tested in a comprehensive care center. Of the 101 subjects 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.

Purpose Breast cancer is the most common malignancy occurring during pregnancy. Because more women delay childbearing, the diagnosis of cancer during pregnancy will likely increase. Case reports exist in the literature regarding the treatment of pregnant women with breast cancer, but few are prospective and few provide long-term follow-up on the neonate exposed to chemotherapy. In this report, 130 women diagnosed with breast cancer were reported to our voluntary national registry and followed up prospectively. Patient and methods The Cancer and Pregnancy Registry is a voluntary registry that monitors the clinical course, treatment, and disease outcome of women diagnosed with cancer during pregnancy and the perinatal and neonatal outcomes of their children. Results Of the 130 diagnosed, 120 were diagnosed with a primary tumor, 8 with a recurrence, and 2 with a new primary cancer. Mean maternal age at diagnosis was 34.8 +/- 4.2 years. Mean gestational age at diagnosis was 13.2 +/- 8.1 weeks. Gestational age was 12.8 +/- 7.8 weeks for patients with primary disease and 16.25 +/- 11 weeks for those with recurrent cancer. One hundred thirteen women were followed up for mean of 3.14 +/- 2.5 years. Of those followed up, 103 were diagnosed with primary breast cancer during pregnancy, 8 with a recurrence, and 2 with a new primary. Recurrence was reported in 30 patients at an average of 16.2 +/- 10.8 months from delivery to recurrence. Twenty-one patients are deceased with an average of 24.71 +/- 15.32 months from delivery to death. Only 42% were diagnosed with an estrogen-positive tumor and 35% of cases had a progesterone receptor-positive tumor. Human epidermal growth factor receptor 2 was positive in 25% of patients. Chemotherapy was given during pregnancy in 104 cases; the first treatment was given at a mean gestational age of 20.4 +/- 5.4 weeks. The malformation rate of exposed neonates was 3 not greater than the general population. Survival by stage for a primary diagnosis in pregnancy is as follows: stage I, 100%; stage II, 86%; stage III, 86%; and stage IV, 0%. Discussion Pregnant women diagnosed with breast cancer can receive treatment comparable with nonpregnant women leading to a similar survival when matched for stage at diagnosis. The majority of children who were exposed to chemotherapy in utero did not demonstrate significant complications. We report the single largest cohort of women diagnosed with breast cancer during pregnancy.

This study examined whether the association between protective buffering and psychological distress was moderated by relationship satisfaction. Protective buffering is defined as hiding worries, denying concerns, and yielding to one's partner in an effort to avoid disagreement and reduce one's partner's upset and burden. Two hundred thirty-five women diagnosed with early stage breast cancer and their partners completed measures of protective buffering, psychological distress, and relationship satisfaction at 3 time points over an 18-month period after cancer diagnosis. The authors hypothesized that protective buffering would result in more distress among patients and partners reporting higher relationship satisfaction than among patients and partners reporting lower levels of relationship satisfaction. Patients' protective buffering predicted more distress among patients rating their relationships as more satisfactory, whereas the patients' buffering did not predict distress among patients rating their relationships as less satisfactory. Partner relationship satisfaction also moderated the association between patients' buffering and partners' distress. These findings elucidate conditions under which protective buffering may have detrimental effects.

Background: Although self-efficacy is considered a key psychological resource in adapting to chronic physical illness, this construct has received less attention among individuals coping with cancer.Purpose: To examine changes in cancer self-efficacy over time among women with early stage breast cancer and associations between task-specific domains of selfefficacy and specific psychological, relationship, and functional outcomes.Methods: Ninety-five women diagnosed with early stage breast cancer completed surveys postsurgery and 1 year later.Results: Cancer-related self-efficacy was relatively stable over 1 year, with only 2 domains of efficacy—(a) Activity Management and (b) Self-Satisfaction—evidencing significant increases over the 1-year time period. Cross-sectional findings were relatively consistent with predictions and suggested that specific domains of self-efficacy were more strongly related to relevant domains of adaptation. Longitudinal findings were not as consistent with the domain-specificity hypothesis but did suggest several predictive associations between self-efficacy and outcomes. Personal Management self-efficacy was associated with higher relationship satisfaction, higher Communication Self-Efficacy was associated with less functional impairment, and higher Affective Management self-efficacy was associated with higher self-esteem 1 year later.Conclusions: Specific domains of cancer-related self-efficacy are most closely related to relevant areas of adaptation when considered cross-sectionally, but further study is needed to clarify the nature of these relationships over time.

This study evaluated H. Reis and P. Shaver's (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.

Tamoxifen has been the mainstay of endocrine treatment for postmenopausal patients with early and advanced breast cancer for many years. However, as an anti-estrogen with partial estrogenic effects, tamoxifen also has some serious safety and tolerability issues. Following tamoxifen treatment failure there were initially limited options for subsequent therapy. Therefore, new agents, including new anti-estrogens and aromatase inhibitors (AIs) were developed.Data for this review were identified by searches of PubMed and references from relevant articles. Abstracts were included only when the relevant information had not been published in full elsewhere. Only papers published in English were included.The AIs have been shown to be effective treatments for hormone-sensitive metastatic breast cancer.Current clinical trial data in early breast cancer show longer disease-free survival and time to recurrence with anastrozole than that demonstrated with tamoxifen and very good general tolerability, although longer follow-up is warranted. Clinical trials of the use of AIs in breast cancer prevention and preliminary data for the combination of anastrozole with a gonadotrophin-releasing hormone for the treatment of premenopausal women with early stage breast cancer are also discussed here.

OBJECTIVE The purpose of this study was to evaluate posttraumatic growth among breast cancer patients and their significant others over a 1(1/2)-year time span after diagnosis and to examine cognitive and emotional processes in posttraumatic growth. METHODS One hundred sixty-two women with breast cancer and their partners completed surveys assessing posttraumatic growth, cognitive and emotional processing, and marital satisfaction at 3 time points spaced 9 months apart. RESULTS Posttraumatic growth increased for both partners during this period. Patient posttraumatic growth was predicted by younger age, contemplating reasons for cancer, and more emotional expression at time 1. Partner posttraumatic growth was predicted by younger age, more intrusive thoughts, and greater use of positive reappraisal and emotional processing at time 1. CONCLUSION Posttraumatic growth is reported by patients and by significant others. Cognitive and emotional processes predict growth. Patient growth is associated with the significant other's cognitive and emotional processing of breast cancer.

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.

Bevacizumab (Avastin, Genentech, Inc, San Francisco, CA), a humanized monoclonal antibody against vascular endothelial growth factor, was recently approved for the treatment of metastatic breast cancer.A PubMed and OVID search was performed using keywords: bevacizumab, Avastin, wound healing, VEGF, angiogenesis, and colorectal cancer. Our objective was to review the current literature in regard to bevacizumab and its adverse effects on surgical wound healing.Bevacizumab has been associated with multiple complications in regard to wound healing, such as dehiscence, ecchymosis, surgical site bleeding, and wound infection. Current literature suggests patients should wait at least 6 to 8 weeks (>40 days) after cessation to have surgery (half-life = 20 days). In addition, postoperative reinitiation of bevacizumab must wait > or =28 days to prevent an increased risk of wound healing complications, and the surgical incision should be fully healed.The adverse effects of bevacizumab in regard to wound healing must be considered in all surgical patients.

Introduction. The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners' psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined. Materials and methods. Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner's diagnosis (N=253), 9 (N=167), and 18 months (N=149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning making, and general and cancer-specific distress at all time points. Results. Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer-specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer-specific distress were found. Conclusions. Results indicate several cognitive–social processes directly predict partner distress. However, moderator effect models in which the effects of partners' processing depends upon whether these efforts result in changes in perceptions of the cancer experience may add to the understanding of partners' adaptation to cancer.

Tamoxifen is the established adjuvant treatment for postmenopausal women with hormone-sensitive early breast cancer. However, the side-effects associated with tamoxifen therapy have prompted a search for safer and potentially more effective endocrine agents. Results from randomized trials of the third-generation aromatase inhibitors, anastrozole, letrozole and exemestane, demonstrating improved efficacy compared with tamoxifen and favorable tolerability profiles, are discussed in this review.

This 18-month longitudinal study examined the associations among partner unsupportive behavior, avoidant coping, and distress experienced by 219 women with early stage breast cancer. The role of patient and partner ratings of unsupportive behavior were evaluated. Results indicated that patient and partner ratings of unsupportive behavior were highly correlated. Growth curve modeling suggested that unsupportive behavior, from both patient and partner perspectives, predicted more avoidant coping and distress. When partner and patient perceptions were placed in the same model, patient perceptions mediated the association between partners' ratings of their unsupportive behavior and patient distress. Avoidance also mediated the association between unsupportive behavior and distress, extending prior cross-sectional findings. Results highlight the long-term detrimental effects of partners' unsupportive behavior on the quality of life of women with early stage breast cancer.

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions of a couple-focused group intervention or usual care. Intent-to-treat growth curve analyses indicated that participants assigned to the couples' group reported lower depressive symptoms. Women rating their partners as more unsupportive benefited more from the intervention than did women with less unsupportive partners, and women with more physical impairment benefited more from the intervention group than did women with less impairment. Subgroup analyses comparing women attending the couple-focused group intervention with women not attending groups and with usual care participants indicated that women attending sessions reported significantly less distress than did women receiving usual care and women who dropped out of the intervention.

This longitudinal study examined the association between three types of communication strategies couples may use to handle stressors they experience during and after breast cancer treatment and psychological distress and relationship satisfaction of women with early stage breast cancer and their partners. Mutual constructive communication, mutual avoidance, and demand-withdraw communication strategies as well as psychological distress and marital satisfaction were rated by 147 patients and 127 partners during cancer treatment and 9 months later. Mutual constructive communication was associated with less distress and more relationship satisfaction for both patient and partner. Demand-withdraw communication was associated with higher distress and lower relationship satisfaction for both patient and partner. Mutual avoidance was associated with more distress for patient and partner but was not associated with relationship satisfaction. The negative association between mutual constructive communication and patient distress was stronger for patients with more physical impairment. Patients' perceptions of mutual constructive communication and mutual avoidance were associated with partners' distress, and patients' perceptions of mutual constructive and demand/withdraw communication were associated with partners' marital satisfaction. Clinical implications for couple-focused communication skills training for cancer patients and their partners are discussed.

Traditionally, systemic 5-fluorouracil has been associated with a reaction that produces inflammation of preexisting and subclinical actinic keratoses (AKs). We report a case of an inflammatory reaction occurring in AKs secondary to the use of doxorubicin. The cutaneous reaction was successfully managed with the application of high-potency topical steroids over the body and with pain management. When the doxorubicin was discontinued and another agent (paclitaxel) was instituted, the cutaneous reaction gradually diminished.

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.

In an effort to decrease the relapse rate following autologous bone marrow transplantation for non-Hodgkin's lymphoma, patients were given cyclosporine and interferon following autologous marrow transplantation. Forty patients with intermediate grade non-Hodgkin's lymphoma that was relapsed or refractory to standard chemotherapy underwent autologous marrow transplantation. The preparative regimen consisted of cyclophosphamide 6.8 g/m2, etoposide 1600 mg/m2, and carmustine 400 mg/m2 over 4 days followed by reinfusion of bone marrow. Intravenous cyclosporine was started on day -1 as a 16 mg/kg loading dose followed by 3.6 mg/kg/day for 28 days after transplant. Patients were begun on alpha-interferon (starting dose, 0.5 million units s.c. every other day) following platelet engraftment (median day 24 post-transplant) and continued on 1.5 million units s.c. daily for 2 years. Regimen-related toxicities resulted in four (10%) deaths. Twenty-one (53%) patients developed marked erythema of the palms, soles, and arms. Biopsies of the erythema were consistent with grade I GVHD. Patients who did not develop rashes were not biopsied. The erythema persisted for a median of 10 days and resolved in all cases without treatment. Visceral GVHD was not apparent. All patients have been followed for a median of 24 months (range 12-54 months). To date, only five patients (13%) have relapsed after bone marrow transplant. Multivariant analysis could not identify risk factors for relapse post-transplant. Disease-free survival of all patients is 77% (95% confidence interval, 67-93%). The results of this pilot study suggest that the administration of cyclosporine and interferon may decrease the relapse rate of relapsed/refractory non-Hodgkin's lymphoma following autologous bone marrow transplantation.

Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention.