Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Uptake of cancer risk management strategies among women who undergo cascade genetic testing for breast cancer susceptibility genes.

BACKGROUND: Uptake of cancer risk management based on inherited predispositions, which encompasses bilateral mastectomy (BLM), bilateral salpingo-oophorectomy (BSO), and intensified screening, is the primary motivation for cascade testing for hereditary breast and ovarian cancer (HBOC). However, long-term outcome data for cascade testers are lacking. METHODS: Medical records were abstracted for all unaffected women with pathogenic variants in HBOC genes from 2 cancer hospitals (2013-2019) with at least 1 year of follow-up to compare the uptake of surgery and screening between cascade and noncascade testers. RESULTS: Cascade testers (79.8%) were younger than noncascade testers (mean age, 37.6 vs 43.5 years; P = .002). Among women aged ≥40 years, 43% underwent BLM, and 71.6% underwent BSO, with no significant difference in uptake between cascade and noncascade testers. The mean time to BSO among cascade testers was shorter among women aged ≥40 years versus those aged <40 years (11.8 vs 31.9 months; P = .04); no such difference was observed among noncascade testers. Mammography and breast magnetic resonance imaging rates were low in the recorded 6 years for both groups after genetic counseling. CONCLUSIONS: Management uptake among cascade testers is high with rates comparable to those for unaffected BRCA-positive women. A large proportion of women act on cascade test results, and this represents a novel report of utilization of cancer management strategies.

Longitudinal follow-up after telephone disclosure in the randomized COGENT study.

PURPOSE: To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multigene panel testing. 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) (i.e., usual care) of test results. All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations. RESULTS: Four hundred seventy-three 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 < 0.0001), being female (p = 0.047), and not having a true negative result (p < 0.002). Mammography was lower at 12 months among those who had TD and did not return for medical follow-up (70%) compared with those who had TD and returned (86%) and those who had IPD (87%, adjusted p < 0.01). CONCLUSION: Telephone disclosure of genetic test results is a reasonable alternative to in-person disclosure, but attention to medical follow-up may remain important for optimizing appropriate use of genetic results.

Preferences for in-person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study.

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.

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

OBJECTIVE: 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. METHODS: Fifty-five women considering mastectomy were randomly assigned to receive the BRAID versus the Cancer Support Community's Frankly Speaking About Cancer: Breast Reconstruction pamphlet. Participants completed measures of breast reconstruction (BR) knowledge, preparation to make a decision, decisional conflict, anxiety, and BR intentions before randomization and 2 weeks later. RESULTS: In terms of acceptability, enrollment into the study was satisfactory, but the rate of return for follow-up surveys was lower among BRAID participants than pamphlet participants. Both interventions were evaluated favorably in terms of their value in facilitating the BR decision, and the majority of participants completing the follow-up reported viewing the materials. In terms of preliminary efficacy, both interventions resulted in significant increases in BR knowledge and completeness and satisfaction with preparation to make a BR decision, and both interventions resulted in a significant reduction in decision conflict. However, there were no differences between interventions. CONCLUSION: A widely available free pamphlet and a web-based customized decision aid were highly utilized. The pamphlet was as effective in educating women about BR and prepared women equally as well to make the BR decision as compared with a more costly, customized web-based decision support aid. Copyright © 2015 John Wiley & Sons, Ltd.

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.

A multicenter study of clinical impact of variant of uncertain significance reclassification in breast, ovarian and colorectal cancer susceptibility genes.

BACKGROUND: Clinical interpretation of genetic test results is complicated by variants of uncertain significance (VUS) that have an unknown impact on health but can be clarified through reclassification. There is little empirical evidence regarding VUS reclassification in oncology care settings, including the prevalence and outcomes of reclassification, and racial/ethnic differences. METHODS: This was a retrospective analysis of persons with and without a personal history of cancer carrying VUS (with or without an accompanying pathogenic or likely pathogenic [P/LP] variant) in breast, ovarian, and colorectal cancer predisposition genes seen at four cancer care settings (in Texas, Florida, Ohio, and New Jersey) between 2013 and 2019. RESULTS: In 2715 individuals included in the study, 3261 VUS and 313 P/LP variants were reported; 8.1% of all individuals with VUS experienced reclassifications and rates varied significantly among cancer care settings from 4.81% to 20.19% (overall p < 0.001). Compared to their prevalence in the overall sample, reclassification rates for Black individuals were higher (13.6% vs. 19.0%), whereas the rates for Asian individuals were lower (6.3% vs. 3.5%) and rates for White and Hispanic individuals were proportional. Two-year prevalence of VUS reclassification remained steady between 2014 and 2019. Overall, 11.3% of all reclassified VUS resulted in clinically actionable findings and 4.6% subsequently changed individuals' clinical managements. CONCLUSIONS: The findings from this large multisite study suggest that VUS reclassification alters clinical management, has implications for precision cancer prevention, and highlights the need for implementing practices and solutions for efficiently returning reinterpreted genetic test results.

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.

Cognitive and social processes predicting partner psychological adaptation to early stage breast cancer.

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.

A review on bevacizumab and surgical wound healing: an important warning to all surgeons.

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.

Use and Patient-Reported Outcomes of Clinical Multigene Panel Testing for Cancer Susceptibility in the Multicenter Communication of Genetic Test Results by Telephone Study.

PURPOSE: Multigene panels (MGPs) are increasingly being used despite questions regarding their clinical utility and no standard approach to genetic counseling. How frequently genetic providers use MGP testing and how patient-reported outcomes (PROs) differ from targeted testing (eg, BRCA1/2 only) are unknown. METHODS: We evaluated use of MGP testing and PROs in participants undergoing cancer genetic testing in the multicenter Communication of Genetic Test Results by Telephone study (ClinicalTrials.gov identifier: ), a randomized study of telephone versus in-person disclosure of genetic test results. PROs included genetic knowledge, general and state anxiety, depression, cancer-specific distress, uncertainty, and satisfaction. Genetic providers offered targeted or MGP testing based on clinical assessment. RESULTS: Since the inclusion of MGP testing in 2014, 395 patients (66%) were offered MGP testing. MGP testing increased over time from 57% in 2014 to 66% in 2015 (P = .02) and varied by site (46% to 78%; P < .01). Being offered MGP testing was significantly associated with not having Ashkenazi Jewish ancestry, having a history of cancer, not having a mutation in the family, not having made a treatment decision, and study site. After demographic adjustment, patients offered MGP testing had lower general anxiety (P = .04), state anxiety (P = .03), depression (P = .04), and uncertainty (P = .05) pre-disclosure compared with patients offered targeted testing. State anxiety (P = .05) and cancer-specific distress (P = .05) were lower at disclosure in the MGP group. There was a greater increase in change in uncertainty (P = .04) among patients who underwent MGP testing. CONCLUSION: MGP testing was more frequently offered to patients with lower anxiety, depression, and uncertainty and was associated with favorable outcomes, with the exception of a greater increase in uncertainty compared with patients who had targeted testing. Addressing uncertainty may be important as MGP testing is increasingly adopted.

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.

Protective buffering and psychological distress among couples coping with breast cancer: The moderating role of relationship satisfaction.

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.

Partner unsupportive responses, avoidant coping, and distress among women with early stage breast cancer: patient and partner perspectives.

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.

Couple-focused group intervention for 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.

Inflammatory actinic keratoses secondary to systemic chemotherapy.

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.

Shifting paradigms in hormonal therapy for breast cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: The AIs have been shown to be effective treatments for hormone-sensitive metastatic breast cancer. CONCLUSIONS: 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.

Posttraumatic growth after breast cancer: patient, partner, and couple perspectives.

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.

New developments in endocrine therapy: role of adjuvant therapy for early breast cancer.

Tamoxifen has become the standard of care in relation to hormonal therapy for women with hormone-sensitive tumors. However, recently completed and ongoing studies indicate that third-generation aromatase inhibitors may be more effective than tamoxifen for a wide range of patients with breast cancer. Drugs in this class currently are approved as first-line endocrine therapy for postmenopausal women with metastatic hormone-dependent breast cancer, and as second-line endocrine therapy after failure of antiestrogen therapy alone or multiple hormonal therapies. The interim results from the Arimidex, Tamoxifen Alone or in Combination Trial support the use of an aromatase inhibitor as an alternative to tamoxifen for adjuvant therapy in postmenopausal women with operable breast cancer that is hormone positive. In this trial, anastrozole had a favorable side effect profile, with fewer cases of endometrial cancer and fewer thromboembolic events than tamoxifen. Other recent studies have indicated that an aromatase inhibitor may be superior to tamoxifen as preoperative treatment for women with hormone-sensitive, primary breast cancer. Numerous clinical trials currently are comparing the efficacy of aromatase inhibitors with that of tamoxifen used as adjuvant therapy for postmenopausal women who have early-stage breast cancer. The results of these trials will provide additional information about the best ways to use these powerful agents for patients with breast cancer.

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. 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.