Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer.

Importance: National Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration. Objective: To examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making. Design, Setting, and Participants: Patients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022. Exposure: New and/or previous diagnosis of breast cancer. Main Outcomes and Measures: Disease management recommendations that were changed as a result of genetic testing results are reported. Results: Clinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]). Conclusions and Relevance: In this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Long-term cost of breast cancer treatment to the United States Medicare Program by stage at diagnosis.

INTRODUCTION: Breast cancer treatment includes increasingly complex and expensive treatments. Accordingly, the current estimates of the cost of breast cancer treatment are out of date. METHODS: The SEER-Medicare Data Link provided 142,837,978 paid Medicare claims from 398,148 female beneficiaries between the ages of 22 and 110 diagnosed with breast cancer between 2007 and 2016. These claims were compared with 153,071,044 claims from 443,952 Medicare beneficiaries without a cancer diagnosis. The total, fully adjudicated, amounts for each claim were summed to determine total treatment cost for each beneficiary. These costs were then aggregated by year after diagnosis and stage at diagnosis. The actuarial survival of beneficiaries with cancer was calculated using the Kaplan-Meier method. RESULTS: Mean costs for the control group were $8,019 per year. The 10-year cost of cancer treatment in Medicare beneficiaries was directly related to stage at diagnosis and ranged from $103,573 for stage 0 cancers to $376,573 for stage 4 cancers. The highest cost occurred during the first 2 years after diagnosis, the time of the beneficiary's initial treatment. Following the first 2 years, healthcare costs remained elevated for at least 10 years after diagnosis. CONCLUSIONS: The 10-year treatment cost of female Medicare beneficiaries with breast cancer increases with increasing stage at diagnosis. Any effective screening technology that reduces stage at diagnosis will result in significant treatment cost savings to the Medicare program.

Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

PURPOSE: An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. METHODS: An institutional review board-approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act-compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. RESULTS: More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher's exact test P = .4241). CONCLUSION: Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

The Addition of Automated Breast Ultrasound to Mammography in Breast Cancer Screening Decreases Stage at Diagnosis.

RATIONALE AND OBJECTIVES: This study aimed to determine the best screening strategy using automated whole-breast ultrasound and mammography in women with increased breast density or an elevated risk of breast cancer. MATERIALS AND METHODS: After an institutional review board waiver was obtained, a retrospective review of 122 cancer cases diagnosed in 3435 women with increased breast density or an elevated risk of breast cancer, screened with mammography and supplemental automated whole-breast ultrasound, was performed. The imaging modality on which each cancer was seen was noted. Screening strategies were postulated. For each screening strategy, rates of advanced cancer diagnosis, with 95% confidence limits, are calculated using the Clopper-Pearson method. Differences in outcomes were calculated using Cochrane Q test and McNemar test for paired observations. Results were expressed for all stages of cancer and for invasive cancers only. RESULTS: When all cancer stages are considered, mammographic screening reduces advanced cancers by 31% over no screening. Ultrasound-only screening results in a 32% reduction. The combination of mammographic and ultrasound screening reduces advanced cancers by 40% (P < .05). Compared to mammographic screening, mammographic plus ultrasound screening reduces advanced-stage cancers by 5.7% (P = 0.03) for all stages and 10.8% (P = 0.02) for invasive cancers. CONCLUSIONS: For women with increased breast density or who are at high risk of developing breast cancer, a combination of screening mammography and whole-breast automated ultrasound is superior to mammographic screening. Screening ultrasound alone is also an effective screening strategy.

Ultrasound-Guided Core-Needle Versus Vacuum-Assisted Breast Biopsy: A Cost Analysis Based on the American Society of Breast Surgeons' Mastery of Breast Surgery Registry.

PURPOSE: To evaluate the cost-efficacy of vacuum-assisted ultrasound-guided breast biopsy instruments compared to ultrasound-guided 14-gauge spring-loaded core-needle biopsy. METHODS: The American Society of Breast Surgeons' Mastery of Breast Surgery Registry was reviewed. Biopsy findings, any rebiopsy, and the instrument used were abstracted for 31,451 ultrasound-guided biopsy procedures performed between 2001 and July 2014. Rates of cancer diagnosis and rebiopsy were calculated for each instrument. A linear mathematical model was developed to calculate total cost per cancer diagnosis, including procedural costs and the costs of any additional surgical rebiopsy procedures. Mean cost per cancer diagnosis with confidence limits was then determined for 14-gauge spring-loaded core-needle biopsy and 14 different vacuum-assisted instruments. For 14-gauge spring-loaded core-needle biopsy, mean cost per cancer diagnosis was $4346 (4327-$4366). For the vacuum-assisted instruments, mean cost per cancer diagnosis ranged from a low of $3742 ($3732-$3752) to a high of $4779 ($4750-$4809). RESULTS: Vacuum-assisted instruments overall were more cost-effective than core with a mean cost per cancer diagnosis of $4052 ($4038-$4067) (p < 0.05). Tethered vacuum-assisted instruments performed best with a mean cost per cancer diagnosis of $3978 ($3964-$3991) (p < 0.05). Nontethered devices had a mean cost per cancer diagnosis of $4369 ($4350-$4388), a result no better than core (p < 0.05). CONCLUSIONS: Ultrasound-guided vacuum-assisted breast biopsy had a lower mean cost per cancer diagnosis than 14-gauge spring-loaded core-needle biopsy. This advantage was only seen in tethered vacuum-assisted instruments. Within device families, larger instruments tended to outperform smaller instruments.

The development of counselling psychology in Ireland.

This paper discusses the distinctive nature of the specialism of counselling psychology and outlines the development of the discipline in Ireland in the context of international developments and its recognition as a professional branch of applied psychology. Today, counselling psychologists are employed in varied clinical and non-clinical settings including health and mental health services (statutory, private and voluntary sector) along with education, forensic, justice, industry and private practices. Counselling psychologist is the primary professional identity of many practising psychologists in Ireland and the Psychological Society of Ireland's Division of Counselling Psychology is the main affiliation of at least 179 members. With its focus on facilitating personal and interpersonal functioning across the life span and its emphasis on the therapeutic process, the specialism continues to bridge the disciplines of psychology, counselling and psychotherapy. In this article, some of the challenges still faced by counselling psychology are explored as it navigates its way through the changing landscape of further development and evolution.

Preoperative staging with magnetic resonance imaging, with confirmatory biopsy, improves surgical outcomes in women with breast cancer without increasing rates of mastectomy.

Needle biopsy to evaluate findings on MRI that could alter surgical planning has been recommended. This study is a retrospective review to evaluate MRI preoperative staging with biopsy confirmation of suspicious findings. A total of 184 women were diagnosed with breast cancer between January 2004 and June 2008. Of these, 79 underwent bilateral MRI before definitive surgery and 105 did not. Suspicious findings on MRI, mammography, or clinical exam underwent additional needle biopsy at the discretion of the surgeon. A retrospective chart review was performed to compare the two groups with respect to rates of reoperative surgery, successful breast conservation, and confirmatory biopsies. Sensitivity and specificity of MRI for preoperative staging is 0.81 and 0.84, respectively. There were no significant differences in demographics or cancer characteristics between the MRI and non-MRI groups. Fewer women who underwent preoperative MRI staging required repeat breast surgery (11% versus 26%, p = .04) or repeat axillary surgery (10% versus 20%, p = .05). There is no difference in the proportion of women who successfully completed conservative therapy and those treated radically (52% versus 53%), but there is a significant increase in women who undergo additional needle biopsy to confirm suspicious findings after initial diagnosis in the MRI group (25% versus 11% p = .04). In this study, mastectomy rates are not increased; suggesting that women who undergo mastectomy following staging would undergo mastectomy following failed conservative therapy if they were not staged. The downside of this improvement is a 14% increase in women who require confirmatory biopsy.

Long-term outcome of benign fibroadenomas treated by ultrasound-guided percutaneous excision.

Surgical as well as conservative treatment has been described for fibroadenomas. Both have disadvantages. A minimally invasive treatment, ultrasound-guided, vacuum-assisted percutaneous excision has been shown to facilitate the removal of all imaged evidence of benign breast lesions, including fibroadenomas up to 3 cm in diameter. This study is performed to assess the long-term outcome of ultrasound-guided percutaneous excision as a minimally invasive treatment for fibroadenomas. A retrospective review of 69 consecutive fibroadenomas treated with ultrasound-guided percutaneous excision between May, 2001 and December, 2005 was carried out. All these lesions underwent percutaneous excision of all imaged lesion evidence. Clinical and sonographic follow-up was recommended for all patients every 6 months. Initial size, location, and patient age were recorded for each treated lesion. Of 69 lesions treated, 52 were available for follow-up. The median follow-up period was 22 months, with a range of 7 to 59 months. At 6 months, there were no fibroadenoma recurrences. Follow-up sonography demonstrated recurrences in 13 lesions distributed across eight patients. The overall recurrence rate was 15% (8/52) with an actuarial recurrence rate of 33% at 59 months. All of the recurrences were in lesions which were larger than 2 cm in size at initial presentation. Our data suggest that the mechanism of recurrence is the regrowth of retained lesion fragments too small to be detected by ultrasound--not the incomplete excision of all imaged lesion evidence. Despite successful percutaneous excision, fibroadenomas do recur. Lesions smaller than 2 cm in size, so treated, do not need additional therapy or surveillance. Fibroadenomas larger than 2 cm are prone to recurrence and require additional treatment.

Ultrasound-guided, vacuum-assisted, percutaneous excision of breast lesions: an accurate technique in the diagnosis of atypical ductal hyperplasia.

BACKGROUND: In October 2002, ultrasound-guided, vacuum-assisted, percutaneous excision was shown to facilitate the complete removal of benign breast lesions up to 3 cm in diameter. This study was performed to ascertain the overall accuracy of ultrasound-guided, vacuum-assisted, percutaneous excision as evidenced by the frequency of atypical ductal hyperplasia (ADH) underestimation. STUDY DESIGN: A retrospective review was conducted of 542 consecutive ultrasound-guided, vacuum-assisted breast biopsies performed between February 2000 and September 2004. Before July 2002, no attempt was made to completely remove all imaged lesion evidence. After July 2002, all patients underwent complete percutaneous excision of all imaged lesion evidence. Pathology review revealed 52 lesions that demonstrated ADH and no evidence of malignancy. Each patient with this diagnosis was offered surgical excision. Pathologic reports for each group were compared with the subsequent open surgical specimens. RESULTS: Of 542 consecutively diagnosed lesions, 52 displayed ADH with no evidence of malignancy (10%). Five patients refused operation. Of the 47 patients who underwent open excision, 6 (13%) were found to have malignancies. The rate of ADH underestimation was 6 of 18 (33%) in incisional biopsies and 0 of 29 performed with complete imaged lesion evidence (p=0.002). The rate of ADH underestimation in women who underwent ultrasound-guided, vacuum-assisted, percutaneous excision was zero, a result equivalent to open surgical biopsy. CONCLUSIONS: ADH is a more common finding in sonographic lesions than has been previously reported. Complete ultrasound-guided, vacuum-assisted, percutaneous excision is more accurate than nonexcisional ultrasound-guided biopsy. Patients so diagnosed have very low underestimation rates and may not require open surgical reexcision.