Male Breast Cancer Risk Assessment and Screening Recommendations in High-Risk Men Who Undergo Genetic Counseling and Multigene Panel Testing.

BACKGROUND: Emerging data suggest screening mammography may be effective in detecting breast cancer early in high-risk men. We evaluated current screening recommendations as a risk management strategy in men at elevated risk for breast cancer. PATIENTS AND METHODS: This institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study reviewed consecutive men who underwent genetic counseling and multigene panel testing (MGPT) for breast cancer risk assessment at our institution between 2012 and 2018. Patient risk factors, test indications, and MGPT outcomes were recorded, then correlated with screening recommendations by either clinical breast examination or screening mammography. Recommendation consistency among practitioners was evaluated. Patient adherence to screening mammography (defined as undergoing screening mammography as recommended) was assessed. Statistical analysis was performed at the 2-sided 5% significance level. RESULTS: A total of 414 asymptomatic men underwent both genetic counseling and MGPT (mean age, 47 years; range, 18-91 years) for breast cancer risk assessment. Of this group, 18 (4.3%) of 414 had a personal history of breast cancer, and 159 (38.4%) of 414 had a family history of breast cancer before MGPT. Among 112 men with positive MGPT results, BRCA1/2 mutations were the most common (56.3%, 63/112). Most BRCA mutation carriers (80.9%, 51/63) were recommended clinical breast examination only. Only 5.9% (2/34) BRCA2 and 10.3% (3/29) BRCA1 carriers were recommended screening mammograms (7.9%, 5/63 of all BRCA carriers). Among men with a personal history of breast cancer, only 9 (50%) of 18 were recommended screening mammograms. Overall adherence to screening mammogram in men was 71.4% (10/14), which ultimately yielded two cancers. Breast cancer screening recommendations varied widely among practitioners, with some recommending clinical breast examination only, and others also recommending mammography. CONCLUSION: Men who are found to be at an elevated risk for breast cancer after undergoing genetic counseling and testing currently receive relatively inconsistent screening recommendations.

Impact of Body Mass Index on Outcomes After Breast Cancer Surgery: Nationwide Inpatient Database Study in Japan.

BACKGROUND: Recent studies have shown better postoperative outcomes in mildly obese patients, a phenomenon called the obesity paradox. In the field of breast cancer surgery, however, previous studies have only shown an association between obesity and worse postoperative outcomes using multivariable analysis; the obesity paradox has not been investigated in patients undergoing breast cancer surgery. PATIENTS AND METHODS: We identified patients who underwent mastectomy for stage 0 to III breast cancer from July 2010 to March 2017 using a Japanese nationwide inpatient database. We used restricted cubic spline analyses to investigate potential nonlinear associations between body mass index (BMI) and outcomes (postoperative complications, 30-day readmission, duration of anesthesia, length of hospital stay, and hospitalization costs). We also performed multivariable regression analyses for the outcomes. RESULTS: Among 239,108 eligible patients, 25.6% had a BMI of > 25.0 kg/m2. BMI showed U-shaped associations with postoperative complications, length of stay, and hospitalization costs, and a linear association with duration of anesthesia. The proportion of postoperative complications was lowest at a BMI of around 22.0 kg/m2, while the length of stay was shortest and total costs were lowest at a BMI of around 20.0 kg/m2. Compared to a BMI of 22.0 kg/m2, a BMI of > 30.0 kg/m2 was significantly associated with greater postoperative complications, 30-day readmission, duration of anesthesia, length of stay, and hospitalization costs. CONCLUSION: Restricted cubic spline analyses displayed U-shaped associations between BMI and in-hospital complications, length of stay, and hospitalization costs, but none of the associations showed the obesity paradox.

Association of 21-Gene Assay (OncotypeDX) Testing and Receipt of Chemotherapy in the Medicare Breast Cancer Patient Population Following Initial Adoption.

BACKGROUND: Our objective was to investigate why early studies regarding adoption of the 21-gene recurrence score (RS) assay did not show an initial reduction in the number of patients with breast cancer receiving real-world chemotherapy. MATERIALS AND METHODS: We addressed 2 sources of confounding suspected in previous studies: (1) the early time frame during the initial adoption phase of the RS assay, and (2) suspected selective, increased administration to patients more likely to have been chemotherapy candidates. To address selective use during initial adoption, we used updated SEER-Medicare data from 2004 and 2011. To address individual selection bias, we examined whether RS test utilization was negatively associated with rates of local chemotherapy use assessed at the hospital referral region level using conventional ordinary least squares and instrumental variable approaches to adjust for selection bias. RESULTS: A total of 26,009 patients met inclusion criteria. Assay use was associated with a decrease in absolute percentage use of chemotherapy of 4.5% (95% confidence interval [CI], 3.2%-5.7%), which was even more pronounced in sensitivity analyses limited to later study years (2008-2011), with a decrease of 6.8% (95% CI, 5.3%-8.3%). Instrumental variable models yielded similar point estimates but were insufficiently powered to draw conclusions. CONCLUSION: Receipt of the 21-gene assay was associated with decreased utilization of chemotherapy by 2008.

Assessing preferences for receiving supportive care resources among patients seen at a Breast Care Center.

BACKGROUND: Patients with breast cancer or at high risk for breast cancer have supportive care needs. Although cancer centers offer social, psychological, and other support to these patients, these services are not always utilized, and patients continue to report unmet supportive care needs. Reasons for non-utilization of these services have not been well documented. In this analysis, we examine patient reasons for service non-utilization and evaluate patients' interest in receiving information about and paying for other supportive care services. METHODS: Study participants were contacted by email 7-14 months following appointments at the University of California, San Francisco (UCSF) Breast Care Center (BCC) and were invited to complete a 26-question survey about supportive care utilization at UCSF. RESULTS: In total, 195 patients (45%) completed surveys. Of these, 68% had breast cancer. Among patients with breast cancer, fewer than half completed appointments with psychological services. Lack of self-perceived need was the primary reason patients did not pursue psychological services. Overall, 61% of participants were interested in learning more about psychological services, 27% in nutrition counseling, and 20% in exercise counseling. Participants were more interested in individual counseling than in group counseling but were less interested in paying for services. CONCLUSION: Patients often feel that they do not need supportive services. Breast cancer patients are interested in learning more about psychological services, exercise counseling, and nutrition counseling. Although many cancer centers offer group coaching and counseling sessions on these topics, patients may be more willing to engage in individual counseling.

Chinesization of the quality of life assessment, venous device-port, and its reliability and validity tests for patients with breast cancer.

OBJECTIVE: To translate the assessment item sets of the Canadian version of the quality of life assessment, venous device-port for breast cancer patients with chest and arm ports (i.e. different implanting sites) into Chinese version, and to conduct a test of reliability and validity for it. METHODS: According to the Brislin translation model, quality of life assessment, venous device-port underwent literal and back translations, and the Chinese version of quality of life assessment, venous device-port was preliminarily revised by consulting an expert and a preliminary test. A total of 270 cancer patients undergoing chemotherapy were assessed during the use of ports, and the reliability and the validity of the Chinese version of quality of life assessment, venous device-port scale were then tested. RESULTS: The scale consisted of 23 yes/no items and seven numerical rating scales. The total Cronbach's α coefficient of the scale was 0.829, and each item ranged from 0.812 to 0.845. The item-level content validity index was 0.67-1.00, and the scale-level content validity index/average and the scale-level content validity index/universal agreement were 0.98 and 0.90, respectively. The correlation coefficient of the repeated measurement results of the scale was 0.554 (p < 0.01). Exploratory factor analysis showed that the cumulative explained variance of five common factors was 64.197%. CONCLUSION: The Chinese version of quality of life assessment, venous device-port scale is an effective assessment tool for quality of life with good reliability and validity in breast cancer patients with different implantation sites for totally implanted venous access devices in northern China.

Ultrasonographic assessment of male breast diseases.

Although rare and accounting for less than 1% of all breast cancers, the incidence of breast cancer in men has increased by 26% over the past few decades. Very little has been reported on the sonographic appearance of benign and malignant male breast conditions. The aim of this study was to describe the ultrasonographic features of male breast disease and the value of ultrasound in the evaluation of male breast disease. Between December 2006 and October 2014, ultrasound examinations were performed in 560 male patients presenting with enlargement of, pain in, and/or a lump in the breast. One hundred and thirty-six patients (24.3%) underwent surgical excision, and 424 patients (75.7%) were diagnosed by ultrasound. Their ultrasonographic features were retrospectively evaluated. The final diagnoses were gynecomastia (n = 537), primary breast cancer (n = 9), lipoma (n = 7), chronic mastitis (n = 6), and fibroadenoma (n = 1). Of the 560 lesions, 356 (63.6%) were classified as Breast Imaging Reporting and Data System (BI-RADS) category 2, 191 (34.1%) were classified as BI-RADS category 3, and 13 (2.3%) were classified as BI-RADS 4 or 5. The sensitivity, specificity, PPV, NPV, and accuracy of the detection of malignant breast masses according to ultrasound were 100%, 99.3%, 69.2%, 100%, and 97.7% respectively. The sonographic patterns of gynecomastia were nodular (n = 131, 24.4%), dendritic (n = 50, 9.3%), and diffuse glandular (n = 356, 66.3%). Color Doppler flow imaging revealed hypervascularity in five of these malignant masses, moderate vascularity in two of the masses, and mild vascularity in the remaining two masses. Other diseases included in the study are also described. Ultrasonography (US) is useful in the diagnosis of male breast diseases, especially in differentiating cancer from benign lesions.

The challenge of rapid diagnosis in oncology: Diagnostic accuracy and cost analysis of a large-scale one-stop breast clinic.

PURPOSE: Rapid diagnosis is a key issue in modern oncology, for which one-stop breast clinics are a model. We aimed to assess the diagnosis accuracy and procedure costs of a large-scale one-stop breast clinic. PATIENTS AND METHODS: A total of 10,602 individuals with suspect breast lesions attended the Gustave Roussy's regional one-stop breast clinic between 2004 and 2012. The multidisciplinary clinic uses multimodal imaging together with ultrasonography-guided fine needle aspiration for masses and ultrasonography-guided and stereotactic biopsies as needed. Diagnostic accuracy was assessed by comparing one-stop diagnosis to the consolidated diagnosis obtained after surgery or biopsy or long-term monitoring. The medical cost per patient of the care pathway was assessed from patient-level data collected prospectively. RESULTS: Sixty-nine percent of the patients had masses, while 31% had micro-calcifications or other non-mass lesions. In 75% of the cases (87% of masses), an exact diagnosis could be given on the same day. In the base-case analysis (i.e. considering only benign and malignant lesions at one-stop and at consolidated diagnoses), the sensitivity of the one-stop clinic was 98.4%, specificity 99.8%, positive and negative predictive values 99.7% and 99.0%. In the sensitivity analysis (reclassification of suspect, atypical and undetermined lesions), diagnostic sensitivity varied from 90.3% to 98.5% and specificity varied from 94.3% to 99.8%. The mean medical cost per patient of one-stop diagnostic procedure was €420. CONCLUSIONS: One-stop breast clinic can provide timely and cost-efficient delivery of highly accurate diagnoses and serve as models of care for multiple settings, including rapid screening-linked diagnosis.

Time to Surgery and Breast Cancer Survival in the United States.

IMPORTANCE: Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE: To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States. DESIGN, SETTING, AND PARTICIPANTS: Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors. RESULTS: The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors. CONCLUSIONS AND RELEVANCE: Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

Large field, high resolution full-field optical coherence tomography: a pre-clinical study of human breast tissue and cancer assessment.

We present a benchmark pilot study in which high-resolution Full-Field Optical Coherence Tomography (FF-OCT) was used to image human breast tissue and is evaluated to assess its ability to aid the pathologist's management of intra-operative diagnoses. FF-OCT imaging safety was investigated and agreement between FF-OCT and routinely prepared histopathological images was evaluated. The compact setup used for this study provides 1 mm3 resolution and 200 mm imaging depth, and a 2.25 cm2 specimen is scanned in about 7 minutes. 75 breast specimens were imaged from 22 patients (21 women, 1 man) with a mean age of 58 (range: 25-83). Pathologists blind diagnosed normal/benign or malignant tissue based on FF-OCT images alone, diagnosis from histopathology followed for comparison. The contrast in the FF-OCT images is generated by intrinsic tissue scattering properties, meaning that no tissue staining or preparation is required. Major architectural features and tissue structures of benign breast tissue, including adipocytes, fibrous stroma, lobules and ducts were characterized. Subsequently, features resulting from pathological modification were characterized and a diagnosis decision tree was developed. Using FF-OCT images, two breast pathologists were able to distinguish normal/benign tissue from lesional with a sensitivity of 94% and 90%, and specificity of 75% and 79% respectively.

The value of fine needle aspiration biopsy in the diagnosis and prognostic assessment of palpable breast lesions.

In recent years there appears to be a growing movement toward the use of core needle biopsy (CNB) over fine needle aspiration biopsy (FNAB) for the detection of breast carcinoma. This tendency is caused in part by the idea that CNB can provide a more specific or definitive diagnosis as well as the belief that the assessment of prognostic/predictive factor is not possible or reliable on cytologic specimens. At our institution, FNAB of breast has been practiced for over 25 years with excellent cytologic-histological correlation. This practice has been beneficial not only for patients, but also for training physicians since nowadays a very small number of centers in the United States still routinely perform fine needle aspiration as a diagnostic tool in breast cases. To assess the diagnostic accuracy of FNAB in palpable breast lesions, we reviewed our experience during an 8-year-period and compared fine needle aspiration results with follow-up surgical specimens. From the cytology point of view, the lesions were divided as negative/benign, atypical/suspicious, positive, and insufficient. Only cases performed by pathologists were included. A total of 1,583 cases were retrieved from our archives. A definitive malignant diagnosis was reached in 357 cases. One-hundred and thirty-nine cases were classified as atypical/ suspicious, 135 cases had insufficient cells for establishing a diagnosis, and 952 were categorized as negative. A total of 408 follow-up surgical specimens were available for comparison with cytologic results. There were 19 false-negative, and no false-positive results were found. The majority of false-negative results were secondary to sampling errors. In 93% of the malignant cases, there was enough material obtained in cytological specimens to perform prognostic/predictive factors studies. Our data proves once again that FNAB is a reliable method for the initial evaluation and diagnosis of palpable masses of the breast. In addition, it also has the ability of providing necessary prognostic/predictive information, particularly for patients that may undergo neoadjuvant therapy.

Utilization of minimally invasive breast biopsy for the evaluation of suspicious breast lesions.

BACKGROUND: Percutaneous needle biopsy, also known as minimally invasive breast biopsy (MIBB), has become the gold standard for the initial assessment of suspicious breast lesions. The purpose of this study is to determine modern rates of MIBB and open breast biopsy. METHODS: The Florida Agency for Health Care Administration outpatient surgery and procedure database was queried for patients undergoing open surgical biopsy and MIBB between 2003 and 2008. RESULTS: Although there was an increase in the use of MIBB, the overall rate of open surgical biopsy remained high (∼30%). A reduction in the open biopsy rate from 30% to 10% could be associated with a charge reduction of >$37.2 million per year. CONCLUSIONS: The current rate of open surgical breast biopsy remains high. Interventions and quality initiatives are warranted, which could lead to a reduction in unnecessary operations for women, improved patient care, and a reduction in breast health care costs.

Verification of consumers' experiences and perceptions of genetic discrimination and its impact on utilization of genetic testing.

PURPOSE: To undertake a systematic process of verification of consumer accounts of alleged genetic discrimination. METHODS: Verification of incidents reported in life insurance and other contexts that met the criteria of genetic discrimination, and the impact of fear of such treatment, was determined, with consent, through interview, document analysis and where appropriate, direct contact with the third party involved. The process comprised obtaining evidence that the alleged incident was accurately reported and determining whether the decision or action seemed to be justifiable and/or ethical. RESULTS: Reported incidents of genetic discrimination were verified in life insurance access, underwriting and coercion (9), applications for worker's compensation (1) and early release from prison (1) and in two cases of fear of discrimination impacting on access to genetic testing. Relevant conditions were inherited cancer susceptibility (8), Huntington disease (3), hereditary hemochromatosis (1), and polycystic kidney disease (1). In two cases, the reversal of an adverse underwriting decision to standard rate after intervention with insurers by genetics health professionals was verified. The mismatch between consumer and third party accounts in three life insurance incidents involved miscommunication or lack of information provision by financial advisers. CONCLUSION: These first cases of verified genetic discrimination make it essential for policies and guidelines to be developed and implemented to ensure appropriate use of genetic test results in insurance underwriting, to promote education and training in the financial industry, and to provide support for consumers and health professionals undertaking challenges of adverse decisions.

Accurate and cost-effective evaluation of breast masses in males.

BACKGROUND: Because the majority of breast masses in males are benign and need not be excised if asymptomatic, we studied the combination of physical examination (PE) and fine needle aspiration (FNA), with or without mammography, as a diagnostic alternative to routine surgical biopsy of these lesions. METHODS: A diagnostic test study and cost-effectiveness analysis was performed in three participating multidisciplinary breast clinics, involving a consecutive sample of 51 males with unilateral breast masses. Each lesion was tested with both PE and FNA; 13 were also studied with mammography, and each test was scored as benign or suspicious. Lesions for which all tests were benign were followed up clinically (mean 19 months). Lesions for which any test was suspicious were excised. RESULTS: All tests were benign in 38 cases. No cancers developed at the index sites during follow-up of these lesions, including 8 excisional biopsies done for symptoms (negative predictive value and specificity 100%). Open biopsy confirmed malignancy in all 6 cases for which all tests were suspicious (positive predictive value and sensitivity 100%). In all 7 cases where the tests were not in agreement, open biopsy was benign. In these cases FNA (2 false positives) proved more accurate than PE (5 false positives). Mammography added no additional diagnostic information to the combination of PE and FNA. Compared with routine open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the 51 lesions, and was associated with an average decrease in charges of up to $510 per case. CONCLUSIONS: The combination of PE and FNA for the evaluation of breast masses in males is diagnostically accurate and results in a reduction in patient charges compared with routine open biopsy.