Relationships between computer-extracted mammographic texture pattern features and BRCA1/2 mutation status: a cross-sectional study.

INTRODUCTION: Mammographic density is similar among women at risk of either sporadic or BRCA1/2-related breast cancer. It has been suggested that digitized mammographic images contain computer-extractable information within the parenchymal pattern, which may contribute to distinguishing between BRCA1/2 mutation carriers and non-carriers. METHODS: We compared mammographic texture pattern features in digitized mammograms from women with deleterious BRCA1/2 mutations (n = 137) versus non-carriers (n = 100). Subjects were stratified into training (107 carriers, 70 non-carriers) and testing (30 carriers, 30 non-carriers) datasets. Masked to mutation status, texture features were extracted from a retro-areolar region-of-interest in each subject's digitized mammogram. Stepwise linear regression analysis of the training dataset identified variables to be included in a radiographic texture analysis (RTA) classifier model aimed at distinguishing BRCA1/2 carriers from non-carriers. The selected features were combined using a Bayesian Artificial Neural Network (BANN) algorithm, which produced a probability score rating the likelihood of each subject's belonging to the mutation-positive group. These probability scores were evaluated in the independent testing dataset to determine whether their distribution differed between BRCA1/2 mutation carriers and non-carriers. A receiver operating characteristic analysis was performed to estimate the model's discriminatory capacity. RESULTS: In the testing dataset, a one standard deviation (SD) increase in the probability score from the BANN-trained classifier was associated with a two-fold increase in the odds of predicting BRCA1/2 mutation status: unadjusted odds ratio (OR) = 2.00, 95% confidence interval (CI): 1.59, 2.51, P = 0.02; age-adjusted OR = 1.93, 95% CI: 1.53, 2.42, P = 0.03. Additional adjustment for percent mammographic density did little to change the OR. The area under the curve for the BANN-trained classifier to distinguish between BRCA1/2 mutation carriers and non-carriers was 0.68 for features alone and 0.72 for the features plus percent mammographic density. CONCLUSIONS: Our findings suggest that, unlike percent mammographic density, computer-extracted mammographic texture pattern features are associated with carrying BRCA1/2 mutations. Although still at an early stage, our novel RTA classifier has potential for improving mammographic image interpretation by permitting real-time risk stratification among women undergoing screening mammography.

Breast cancer screening patterns among military beneficiaries: racial variations in screening eliminated in an equal-access model.

BACKGROUND: African American women present with more aggressive breast tumors and at later stages than white women. Many factors have been proposed to explain these findings, including socioeconomic status, cultural beliefs, and access to medical care. The purpose of this project was to determine if stage at presentation would be equivalent in a system providing equal access to care and if screening was equivalent. METHODS: The Naval Medical Center San Diego (NMCSD) tumor registry from 2007 to 2012 was queried for this cross-sectional study. Eligible women included all those diagnosed and treated for breast cancer at NMCSD. Distribution of tumor stage (early vs. advanced) between racial groups was compared by age, treatment, and receptor status. RESULTS: A total of 624 women were eligible; 88 % were early stage (0-II) and 12 % presented with advanced stage (III or IV). Racial differences in distribution were significant among African American and Hispanic women for early versus advanced presentation (p = 0.011). No racial disparity was seen in screening patterns among women. CONCLUSIONS: In a military health system with equal access to care and standard screening recommendations, screening patterns did not vary with race but did vary with stage and active duty status. African American women present with breast cancer at later stages and with more hormone-receptor negative tumors, suggesting that biology rather than socioeconomic or access factors may be the most important determinant of stage at presentation of breast cancer for African American women.

Single-cell genetic analysis of ductal carcinoma in situ and invasive breast cancer reveals enormous tumor heterogeneity yet conserved genomic imbalances and gain of MYC during progression.

Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the IDC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum.

A prospective model of care for breast cancer rehabilitation: postoperative and postreconstructive issues.

Appropriate and timely rehabilitation is vital in the recovery from breast cancer surgeries, including breast conserving surgery, mastectomy, axillary lymph node dissection (ALND), and breast reconstruction. This article describes the incidence, prevalence, risk factors and time course for early postoperative effects and the role of prospective surveillance as a rehabilitation strategy to prevent and mitigate them. The most common early postoperative effects include wound issues such as cellulitis, flap necrosis, abscess, dehiscence, hematoma, and seroma. Appropriate treatment is necessary to avoid delay in wound healing that may increase the risk of long-term morbidity, unduly postpone systemic and radiation therapy, and delay rehabilitation. The presence of upper quarter dysfunction (UQD), defined as restricted upper quarter mobility, pain, lymphedema, and impaired sensation and strength, has been reported in over half of survivors after treatment for breast cancer. Moreover, evidence suggests that survivors who undergo breast reconstruction may be at higher risk of UQD. Ensuring the survivor's optimum functioning in the early postoperative time period is critical in the overall recovery from breast cancer. The formal collection of objective measures along with patient-reported outcome measures is recommended for the early detection of postoperative morbidity. Prospective surveillance, including preoperative assessment and structured surveillance, allows for early identification and timely rehabilitation. Early evidence supports a prospective approach to address and minimize postoperative effects.

A prospective surveillance model for rehabilitation for women with breast cancer.

BACKGROUND: The current model of care for individuals with breast cancer focuses on treatment of the disease, followed by ongoing surveillance to detect recurrence. This approach lacks attention to patients' physical and functional well-being. Breast cancer treatment sequelae can lead to physical impairments and functional limitations. Common impairments include pain, fatigue, upper-extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis. Evidence supports prospective surveillance for early identification and treatment as a means to prevent or mitigate many of these concerns. This article proposes a prospective surveillance model for physical rehabilitation and exercise that can be integrated with disease treatment to create a more comprehensive approach to survivorship health care. The goals of the model are to promote surveillance for common physical impairments and functional limitations associated with breast cancer treatment; to provide education to facilitate early identification of impairments; to introduce rehabilitation and exercise intervention when physical impairments are identified; and to promote and support physical activity and exercise behaviors through the trajectory of disease treatment and survivorship. METHODS: The model is the result of a multidisciplinary meeting of research and clinical experts in breast cancer survivorship and representatives of relevant professional and advocacy organizations. RESULTS/CONCLUSIONS: The proposed model identifies time points during breast cancer care for assessment of and education about physical impairments. Ultimately, implementation of the model may influence incidence and severity of breast cancer treatment-related physical impairments. As such, the model seeks to optimize function during and after treatment and positively influence a growing survivorship community.

Pre-operative assessment enables early diagnosis and recovery of shoulder function in patients with breast cancer.

In order to determine the extent and time course of upper limb impairment and dysfunction in women being treated for breast cancer (BC), and followed prospectively, a novel physical therapy surveillance model post-treatment was used. Subjects included adult women with newly diagnosed, untreated, unilateral, Stage I to III BC, and normal physiological and biomechanical shoulder function. Subjects were excluded if they had a previous history of BC, or prior injury or surgery of the affected upper limb. Measurements included body weight, shoulder ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and an upper limb disability questionnaire (ULDQ). Measurements were taken at baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects received pre-operative education and exercise instruction and specific physical therapy (PT) protocol after surgery including ROM and strengthening exercises. All measures of function were significantly reduced 1 month post-surgery, but most recovered to baseline levels by 1-year post-surgery. Some subjects developed signs of lymphedema 3-12 months post-surgery, but this did not compromise function. Shoulder abduction, flexion, and external rotation, but not internal rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing surgery for BC who receive PT intervention may expect a return to baseline ROM and strength by 3 months. Those who do not reach baseline, often continue to improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema develops independently of shoulder function 3-12 months post-surgery, necessitating continued monitoring. A prospective physical therapy model of surveillance allows for detection of early and later onset of impairment following surgery for BC in this specific cohort of patients.

Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer.

Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute's Clinical Genetics Branch's Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center's Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.

Axillary sentinel lymph node biopsy after mastectomy: a case report.

BACKGROUND: Sentinel lymph node biopsy has been established as the preferred method for staging early breast cancer. A prior history of mastectomy is felt to be a contraindication. CASE PRESENTATION: A patient with recurrent breast cancer in her skin flap was discovered to have positive axillary sentinel nodes by sentinel lymph node biopsy five years after mastectomy for ductal carcinoma in situ. CONCLUSION: A prior history of mastectomy may not be an absolute contraindication to sentinel lymph node biopsy.

The influence of a gene expression profile on breast cancer decisions.

PURPOSE: The Oncotype Dx Recurrence Score (RS), is often employed in patients with estrogen receptor-positive, node negative (ER+LN-) breast cancer. We investigated the impact of the RS on actual chemotherapy administration and the effect of the assay on a panel of breast oncology experts. PATIENTS AND METHODS: The prospective adjuvant chemotherapy recommendations (prior to RS) and actual adjuvant therapy (after RS) for consecutive patients with ER+LN- breast cancer were recorded. After 6 months and with the same information, a panel of five experts made adjuvant therapy recommendations with and without RS and rated the strength of their recommendations. Rates of panel consensus, recommendation changes, and changes in recommendation strength were compared. RESULTS: There were 29 patients (28 women). RS results altered the plan for chemotherapy in 9 patients (31%); 7 of 13 patients (54%) initially recommended for chemotherapy did not receive it, and 2 of 16 (13%) received chemotherapy following initial recommendations against it. RS results changed the panel's chemotherapy recommendation in 7 patients (24%): 5 of 12 (42%) recommendations for changed to against, and 2 of 17 (12%) recommendations against changed to for chemotherapy. RS increased consensus by the panel 10%, but did not increase the reported strength in chemotherapy recommendations. CONCLUSIONS: RS results were associated with real-world decision changes in 31% of patients and 24% of panel recommendations and increased panel consensus by 10%. However RS did not increase the strength of panelist's recommendations.

Genetic testing for cancer susceptibility.

Genetic testing for mutations in genes associated with an inherited predisposition to cancer is rapidly moving outside specialty genetic services and into mainstream health care. Surgeons, as front-line providers of cancer care, are uniquely positioned to identify those who may benefit from genetic testing and institute changes to their health care management based on those results. This article provides an overview of the critical elements of the process of genetic testing for cancer susceptibility.

Randomized comparison of phone versus in-person BRCA1/2 predisposition genetic test result disclosure counseling.

PURPOSE: This study evaluated whether phone results were equivalent to in-person result disclosure for individuals undergoing BRCA1/2 predisposition genetic testing. METHODS: A total of 111 of 136 subjects undergoing education and counseling for BRCA1/2 predisposition genetic testing agreed to randomization to phone or in-person result disclosure. Content and format for both sessions were standardized. Data from the State-Trait Anxiety Inventory and the Psychological General Well-Being index were collected at baseline and then again at 1 week and 3 months after disclosure of test results. Baseline measures were administered after the following had occurred: counseling/education session had been conducted, informed consent had been obtained, and decision to be tested had been made. Satisfaction and cost assessments were administered after the result session. At 1 week, participants were asked their preferred method of result disclosure. RESULTS: There were no differences in anxiety and general well-being measures between 50 phone and 52 in-person results disclosure. Both groups reported similar rates of satisfaction with services. Among those with a preference, 77% preferred the notification method assigned. There was a statistically significant preference for phone results among the 23% who did not prefer the method assigned. Greater costs were associated with in-person result disclosure. CONCLUSIONS: These data suggest that phone results are a reasonable alternative to traditional in-person BRCA1/2 genetic test disclosure without any negative psychologic outcomes or compromise in knowledge. However, further study is needed in a more clinically representative population to confirm these findings.

Randomized comparison of group versus individual genetic education and counseling for familial breast and/or ovarian cancer.

PURPOSE: An efficient approach to education and counseling before BRCA1 and BRCA2 mutation testing is necessary for effective utilization of testing in the community. Education and counseling, when delivered individually, are limited by a shortage of trained health care providers as well as by financial and time constraints. The purpose of this study was to determine whether pretest education and counseling for breast cancer genetics in a group setting is equivalent to that provided on an individual basis. PATIENTS AND METHODS: One hundred forty-two patients at high risk for harboring a BRCA mutation were randomly assigned to group or individual education and counseling sessions. Group education was followed by brief individual counseling. Knowledge and Impact of Events Scales (IES) were administered at baseline and after education and counseling and at 1 week and 3, 6, and 12 months. Satisfaction with education and counseling was measured at completion of the session. Preferred method of education and counseling was solicited at 3 months. RESULTS: There was no difference in knowledge or IES scores between groups. When stratified by genetic test results, knowledge scores showed no difference. Regardless of group, post-test IES scores in patients with positive results were higher than patients with negative or uninformative results but returned to baseline by 12 months. Participants were equally satisfied with either method they were assigned. Significantly more time was spent per patient in individual sessions (1.25 hours) than in group education (0.74 hours). CONCLUSION: Our data suggest that group education and counseling may confer similar benefits compared with traditional individual sessions. Additional investigation of this approach in larger numbers of patients is warranted.

Thoracic gallstones: a delayed complication of laparoscopic cholecystectomy.

BACKGROUND: Thoracic complications resulting from gallstone spillage during laparoscopic cholecystectomy are rare and may occur years after the index surgery. We present the case of a chronic lung abscess resulting from trans-diaphragmatic migration of gallstones spilled and "lost" during a laparoscopic cholecystectomy. METHODS: Case report and literature review. CASE REPORT: A 66-year-old female who had undergone a laparoscopic cholecystectomy 5 y previously presented with hemoptysis and was found to have a chronic lung abscess caused by "lost" gallstones. Her symptoms resolved with video-assisted thorascopic surgery, pulmonary decortication, and wedge resection. CONCLUSIONS: Thoracic complications from "lost" gallstones following laparoscopic cholecystectomy include empyema, hemoptysis, and cholelithoptysis. These rare complications sometimes require surgery but not all presentations of thoracic gallstones mandate operative intervention. Because of these potential complications of "lost" gallstones, reasonable efforts should be made to retrieve gallstones spilled during cholecystectomy. Persistent pulmonary symptoms following laparoscopic cholecystectomy mandate further radiologic examination and a review of the patient's operative report for "lost" gallstones.

Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care.

Secondary prevention involves monitoring and screening to prevent negative sequelae from chronic diseases such as cancer. Breast cancer treatment sequelae, such as lymphedema, may occur early or late and often negatively affect function. Secondary prevention through prospective physical therapy surveillance aids in early identification and treatment of breast cancer-related lymphedema (BCRL). Early intervention may reduce the need for intensive rehabilitation and may be cost saving. This perspective article compares a prospective surveillance model with a traditional model of impairment-based care and examines direct treatment costs associated with each program. Intervention and supply costs were estimated based on the Medicare 2009 physician fee schedule for 2 groups: (1) a prospective surveillance model group (PSM group) and (2) a traditional model group (TM group). The PSM group comprised all women with breast cancer who were receiving interval prospective surveillance, assuming that one third would develop early-stage BCRL. The prospective surveillance model includes the cost of screening all women plus the cost of intervention for early-stage BCRL. The TM group comprised women referred for BCRL treatment using a traditional model of referral based on late-stage lymphedema. The traditional model cost includes the direct cost of treating patients with advanced-stage lymphedema. The cost to manage early-stage BCRL per patient per year using a prospective surveillance model is $636.19. The cost to manage late-stage BCRL per patient per year using a traditional model is $3,124.92. The prospective surveillance model is emerging as the standard of care in breast cancer treatment and is a potential cost-saving mechanism for BCRL treatment. Further analysis of indirect costs and utility is necessary to assess cost-effectiveness. A shift in the paradigm of physical therapy toward a prospective surveillance model is warranted.

Perceptions of cancer risks and predictors of colon and endometrial cancer screening in women undergoing genetic testing for Lynch syndrome.

PURPOSE: Lynch syndrome poses multiple cancer risks, yet attention has focused on screening for colorectal cancer. Estimated risks for endometrial cancer equal risks for colorectal cancer. This study (1) evaluated women's perceived risks for cancers, (2) compared endometrial cancer screening and colonoscopy, and (3) identified predictors of screening before and after genetic testing. PATIENTS AND METHODS: Sixty-five adult women at 50% risk for carrying a cancer-predisposing mutation, without a history of endometrial cancer or hysterectomy, participated in genetic counseling and received unequivocal genetic test results for Lynch syndrome. Participants completed questionnaires before and after receipt of genetic results. RESULTS: Pretest, perceived risks for colon cancer were significantly higher than for extracolonic cancers (P < .0001). Use of colonoscopy was significantly higher (P = .006) than endometrial cancer screening. Post-test, carriers demonstrated a significant (P < .0001) increase in their perceived risk for extracolonic cancers and increased both colonoscopy (P = .79) and endometrial cancer screening (P = .11). Mutation status, age, perceived likelihood of carrying a mutation, and communication of test results to their physician independently predicted cancer screening at follow-up. CONCLUSION: Women in families with Lynch syndrome are less aware of their risks for extracolonic cancers and undergo endometrial cancer screening significantly less often than colonoscopy before genetic counseling. Given the significantly increased risks for endometrial and ovarian cancers and the mortality associated with ovarian cancer, additional efforts to inform families of cancer risks and screening recommendations seem prudent. Physicians play a critical role in ensuring appropriate cancer screening in women with Lynch syndrome.

Development of the breast cancer education and risk assessment program.

PURPOSE/OBJECTIVES: To provide a description of the inception and evolution of the Breast Cancer Education and Risk Assessment Program. DATA SOURCES: Computerized database (e.g., Personal Family History Risk Assessment Model, Knowledge Assessment Tool, risk perception, evaluation form) and author experience. DATA SYNTHESIS: A total of 749 women participated in the group education and risk-assessment program from March 1999 through March 2002. Advanced practice nurses provided information about calculated risks, corrected misperceptions among participants, and highlighted options available to decrease breast cancer risk. Knowledge scores improved, and, in general, participants were very satisfied with the content and comprehensibility of the educational session. CONCLUSIONS: Results from the evaluation of the Breast Cancer Education and Risk Assessment Program suggest that group education is a viable and acceptable way to bring new advances in breast cancer prevention to large groups of women. The data sources support the conclusion that women can be effectively taught general breast cancer risk information in a group setting and be placed into specific risk categories to streamline discussion of risk-management options and relevant research studies. IMPLICATIONS FOR NURSING: Advanced practice nurses are a vital link in the assessment of women at high risk for breast cancer, education, and appropriate referrals for management options and relevant clinical trials.