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Background: Cancer risk prediction tools provide valuable information to clinicians but remain computationally challenging. Many clinics find that Ca Gene or Hughes Risk Apps fit their needs for easy- and ready-to-use software to obtain cancer risks; however, these resources may not fit all clinics’ needs. The Hughes Risk Apps Group and Bayes Mendel Lab therefore developed a web service, called “Risk Service", which may be integrated into any client software to quickly obtain standardized and up-to-date risk predictions for Bayes Mendel tools (BRCAPRO, MMRpro, PancPRO, and MelaPRO), the Tyrer-Cuzick IBIS Breast Cancer Risk Evaluation Tool, and the Colorectal Cancer Risk Assessment Tool. Findings: Software clients that can convert their local structured data into the HL7 XML-formatted family and clinical patient history (Pedigree model) may integrate with the Risk Service. The Risk Service uses Apache Tomcat and Apache Axis2 technologies to provide an all Java web service. The software client sends HL7 XML information containing anonymized family and clinical history to a Dana-Farber Cancer Institute (DFCI) server where it is parsed, interpreted, and processed by multiple risk tools. The Risk Service then formats the results into an HL7 style message and returns the risk predictions to the originating software client. Upon consent, users may allow DFCI to maintain the data for future research. The Risk Service implementation is exemplified through Hughes Risk Apps. Conclusions: The Risk Service broadens the availability of valuable, up-to-date cancer risk tools and allows clinics and researchers to integrate risk prediction tools into their own software interface designed for their needs. Each software package can collect risk data using its own interface, and display the results using its own interface, while using a central, up-to-date risk calculator. This allows users to choose from multiple interfaces while always getting the latest risk calculations. Consenting users contribute their data for future research, thus building a rich multi-center resource.

Purpose: Health care providers need simple tools to identify patients at genetic risk of breast and ovarian cancers. Genetic risk prediction models such as BRCAPRO could fill this gap if incorporated into Electronic Medical Records or other Health Information Technology solutions. However, BRCAPRO requires potentially extensive information on the counselee and her family history. Thus, it may be useful to provide simplified version(s) of BRCAPRO for use in settings that do not require exhaustive genetic counseling. Methods: We explore four simplified versions of BRCAPRO, each using less complete information than the original model. BRCAPROLYTE uses information on affected relatives only up to second degree. It is in clinical use but has not been evaluated. BRCAPROLYTE-Plus extends BRCAPROLYTE by imputing the ages of unaffected relatives. BRCAPROLYTE-Simple reduces the data collection burden associated with BRCAPROLYTE and BRCAPROLYTE-Plus by not collecting the family structure. BRCAPRO-1Degree only uses first-degree affected relatives. We use data on 2713 individuals from seven sites of the Cancer Genetics Network and MD Anderson Cancer Center to compare these simplified tools with the Family History Assessment Tool (FHAT) and BRCAPRO, with the latter serving as the benchmark. Results: BRCAPROLYTE retains high discrimination, however, because it ignores information on unaffected relatives, it overestimates carrier probabilities. BRCAPROLYTE-Plus and BRCAPROLYTE-Simple provide better calibration than BRCAPROLYTE, so they have higher specificity for similar values of sensitivity. BRCAPROLYTE-Plus performs slightly better than BRCAPROLYTE-Simple. The Areas Under the ROC curve are 0.783 (BRCAPRO), 0.763 (BRCAPROLYTE), 0.772 (BRCAPROLYTE-Plus), 0.773 (BRCAPROLYTE-Simple), 0.728 (BRCAPRO-1Degree), and 0.745 (FHAT). The simpler versions, especially BRCAPROLYTE-Plus and BRCAPROLYTE-Simple, lead to only modest loss in overall discrimination compared to BRCAPRO in this dataset. Conclusion: Simplified implementations of BRCAPRO can be used for genetic risk prediction in settings where collection of complete pedigree information is impractical.

Objective: The opportunity to integrate clinical decision support systems into clinical practice is limited due to the lack of structured, machine readable data in the current format of the electronic health record. Natural language processing has been designed to convert free text into machine readable data. The aim of the current study was to ascertain the feasibility of using natural language processing to extract clinical information from >76,000 breast pathology reports. Approach and Procedure: Breast pathology reports from three institutions were analyzed using natural language processing software (Clearforest, Waltham, MA) to extract information on a variety of pathologic diagnoses of interest. Data tables were created from the extracted information according to date of surgery, side of surgery, and medical record number. The variety of ways in which each diagnosis could be represented was recorded, as a means of demonstrating the complexity of machine interpretation of free text. Results: There was widespread variation in how pathologists reported common pathologic diagnoses. We report, for example, 124 ways of saying invasive ductal carcinoma and 95 ways of saying invasive lobular carcinoma. There were >4000 ways of saying invasive ductal carcinoma was not present. Natural language processor sensitivity and specificity were 99.1% and 96.5% when compared to expert human coders. Conclusion: We have demonstrated how a large body of free text medical information such as seen in breast pathology reports, can be converted to a machine readable format using natural language processing, and described the inherent complexities of the task.

Women diagnosed with or at high risk for breast cancer increasingly choose prophylactic mastectomy. It is unknown if adding sentinel lymph node biopsy (SLNB) to prophylactic mastectomy increases the risk of lymphedema. We sought to determine the risk of lymphedema after mastectomy with and without nodal evaluation. 117 patients who underwent bilateral mastectomy were prospectively screened for lymphedema. Perometer arm measurements were used to calculate weight-adjusted arm volume change at each follow-up. Of 234 mastectomies performed, 15.8 % (37/234) had no axillary surgery, 63.7 % (149/234) had SLNB, and 20.5 % (48/234) had axillary lymph node dissection (ALND). 88.0 % (103/117) of patients completed the LEFT-BC questionnaire evaluating symptoms associated with lymphedema. Multivariate analysis was used to assess clinical characteristics associated with increased weight-adjusted arm volume and patient-reported lymphedema symptoms. SLNB at the time of mastectomy did not result in an increased mean weight-adjusted arm volume compared to mastectomy without axillary surgery (p = 0.76). Mastectomy with ALND was associated with a significantly greater mean weight-adjusted arm volume change compared to mastectomy with SLNB (p < 0.0001) and without axillary surgery (p = 0.0028). Patients who underwent mastectomy with ALND more commonly reported symptoms associated with lymphedema compared to those with SLNB or no axillary surgery (p < 0.0001). Patients who underwent mastectomy with SLNB or no axillary surgery reported similar lymphedema symptoms. Addition of SLNB to mastectomy is not associated with a significant increase in measured or self-reported lymphedema rates. Therefore, SLNB may be performed at the time of prophylactic mastectomy without an increased risk of lymphedema.

Background: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. Methods: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor– node–metastasis classification), estrogen-receptor–positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer–specific survival, the time to distant metastasis, and overall survival. Results: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. Conclusions: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor–positive breast cancer.

In an investigation of the indications for hepatic resection in the treatment of colorectal carcinoma metastases, the records of 859 patients who had undergone this procedure were reviewed. This patient group, from 24 institutions, was found to have a 5-year actuarial survival of 33% and a 5-year actuarial disease-free survival of 21%. The only factors that might by themselves be considered contraindications to hepatic resection are the presence of positive hepatic nodes, the presence of resectable extrahepatic metastases, or the presence of four or more metastases. Other factors that had a negative effect on long-term survival were margins of resection on the liver metastases less than or equal to 1 cm (S [5-year actuarial survival = 23%), the presence of positive mesenteric nodes in the primary tumor specimen (S = 23%), and a disease-free interval of less than 1 year (S = 24%). The effect of any one of these factors was not great enough to contraindicate resection. However, combinations of prognostic factors must be considered before resection is recommended. The overall 5-year survival rate for this large series has been very satisfying. Decision making in the future must take into account such factors as number of metastases, extrahepatic involvement, and stage of the primary tumor.

The authors reflect on a research entitled "Early breast cancer in the elderly: assessment and management considerations." They state that the researchers of the study offered a wonderful overview of the new approach to breast cancer in the elderly. However, the authors stress that oncologists should adopt the techniques of the geriatricians and begin to understand the concepts of chronological and physiological age.

Context: Clinicians document cancer patients' symptoms in free-text format within electronic health record visit notes. Although symptoms are critically important to quality of life and often herald clinical status changes, computational methods to assess the trajectory of symptoms over time are woefully underdeveloped.Objectives: To create machine learning algorithms capable of extracting patient-reported symptoms from free-text electronic health record notes.Methods: The data set included 103,564 sentences obtained from the electronic clinical notes of 2695 breast cancer patients receiving paclitaxel-containing chemotherapy at two academic cancer centers between May 1996 and May 2015. We manually annotated 10,000 sentences and trained a conditional random field model to predict words indicating an active symptom (positive label), absence of a symptom (negative label), or no symptom at all (neutral label). Sentences labeled by human coder were divided into training, validation, and test data sets. Final model performance was determined on 20% test data unused in model development or tuning.Results: The final model achieved precision of 0.82, 0.86, and 0.99 and recall of 0.56, 0.69, and 1.00 for positive, negative, and neutral symptom labels, respectively. The most common positive symptoms were pain, fatigue, and nausea. Machine-based labeling of 103,564 sentences took two minutes.Conclusion: We demonstrate the potential of machine learning to gather, track, and analyze symptoms experienced by cancer patients during chemotherapy. Although our initial model requires further optimization to improve the performance, further model building may yield machine learning methods suitable to be deployed in routine clinical care, quality improvement, and research applications. [ABSTRACT FROM AUTHOR]

Background Our aim was to compare the pathologic upgrade rates of high-risk breast lesions (HRLs) on digital two-dimensional mammography (DM) vs digital breast tomosynthesis (DBT). Study Design The study cohort was composed of patients with HRLs diagnosed by image-guided core needle biopsy from December 2007 to February 2011 (DM group, before DBT integration) and from January 2013 to March 2016 (DBT group, after complete DBT integration). Medical records were reviewed for surgical outcomes and follow-up imaging. Results Eight hundred and ninety-three patients with 900 biopsy-proven HRLs underwent surgical excision (97.0% [873 of 900]) or had at least 2 years of imaging follow-up (3.0% [27 of 900]). The most common HRL was atypical ductal hyperplasia in the DM and DBT groups (37.4% [337 of 900]). The overall upgrade rate of HRLs to malignancy was 11.3% (102 of 900). There were no statistically significant differences in overall upgrades rates of HRLs on DM vs DBT (11.4% [54 of 475] vs 11.3% [48 of 425]; p = 0.97) or in upgrade rates of HRL subtypes. However, HRLs that upgraded on DBT were more likely to be invasive rather than in situ carcinoma compared with HRLs that upgraded on DM (39.6% [19 of 48] vs 20.4% [11 of 54]; p = 0.03). Overall, the most common HRL to upgrade was atypical ductal hyperplasia (18.4% [62 of 337]). The least common HRLs to upgrade in the DBT group were biphasic neoplasms (0% [0 of 22]), flat epithelial atypia (1.6% [1 of 62]), and papillomas without atypia (4.5% [2 of 44]). Conclusions There is no difference in the upgrade rates of HRLs on DM vs DBT, but the proportion of HRL upgrades that are invasive rather than in situ carcinoma is higher with DBT. [ABSTRACT FROM AUTHOR]

Background: The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID‐19) on breast cancer screening, breast surgery, and genetics consultations. Methods: User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed. Results: All 3 services experienced significant declines after the COVID‐19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non–breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre‐COVID average weekly volume for non–breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID‐19. Conclusions: COVID‐19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment. Coronavirus disease 2019 (COVID‐19) has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment in the United States. In the current study, user data from a risk assessment company were collected from February 2 to April 11, 2020, with the use of risk assessment used as a proxy to analyze changes in the use of 3 breast cancer services: breast imaging, breast surgery, and genetics consultation. [ABSTRACT FROM AUTHOR]

Background: The rising incidence of ductal carcinoma in situ (DCIS) since the widespread enactment of mammography screening has been well documented. Patterns in DCIS incidence among women of various ages and across different racial and ethnic groups have not been well described.Study Design: The Surveillance, Epidemiology, and End Results public-use data set was queried for all women aged 40 years and older diagnosed with DCIS between 1990 and 2014. Annual age-adjusted incidence rates were compared among white, black, Hispanic, and Asian-Pacific Islander women. Additionally, using mammography screening data obtained from the CDC, patterns in mammography screening over time and as they relate to DCIS incidence rates by race and ethnicity were evaluated.Results: We identified 200,400 women aged 40 years or older with DCIS. Between 1998 and 2014, a period that saw flux in national breast screening guidelines, DCIS incidence rates increased in blacks, Hispanics, and Asian-Pacific Islanders, but remained relatively unchanged in whites (increase in number of DCIS diagnoses per 100,000 individuals in the population per year among blacks +0.66/p < 0.01, Hispanics +3.0/p < 0.01, Asian-Pacific Islanders +0.53/p < 0.01, and whites +0.07/p = 0.21). After accounting for age, year of diagnosis, and mammography screening rates, DCIS incidence was found to be similar between white and black women (0.8 fewer diagnoses per 100,000 individuals compared with whites; p = 0.36) but lower for Hispanic women (9.7 fewer diagnoses per 100,000 individuals compared with whites; p < 0.01).Conclusions: The DCIS incidence rates are influenced substantially by breast cancer mammography screening patterns. However, differences exist by race and ethnicity and are not fully explained by screening mammography trends alone. Consideration should be given to including race and ethnicity in determining optimal breast screening guidelines. [ABSTRACT FROM AUTHOR]

BACKGROUND: In breast conserving surgery, the concordance between lumpectomy margin (LM) status and the status of the corresponding lumpectomy cavity remains uncertain. METHODS: We analyzed pathology reports of lumpectomies from 2004 to 2006. We included those which contained both ink-directed LM and complete (≥4) separate corresponding shaved cavity margins (SCMs). SCM pathology was used as a surrogate for lumpectomy cavity status, to determine the predictive value of LM for residual disease. RESULTS: Pathology from 1,201 pairs of LM and SCM from 242 patients was compared. LM status predicted corresponding lumpectomy cavity status with 50.9% sensitivity, 69.5% specificity, 35% positive predictive value, and 81.4% negative predictive value, giving an overall accuracy of 64.9%. CONCLUSIONS: Oriented LMs are not reliable for predicting lumpectomy cavity status, and therefore not reliable for directing re-excision. Taking complete, oriented SCMs at the time of lumpectomy may improve accuracy compared with traditional LM assessment. [ABSTRACT FROM AUTHOR]

Background: Mastectomy is often recommended when mammography shows a breast cancer with extensive calcifications. We wished to determine whether the use of multiple localizing wires to guide lumpectomy in this setting was associated with increased rates of breast conservation. We also wanted to identify factors that predicted a poor chance of successful lumpectomy, to avoid multiple lumpectomy attempts in a patient who would ultimately require mastectomy. Study Design: Records of 153 women with breast cancer who underwent lumpectomy for larger lesions that required multiple wire localization and 196 controls who required only single wire localization were reviewed retrospectively. The number of localizing wires, specimen volume, largest specimen dimension, number of surgical procedures, and rates of breast conservation were scored. Results: Seventy-seven percent of patients requiring multiple wire localization had successful breast conservation, compared with 90% of those needing only single wire localization. Only 28% of multiple wire patients required more than 1 excision to achieve clear margins, compared with 36% of single wire patients (p < 0.01). Conclusions: Breast conservation is possible in the great majority of breast cancer patients whose mammographic lesions require multiple localizing wires for excision. The use of multiple wires can decrease the number of procedures required to obtain clear lumpectomy margins. [ABSTRACT FROM AUTHOR]

Purpose: Few breast cancer risk assessment models account for the risk profiles of different tumor subtypes. This study evaluated whether a subtype-specific approach improves discrimination., Methods: Among 3389 women who had a screening mammogram and were later diagnosed with invasive breast cancer we performed multinomial logistic regression with tumor subtype as the outcome and known breast cancer risk factors as predictors. Tumor subtypes were defined by expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) based on immunohistochemistry. Discrimination was assessed with the area under the receiver operating curve (AUC). Absolute risk of each subtype was estimated by proportioning Gail absolute risk estimates by the predicted probabilities for each subtype. We then compared risk factor distributions for women in the highest deciles of risk for each subtype., Results: There were 3,073 ER/PR+ HER2 - , 340 ER/PR +HER2 + , 126 ER/PR-ER2+, and 300 triple-negative breast cancers (TNBC). Discrimination differed by subtype; ER/PR-HER2+ (AUC: 0.64, 95% CI 0.59, 0.69) and TNBC (AUC: 0.64, 95% CI 0.61, 0.68) had better discrimination than ER/PR+HER2+ (AUC: 0.61, 95% CI 0.58, 0.64). Compared to other subtypes, patients at high absolute risk of TNBC were younger, mostly Black, had no family history of breast cancer, and higher BMI. Those at high absolute risk of HER2+ cancers were younger and had lower BMI., Conclusion: Our study provides proof of concept that stratifying risk prediction for breast cancer subtypes may enable identification of patients with unique profiles conferring increased risk for tumor subtypes., (© 2024. The Author(s).)

Background: Currently, racial disparities exist in access to genetic testing. Recent developments have helped narrow the gap in accessibility. The purpose of this study was to determine whether racial disparities in genetic consultation attendance and completion of genetic testing persist, and, if so, factors that contribute to under-utilization of these resources., Methods: A single-institution retrospective review of breast patients referred for genetic counseling between 2017 and 2019 was performed. Univariate and multivariate logistic regression evaluated factors associated with genetic counseling attendance and genetic testing., Results: A total of 596 patients were referred for genetic counseling: 433 (72.7%) white; 138 (23.2%) black; and 25 (4.2%) other or unknown. In multivariate analysis, black patients, patients without breast cancer family history, and patients without a current cancer diagnosis, classified as high risk, were significantly less likely to attend their genetics appointment (p = 0.010, p = 0.007, p = 0.005, respectively). Age, insurance type, distance from facility, and need for chemotherapy did not significantly impact consult completion rate. Of the patients who completed a genetic consult, 84.4% (n = 248) had genetic testing and 17.7% (n = 44) had a pathogenic variant. For patients who attended counseling, there were no significant factors that were predictive with receipt of genetic testing., Conclusions: In this study, there was a significant association between race and attending genetic counseling. Once counseled, most patients went on to receive genetic testing, and racial disparities in testing disappeared, emphasizing the value of providing additional education about the importance and purpose of genetic testing., (© 2024. The Author(s).)

This study evaluated the impact of mainstreamed genetic testing (MGT) on the timing and uptake of testing in an academic breast surgeon's practice. Before September 2019 (pre-MGT phase), a breast surgery practice at Massachusetts General Hospital followed a traditional model of a pre-test consultation with a genetic counselor (GC) following a referral. After September 2019 (post-MGT phase), the same practice offered patients genetic testing in a single clinical encounter with a breast surgeon. We evaluated the waiting time between referral and GC visit in the pre-MGT phase and compared the uptake and positivity rates between both phases. In the pre-MGT phase (204 patients), the median waiting time for GC visit was seven days for patients with a newly diagnosed cancer, 211 days for patients with a personal history of cancer, and 224 days for non-cancer patients who had a family history. A total of 105 (51.5%) patients completed a GC appointment. In the post-MGT phase (202 patients), a significantly higher proportion of patients (88.1%, p < 0.001) consented to genetic testing, while the proportion of patients who tested positive was lower (pathogenic variant: 11.9% vs. 20.0%; variant of uncertain significance: 19.9% vs. 28.0%; p = 0.047). Implementing MGT can reduce the number of clinical visits, significantly shorten patients' wait time to test initiation, and increase the completion of genetic testing. Successful integration of this model relied on the genetic expertise of the breast surgeon involved and the support of the GC team., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Magnetic seeds have emerged as an alternative to wires for localization of nonpalpable breast lesions. The purpose of this study was to evaluate the utility of magnetic seeds compared to wires for preoperative localization., Materials and Methods: A retrospective cohort analysis of magnetic seed localization (MSL) and wire localization (WL) excisional biopsies and lumpectomies performed at a single institution was conducted. Indication, age, BMI, number of markers, procedure type, operative time, and postoperative opioid administration were reviewed. Impact of localization method on operative time, specimen volume, postoperative opioid administration, and re-excision rate were assessed., Results: A total of 608 MSL procedures in 601 patients were compared to 628 WL procedures in 620 patients. MSL excisional biopsies were significantly longer (37.0 minutes) than WL excisional biopsies (31.9 minutes, P< .001), but in lumpectomies without axillary surgery, MSL procedures (42.3 minutes) were significantly shorter than WL procedures (46.9 minutes, P = .017). Significantly less tissue was excised during MSL lumpectomies (68.5 cm 3 ) and excisional biopsies (32.3 cm 3 ) than WL lumpectomies (78.1 cm 3 , P = .039) and excisional biopsies (38.7 cm 3 , P = .018). Postoperative opioid administration was similar for MSL and WL procedures (P = .076). Re-excision rates for MSL lumpectomies were significantly higher for ductal carcinoma in situ (35.3% MSL vs. 18.5% WL, P = .013), but were similar for invasive carcinoma (14.4% MSL vs. 17.7% WL, P = .290). Logistic regression analysis showed no association between localization method and re-excision (OR 1.007, 95% CI 0.681-1.488; P = .973)., Conclusion: MSL is a feasible alternative to WL for excision of nonpalpable breast lesions with regard to surgical outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Background: Determining how many female patients who underwent breast imaging meet the eligibility criteria for genetic testing for familial pancreatic cancer (FPC)., Methods: A total of 42,904 patients seen at the Newton-Wellesley Hospital between 2007 and 2009 were retrospectively reviewed. The first four categories were based on pancreatic cancer-associated syndromes: (1) hereditary breast and ovarian cancer (HBOC), (2) Lynch syndrome (LS), (3) familial atypical multiple mole melanoma (FAMMM), and (4) family history of FPC (FH-FPC). PancPRO (5) and MelaPRO (6) categories were based on risk scores from Mendelian risk prediction tool., Results: Exactly 4445 of 42,904 patients were found to be in at least one of the six risk categories. About 5.7% of patients were classified as being at high risk for HBOC, 2.3% as being at high risk for LS, 0.1% as being at high risk for FAMMM, 0.1% as being at high risk for FH-FPC, 2.7% as being at high risk based on PancPRO, and 0.2% as being at high risk based on MelaPRO., Conclusion: About 10.4% of the female patients were classified as being at high risk for FPC. This finding emphasizes the importance of applying criteria to the general population, in order to ensure that individuals with high risk are identified early., (© 2021. Royal Academy of Medicine in Ireland.)

Background: Nipple-sparing mastectomy (NSM) is an oncologically safe alternative to skin-sparing mastectomy (SSM). This study evaluated whether NSM patients were more satisfied than SSM patients in short- and long-term follow-up., Methods: Women who underwent NSM or SSM between 2009 and 2019 completed a postoperative BREAST-Q survey at least 1 year after surgery and patient characteristics were compared. Patient satisfaction at 1-5 years and 6-10 years after NSM and SSM were analyzed., Results: Overall, 431 patients were included; 247 had NSM and 184 had SSM 1-10 years prior to BREAST-Q survey completion. SSM patients were older, had higher body mass index (BMI), larger breast weight, and more hypertension than NSM patients, but oncologic treatments were similar between groups. BREAST-Q Psychosocial Well-Being and Sexual Well-Being scores were significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort; however, scores attenuated in the 6-10 years cohort. Satisfaction with breasts was nearly significantly higher in NSM patients compared with SSM patients in the 1-5 years cohort (p = 0.056), but no different in the 6-10 years cohort. Receipt of adjuvant chemotherapy, receipt of postmastectomy radiation therapy, and BMI ≥30 were independent risk factors for dissatisfaction with breasts., Conclusions: Women who are not candidates for NSM should be reassured that long-term qualify of life is not significantly different between SSM and NSM. Dissatisfaction with reconstructed breasts is linked with other factors (besides the nipple), which patients should be made aware of at the time of surgical decision making., (© 2021. Society of Surgical Oncology.)

Purpose: Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance., Methods: A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies' bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study., Results: Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case-control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant., Conclusion: This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genetic testing offers providers a potentially life saving tool for identifying and intervening in high-risk individuals. However, disparities in receipt of genetic testing have been consistently demonstrated and undoubtedly have significant implications for the populations not receiving the standard of care. If correctly used, there is the potential for genetic testing to play a role in decreasing health disparities among individuals of different races and ethnicities. However, if genetic testing continues to revolutionize cancer care while being disproportionately distributed, it also has the potential to widen the existing mortality gap between various racial and ethnic populations., Competing Interests: Disclosure K.S. Hughes receives Honoraria from Hologic (surgical implant for radiation planning with breast conservation and wire-free breast biopsy) and Myriad Genetics and has a financial interest in CRA Health (Formerly Hughes RiskApps). CRA Health develops risk assessment models/software with a particular focus on breast cancer and colorectal cancer. K.S. Hughes is a founder and owns equity in the company. K.S. Hughes is the Co-Creator of Ask2Me.Org, which is freely available for clinical use and is licensed for commercial use by the Dana Farber Cancer Institute and the MGH. KH’s interests in CRA Health and Ask2Me.Org were reviewed and are managed by Massachusetts General Hospital and Partners Health Care in accordance with their conflict-of-interest policies. JP is the recipient of a research grant from the Color Foundation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention., Objective: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes., Methods: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity., Results: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions., Conclusion: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk., (© 2021. Society of Surgical Oncology.)

Objective: Second breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments., Methods: 168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis., Results: With median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly., Conclusion: Patients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Genetic testing for germline cancer susceptibility genes is widely available. The Ask2Me.org (All Syndromes Known to Man Evaluator) tool is a clinical decision support tool that provides evidence-based risk predictions for individuals with pathogenic variants in cancer susceptibility genes., Objective: The aim of this study was to understand the search behavior of the Ask2Me.org tool users, identify the patterns of queries entered, and discuss how to further improve the tool., Methods: We analyzed the Ask2Me.org user-generated queries collected between December 12, 2018, and October 8, 2019. The gene frequencies of the user-generated queries were compared with previously published panel testing data to assess the correspondence between usage and prevalence of pathogenic variants. The frequencies of prior cancer in the user-generated queries were compared with the most recent US population-based cancer incidence., Results: A total of 10,085 search queries were evaluated. The average age submitted in the queries was 48.8 (SD 16.5) years, and 84.1% (8478/10,085) of the submitted queries were for females. BRCA2 (1671/10,085, 16.6%), BRCA1 (1627/10,085, 16.1%), CHEK2 (994/10,085, 9.9%), ATM (662/10,085, 6.6%), and APC (492/10,085, 4.9%) were the top 5 genes searched by users. There was a strong linear correlation between genes queried by users and the frequency of pathogenic variants reported in published panel testing data (r=0.95, r 2 =0.90, P<.001). Over half of the queries (5343/10,085, 53.0%) included a prior personal history of cancer. The frequencies of prior cancers in the queries on females were strongly correlated with US cancer incidences (r=0.97, r 2 =0.95, P<.001), while the same correlation was weaker among the queries on males (r=0.69, r 2 =0.47, P=.02)., Conclusions: The patients entered in the Ask2Me.org tool are a representative cohort of patients with pathogenic variants in cancer susceptibility genes in the United States. While a majority of the queries were on breast cancer susceptibility genes, users also queried susceptibility genes with lower prevalence, which may represent a transformation from single gene testing to multigene panel testing. Owing to these changing tides, more efforts are needed to improve evidence-based clinical decision support tools to better aid clinicians and their practice., (©Kanhua Yin, Jingan Zhou, Preeti Singh, Jin Wang, Danielle Braun, Kevin S Hughes. Originally published in JMIR Cancer (https://cancer.jmir.org), 13.07.2021.)

Background: Fewer than 1% of all breast cancers occur in men. As a result, a distinct lack of data exists regarding the management and outcomes in this cohort., Methods: Any male patient with pathologically confirmed breast cancer diagnosed between August 2000 and October 2017 at either Massachusetts General Hospital or Brigham and Women's Hospital/Dana-Farber Cancer Institute and their affiliate satellite locations were included. Primary chart review was used to assess clinical and pathologic characteristics. Patient and treatment variables were reported via descriptive statistics. Local-regional failure (LRF), overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method., Results: 100 patients were included in this study. Median follow-up was 112 months (range 1-220 months). Approximately 1/3 of patients experienced at least a 3-month delay to presentation. 83 patients ultimately underwent mastectomy as definitive surgical treatment. 46 patients received adjuvant radiation therapy, and 37 patients received chemotherapy. Of 82 hormone receptor-positive patients with invasive cancer, 94% (n = 77) received endocrine therapy. Of the fifty-eight patients who underwent genetic testing, 15 (26%) tested positive. The 5-year OS, BCSS, DFS, and LRF rates were 91.5%, 96.2%, 86%, and 4.8%, respectively. Delay to presentation was not associated with worse survival., Conclusions: Male breast cancer remains a rare diagnosis. Despite this, the majority of patients in this study received standard of care therapy and experienced excellent oncologic outcomes. Penetration for genetic testing improved over time.

Purpose: Safe breast cancer lumpectomies require microscopically clear margins. Real-time margin assessment options are limited, and 20-40% of lumpectomies have positive margins requiring re-excision. The LUM Imaging System previously showed excellent sensitivity and specificity for tumor detection during lumpectomy surgery. We explored its impact on surgical workflow and performance across patient and tumor types., Methods: We performed IRB-approved, prospective, non-randomized studies in breast cancer lumpectomy procedures. The LUM Imaging System uses LUM015, a protease-activated fluorescent imaging agent that identifies residual tumor in the surgical cavity walls. Fluorescent cavity images were collected in real-time and analyzed using system software., Results: Cavity and specimen images were obtained in 55 patients injected with LUM015 at 0.5 or 1.0 mg/kg and in 5 patients who did not receive LUM015. All tumor types were distinguished from normal tissue, with mean tumor:normal (T:N) signal ratios of 3.81-5.69. T:N ratios were 4.45 in non-dense and 4.00 in dense breasts (p = 0.59) and 3.52 in premenopausal and 4.59 in postmenopausal women (p = 0.19). Histopathology and tumor receptor testing were not affected by LUM015. Falsely positive readings were more likely when tumor was present < 2 mm from the adjacent specimen margin. LUM015 signal was stable in vivo at least 6.5 h post injection, and ex vivo at least 4 h post excision., Conclusions: Intraoperative use of the LUM Imaging System detected all breast cancer subtypes with robust performance independent of menopausal status and breast density. There was no significant impact on histopathology or receptor evaluation.

Background: Pathogenic variants in cancer susceptibility genes can increase the risk of a spectrum of diseases, which clinicians must manage for their patients. We evaluated the disease spectrum of breast cancer susceptibility genes (BCSGs) with the aim of developing a comprehensive resource of gene-disease associations for clinicians., Methods: Twelve genes ( ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RECQL, STK11 , and TP53 ), all of which have been conclusively established as BCSGs by the Clinical Genome Resource (ClinGen) and/or the NCCN guidelines, were investigated. The potential gene-disease associations for these 12 genes were verified and evaluated based on six genetic resources (ClinGen, NCCN, OMIM, Genetics Home Reference, GeneCards, and Gene-NCBI) and an additional literature review using a semiautomated natural language processing (NLP) abstract classification procedure., Results: Forty-two diseases were found to be associated with one or more of the 12 BCSGs for a total of 86 gene-disease associations, of which 90% (78/86) were verified by ClinGen and/or NCCN. Four gene-disease associations could not be verified by either ClinGen or NCCN but were verified by at least three of the other four genetic resources. Four gene-disease associations were verified by the NLP procedure alone., Conclusion: This study is unique in that it systematically investigates the reported disease spectrum of BCSGs by surveying multiple genetic resources and the literature with the aim of developing a single consolidated, comprehensive resource for clinicians. This innovative approach provides a general guide for evaluating gene-disease associations for BCSGs, potentially improving the clinical management of at-risk individuals., Competing Interests: KH receives Honoraria from Hologic (Surgical implant for radiation planning with breast conservation and wire-free breast biopsy) and Myriad Genetics and has a financial interest in CRA Health (Formerly Hughes RiskApps). CRA Health develops risk assessment models/software with a particular focus on breast cancer and colorectal cancer. KH is a founder and owns equity in the company. KH is the Co-Creator of Ask2Me.Org, which is freely available for clinical use and is licensed for commercial use by the Dana Farber Cancer Institute and the MGH. KH’s interests in CRA Health and Ask2Me.Org were reviewed and are managed by Massachusetts General Hospital and Partners Health Care in accordance with their conflict of interest policies. DB co-leads the BayesMendel laboratory, which licenses software for the computation of risk prediction models. She does not derive any personal income from these licenses. All revenues are assigned to the lab for software maintenance and upgrades. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Singh, Yin, Zhou, Bao, Wu, Pathak, McKinley, Braun and Hughes.)

Pathogenic variants in germline cancer susceptibility genes can increase the risk of a large number of diseases. Our study aims to assess the disease spectrum of gastric cancer susceptibility genes and to develop a comprehensive resource of gene-disease associations for clinicians. Twenty-seven potential germline gastric cancer susceptibility genes were identified from three review articles and from six commonly used genetic information resources. The diseases associated with each gene were evaluated via a semi-structured review of six genetic resources and an additional literature review using a natural language processing (NLP)-based procedure. Out of 27 candidate genes, 13 were identified as gastric cancer susceptibility genes (APC, ATM, BMPR1A, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH-Biallelic, PALB2, SMAD4, and STK11). A total of 145 gene-disease associations (with 45 unique diseases) were found to be associated with these 13 genes. Other gastrointestinal cancers were prominent among identified associations, with 11 of 13 gastric cancer susceptibility genes also associated with colorectal cancer, eight genes associated with pancreatic cancer, and seven genes associated with small intestine cancer. Gastric cancer susceptibility genes are frequently associated with other diseases as well as gastric cancer, with potential implications for how carriers of these genes are screened and managed. Unfortunately, commonly used genetic resources provide heterogeneous information with regard to these genes and their associated diseases, highlighting the importance of developing guides for clinicians that integrate data across available resources and the medical literature.

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices., Competing Interests: Conflicts of interest The development of these guidelines was wholly funded by SFMPP. The panelists received no payments. The complete CoI for researchers who contributed to the guidelines are provided in supplementary data. Categories for disclosure of CoI include employment; leadership; stock or other ownership; honoraria, consulting or advisory role; speaker’s bureau; research funding; patents, royalties, other intellectual property; expert testimony; travel, accommodations, expenses; and other relationships., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We evaluated the risk of cardiac mortality in older patients who receive adjuvant radiation therapy (RT) for stage I breast cancer to determine whether this risk persists in the modern era., Methods and Materials: Using the 2000 to 2015 Surveillance, Epidemiology, and End Results program data, we performed a population-based cohort study to evaluate the association between adjuvant breast RT, tumor laterality, and cardiac-specific survival (CSS) among patients 60 and older with stage I estrogen receptor positive breast cancer who received breast-conserving surgery and RT., Results: At a median follow-up of 6 years (range, 0-15.9 years), patients receiving RT for left-sided breast cancer demonstrated no difference in 5- and 10-year CSS compared with those with right-sided breast cancer (5 year 98.3% vs 98.2%, 10 year 94.3% vs 93.9%; log-rank P = .56). Cox proportional hazards regression analysis confirmed the lack of association of tumor laterality on adjusted 5-year CSS (hazard ratio [HR] = 0.96; 95% confidence interval [CI] = 0.87-1.06), breast-cancer specific survival (HR = 0.96; 95% CI = 0.85-1.09), and overall survival (HR = 0.98; 95% CI = 0.94-1.03). There was also no association of inner versus outer quadrant location on adjusted 5-year CSS for right-sided (HR = 1.06; 95% CI = 0.89-1.12) and left-sided breast cancer (HR = 0.95; 95% CI = 0.79-1.15)., Conclusions: With modern radiation therapy techniques, older patients who received left-sided RT for stage I estrogen-receptor positive breast cancer do not demonstrate an increased risk of cardiac mortality compared with patients with right-sided breast cancer. RT can be offered to older patients without concern for inducing cardiac-related death., (© 2020 The Authors.)

Background: Targeted axillary dissection (TAD) involves sentinel lymph node biopsy (SLNB) and excision of a biopsy-proven node marked by a clip. This study evaluates the feasibility of non-radioactive wireless localizers for targeted excision of clipped axillary lymph nodes., Methods: We identified biopsy-proven, node-positive breast cancer patients treated with neoadjuvant therapy (NAT) and TAD from 2016 to 2020, and included those with a clipped node localized using SAVI SCOUT, Magseed, or RFID Tag. Primary outcome measures were (1) successful localization (ultrasound or mammographic-guided placement < 10 mm from target), and (2) retrieval of the clipped node during TAD, documented by specimen radiography or gross visualization. Secondary outcomes included rates of completion axillary lymph node dissection (cALND) and complications., Results: Overall, 57 patients were included; 1 (1.8%) patient had no clip visible at the time of localization, and no radiographic confirmation of clip placement at the time of biopsy, and was therefore excluded. In the remaining 56 patients, localization was successful in 53 (94.6%) patients and the clipped node was retrieved during TAD in 51 (91.1%) patients. Twenty-three of 27 (85.2%) ypN0 patients were spared cALND; 3 (11.1%) patients had cALND for failed clipped node retrieval during TAD, and 1 (3.7%) for false-positive frozen section. In patients with TAD alone, the rates of axillary seroma and infection were 20.0% and 8.6%, respectively., Conclusions: Wireless non-radioactive localizers are feasible for axillary localization after NAT, with high success rates of retrieving clipped nodes. The lack of signal decay is an advantage of these devices, allowing flexibility in timing of placement.

Purpose: The classification of germline variants may differ between labs and change over time. We apply a variant harmonization tool, Ask2Me VarHarmonizer, to map variants to ClinVar and identify discordant variant classifications in a large multipractice variant dataset., Methods: A total of 7496 variants sequenced between 1996 and 2019 were collected from 11 clinical practices. Variants were mapped to ClinVar, and lab-reported and ClinVar variant classifications were analyzed and compared., Results: Of the 4798 unique variants identified, 3699 (77%) were mappable to ClinVar. Among mappable variants, variants of unknown significance (VUS) accounted for 74% of lab-reported classifications and 60% of ClinVar classifications. Lab-reported and ClinVar discordances were present in 783 unique variants (21.2% of all mappable variants); 121 variants (2.5% of all unique variants) had within-practice lab-reported discordances; and 56 variants (1.2% of all unique variants) had lab-reported discordances across practices. The unmappable variants were associated with a higher proportion of lab-reported pathogenic classifications (50% vs. 21%, p < 0.0001) and a lower proportion of lab-reported VUS classifications (46% vs. 74%, p < 0.0001)., Conclusions: Our study shows that discordant variant classification occurs frequently, which may lead to inappropriate recommendations for prophylactic treatments or clinical management.

Objective: The aim of the study was to determine abdominal and breast adipose tissue parameters on 18-fluorodeoxyglucose positron emission tomography/computed tomography (CT) that may serve as outcome predictors in breast angiosarcoma patients., Materials: Women with breast angiosarcoma (n = 13) who underwent 18-fluorodeoxyglucose positron emission tomography/CT were identified. A control group was selected (n = 25). Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) were assessed on unenhanced computed tomographies. Breast adipose tissue (BAT) volumes of the uninvolved breast were quantified. Metabolic activity of VAT, SAT, and BAT was calculated (standardized uptake value [SUV])., Results: Breast angiosarcoma patients had higher metabolic activity of VAT compared with controls (SUV 0.93 ± 0.39 vs 0.64 ± 0.11, P = 0.044). Within the patient group, there were 6 deaths (46.2%). Patients who died had higher SAT activity (SUV 0.52 ± 0.24 vs 0.29 ± 0.06, P = 0.027) and higher BAT metabolic activity (SUV 0.48 ± 0.20 vs 0.27 ± 0.11, P = 0.045) compared with nondeceased patients., Conclusions: Patients with breast angiosarcoma have higher metabolic activity of VAT. Higher abdominal SAT and higher BAT metabolic activity of the uninvolved breast might predict mortality.