A radiation therapy contouring atlas for delineation of the level I-II axilla in the prone position: a single institution experience.

PURPOSE: With transition from supine to prone, tenting of the pectoralis major occurs displacing the muscle from the chest wall and shifting the level I-II axillary spaces. For patients whom we aim to treat the level I-II axilla using the prone technique, accurate delineation of these nodal regions is necessary. While different consensus guidelines exist for delineation of nodal anatomy supine, to our knowledge there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I-II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by two radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I-II axilla on non-contrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I-II axilla prone using bone, muscle and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior border of level II, and the anterior, posterior, medial and lateral border of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I-II axilla when the axilla is a target in addition to the breast.

Effectiveness and toxicity of five-fraction prone accelerated partial breast irradiation.

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.

Low Cancer Occurrence Rate following Prophylactic Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS: All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS: A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS: Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

DNA Methylation Identifies Epigenetic Subtypes of Triple-Negative Breast Cancers With Distinct Clinicopathologic and Molecular Features.

Triple-negative breast cancers (TNBC) include diverse carcinomas with heterogeneous clinical behavior. DNA methylation is a useful tool in classifying a variety of cancers. In this study, we analyzed TNBC using DNA methylation profiling and compared the results to those of mutational analysis. DNA methylation profiling (Infinium MethylationEPIC array, Illumina) and 50-gene panel-targeted DNA sequencing were performed in 44 treatment-naïve TNBC. We identified 3 distinct DNA methylation clusters with specific clinicopathologic and molecular features. Cluster 1 (phosphoinositide 3-kinase/protein kinase B-enriched cluster; n = 9) patients were significantly older (mean age, 71 years; P = .008) with tumors that were more likely to exhibit apocrine differentiation (78%; P < .001), a lower grade (44% were grade 2), a lower proliferation index (median Ki-67, 15%; P = .002), and lower tumor-infiltrating lymphocyte fractions (median, 15%; P = .0142). Tumors carried recurrent PIK3CA and AKT1 mutations and a higher percentage of low HER-2 expression (89%; P = .033). Cluster 3 (chromosomal instability cluster; n = 28) patients were significantly younger (median age, 57 years). Tumors were of higher grade (grade 3, 93%), had a higher proliferation index (median Ki-67, 75%), and were with a high fraction of tumor-infiltrating lymphocytes (median, 30%). Ninety-one percent of the germline BRCA1/2 mutation carriers were in cluster 3, and these tumors showed the highest level of copy number alterations. Cluster 2 represented cases with intermediate clinicopathologic characteristics and no specific molecular profile (no specific molecular profile cluster; n = 7). There were no differences in relation to stage, recurrence, and survival. In conclusion, DNA methylation profiling is a promising tool to classify patients with TNBC into biologically relevant groups, which may result in better disease characterization and reveal potential targets for emerging therapies.

Results of Magnetic Resonance Imaging (MRI) Screening in Patients at High Risk for Breast Cancer.

BACKGROUND: Screening MRI as an adjunct to mammography is recommended by the ACS for patients with a lifetime risk for breast cancer > 20%. While the benefits are clear, MRI screening is associated with an increase in false-positive results. The purpose of this study was to analyze our institutional database of high-risk patients and assess the uptake of screening MRI examinations and the results of those screenings. METHODS: Our institutional review board-approved High-Risk Breast Cancer Database was queried for patients enrolled from January 2017 to January 2023 who were at high risk for breast cancer in a comparative analysis between those who were screened versus not screened with MRIs. Variables of interest included risk factor, background, MRI screening uptake, and frequency and results of image-guided breast biopsies. RESULTS: A total of 254 of 1106 high-risk patients (23%) had MRI screening. Forty-six of 852 (5.3%) patients in the non-MRI-screened cohort and nine of 254 (3.5%) patients in the MRI-screened cohort were diagnosed with a malignant lesion after image-guided biopsy (p = 0.6). There was no significant difference between MRI and non-MRI guided biopsies in detecting breast cancer. All malignant lesions were T1 or in situ disease. The 254 patients in the MRI-screened group underwent 185 biopsies. Fifty-seven percent of MRI-guided biopsies yielded benign results. CONCLUSIONS: Although the addition of MRI screening in our high-risk cohort did not produce a significant number of additional cancer diagnoses, patients monitored in our high-risk cohort who developed breast cancer were diagnosed at very early stages of disease, underscoring the benefit of participation in the program.

Improving Information Extraction from Pathology Reports using Named Entity Recognition.

Pathology reports are considered the gold standard in medical research due to their comprehensive and accurate diagnostic information. Natural language processing (NLP) techniques have been developed to automate information extraction from pathology reports. However, existing studies suffer from two significant limitations. First, they typically frame their tasks as report classification, which restricts the granularity of extracted information. Second, they often fail to generalize to unseen reports due to variations in language, negation, and human error. To overcome these challenges, we propose a BERT (bidirectional encoder representations from transformers) named entity recognition (NER) system to extract key diagnostic elements from pathology reports. We also introduce four data augmentation methods to improve the robustness of our model. Trained and evaluated on 1438 annotated breast pathology reports, acquired from a large medical center in the United States, our BERT model trained with data augmentation achieves an entity F1-score of 0.916 on an internal test set, surpassing the BERT baseline (0.843). We further assessed the model's generalizability using an external validation dataset from the United Arab Emirates, where our model maintained satisfactory performance (F1-score 0.860). Our findings demonstrate that our NER systems can effectively extract fine-grained information from widely diverse medical reports, offering the potential for large-scale information extraction in a wide range of medical and AI research. We publish our code at https://github.com/nyukat/pathology_extraction.

Changes in Breast Cancer Presentation during COVID-19: Experience in an Urban Academic Center.

The COVID-19 pandemic strained healthcare systems worldwide, delaying breast cancer screening and surgery. In 2019, approximately 80% of breast cancers in the U.S. were diagnosed on screening examinations, with 76.4% of eligible Medicare patients undergoing screening at least every two years. Since the start of the pandemic, many women have been reluctant to seek elective screening mammography, even with the lifting of pandemic-related restrictions in access to routine healthcare. We describe the effect of the COVID-19 pandemic on breast cancer presentation at a tertiary academic medical center greatly impacted by the pandemic.

No Cancer Occurrences in 10-year Follow-up after Prophylactic Nipple-sparing Mastectomy.

Prophylactic nipple-sparing mastectomies (NSM) have become increasingly common, although there is little long-term data on its efficacy in prevention of breast cancer. The objective of this study was to assess the incidence of breast cancer in a cohort of patients undergoing prophylactic NSM with a median follow-up of 10 years. Methods: Patients receiving prophylactic NSM at a single institution from 2006 to 2019 were included in a retrospective nature. Patient demographics, genetic mutations, operative details, and specimen pathology were recorded, and all postoperative patient visits and documentation were screened for cancer occurrence. Descriptive statics were performed where appropriate. Results: Two hundred eighty-four prophylactic NSMs were performed on 228 patients with a median follow-up of 120.5 ± 15.7 months. Roughly, a third of patients had a known genetic mutation, with 21% BRCA1 and 12% BRCA2. The majority (73%) of prophylactic specimens had no abnormal pathology. The most commonly observed pathologies were atypical lobular hyperplasia (10%) and ductal carcinoma in situ (7%). Cancer was identified in 10% of specimens, with only one case of lymphovascular invasion. Thus far, there have been no incidences of locoregional breast cancer occurrence in this cohort. Conclusions: The long-term breast cancer occurrence rate in this cohort of prophylactic NSM patients at the time of this study is negligible. Despite this, continued surveillance of these patients is necessary until lifetime risk of occurrence following NSM has been established.

Single-Dose of Postoperative Ketamine for Postoperative Pain After Mastectomy: A Pilot Randomized Controlled Trial.

Background and Objectives: Perioperative ketamine has been shown to reduce opioid consumption and pain after surgery. Ketamine is most often given as an infusion, but an alternative is single-dose ketamine. Single-dose ketamine at up to 1 mg/kg has been shown to reduce symptoms of depression, and a wide range of dosages has been used for pain in the emergency department. However, limited data exists on the tolerability and efficacy of a single-dose of ketamine at 0.6 mg/kg for pain when administered immediately after surgery. We conducted a pilot study of single-dose ketamine in patients undergoing mastectomy with reconstruction, hypothesizing that a single-dose of ketamine is well tolerated and can relieve postoperative pain and improve mood and recovery. Methods: This is a randomized, single-blind, placebo-controlled, two-arm parallel, single-center study. Thirty adult women undergoing mastectomy with reconstruction for oncologic indication received a single-dose of ketamine (0.6mg/kg) or placebo after surgery in the post-anesthesia care unit (PACU). Patients were followed through postoperative day (POD) 7. The primary outcome was postoperative pain measured by the Brief Pain Inventory (BPI) pain subscale on POD 1 and 2. Secondary outcomes include effects on opioid use, PROMIS fatigue and sleep, mood, Quality of Recovery-15, and the Breast Cancer Pain Questionnaire. Results: Side effects were minor and not significantly different in frequency between groups. The ketamine group reported lower scores on the BPI pain severity subscale, especially at POD 7; however, the difference was not statistically significant. There were no statistically significant differences between ketamine and placebo groups for the secondary outcomes. Conclusion: A single-dose of ketamine at 0.6mg/kg administered postoperatively in the PACU is well tolerated in women undergoing mastectomy and may confer better pain control up to one week after surgery. Future studies with larger sample sizes are necessary to adequately characterize the effect of postoperative single-dose ketamine on pain control in this population.

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.

Radar reflector guided axillary surgery in node positive breast cancer patients.

INTRODUCTION: In patients with non-palpable breast cancer, the availability of wireless localization techniques facilitates removal of the target lesion. One such technique uses a radar reflector for localization (RRL). This study evaluates the feasibility and effectiveness of RRL to guide excision of axillary lymph nodes in patients with node-positive breast cancer. METHODS: Our Breast Cancer Database was queried for patients diagnosed with breast cancer, between 5/2017 and 10/2021, who underwent preoperative placement of a radar reflector into a biopsy proven axillary lymph node. Clinicopathologic data were reported using descriptive statistics. RESULTS: Twenty patients underwent preoperative placement of a radar reflector into the axilla. Intraoperatively, the clip and radar reflector were successfully removed in all patients. Among the 10 patients treated with NAC, 5 patients achieved an axillary pathologic complete response (pCR) and were spared a complete axillary lymph node dissection (cALND). Among the entire cohort, RRL resulted in a 53% reduction in the number of lymph nodes removed. CONCLUSIONS: Wireless localization of axillary lymph nodes is safe and feasible. The technique ensures excision of biopsy proven positive axillary lymph nodes and enables a targeted approach to assessing the axilla, both in the setting of NAC and upfront surgery.

Long-Term Cancer Recurrence Rates following Nipple-Sparing Mastectomy: A 10-Year Follow-Up Study.

BACKGROUND: Despite the increased use of nipple-sparing mastectomies, there are limited data examining long-term cancer recurrence rates in these patients. The objective of this study was to analyze breast cancer recurrence in patients who underwent therapeutic nipple-sparing mastectomy with a median of 10 years of follow-up. METHODS: All patients undergoing nipple-sparing mastectomy at a single institution were retrospectively reviewed temporally to obtain a median of 10 years of follow-up. Patient demographic factors, mastectomy specimen pathologic findings, and oncologic outcomes were analyzed. Univariate analysis was performed to identify independent risk factors for locoregional recurrence. RESULTS: One hundred twenty-six therapeutic nipple-sparing mastectomies were performed on 120 patients. The most frequently observed tumor histology included invasive ductal carcinoma (48.4 percent) and ductal carcinoma in situ (38.1 percent). Mean tumor size was 1.62 cm. Multifocal or multicentric disease and lymphovascular invasion were present in 31.0 percent and 10.3 percent of nipple-sparing mastectomy specimens, respectively. Sentinel lymph node biopsy was performed in 84.9 percent of nipple-sparing mastectomies, and 17.8 percent were positive. The rate of positive frozen subareolar biopsy was 7.3 percent ( n = 82) and that of permanent subareolar pathology was 9.5 percent ( n = 126). The most frequently observed pathologic tumor stages were stage I (44.6 percent) and stage 0 (33.9 percent). The incidence of recurrent disease was 3.17 percent per mastectomy and 3.33 percent per patient. On univariate analysis, no demographic, operative, or tumor-specific variables were independent risk factors for locoregional recurrence. CONCLUSIONS: Overall recurrence rates are low in patients undergoing nipple-sparing mastectomy at a median follow-up of 10-years. Close surveillance should remain a goal for patients and their providers to promptly identify potential recurrence. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Outcomes of Breast Cancer Patients Treated with Chemotherapy, Biologic Therapy, Endocrine Therapy, or Active Surveillance During the COVID-19 Pandemic.

PURPOSE: Provide real-world data regarding the risk for SARS-CoV-2 infection and mortality in breast cancer (BC) patients on active cancer treatment. METHODS: Clinical data were abstracted from the 3778 BC patients seen at a multisite cancer center in New York between February 1, 2020 and May 1, 2020, including patient demographics, tumor histology, cancer treatment, and SARS-CoV-2 testing results. Incidence of SARS-CoV-2 infection by treatment type (chemotherapy [CT] vs endocrine and/or HER2 directed therapy [E/H]) was compared by Inverse Probability of Treatment Weighting. In those diagnosed with SARS-CoV-2 infection, Mann-Whitney test was used to a assess risk factors for severe disease and mortality. RESULTS: Three thousand sixty-two patients met study inclusion criteria with 641 patients tested for SARS-COV-2 by RT-PCR or serology. Overall, 64 patients (2.1%) were diagnosed with SARS-CoV-2 infection by either serology, RT-PCR, or documented clinical diagnosis. Comparing matched patients who received chemotherapy (n = 379) with those who received non-cytotoxic therapies (n = 2343) the incidence of SARS-CoV-2 did not differ between treatment groups (weighted risk; 3.5% CT vs 2.7% E/H, P = .523). Twenty-seven patients (0.9%) expired over follow-up, with 10 deaths attributed to SARS-CoV-2 infection. Chemotherapy was not associated with increased risk for death following SARS-CoV-2 infection (weighted risk; 0.7% CT vs 0.1% E/H, P = .246). Advanced disease (stage IV), age, BMI, and Charlson's Comorbidity Index score were associated with increased mortality following SARS-CoV-2 infection (P ≤ .05). CONCLUSION: BC treatment, including chemotherapy, can be safely administered in the context of enhanced infectious precautions, and should not be withheld particularly when given for curative intent.

Macrophage density is an adverse prognosticator for ipsilateral recurrence in ductal carcinoma in situ.

INTRODUCTION: There is evidence that supports the association of dense tumor infiltrating lymphocyte (TILs) with an increased risk of ipsilateral recurrence in ductal carcinoma in situ (DCIS). However, the association of cellular composition of DCIS immune microenvironment with the histopathologic parameters and outcome is not well understood. METHODS: We queried our institutional database for patients with pure DCIS diagnosed between 2010 and 2019. Immunohistochemical studies for CD8, CD4, CD68, CD163, and FOXP3 were performed and evaluated in the DCIS microenvironment using tissue microarrays. Statistical methods included Fisher's exact test for categorical variables and the two-sample t-test or the Wilcoxon Rank-Sum test for continuous variables. RESULTS: The analytic sample included 67 patients. Median age was 62 years (range = 53 to 66) and median follow up was 6.7 years (range = 5.3 to 7.8). Thirteen patients had ipsilateral recurrence. Of all the clinicopathologic variables, only the DCIS size and TIL density were significantly associated with recurrence (p = 0.023 and 0.006, respectively). After adjusting for age and TIL density, only high CD68 (>50) and high CD68/CD163 ratio (>0.46) correlated with ipsilateral recurrence (p = 0.026 and 0.013, respectively) and shorter time to recurrence [hazard ratio 4.87 (95% CI: 1.24-19, p = 0.023) and 10.32 (95% CI: 1.34-80, p = 0.025), respectively]. CONCLUSIONS: In addition to DCIS size and TIL density, high CD68+ tumor-associated macrophages predict ipsilateral recurrence in DCIS. High CD68+ macrophage density and CD68/CD163 ratio also predict a shorter time to recurrence.

Breast Cancer Characteristics in the Population of Survivors Participating in the World Trade Center Environmental Health Center Program 2002-2019.

The destruction of World Trade Center on 11 September 2001 exposed local community members to a complex mixture of known carcinogens and potentially carcinogenic substances. To date, breast cancer has not been characterized in detail in the WTC-exposed civilian populations. The cancer characteristics of breast cancer patients were derived from the newly developed Pan-Cancer Database at the WTC Environmental Health Center (WTC EHC). We used the Surveillance, Epidemiology, and End Results (SEER) Program breast cancer data as a reference source. Between May 2002 and 31 December 2019, 2840 persons were diagnosed with any type of cancer at the WTC EHC, including 601 patients with a primary breast cancer diagnosis (592 women and 9 men). There was a higher proportion of grade 3 (poorly differentiated) tumors (34%) among the WTC EHC female breast cancers compared to that of the SEER-18 data (25%). Compared to that of the SEER data, female breast cancers in the WTC EHC had a lower proportion of luminal A (88% and 65%, respectively), higher proportion of luminal B (13% and 15%, respectively), and HER-2-enriched (5.5% and 7%, respectively) subtypes. These findings suggest considerable differences in the breast cancer characteristics and distribution of breast cancer intrinsic subtypes in the WTC-exposed civilian population compared to that of the general population. This is important because of the known effect of molecular subtypes on breast cancer prognosis.

A case report of COVID-19 in an asymptomatic patient with newly diagnosed breast cancer.

COVID-19 can be especially dangerous in vulnerable populations such as those with cancer undergoing treatment. When it is discovered in an asymptomatic patient through imaging, there is a paucity of evidence-based treatment recommendations.

Impact of changing guidelines on genetic testing and surveillance recommendations in a contemporary cohort of breast cancer survivors with family history of pancreatic cancer.

Changing practice guidelines and recommendations have important implications for cancer survivors. This study investigated genetic testing patterns and outcomes and reported family history of pancreatic cancer (FHPC) in a large registry population of breast cancer (BC) patients. Variables including clinical and demographic characteristics, FHPC in a first or second-degree relative, and genetic testing outcomes were analyzed for BC patients diagnosed between 2010 and 2018 in the NYU Langone Health Breast Cancer Database. Among 3334 BC patients, 232 (7%) had a positive FHPC. BC patients with FHPC were 1.68 times more likely to have undergone genetic testing (p < 0.001), but 33% had testing for BRCA1/2 only and 44% had no genetic testing. Pathogenic germline variants (PGV) were identified in 15/129 (11.6%) BC patients with FHPC, and in 145/1315 (11.0%) BC patients without FHPC. Across both groups, updates in genetic testing criteria and recommendations could impact up to 80% of this cohort. Within a contemporary cohort of BC patients, 7% had a positive FHPC. The majority of these patients (56%) had no genetic testing, or incomplete testing by current standards, suggesting under-diagnosis of PC risk. This study supports recommendations for survivorship care that incorporate ongoing genetic risk assessment and counseling.

Multinuclear MRI to disentangle intracellular sodium concentration and extracellular volume fraction in breast cancer.

The purpose of this work was to develop a novel method to disentangle the intra- and extracellular components of the total sodium concentration (TSC) in breast cancer from a combination of proton ([Formula: see text]H) and sodium ([Formula: see text]) magnetic resonance imaging (MRI) measurements. To do so, TSC is expressed as function of the intracellular sodium concentration ([Formula: see text]), extracellular volume fraction (ECV) and the water fraction (WF) based on a three-compartment model of the tissue. TSC is measured from [Formula: see text] MRI, ECV is calculated from baseline and post-contrast [Formula: see text]H [Formula: see text] maps, while WF is measured with a [Formula: see text]H chemical shift technique. [Formula: see text] is then extrapolated from the model. Proof-of-concept was demonstrated in three healthy subjects and two patients with triple negative breast cancer. In both patients, TSC was two to threefold higher in the tumor than in normal tissue. This alteration mainly resulted from increased [Formula: see text] ([Formula: see text] 30 mM), which was [Formula: see text] 130% greater than in healthy conditions (10-15 mM) while the ECV was within the expected range of physiological values (0.2-0.25). Multinuclear MRI shows promise for disentangling [Formula: see text] and ECV by taking advantage of complementary [Formula: see text]H and [Formula: see text] measurements.