Faculty Bibliography

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.

The management of intraductal papilloma (IDP) diagnosed on core needle biopsy (CNB) is controversial due to the variable upgrade rates to breast carcinoma (BC) on subsequent surgical excision reported in the literature. The purpose of our study was to investigate the upgrade rate of IDP diagnosed on CNB to BC in subsequent surgical excision and the impact of clinical, pathologic and radiologic variables. This is a retrospective cohort of all women who had a diagnosis of IDP on a CNB between 2005 and 2018 in a tertiary academic center with subsequent surgical excision. Upgrade was defined as ductal carcinoma in situ (DCIS) and invasive carcinoma on surgical excision. Statistical analyses included Pearson's chi-square, Wilcoxon rank-sum and logistic regression. A total of 216 women with IDP in a CNB were included. Nineteen patients (8.8%) upgraded to BC in the overall cohort, including 14 DCIS and 5 invasive carcinomas. An upgrade rate of 27% was found in atypical IDP (14 of 51 cases), while only 3% of pure IDP upgraded to BC (5 of 165 cases). Older age (>53 years) at time of biopsy (OR=1.05, 95%CI 1.01-1.09, p=0.027) and concomitant atypical ductal hyperplasia (ADH) (OR=9.69, 95%CI 3.37-27.81, p<0.0001) were significantly associated with upgrade. Our results support surgical excision of IDP on CNB when associated with ADH or diagnosed in women older than 53 years of age. The low surgical upgrade rate of 3% for pure IDP on CNB in younger women should be part of the management discussion.

Women with breast biopsies showing high-risk proliferative lesions such as atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) have an increased risk of developing breast cancer. Other factors including age, family history of breast cancer, and extent of AH may play a role in increasing breast cancer risk. In addition to women with AH, there is a subset of women with a positive family history of breast cancer, without a known germline mutation, which places them also at an increased risk for breast cancer. Clinical management, screening, chemoprevention, and surgical risk-reduction are discussed in this review to inform the management of these high-risk women. Advanced imaging technology, pharmacologic research into different targets, and innovations in breast reconstruction are changing the way in which patients are counseled of their individual risk.

Current guidelines recommend sentinel lymph node biopsy (SLNB) for patients undergoing mastectomy for a preoperative diagnosis of ductal carcinoma in situ (DCIS). We examined the factors associated with sentinel lymph node positivity for patients undergoing mastectomy for a diagnosis of DCIS on preoperative core biopsy (PCB). The Institutional Breast Cancer Database was queried for patients with PCB demonstrating pure DCIS followed by mastectomy and SLNB from 2010 to 2018. Patients were divided according to final pathology (DCIS or invasive cancer). Clinico-pathologic variables were analyzed using Pearson's chi-squared, Wilcoxon Rank-Sum and logistic regression. Of 3145 patients, 168(5%) had pure DCIS on PCB and underwent mastectomy with SLNB. On final mastectomy pathology, 120(71%) patients had DCIS with 0 positive sentinel lymph nodes (PSLNs) and 48(29%) patients had invasive carcinoma with 5(10%) cases of ≥1 PSLNs. Factors positively associated with upstaging to invasive cancer in univariate analysis included age (P = .0289), palpability (P < .0001), extent of disease on imaging (P = .0121), mass on preoperative imaging (P = .0003), multifocality (P = .0231) and multicentricity (P = .0395). In multivariate analysis, palpability (P = .0080), extent of disease on imaging (P = .0074) and mass on preoperative imaging (P = .0245) remained significant (Table 2). In a subset of patients undergoing mastectomy for DCIS with limited disease on preoperative evaluation, SLNB may be omitted as the risk of upstaging is low. However, patients who present with clinical findings of palpability, large extent of disease on imaging and mass on preoperative imaging have a meaningful risk of upstaging to invasive cancer, and SLNB remains important for management.

Pregnancy-associated breast cancer (PABC) refers to breast cancer (BC) diagnosed during pregnancy, lactation, or in the postpartum period. There is evidence that PABC is associated with a poorer prognosis, and that the development of the disease is influenced by the unique hormonal milieu of pregnancy. The purpose of this study was to investigate the clinicopathologic characteristics associated with PABC in a contemporary cohort of women with newly diagnosed BC. Our institutional Breast Cancer Database was queried for women diagnosed with BC between 2009-2018 who had at least one full-term pregnancy (FTP). Variables of interest included patient demographics and clinical and tumor characteristics. PABC was defined as breast cancer diagnosed within 24 months of delivery. Statistical analyses included Pearson's chi-square and logistic regression. Out of a total of 2202 women, 46 (2.1%) had PABC. Median follow-up in the total cohort was 5.5 years. After adjusting for age at first FTP, PABC was associated with younger age at diagnosis, older age at first FTP, non-Caucasian race, BRCA positivity, presentation with a palpable mass, higher pathologic stage, higher histologic grade, and ER-negative and triple-negative receptor status. The association of PABC with non-Caucasian race may be reflected in the increased proportion of triple-negative breast cancers in the PABC group. PABC was also associated with older age at first FTP. As more women delay childbearing, risk for PABC may increase. Our findings suggest that women who become pregnant at older ages should be followed carefully during pregnancy and the postpartum period, especially if they are BRCA mutation carriers. The optimal approach for monitoring older women during pregnancy and the postpartum period is unclear.

BACKGROUND:Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM/OBJECTIVE:To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS:Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS:= 0.004) decreased the risk of IBTR. CONCLUSION/CONCLUSIONS:Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

PURPOSE/OBJECTIVE:To evaluate the relationship between mammographic density, background parenchymal enhancement and fibroglandular tissue on MRI in women with triple negative breast cancer (TNBC) compared to women with non-triple negative breast cancer (non-TNBC). METHODS:The institutional Breast Cancer Database was queried to identify the clinicopathologic and imaging characteristics among women who underwent mammography and breast MRI between 2010-2018. Statistical analyses included Pearson's Chi Square, Wilcoxon Rank-Sum and logistic regression. RESULTS:Of 2995 women, 225 (7.5 %) had TNBC with a median age of 60 years (23-96) and median follow-up of 5.69 years. Compared to women with non-TNBC, TNBC was associated with African-American race 36/225 (16 %), BRCA1,2 positivity 34/225 (15.1 %), previous history of breast cancer 35/225 (15.6 %), presenting on breast exam 126/225 (56 %) or MRI 13/225 (5.8 %), palpability 133/225 (59.1 %), more invasive ductal carcinoma (IDC) 208/225 (92.4 %), higher stage (stage III) 37/225 (16.5 %), higher grade (grade 3) 186/225 (82.7 %) (all p < 0.001), lower mammographic breast density (MBD) 18/225 (8 %) (p = 0.04), lower fibroglandular tissue (FGT) 17/225 (7.6 %) (p = 0.01), and lower background parenchymal enhancement (BPE) 89/225 (39.8 %) (p = 0.02). Nine of 225 (4 %) women with TNBC experienced recurrence with no significant association with MBD, FGT, or BPE. There was no significant difference in median age of our TNBC and non-TNBC cohorts. CONCLUSIONS:The higher proportion of women with lower MBD, FGT and BPE in women with TNBC suggests that MBD, amount of FGT and degree of BPE may be associated with breast cancer risk in women with TNBC.

Introduction The use of neoadjuvant chemotherapy (NAC) has enabled more patients to be eligible for breast-conservation surgery (BCS). Achieving negative lumpectomy margins, however, may be challenging after NAC due to changes in tissue density and the potential for residual carcinoma to be scattered in the tumor bed. Data regarding patients undergoing BCS after NAC has shown variable re-excision rates. MarginProbe (Dune Medical Devices Ltd, Israel) has been shown to identify positive resection margins intraoperatively and reduce the number of re-excisions in primary BCS, but has not been previously studied in NAC+BCS cases. The purpose of our study was to investigate the clinicopathologic characteristics, including margin status, and re-excision rates in patients who had NAC+BCS with and without the use of MarginProbe at our institution. Methods The Institutional Breast Cancer Database was queried for all patients who received NAC and had subsequent BCS from 2010-2019. Variables of interest included demographics, tumor characteristics, pathologic complete response (pCR), MarginProbe use, treatment and outcomes. Statistical methods included Chi-Square and Fisher's Exact tests. Results A total of 214 patients had NAC in our study population, and 61 (28.5%) of those patients had NAC+BCS. The median age was 53.5 years. A total of 19 (31.1%) patients had pCR. Of the remaining 42 patients, 9 (21%) had close or positive margins that required re-excision. Re-excision was associated with a larger residual tumor size (p=0.025), and ER-positive disease before NAC (p=0.041). Breast density and the presence of palpable disease did not differ between the groups. MarginProbe use was associated with a lower re-excision rate in patients with NAC+BCS (6% vs. 31%, respectively). Conclusion The use of NAC may enable more patients to undergo BCS. Patients with larger residual tumor burden and ER-positive disease were at an increased risk for inadequate margins at the time of surgery. The use of Margin-Probe was associated with a lower re-excision rate. Techniques to reduce the need for re-excision will support the use of BCS after NAC