Faculty Bibliography

This pilot, double-blind, randomized, placebo-controlled study is aimed at evaluating the effectiveness of low-level laser therapy (LLLT) as a complementary treatment to complete decongestive therapy (CDT) treating lymphedema among breast cancer patients for 12 months post-intervention. Study population was breast cancer patients who were diagnosed and referred to lymphedema clinic for CDT. Participants (n = 22) were randomized and assigned into either an active laser intervention group or an inactive laser placebo-control group. Active LLLT was administered to participants twice a week at the beginning of each CDT session. Outcome measures included lymphedema symptoms, symptom distress, and limb volume by an infrared perometer. Participants in the active and placebo laser groups were comparable in demographic and clinical predictors of lymphedema. In comparison with the placebo group (83.3%), significantly fewer participants in the active laser group (55.6%) reported more than one lymphedema symptom (p = 0.012) at 12 months post-intervention. Significantly, more patients in the active laser group (44.4%) reported less than two impaired limb mobility symptoms in comparison with the placebo group (33.3%) at 12 months post-intervention (p = 0.017). The active laser group had statistically significant improvements in symptom distress of sadness (p = 0.005) from 73 to 11% and self-perception (p = 0.030) from 36 to 0% over time from baseline to 12-months post-intervention. There was no significant reduction in limb volume. Findings of the trial demonstrated significant benefits of complementary LLLT for relieving symptoms and improvement of emotional distress in breast cancer patients with lymphedema.

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

Background/Objective: According to the US Census data, adoptees account for 2.5% of the US population (7.8 million). However, the number of adoptees diagnosed with breast cancer is unknown. Many adoptees face the unique challenge of lacking access to their family health history and limited access to screening and risk-reducing interventions. This important health disparity among adoptees has raised awareness in the importance genetic testing (GT), although it does not completely fill the disparity gap of lacking family history. The National Society of Genetic Counselors (NSGC) released an updated position statement in 2018 that supported the use of genetic testing, including genome-wide testing, for adopted adults. The purpose of our study was to investigate the adoptees in a cohort of newly diagnosed breast cancers and to look at the clinicopathologic characteristics, including the uptake of genetic testing, and to see if there were any differences compared to the non-adopted breast cancer patients.
Method(s): The Institutional Breast Cancer Database was queried for all patients diagnosed with breast cancer between 2010-2018. Variables of interest included adoption status and other clinical and tumor characteristics. Statistical analyses included descriptive and Pearson's Chi Square tests.
Result(s): Out of 3,507 patients newly diagnosed with breast cancer, 34 (1%) were adopted. The median age at diagnosis for the total population was 60 years (range 23-96 years). When we compared the adopted and non-adopted groups, age was not statistically different (p=0.817); race was not statistically different (p=0.077), although there was a slightly higher proportion of Hispanics in the adopted vs. non-adopted cohorts (15% vs. 6%). When we looked at genetic testing, 56% of the adoptees were tested compared to 45% of non-adopted patients, but this was not significant (p=0.229). All adopted patients were negative for BRCA1/2 and other mutations. Interestingly, 29% of the adopted patients had a first-degree relative with breast cancer compared to 31% of non-adopted patients. The tumor characteristics between the adopted and non-adopted cohorts were not statistically different. The majority had early stage (Stage 0, I, II) disease (93%), invasive ductal and lobular carcinoma (73%), and ER/PR-positive and HER2-negative cancers (71%).
Conclusion(s): In a contemporary cohort of newly diagnosed breast cancer patients, we found no difference between the adopted and non-adopted patients based on age, race, education, and tumor characteristics. However, there was a higher proportion of adopted patients who got genetic testing compared to the non-adopted cohort. Both groups also reported a similar proportion of having a first-degree relative with breast cancer, which indicates the increased communication between the adoptees and their biological parents

INTRODUCTION/BACKGROUND:Ductal carcinoma in situ (DCIS) with foci of invasion measuring ≤ 1 mm (DCISM), represents < 1% of all invasive breast cancers. Sentinel lymph node biopsy (SLNB) has been a standard component of surgery for patients with invasive carcinoma or extensive DCIS. We hypothesize that selective performance of SLNB may be appropriate given the low incidence of sentinel node (SN) metastasis for DCISM. We investigated the clinicopathologic predictors for SN positivity in DCISM, to identify which patients might benefit from SLNB. METHODS:A retrospective review of the National Cancer Database was performed for cases from 2012 to 2015. Clinical and tumor characteristics, including SN results, were evaluated, and Pearson's Chi square tests and logistic regression were performed. RESULTS:Of 7803 patients with DCISM, 306 (4%) had at least one positive SN. Patients with positive SNs were younger, more often of Black race, had higher-grade histology and larger tumor size, and were more likely to have lymphovascular invasion (LVI; all p < 0.001). In an adjusted model, the presence of LVI was associated with the highest odds ratio (OR) for node positivity (OR 8.80, 95% confidence interval 4.56-16.96). CONCLUSIONS:Among women with DCISM, only 4% had a positive SN. Node positivity was associated with more extensive and higher-grade DCIS, and the presence of LVI was strongly correlated with node positivity. Our data suggest that LVI is the most important factor in determining which patients with DCISM will benefit from SN biopsy.

BACKGROUND:Growing evidence suggests that the tumor immune microenvironment influences breast cancer development and prognosis. Density of tumor-infiltrating lymphocytes (TILs) within invasive breast cancer is correlated with response to therapy, especially in triple-negative disease. The clinical relevance and outcomes of TILs within ductal carcinoma in situ (DCIS) are less understood. METHODS:Our institutional database of 668 patients with pure DCIS from 2010 to 2018 was queried. TILs were evaluated by International TILs Working Group guidelines. Percentage of TILs was assessed from the densest focus (hotspot) in one high-power field of stroma touching the basement membrane. Statistical methods included cluster analyses (to define sparse versus dense TILs), logistic, and Cox regression models. RESULTS:Sixty-nine patients with DCIS and TILs were evaluated, of whom 54 (78%) were treated by breast-conserving surgery. Thirteen (19%) patients had ipsilateral recurrence. Each recurrence (n = 13) was matched to four controls (n = 56) based on date of surgery. Median follow-up was 6.7 years. TILs were defined as sparse (< 45%) or dense (≥ 45%). Dense TILs were associated with younger age (p = 0.045), larger tumor size (p < 0.001), high nuclear grade (p = 0.010), comedo histology (p = 0.033), necrosis (p = 0.027), estrogen receptor (ER) negativity (p = 0.037), and ipsilateral recurrence (p = 0.001). Nine patients with dense TILs had mean time to recurrence of 73.5 months compared with four patients with sparse TILs with mean time to recurrence of 97.9 months (p = 0.003). CONCLUSIONS:Dense TILs were significantly associated with age, tumor size, nuclear grade, comedo histology, necrosis, and ER status and was a significant predictor of recurrence in patients with pure DCIS.

Disparities in breast cancer treatment have been documented in young and underserved women. This study aimed to determine whether surgical disparities exist among young breast cancer patients by comparing cancer treatment at a public safety-net hospital (BH) and private cancer center (PCC) within a single institution. This was a retrospective study of young women (<45) diagnosed with invasive breast cancer (stage I-III) from 2011-2016. Patient information was abstracted from the breast cancer database at BH and PCC. Demographic variables, surgery type, method of presentation, and stage were analyzed using Pearson's chi-square tests and binary logistic regression. A total of 275 patients between ages 25-45 with invasive breast cancer (Stage I-III) were included in the study. There were 69 patients from BH and 206 patients from PCC. At PCC, the majority of patients were Caucasian (68%), followed by Asian (11%), Hispanic (10%), and African American (8.7%). At BH, patients were mostly Hispanic (47.8%), followed by Asian (27.5%), and African American (10.1%). At PCC, 82% had a college/graduate degree versus 18.6% of patients at BH (P < 0.001). All patients at PCC reported English as their primary language versus 30% of patients at BH (P < 0.001). Patients at PCC were more likely to present with lower stage cancer (P = 0.04), and less likely to present with a palpable mass (P = 0.04). Hospital type was not a predictor of receipt of mastectomy (P = 0.5), nor was race, primary language, or education level. Of patients who received a mastectomy, 87% at BH and 76% at PCC had immediate reconstruction. Surgical management of young women with breast cancer in a public hospital versus private hospital setting was equivalent, even after controlling for race, primary language, stage, and education level.

BACKGROUND:Oncologic outcomes with nipple-sparing mastectomy (NSM) continue to be established. We examine oncologic trends, outcomes, and risk factors, including tumor-to-nipple distance (TND), in therapeutic NSMs. METHODS:Demographics, outcomes, and overall trends for all NSMs undertaken for a therapeutic indication from 2006 to 2017 were analyzed. Oncologic outcomes were investigated with specific focus on recurrence and associated factors, including TND. RESULTS:A total of 496 therapeutic NSMs were performed with average follow-up time of 48.25 months. The most common tumor types were invasive carcinoma (52.4%) and ductal carcinoma in situ (50.4%). Sentinel lymph node sampling was performed in 79.8% of NSMs; 4.1% had positive frozen sentinel lymph node biopsies while 15.7% had positive nodal status on permanent pathologic examination. The most common pathologic cancer stage was stage IA (42.5%) followed by Stage 0 (31.3%).Per NSM, the rate of local recurrence was 1.6% (N=8); the rate of regional recurrence was 0.6% (N=3). In all, 171 NSMs had magnetic resonance imaging available to assess tumor-to-nipple distance (TND). NSMs with TND ≤1 centimeter (25.0% versus 2.4%, p=0.0031/p=0.1129) and ≤2 centimeters (8.7% versus 2.0%; p=0.0218/p=0.1345) trended to higher rates of locoregional recurrence. In univariate analysis, TND ≤1 centimeter was the only significant risk factor for recurrence (OR=13.5833, p=0.0385). No factors were significant in regression analysis. CONCLUSIONS:In this group of early stage and in situ breast carcinoma, therapeutic NSM appears oncologically safe with a locoregional recurrence rate of 2.0%. Tumor-to-nipple distances of ≤1 centimeter and ≤2 centimeters trended to higher rates of recurrence.

BACKGROUND:A positive lumpectomy margin after breast-conserving surgery (BCS) is a significant predictor for ipsilateral cancer recurrence. The MarginProbe, a Food and Drug Administration (FDA)-approved device for intraoperative assessment of lumpectomy margins, is associated with a reduction in re-excision surgery. This study aimed to evaluate the relationship of mammographic breast density (MBD) and clinicopathologic characteristics with margin status in women undergoing BCS with the MarginProbe. METHODS:The institutional database was queried for patients with breast cancer who had BCS with the MarginProbe from 2013 to 2017. Clinicopathologic characteristics were collected. The study defined MBD as less dense (Breast Imaging Reporting and Data System [BI-RADS] A and B) and more dense (BI-RADS C and D). A positive margin was defined as smaller than 1 mm. Pearson Chi square and uni- and multivariate logistic regression were performed. RESULTS:Of 1734 patients, 341 met the study criteria. The median patient age was 63 years. The patients with higher mammographic density were younger (p < 0.0001) and had a lower body mass index (BMI) (p < 0.0001). The patients with higher MBD were more likely to present with a palpable mass (p = 0.0360). Of the 341 patients, 135 (39.6%) had one or more positive margins on the main specimen, and 101 (74.8%) were converted to final negative margins after the MarginProbe directed re-excisions. Positive final margins were associated with larger tumor size (p = 0.0242) and more advanced stage of disease at diagnosis (p = 0.0255). CONCLUSIONS:In this study of patients undergoing BCS, breast density was not correlated with the likelihood of a positive margin. The presence of positive final lumpectomy margins was associated with older age and more extensive disease.

INTRODUCTION/BACKGROUND:Accurate assessment of estrogen receptor (ER) expression is crucial to ensure that patients with early breast cancer are accurately identified for appropriate treatment with endocrine therapy. Reverse transcriptase polymerase chain reaction (RT-PCR), compared with immunohistochemistry (IHC), may provide a more precise indication of ER status. Data were pooled and analyzed from two independent, but similarly designed, studies that examined ER status by IHC and the 21-gene Recurrence Score that employs RT-PCR-based methodology. METHODS:Tumor tissue from patients with early stage breast cancer where ER status could be determined by both IHC and RT-PCR was included. ER status by IHC staining was defined as ER-negative (< 1%), ER-low+ (1-10%), or ER+ (> 10%). ER status by RT-PCR was defined as ER-negative (≤ 6.5) or ER+ (> 6.5). Recurrence Score results from the 21-gene assay were reported on a continuous scale from 0 to 100. A sub-analysis examined the association between ER expression (Allred score 2-7) and response to a 14-day pre-surgery pulse with an aromatase inhibitor. A separate sub-analysis examined the association between ER expression and human epidermal growth factor receptor 2 (HER2) expression. RESULTS:Tumor specimens from 192 patients (aged 25-92 years) were included in the pooled analysis. Correlation between IHC- and RT-PCR-measured ER was strong for IHC-defined ER-negative and ER+ samples (r = 0.646 [95% CI 0.553-0.720]). There was 100% concordance for ER+ tumors; however, 56% of the ER-low+ tumors were negative by RT-PCR. Allred score correlated better with ER status measured by RT-PCR at pre-treatment (r = 0.83) than at post-treatment (r = 0.76). The majority (77%) of ER-negative and ER-low+ tumors were HER2-negative. CONCLUSIONS:RT-PCR provided a more accurate assessment of ER expression in patients with ER-low+ tumors, and data support dual testing for patients with ER-low+ status to ensure appropriate treatment planning as it pertains to endocrine therapy. FUNDING/BACKGROUND:Genomic Health, Inc.

Positron emission tomography / magnetic resonance imaging (PET/MRI) is an emerging imaging technology that allows for the acquisition of multiple MRI parameters simultaneously with PET data. In this review, we address the technical requirements of PET/MRI including protocols and tracers, the potential of integrated localized breast PET/MRI exams, and possible applications of whole-body PET/MRI in breast cancer patients. Currently, PET/MRI can be performed on sequential and integrated PET/MRI scanners but, as not all practices can access these dedicated machines, several studies look at PET and MRI exams that are performed separately on separate scanners within a short time frame. This practice likely provides similar clinical data, although exact colocalization for iso-voxel analysis, currently performed only in research, is not possible. In PET/MRI, the MRI sequences are flexible and can be customized according to the aim of the exam. The most commonly used radiotracer is ¹⁸ F-FDG; however, tracers that image hypoxia and drug targets such as estrogen receptors and HER2 are in development and may increase the utility of PET/MRI. For dedicated breast PET/MRI, a potential advantage over standard breast MRI alone may be the complementary sensitivities of MRI for extent of disease within the breast and PET for axillary and internal mammary nodal metastases. Moreover, layers of multiparametric MRI and PET metrics derived from the index lesion are being investigated as predictors of response to neoadjuvant therapy. These data may eventually be able to be quantified and mined in a way that furthers radiomics and also precision medicine. Finally, in whole-body imaging of breast cancer patients, single-institution studies have found that PET/MRI detects more metastases than PET at about half the radiation dose, although a survival benefit has not been shown. For now, whole-body PET/MRI in breast cancer patients may be most relevant for young patients who may undergo serial surveillance exams.