Faculty Bibliography

Purpose: Well-established risk factors for breast cancer include family history (FH), BRCA mutations and biopsies with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Several mathematical models, including the Gail and Tyrer-Cuzick models, have been developed to quantify a patient's risk for developing breast cancer. These models all differ in the list of variables and risk factors that are included in risk calculations. As a result, there is no single model that best estimates the risk for all high risk patients. The purpose of this study is to examine the application of the Gail and Tyrer-Cuzick models in a contemporary cohort of women who are enrolled in a comprehensive high-risk breast cancer database. Methods: The institutional High Risk Breast Cancer Consortium (HRBCC) was established in January 2011. Patients who were at high risk for developing breast cancer based on family history (maternal and paternal), BRCA mutations, AH and LCIS were eligible to enroll in the database. The following variables were included in this analysis: age, family history, genetic testing results, reproductive history, AH, LCIS, Gail and Tyrer-Cuzick scores, risk reduction strategies, and outcomes. All clinical data are obtained from detailed questionnaires filled out by patients who consent to the database studies and from a review of electronic medical records. Descriptive statistics were performed. Results: A total of 604 women were enrolled between 1/2011-2/2016. The median age was 51 years (range 20-87). The majority of women were Caucasian (83%). 52% had a strong FH, 13% were BRCA1 and 2 positive, 48% had AH, and 22% had LCIS. 47% of patients in our high risk program were not eligible for Gail model analysis (age <35 years, BRCA mutation carriers, history of LCIS). Only one patient was not eligible for Tyrer-Cuzick model calculation based on age >84 years. For patients who were eligible for Gail model analysis, 26 (8%) women did not meet criteria (5-year risk >=1.7%) for being designated as high risk for breast cancer. 34 (6%) of our patients did not have Tyrer- Cuzick scores over 20% (criterion for high risk). Notably, majority of the patients (69%) who were not defined as high-risk based on Gail scores >=1.7% or Tyrer-Cuzick scores >=20%, had a strong family history of breast cancer. Only 14 (2%) patients developed breast cancer during our study period, and the majority (93%) of the cancers were early stage (stage 0, I). Conclusions: Our institutional high-risk database includes women who are at high risk based on well-established risk factors for developing breast cancer (FH, BRCA mutations, AH, LCIS). Current mathematical models including the Gail and Tyrer-Cuzick models did not capture the increased risk of breast cancer in 8% of our population. While the models are helpful, in clinical practice they are not necessarily the be-all and end-all. Using heuristic risk factors is more time efficient and comprehensive risk assessment allows the clinicians and patients to better understand risk. Identifying patients as high risk and enrolling them in a high-risk database and program allow us to capture long term follow up, recommend surveillance for early detection, and better understand the effectiveness of different risk reduction and management strategies for this population

Background/Objective: In a time when clinicians are attempting to identify a cohort of patients with ductal carcinoma in situ (DCIS) who will benefit most from post-lumpectomy radiation therapy (RT), tools have been developed to quantify patients' risk for in-breast recurrence. These tools have not yet been integrated into standard use. At our institution, the recommendation for RT after lumpectomy for DCIS is guided by established clinicopathologic factors and reviewed by a multi-disciplinary group. The purpose of this study was to compare the clinicopathologic characteristics and outcomes of postlumpectomy DCIS patients with and without RT at our institution. Methods: The Institutional Breast Cancer Database was queried for all women who were diagnosed with DCIS from 2010-2016. Variables included age, method of presentation, risk factors, tumor and treatment characteristics, and ipsilateral breast tumor recurrence (IBTR). Statistical analyses included Pearson's Chi Square and Fisher's Exact Tests. Results: Of 480 women with pure DCIS and no prior history of breast cancer, 350 (73%) underwent lumpectomy. The median follow-up was 4 years, and median age was 60 years. Two hundred thirty-six (67%) women underwent RT following lumpectomy. Compared to women who did not undergo RT, these women were younger (p=0.003), had larger tumor size (p=0.0008), higher grade (p=0.0006), and comedo features (p=0.03). Women who underwent post-lumpectomy RT had an IBTR rate of 2% vs. 4% (p=0.32) with no RT. The 10 patients with early IBTR in both groups were younger (median age 54 years), and all had intermediate- or high-grade DCIS. Of the 114 patients who did not undergo adjuvant RT, 70 (61%) met the RTOG 9804 criteria for omission of adjuvant RT. Of the 44 patients who did not receive adjuvant RT and did not meet RTOG 9804 criteria, 20 declined RT, and 24 were not referred. Conclusions: Within a relatively short follow-up period, we found a very low overall rate (3%) of IBTR for our patients who underwent lumpectomy for DCIS. These results are consistent with previously published trials on post-lumpectomy RT in DCIS. RT at our institution is recommended based on wellestablished clinicopathologic factors and multidisciplinary care. Considering the low recurrence rates, we recommend continuing the current trend of using published criteria and multidisciplinary review. It remains to be seen to what extent the newly developed recurrence tools, such as Oncotype DX Breast DCIS ScoreTM, will improve upon these short-term recurrence rates

Oncotype DX recurrence score (ODX) can predict risk of invasive breast cancer recurrence and benefit of chemotherapy. Literature is limited on the relationship of ODX and race in women with hormone receptor positive and node negative/positive disease. Our study examines the relationship between race and clinical characteristics within a population of highly screened women with newly diagnosed breast cancer. The institutional Breast Cancer Database was queried for patients with newly diagnosed breast cancer between January2010 and March2015. We analyzed clinical and tumor characteristics including ODX. Statistical analyses included Pearson's Chi-Square and Fisher's Exact Tests. There were 2,092 women in our study cohort. The majority had college-level education (84%), regular screening (78%), and clinical breast exams (88%). The majority had invasive ductal carcinoma (IDC) (62%), early stage (0, I, II) tumors (93%), ER+ (84%), PR+ (71%), Her2 negative (86%), and node negative disease (83%). There was a significantly higher proportion of later stage disease among African-Americans (p = 0.001) and Asians (p = 0.006) and more triple negative breast cancers among African-Americans (p < 0.0001). A majority of patients had a low ODX (56%). While ODX was not different among the race categories (p = 0.97), there were significant racial differences in Ki-67 (p < 0.0001). In a population of highly screened women, differences were found between races regarding tumor histology. No statistical difference between race and ODX was noted, but there were racial differences in Ki67. Therefore we recommend that further research be focused on refining management algorithms by ethnicity.

Introduction: The treatment of ductal carcinoma in situ (DCIS) remains controversial, and treatment approaches include surgery, post-lumpectomy radiation therapy (RT), and/or hormonal therapy for prevention of recurrent disease. These decisions may be particularly difficult for patients with minimal disease. There is a dearth of information regarding patients who have been diagnosed with DCIS on core-needle biopsy (CNB) who have no residual disease in the area at surgery. The purpose of this study was to explore the frequency of this presentation and short-term outcomes in these patients. Methods: Our institutional Breast Cancer Database was queried for all women who were diagnosed with pure DCIS from 2010-2016. Variables included age, method of presentation, risk factors, tumor characteristics and outcomes. Statistical analyses included Pearson's Chi Square and Fisher's Exact Tests. Results: Out of a total of 548 patients with pure DCIS, 55 (10%) had DCIS on CNB alone with no residual in the surgical specimen. The median age was 55 years (range 36-83). Of the patients with DCIS on CNB alone, 6 (11%) were treated with mastectomies. 14 (25%) had lumpectomy and RT, while 35 (64%) had lumpectomy without RT. The median follow up was 4 years. There were three ipsilateral recurrences in women who were treated by lumpectomy alone. One of these recurrences was invasive carcinoma, and the other two were recurrent pure DCIS. None of the patients who recurred had taken hormonal therapy. There were no contralateral second primaries detected in the study period in this cohort. Conclusions: Despite the minimal extent of disease exhibited in these cases, 3 of 35 patients with DCIS on CNB with no residual disease at surgery and no RT had ipsilateral recurrence at a median follow up of 4 years. These data suggest that even minimal DCIS represents a significant risk of recurrence to the patient. Additional information provided by genomic analysis may better stratify the risk for recurrence in this group and help identify the population that would most benefit from post-lumpectomy RT

PURPOSE: The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC) and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. METHODS: Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. RESULTS: Out of a total of 1964 patients, 190 (10%) patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p = 0.0003) compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p < 0.0001, p = 0.0007). A prior history of breast cancer was significantly associated with TNBC (p = 0.0003). There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. CONCLUSIONS: We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

PURPOSE: The purpose was to evaluate the relationship between body mass index (BMI), mammographic breast density, magnetic resonance (MR) background parenchymal enhancement (BPE), and MR fibroglandular tissue (FGT) in women with breast cancer. METHODS: Our institutional database was queried for patients with preoperative mammography and breast MR imaging. RESULTS: There were 573 women eligible for analysis. Elevated BMI was associated with advanced stage of disease (P=.01), lower mammographic density (P<.0001), lower FGT (P<.0001), higher BPE (P=.005), and nonpalpable lesions (P=.04). CONCLUSIONS: Higher BMI was associated with decreased breast density and FGT. Higher BMI was also associated with advanced stage disease and nonpalpable tumors on clinical exam.

OBJECTIVES: This study was a multicenter evaluation of the SAVI SCOUT(R) breast localization and surgical guidance system using micro-impulse radar technology for the removal of nonpalpable breast lesions. The study was designed to validate the results of a recent 50-patient pilot study in a larger multi-institution trial. The primary endpoints were the rates of successful reflector placement, localization, and removal. METHODS: This multicenter, prospective trial enrolled patients scheduled to have excisional biopsy or breast-conserving surgery of a nonpalpable breast lesion. From March to November 2015, 154 patients were consented and evaluated by 20 radiologists and 16 surgeons at 11 participating centers. Patients had SCOUT(R) reflectors placed up to 7 days before surgery, and placement was confirmed by mammography or ultrasonography. Implanted reflectors were detected by the SCOUT(R) handpiece and console. Presence of the reflector in the excised surgical specimen was confirmed radiographically, and specimens were sent for routine pathology. RESULTS: SCOUT(R) reflectors were successfully placed in 153 of 154 patients. In one case, the reflector was placed at a distance from the target that required a wire to be placed. All 154 lesions and reflectors were successfully removed during surgery. For 101 patients with a preoperative diagnosis of cancer, 86 (85.1 %) had clear margins, and 17 (16.8 %) patients required margin reexcision. CONCLUSIONS: SCOUT(R) provides a reliable and effective alternative method for the localization and surgical excision of nonpalpable breast lesions using no wires or radioactive materials, with excellent patient, radiologist, and surgeon acceptance.

Introduction: Ductal carcinoma in situ (DCIS) and invasive breast cancer have long been viewed as representing two points on the spectrum of one disease. A recent study published by Narod et al. found that women diagnosed with DCIS who developed an invasive recurrence were 18.1 times more likely to die of breast cancer than women who did not. In light of this controversial topic, we investigated DCIS in a contemporary cohort of newly diagnosed women at our institution spanning a five year period. Methods: The institutional Breast Cancer Database was queried for all women with newly diagnosed breast cancer from 2010-2015. Variables included age, race, body mass index (BMI), risk factors, tumor characteristics and outcomes. Statistical analyses included Pearson's Chi Square and Fisher's Exact Tests. Results: Out of a total of 2190 patients, 475 (22%) had pure DCIS while 1715 (78%) had invasive cancer. The median follow up was 3 years. The median age was 59 years (range 22-95). Of the patients with invasive cancer, 36 (2%) had any recurrence. Similarly, of the patients with DCIS, 9 (2%) developed recurrent disease (ipsilateral or contralateral), with 4 patients diagnosed with invasive recurrence (44%). Of the 36 recurrences in patients with invasive cancer, 33% presented with chest wall or distant metastasis. Patients with pure DCIS had a slightly higher proportion of African Americans and Hispanics (11% v. 8%) and higher proportion of women with BMI>30 who developed an invasive recurrence (78% v. 50%). All recurrences in the pure DCIS cohort were detected by routine screening surveillance, with a majority detected by mammography (89%). Conclusions: Within a relatively short follow up period, we found that the rates of in-breast recurrences were the same in women with pure DCIS compared to women with invasive breast cancer. Also, 44% of women developed invasive breast cancer recurrence after an initial DCIS diagnosis, potentially altering their long term survival. These findings suggest that women with all breast cancers, including DCIS, requires intensive surveillance after initial treatment, as consequences of delayed diagnosis may impact on their long term survival

BACKGROUND: Despite current advances in cancer treatment, many breast cancer survivors still face long-term post-operative challenges as a result of suffering from daily pain and other distressing symptoms related to lymphedema, ie, abnormal accumulation of lymph fluid in the ipsilateral upper limb or body. Grounded in research-driven behavioral strategies, The-Optimal-Lymph-Flow is a unique Web- and mobile-based system focusing on self-care strategies to empower, rather than inhibit, how breast cancer survivors manage daily pain and symptoms. It features a set of safe, feasible, and easily-integrated-into-daily-routine exercises to promote lymph flow and drainage, as well as guidance to maintain an optimal body mass index (BMI). OBJECTIVE: To conduct a randomized clinical trial (RCT) to evaluate the efficacy of the Web- and mobile-based The-Optimal-Lymph-Flow system for managing chronic pain and symptoms related to lymphedema. The primary outcome includes pain reduction, and the secondary outcomes focus on symptom relief, limb volume difference by infra-red perometer, BMI, and quality of life (QOL) related to pain. We hypothesize that participants in the intervention group will have improved pain and symptom experiences, limb volume difference, body mass index, and QOL. METHODS: A parallel RCT with a control-experimental, pre- and post-test, repeated-measures design is used in this study. A total of 120 patients will be randomized according to the occurrence of pain. Participants will be recruited face-to-face at the point of care during clinical visits. Participants in the intervention group will receive the Web- and mobile-based The-Optimal-Lymph-Flow intervention and will have access to and learn about the program during the first in-person research visit. Participants in the control group will receive the Web- and mobile-based Arm Precaution program and will have access to and learn about the program during the first in-person research visit. Participants will be encouraged to enhance their learning by accessing the program and following the daily exercises during the study period. Participants will have monthly online self-report of pain and symptoms at 4 and 8 weeks post-intervention. During the two in-person research visits prior to and 12 weeks post-intervention, participants will be measured for limb volume difference, BMI, and complete self-report of pain, symptoms, self-care behaviors, and QOL. RESULTS: This trial is currently open for recruitment. The anticipated completion date for the study is July 2017. The primary endpoint for the study is absence or reduction of pain reported by the participants at week 12 post-intervention. CONCLUSIONS: The-Optimal-Lymph-Flow is a unique Web- and mobile-based self-care and patient-reported outcome system designed to effectively help women treated for breast cancer manage daily pain and symptoms related to lymphedema. Patients learn self-care strategies from a Web- and mobile-based program and track their symptoms. The RCT will directly benefit all women treated for breast cancer who suffer from or at risk for pain and symptoms related to lymph fluid accumulation. TRIAL REGISTRATION: Clinicaltrials.gov NCT02462226; https://clinicaltrials.gov/ct2/show/NCT02462226 (Archived by WebCite at http://www.webcitation.org/6du4IupG5).