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

DCIS is a non-obligate precursor in which epithelial cells with features of cancer reside in and expand otherwise normal appearing mammary ducts and lobules. DCIS increases the relative risk of developing invasive breast cancer (IBC) by up to 10 fold. Treatment of DCIS includes breast conserving surgery (BCS), tumor margins permitting, followed by radiation, or mastectomy. Recently we found that pasireotide, a somatostatin analog inhibitor of IGF-I, was effective in reducing cell proliferation and increasing apoptosis in patients with atypical hyperplasia (AH) and or proliferative disease of the breast. At present there are no recognized medical treatments for DCIS. Here we raise the possibility that pasireotide might also be an effective therapy for some DCIS. To make this determination, 8 patients previously diagnosed with DCIS were treated with pasireotide, 600mug twice daily subcutaneously for a period of 20 days. Lesion size was assessed on DCE-MRIs in 3 planes before and after treatment. Of the eight, two had lesions characterized as low grade DCIS on core biopsy, 4 had intermediate or intermediate to high grade lesions, and two had high grade lesions. After treatment they all had surgical excision biopsies. We also measured proliferation and apoptosis to assess effects of pasireotide by expression of Ki67 and caspase 3. To confirm that the effect of pasireotide was mediated via the IGF-I pathway, p-AKT and p-ERK 1/2 were evaluated. Core and excision samples from 14 untreated patients where used as control. Overall, treatment with pasireotide reduced DCIS lesion size by >=30% according the RECIST criteria in 4 of 8 patients, as measured by DCE-MRI. Of those, pathology of the surgical excision confirmed that there was no remaining DCIS tissue in the two patients with low grade disease. The two additional lesions that were reduced in size one was intermediate to high grade and the other a high grade DCIS. The remaining 4 patients had tumors that were stable in size. Pasireotide reduced cell proliferation and significantly increased apoptosis in the DCIS lesions. While DCIS is less responsive to pasireotide than AH and proliferative disease, it may nevertheless provide a window of opportunity for treatment and possibly eradication of some low grade or higher grade DCIS as well. The main side effect included hyperglycemia, intestinal discomfort and rash or redness at the injection area. Our data show that hyperglycemia disappears relatively fast after ending treatment with pasireotide. In conclusion, treatment with pasireotide eliminated 2 low grade DCIS lesions, shrunk two higher grade ones and also decreased proliferation and increased apoptosis. Additional evidence in a larger number of patients will be necessary

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.

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

Background: To examine the trends in clinicopathologic features, treatment, and survival of male breast cancer (MBC), utilizing the National Cancer Data Base (NC

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.