Jennifer Chun

Incidence and Clinical Significance of Lymph Node Metastasis Detected by Cytokeratin Immunohistochemical Staining in Ductal Carcinoma In Situ

BackgroundThis study explored the long-term prognosis of patients with ductal carcinoma-in-situ (DCIS) and lymph node metastasis detected by cytokeratin immunohistochemical stains (CK-IHC).MethodsUsing the Columbia University breast cancer database, we identified all DCIS patients who had eight or more axillary nodes dissected and free of metastasis. Five-micrometer sections from all paraffin blocks containing lymph node tissue were stained with an anticytokeratin antibody cocktail (AE1/AE3 and KL1). The results of the CK-IHC and updated database were anonymized and merged. Survival of CK-IHC–positive and –negative patients was compared by using Kaplan-Meier curves and log-rank tests.ResultsCK-IHC was performed on 301 DCIS patients, who had an average of 16.7 axillary nodes dissected. Eighteen (6%) of 301 patients tested positive by CK-IHC. Seventy patients with bilateral breast cancer and 2 patients without any follow-up data were excluded, for a final study population of 229 patients. Among the 216 patients with negative CK-IHC, 18 patients died, compared with 1 of 13 patients with positive CK-IHC. The median follow-up for the study group was 127 months. Kaplan-Meier overall and breast cancer–specific survival estimates were similar for CK-IHC–positive and –negative patients (P = .81 and P = .73, respectively).ConclusionsCK-IHC increases the incidence of positive nodes by 6% in DCIS patients. A positive node by CK-IHC does not seem to affect survival in these patients. These results raise concerns regarding the clinical significance of positive nodes by CK-IHC in DCIS patients.

Screening prior to Breast Cancer Diagnosis: The More Things Change, the More They Stay the Same

Purpose. In November 2009, the U.S. Preventative Service Task Force (USPSTF) revised their breast cancer screening guidelines. We evaluated the pattern of screening subsequent to the altered guidelines in a cohort of women. Methods. Our database was queried for the following variables: age, race, method of diagnosis, mass palpability, screening frequency, histology, and stage. Statistical analyses were performed using Pearsons chi-square and Fishers exact tests. Results. 1112 women were diagnosed with breast cancer from January 2010 to 2012. The median age at diagnosis was 60 years. Most cancers were detected on mammography (61%). The majority of patients had invasive ductal carcinoma (59%), stage 0 (23%), and stage 1 (50%) cancers. The frequency of screening did not change significantly over time (P = 0.30). However, nonregular screeners had an increased risk of being diagnosed with later stage breast cancer (P < 0.001) and were more likely to present with a palpable mass compared to regular screeners (56% versus 21%; P < 0.001). Conclusions. In our study, screening behavior did not significantly change in the years following the USPSTF guidelines. These results suggest that women who are not screened annually are at increased risk of a delay in breast cancer diagnosis, which may impact treatment options and outcomes.

Clinical Characteristics in Patients with Triple Negative Breast Cancer

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.

Race, Oncotype DX, and other characteristics in a highly screened population.

32 Background: Oncotype DX breast cancer 21 gene assay recurrence score (RS) is used to predict disease recurrence and response to chemotherapy in order to offer patients the highest treatment benefit to risk ratio. There is a dearth of literature on the relationship of Oncotype RS and race in women with hormone receptor positive and node negative/positive disease. The purpose of this study was to investigate the relationship of race and clinical characteristics (including Oncotype RS) in an insured population of highly screened women with newly diagnosed breast cancer. METHODS The Breast Cancer Database of our institution was queried for patients who were newly diagnosed with breast cancer. We looked at demographics, risk factors, tumor characteristics, and Oncotype RS. Statistical analyses included Pearsons Chi-Square and Fishers Exact Tests. RESULTS A total of 1,767 women were diagnosed with breast cancer from 1/2010 to 4/2014. The median age was 59 years. There was a total of 1327 (75%) Whites, 162 (9%) Blacks, 163 (9%) Asians, and 108 (6%) Hispanics. Majority of patients had a college-level education (83%), had annual/biannual screening mammography (78%), and clinical breast exams (89%). Majority of patients had invasive ductal carcinoma (61%), early stage (0, I, II) tumors (94%), ER+ (85%), PR+ (72%), Her2-negative (86%), and node-negative disease (80%). Compared to Whites, there was a significantly higher proportion of later stage disease among Blacks (p = 0.001) and Asians (p = 0.003), more triple negative breast cancers among Blacks (p < 0.0001) and higher Ki-67 scores among Blacks (p < 0.001) and Asians (p < 0.001). Oncotype RS was not significantly different among the race categories and a majority of patients had a low Oncotype RS (57%). These results did not change after stratifying for nodal status. CONCLUSIONS In a population of women who had health insurance and were highly screened, we found clinical differences among races with respect to tumor histology. However, we did not find a statistically significant difference among race and Oncotype RS, even after stratifying for nodal status. Further studies are warranted to determine which tumor proliferation markers are contributing to ethnic differences in breast cancer mortality.

The relationship of breast density, BMI, and menopausal status in mammography and MRI.

36 Background: Mammographic breast density (BD) is associated with a 4- to 6-fold increased risk for developing breast cancer. A previous study has shown that background parenchymal enhancement (BPE) as measured on MRI can be correlated with breast cancer risk. Being overweight or obese is also an established risk factor for breast cancer. The purpose of this study was to evaluate the relationship between BD, BPE, FGT (assessment of fibroglandular tissue with contiguous MR images), and BMI in pre- and post-menopausal women. METHODS The Breast Cancer Database at NYU Langone Medical Center was queried and a total of 187 women had completed both screening mammograms and MRIs. Variables of interest included BD, BPE, FGT, BMI, and menopausal status. BD was defined by ACR classifications 1-4. FGT was assessed on a similar scale 1-4. BPE was categorized as minimal, mild, moderate, or marked. BMI (kg/m2) was grouped as underweight (≤18), normal (19-24), overweight (25-29), and obese (≥30). Statistical analyses were performed using Spearman Correlation Coefficients and Cochran Mantel Haenszel tests. RESULTS The median age in our cohort was 51 years (range 22-87 years). The majority were Caucasian (71%) with early stage breast cancers (75%). There was no correlation between BD and BPE (r=0.132) and a weak correlation between BPE and FGT (r=0.312). However, there was a strong positive correlation between BD and FGT (r=0.733). After adjusting for menopausal status, these correlations remained the same. When we stratified by BMI, we found the strongest positive association between BD and FGT among women with BMI≥25 (r=0.715). CONCLUSIONS In our cohort of newly diagnosed breast cancer patients, BD and BPE were not correlated, even after adjusting for menopausal status. This implies that BD and BPE may represent different characteristics of breast tissue and may have different implications. We found a strong correlation between FGT and BD. This association was strongest in women who were overweight and obese. FGT is a more objective and quantitative measurement of breast density and may be more useful in quantitative breast cancer risk assessment.Further studies are necessary to determine if BPE and FGT are independent risk factors for breast cancer.

Tumor characteristics in obese women with breast cancer.

179 Background: Obesity is an established risk factor for postmenopausal breast cancer. Though women with high BMI tend to develop less aggressive molecular subtypes, previous studies have shown that they still have a higher risk of recurrence and worse prognosis. The biological mechanisms for this difference in outcome have yet to be identified. The purpose of this study is to determine the correlation between obesity and tumor characteristics, including Ki67, and Oncotype DX scores in both pre- and post-menopausal women. METHODS The Breast Cancer Database of NYU Langone Medical Center was queried for patients who were newly diagnosed with invasive breast cancer. We looked at the following variables: menopausal status, body mass index (BMI), histology, stage, ER/PR/Her2-neu status, Ki67, and Oncotype DX scores. Obesity was defined as having a BMI (kg/m2) ≥30. We looked at Ki67 as a continuous variable. Oncotype scores were categorized as low (<18), intermediate (18-30), and high (>31). Statistical analyses were performed using Spearman Correlation Coefficients. RESULTS Out of a total of 648 patients with a median age of 59 years, 153 (24%) women had a BMI≥30. The majority of the obese women had stage I and II (88%) cancers that were ER positive (84%), PR positive (74%), Her2-neu negative (86%), with mean Ki67 of 22%, and low to intermediate Oncotype DX scores (85%). However, when compared with women of BMI <30, there was no correlation between BMI and tumor characteristics, even when stratified by menopausal status. CONCLUSIONS In our cohort, obesity was not correlated with tumor stage, histology, Ki67 and Oncotype DX scores, even after adjusting for menopausal status. There are other factors that may explain the higher risk of recurrence and worse prognosis of breast cancer in obese women, such as insulin resistance, and obesity-related inflammatory cytokines that are independent of breast cancer subtypes and genomics. Treatment-related factors, such as non-compliance and inadequate dosing of chemotherapeutic agents, may also play a role in the worse outcome seen in this population. Further studies are necessary to identify measurable molecular characteristics of breast cancer in obese women that would allow us to predict more aggressive disease.

Ductal carcinoma in situ on core needle biopsy only with no residual disease at surgery

The treatment of ductal carcinoma in situ (DCIS) remains controversial and 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 lumpectomy specimen. The purpose of this study was to explore the frequency of this presentation and short‐term outcomes in these patients.

The relationship of magnetic resonance (MR) imaging characteristics with race.

10 Background: Research has shown that women of different race have differences in tumor biology. Previous studies have shown that mammographic breast density (BD) and background parenchymal enhancement (BPE) are associated with breast cancer risk. There is data on the relationship of race and BD, but a dearth of information on the relationship of race and MR imaging characteristics such as fibroglandular tissue (FGT) and BPE. The purpose of this study was to evaluate the relationship of race with BD, BPE, and FGT in women with breast cancer. 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), imaging and tumor characteristics. Statistical analyses included Pearsons Chi Square Tests. RESULTS A total of 2,092 women were included in this analysis. The median age was 59 years (range 22-95). Majority of patients had invasive ductal carcinoma (62%), early stage (0, I) tumors (71%), ER-positive (84%), PR-positive (71%), and HER2-negative (86%). However, there was a higher proportion of later stage (p < 0.0001) and triple negative (p = 0.002) disease among blacks. Compared to whites, blacks had higher BMI, lower BD and lower BPE, while Asians had lower BMI <, higher BD, higher FGT and higher BPE (see table). CONCLUSIONS As previously described, we found differences among races with respect to tumor histology. However, the differences in imaging characteristics between races are likely accounted for by differences in BMI and may not be directly related to breast carcinogenesis. [Table: see text].

Prevalence of BRCA2 mutations and other clinical characteristics in women with triple-negative breast cancer.

160 Background: Triple-negative breast cancers (TNBC) represent 10%-20% of invasive breast cancers. Current guidelines recommend genetic testing for women who are diagnosed with TNBC. Studies have shown that BRCA1 mutations are associated with TNBC, but there is little information on the relationship of BRCA2 mutations and TNBC. The purpose of this study was to look at the clinical characteristics of TNBC compared to non-TNBC in a cohort of women with newly diagnosed breast cancer. METHODS The Breast Cancer Database at our institution was queried for patients with invasive breast cancer. We included the following variables: age, race, BRCA1,2, tumor characteristics, and personal history of breast cancer (PHBC). Statistical analyses included Pearsons Chi-Square and Fishers Exact Tests. RESULTS Out of a total of 1,332 women, 125 (9%) had TNBC. The median age for both TNBC and non-TNBC was 59 years. Majority of women had early stage breast cancer (92%) with ductal carcinoma (80%). There was a significantly higher proportion of Blacks and Asians with TNBC (p < 0.0001). Women with TNBC had higher Ki-67 (p < 0.0001). Within the TNBC group, there were 12 (29%) patients who tested positive for BRCA1,2 mutation and 23 (8%) who tested positive for BRCA 1,2 mutations in the non-TNBC group. Interestingly, BRCA1 was not associated with TNBC (p = 0.40) and BRCA2 was significantly associated with TNBC (p < 0.0001). We also found a higher proportion of TNBC in women who had a PHBC (p = 0.01). CONCLUSIONS In our study, women with TNBC were similar in age to women who did not have TNBC. We found that the women with TNBC in our cohort had elevated rates of BRCA2 mutations. We also found that women with a personal history of breast cancer were at risk for developing TNBC. This may be related to the use of hormonal therapy that reduces the risk of ER/PR-positive tumors. Women of all ages are at risk for developing TNBC and older age at TNBC should not deter from genetic testing.

Improving breast-conserving surgery: A focus on margins.

127 Background: Inadequate lumpectomy margins are associated with an increased risk of ipsilateral recurrence in patients undergoing breast conserving surgery for cancer. Multiple procedures are often required to achieve acceptable margins, increasing the burden to the patient and the health care system, and potentially delaying other adjuvant treatments. A novel device for intraoperative assessment of lumpectomy margins (MarginProbe) has been associated with a 25% reduction in the rate of positive margins at the conclusion of primary lumpectomy surgery. Our aim was to establish a baseline re-excision rate among surgeons and to initiate a follow up study to assess the impact of incorporating this new technology for intraoperative margin assessment. METHODS The NYU Langone Medical Center Breast Cancer Database was queried for patients who underwent breast conserving surgery including ≥ 1 re-excision procedure from 1/2010-1/2013. Variables of interest included re-excision rates, stage of disease, and additional margins taken at primary lumpectomy surgery. Statistical analyses included descriptive analyses and Pearsons Chi-Square. RESULTS During the study period 957 patients had breast conserving surgery and 229 required ≥ 1 re-excision procedures (24%). Re-excision rates varied widely among surgeons (10-36%). Stage 0 disease (ductal carcinoma in situ) was associated with an increased frequency of re-excisions (p<0.0001). These parameters will be re-evaluated in patients undergoing breast conserving surgery with adjunctive intraoperative use of the MarginProbe device. Re-excision rates and the accuracy of intraoperative assessment of lumpectomy margins will be compared with the historical cohort. CONCLUSIONS The necessity for multiple surgical procedures to complete breast conserving surgery results in an added burden to the patient and the health care system. Improved intraoperative assessment of lumpectomy margins represents an opportunity to improve the quality of breast cancer surgery. A critical analysis of the impact of a new device on re-excision rates will be important to understand its potential benefit to the conduct of breast conserving surgery.