Background: Neurofibromatosis type 1(NF1) is an autosomal dominant genetic disorder affecting 1 in 3,000 individuals worldwide. Risk of cancer, including breast cancer, is increased, as NF1 is a tumour suppressor gene. There is limited data on the characteristics of breast cancer in individuals with NF1. Objectives: To study the clinical and pathological characteristics of breast cancer in women with NF1. Methodology: Patients with both NF1 and breast cancer were identified retrospectively from hospital records as well as prospectively when seen at National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH). All women had histologically proven breast cancer and fulfilled at least 2 of the 7 criteria developed by the NIH Consensus Conference for clinical diagnosis of NF1. Germline NF1 mutation sequencing is being performed on patients with blood specimens available. Details on patient demographics, tumour grade, stage, receptor status and clinical outcome were evaluated. The pathological characteristics of NF1-associated breast cancer were then compared to sporadic breast cancers in our 2001–2004 cohort, with a focus on grade and HER2 positivity rate. Results: We identified 13 women with NF1 and breast cancer seen at our institutions from 2001 to present date. Average age of breast cancer diagnosis for women testing positive was 48 years (range 30–64). All 13 patients had invasive ductal carcinoma; of which 5 were stage 3 or 4 at diagnosis. To date, 4 out of 12 patients with stage 1–3 breast cancer have relapsed. Grade, estrogen, progesterone and HER2 receptor status were fully available for 12 patients. Ten out of 12 tumours (83%) were grade 3, compared to 45% (705/1578) among our sporadic breast cancers (p = 0.007). Eight out of 12(67%) NF1-associated breast cancers were HER2 positive (IHC 3+ or FISH positive), compared to 27% (367/1367) in sporadic cancers (p = 0.002). Two other NF1-associated tumours were triple negative, and two were hormone receptor positive and HER2 negative. Six out of 12 (50%) NF1-associated cancers were estrogen receptor (ER) positive, compared to 67% (1124/1689) in sporadic cancers (p = 0.2). Conclusion: Our findings suggest that NF1-associated breast cancer tends to be more aggressive, with a higher frequency of grade 3 and HER2 positive tumours compared to sporadic breast cancer. Further genomic profiling of these tumours (in progress) may elucidate the role of NF1 in breast cancer. This may also have implications for sporadic tumours with somatic NF1 mutations in individuals without NF1. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-09.

Importance: A marked disparity exists in the breast cancer mortality of women diagnosed in Eastern North Carolina (ENC) when compared to women diagnosed in the rest of North Carolina (RNC). Objective: To identify modifiable factors associated with the increased mortality of women diagnosed with breast cancer in ENC. Design: Retrospective cohort study of women diagnosed with breast cancer in North Carolina between January 1, 2004 and December 31, 2007. Setting: North Carolina Central Cancer Registry. Participants: Females diagnosed with either invasive or non-invasive breast cancer in North Carolina during the designated time period. Main Outcome Measures: Race/ethnicity, hormone receptor status, pathologic T, N and stage grouping at the time of diagnosis, delivery of adjuvant chemotherapy, and survival. Results: A total of 27,631 women were diagnosed with breast cancer during the study period. Women in ENC were slightly older than in RNC (59.2 y v. 58.5 y, p<0.001). There was no difference in the pathologic T (p = 0.62), N (p = 0.26) or Stage Grouping (p = 0.25) at diagnosis between ENC and RNC patients. Women in ENC were less likely to be White (68.9% v. 80.0%, <0.001)), ER positive (53.4% v. 59.4%, p<0.001), PR positive (44.8% v. 49.4%, p<0.001), or to receive adjuvant chemotherapy (78.7% v. 81.3%, p = 0.02). The median survival of ENC patients was significantly worse than RNC patients (39 months v. 43 months, p = 0.003). By univariate analysis, improved median survival was associated with ER status (p<0.001), PR status (p<0.001), Race/ethnicity (p<0.001) and delivery of timely chemotherapy (p<0.0001). By Cox Regression analysis, ER negative status (RR 1.03; 95% CI 0.85 to 0.98, p = 0.01), African American (RR 0.94; 95% CI 0.89 to 0.99, p = 0.03), and adjuvant chemotherapy within 90 days of surgery (RR 1.40; 95% CI 1.30 to 1.50, p<0.001) remained significant predictors of survival. Conclusions: The poor outcomes observed in ENC can be attributed to recognized prognostic primary patient and tumor characteristics. However a failure in process of care remains significantly associated with poorer outcomes. Improved timing of delivery of chemotherapy could affect breast cancer mortality. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-12.

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Background and Aim: The five-year survival for women with stage I-II breast cancer is 93-100%. Despite standard of care treatment, a small subset of these women suffer early breast cancer-specific mortality and die within 12 months of diagnosis. This subset of women has not been previously described. The aim of this study is to characterize the incidence, demographics, and clinical characteristics of women with early stage breast cancer who suffer early breast cancer-specific mortality. Methods: Retrospective population study of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry of women diagnosed with stage I, IIA, or IIB breast cancer between 2004 and 2010. Data were filtered to histology codes 8500-8543 and 8575. Patient demographics (age, race, ethnicity) and clinical characteristics (stage, T stage, N stage, grade, ER status, PR status) of women in the early mortality subset were compared with those of women who survived > 12 months via the Chi-square test and the student t-test. Results: 259,380 women formed the basis of our analysis. 4,572 women (0.018%) died within 12 months of diagnosis. Compared with those who survived > 12 months, women who suffered early breast cancer-specific mortality were on average older (mean age 65.7 years versus 60.3 years, p<0.00001) and more likely to be Hispanic (14.3% versus 8.9%, p<0.00001) or black (11.0% versus 9.1%, p<0.00001). Clinical characteristics associated with early mortality included higher stage (stage IIA 34.2% versus 29.4%, stage IIB 21.8% versus 12.9%, p<0.00001), higher T stage (T2 40.5% versus 28.1%, T3 3.1% versus 1.6%, p<0.00001), higher N stage (N1 29.7% versus 23.2%, N2 0.8% versus 0.4%, N3 0.4% versus 0.1%, p<0.00001), higher grade (moderate 39.3% versus 42.5%, high 40.0% versus 31.5%, p<0.00001), higher rates of ER negativity (27.2% versus 19.0%, p<0.00001), and higher rates of PR negativity (38.5% versus 30.2%, p<0.00001). Conclusions: Breast cancer-specific mortality within 12 months of diagnosis of stage I-II breast cancer is a rare phenomenon which has not been previously characterized. There are several demographic and clinical features associated with early mortality, however further research is needed to identify specific prognostic factors that will allow identification of women at risk for early mortality at the time of diagnosis. Citation Format: Johnson HM, Wong JH, Vohra NA, Muzaffar M. Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-21.

Background and Aim: Reduction in breast density has been proposed as a biomarker of response to endocrine therapy (ET). The vast majority of current data are derived from white or Asian women. Because baseline breast density is associated with race, it is possible that changes in breast density with treatment may also be affected by race. Our objective was to assess the impact of ET on volumetric breast density (VBD) and fibroglandular volume (FGV) in African American (AA) women with invasive breast cancer. Methods: We conducted a retrospective study of AA women diagnosed with estrogen receptor positive invasive breast cancer at our institution from 2009-2013. Mammograms within two years prior to diagnosis and at least 6 months post-diagnosis were utilized for comparing density measurements. Using Volpara automated software, VBD and FGV were measured for the contralateral normal breast by averaging the respective values measured on the craniocaudal and mediolateral oblique views. Results: 51 women met the inclusion criteria and were confirmed to have received ET. Sixteen women received tamoxifen, 34 received an aromatase inhibitor, and medication data was unavailable in one case. The mean age at diagnosis was 56 years (range 29-72, median 55). 53% of women had stage I disease, 29% had stage II disease, and 18% had stage III disease. The majority of women had ER+ PR+ HER2 - disease (82.4%). 53.0% of women received systemic chemotherapy and all but one woman were treated surgically. Average body mass index (BMI) at diagnosis was 36.5, with data not available for 22 women. The mean time between diagnosis and baseline mammogram was 32 days, and the mean time between follow-up mammogram and baseline mammogram was 401 days. Average BMI at one year follow up was 33.7, with data not available for 19 women. The mean baseline VBD was 7.5% (range 1.9-21.5%, median 6.3%) and the mean follow-up VBD was 6.9% (range 2.0-23.6%, median 5.6%). Fifteen women had a longitudinal increase in VBD. The mean absolute change in VBD was -0.6% (range -3.4% to +9.8%, median 0.7%), with a mean 8.0 percent decrease from baseline to follow-up (range -0.7 to +0.5, median 0.1). The mean baseline FGV was 72.3 cm3 (range 18.5-208.4, median 65.3) and the mean follow-up FGV was 69.7 cm3 (range 22.7-197.5, median 60.5). Nineteen women had a longitudinal increase in FGV. The mean absolute reduction in FGV was 2.6 cm3 (range -53.3 to 49.3, median 4.8), with a mean 0.9 percent decrease from baseline to follow-up (range -111.6 to +53.0, median 5.2). Conclusions: We observed an overall decrease in Volpara-calculated VBD and FGV in our cohort of AA women treated with ET. It remains to be determined whether changes in VBD and FGV across serial mammograms may be a biomarker for response to ET in women of all races. Large prospective studies are needed to evaluate the effects of ET on longitudinal changes in VBD and FGV while controlling for confounders such as menopausal status, BMI, and chemotherapy. Citation Format: Johnson HM, Shivalingappa H, Wong JH, Muzaffar M, Verbanac K, Vohra NA. Longitudinal changes in volumetric breast density and fibroglandular volume with endocrine therapy in African American women with estrogen receptor positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-11-12.