Faculty Bibliography

The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.

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 Pearson's chi-square and Fisher's 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.

112 Background: Maintaining a healthy weight after breast cancer diagnosis has been associated with improved survival outcomes. Lifestyle interventions are particularly important in overweight women who are at an increased risk of overall and breast-cancer specific death compared to non-overweight women. The purpose of this study is to examine the barriers and acceptance of a lifestyle intervention program among overweight women with newly diagnosed breast cancer. METHODS: The Breast Cancer Database of NYU Langone Medical Center was queried for women who were newly diagnosed with breast cancer and who had a body mass index (BMI) >/=25kg/m2. Eligible patients participated in the Moving for Life (MFL) exercise program for 16 sessions. Questionnaires were administered at baseline and at the end of the intervention. Descriptive statistics were used to summarize patient characteristics and paired t-tests were used to see if there were any significant differences before and after the intervention. RESULTS: A total of 40 women were eligible to participate in the MFL exercise program. A total of 20 women declined to participate due to location, transportation limitations, and conflicts in schedule. Of the 18 women who enrolled in the MFL program, 13 (72%) were regular attendees and completed the study. The median age was 61 years (range: 38-76) and the average baseline BMI was 31kg/m2(range: 25-42). After completing the MFL intervention, there was a significant decrease in weight and BMI (p=0.04). The average weight loss was 10lbs. Participants also reported a greater enjoyment of exercise (p=0.02), as well as a decrease in pain related to treatment (p=0.05). CONCLUSIONS: Moving for Life is a unique exercise program for breast cancer patients and had a high rate of acceptance and completion in a cohort of overweight breast cancer patients. This study resulted in a statistically significant average weight loss of 10lbs, as well as a greater enjoyment of exercise and decrease in treatment-related pain which may impact long-term lifestyle changes. Longitudinal follow-up at 6- and 12-months will allow assessment of secondary endpoints, including exercise frequency and attitudes about exercise, allowing us to examine sustainability and changes in behaviors and attitudes over time.

ABSTRACT: INTRODUCTION: Pregnancy-associated breast cancer refers to breast cancer diagnosed during pregnancy, lactation, or within twelve months postpartum. Recent studies suggest that, when matched for age and stage, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer. However, the risk for breast cancer recurrence associated with subsequent pregnancies in this population is not clear. CASE PRESENTATION: We describe the case of a Caucasian woman who was initially treated for pregnancy-associated breast cancer at age 23, three months after the birth of her third child. She underwent a total mastectomy with axillary node dissection, followed by chemotherapy and hormonal therapy. Ten years later, when the patient was 24 weeks pregnant with her fourth child, she presented with an ipsilateral chest wall recurrence of breast cancer. To the best of our knowledge, this represents the first reported case of a pregnancy-associated recurrence in a patient previously treated for pregnancy-associated breast cancer. CONCLUSION: The case described here is the first report of a second occurrence of pregnancy-associated breast cancer. This case raises the possibility that pregnancy may represent a unique trigger for breast malignancy in a specific cohort of women. Although there is data showing no increase in the risk of recurrence for women who become pregnant after breast cancer treatment, pregnancy-associated breast cancer may be a distinct clinical category where subsequent pregnancies after treatment may confer an increased risk of recurrent disease.

OBJECTIVE: Breast density is increasingly recognized as an independent risk factor for the development of breast cancer, because it has been shown to be associated with a four- to sixfold increase in a woman's risk of malignant breast disease. Increased breast density as identified on mammography is also known to decrease the diagnostic sensitivity of the examination, which is of great concern to women at increased risk for breast cancer. Dense tissue has generally been associated with younger age and premenopausal status, with the assumption that breast density gradually decreases after menopause. However, the actual proportion of older women with dense breasts is unknown. The purpose of this study was to examine the relationship between age and breast density, particularly focusing on postmenopausal women. MATERIALS AND METHODS: All screening mammograms completed at the New York University Langone Medical Center in 2008 were retrospectively reviewed. Analysis of variance and descriptive analyses were used to evaluate the relationship between patient age and breast density. RESULTS: A total of 7007 screening mammograms were performed. The median age of our cohort was 57 years. Within each subgroup categorized by decade of age, there was a normal distribution among the categories of breast density. There was a significant inverse relationship between age and breast density (p < 0.001). Seventy-four percent of patients between 40 and 49 years old had dense breasts. This percentage decreased to 57% of women in their 50s. However, 44% of women in their 60s and 36% of women in their 70s had dense breasts as characterized on their screening mammograms. CONCLUSION: In general, we found an inverse relationship between patient age and mammographic breast density. However, there were outliers at the extremes of age. A meaningful proportion of young women had predominantly fatty breasts and a subset of older women had extremely dense breasts. Increased density renders mammography a less sensitive tool for early detection. Breast density should be considered when evaluating the potential benefit of extended imaging for breast cancer screening, especially for women at increased risk for the disease.