Gansler, Ted

Abstract Identifying risk factors for women at high risk of symptom-detected breast cancers that were missed by screening would enable targeting of alternative prevention strategies. To identify breast cancer risk factors by mode of detection, we examined these associations in heavily-screened women from the Cancer Prevention Study (CPS)-II Nutrition Cohort. Among 76,406 women followed for a median of 13.8 years, 2,469 screen-detected and 1,189 symptom-detected breast cancer cases were diagnosed. Multivariable-adjusted associations were estimated using joint Cox proportional hazards regression models with person-time calculated contingent on screening. The mean (standard deviation) age at baseline was 62.0 (6.6) years for non-cases, 61.6 (6.1) for screen-detected cases, and 61.5 (6.2) for symptom-detected cases. Women with symptom-detected tumors were diagnosed at a slightly younger age (mean=69.4) and less likely to be diagnosed with a localized tumor (65.3%), than women with a screen-detected tumor (mean age at diagnosis=70.4 and localized tumors=83.3%). Factors associated with higher risks of symptom detected vs. screen detected breast cancer, included: current combined menopausal hormone use (HR=2.04, 95% CI 1.70 - 2.46 vs. HR=1.43, 95% CI 1.25 - 1.63), current estrogen only menopausal hormone use (HR=1.41, 95% CI 1.15 - 1.72 vs. HR=0.94, 95% CI 0.82 - 1.09), and history of benign breast disease (HR=1.89, 95% CI 1.67 - 2.13 vs. HR=1.49, 95% CI 1.36 - 1.62). The opposite pattern of higher risk of screen detected vs. symptom detected breast cancer was observed for greater adult weight gain (HR=2.32, 95% CI 1.91 - 2.82 vs. HR=1.42, 95% CI 1.10 - 1.84) and alcohol intake (HR=1.39, 95% CI 1.24 - 1.64 vs. HR=1.20, 95% CI 0.92 - 1.58). Our results suggest that understanding risk factors for symptom-detected cancers may help identify women who would benefit from more intensive screening to facilitate early detection. Citation Format: Mia M. Gaudet, Emily Deubler, W. Ryan Diver, Samantha Puvanesarajah, Alpa V. Patel, Ted Gansler, Dana Flanders, Mark Sherman, Susan Gapstur. Breast cancer risk factors by mode of detection among screened women in the Cancer Prevention Study-II [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4211.

Abstract Stromal tumor-infiltrating lymphocytes (sTILs) are often prominent in HER2-enriched and triple negative breast cancers and predict a favorable prognosis for these subtypes. Clinical and epidemiological determinants of sTILs have not been defined in large cohorts. Accordingly, we analyzed these associations for 702 eligible, postmenopausal invasive breast cancer cases from the Cancer Prevention Study (CPS)-II Nutrition cohort. CPS-II included 97,786 women who completed baseline and follow-up surveys since 1992. Women with self-reported breast cancer diagnoses were consented for medical record and tumor tissue retrieval. We analyzed pre-diagnostic data from the survey prior to diagnosis on personal history of benign breast disease (BBD), menopausal hormone use, alcohol intake, cigarette smoking status, waist circumference, body mass index, adult weight gain, nonsteroidal anti-inflammatory drugs, and physical activity. One pathologist (TG) evaluated sTILs using whole slide images of H&E stained sections according to recommendations by the International TILs Working Group 2014. sTIL levels were dichotomized: none/minimal (0-10%) and moderate/high (>10%). We compared the sTIL levels by clinical and epidemiologic risk factors using chi-square statistics. Odds ratio (ORs) and 95% confidence intervals (CIs) for the associations of clinical and epidemiologic risk factors with sTILs were estimated with multivariable logistic regression. Mean age at diagnosis was 71.9 years; 44% of cancers were moderate grade, 74% were localized staged and 88% were luminal-like. Cancers with high/moderate sTIL levels (n=614), compared to none/minimal (n=88), were more likely to be high grade (54% vs. 20%; p-value <0.001), node-positive (41% vs. 22%; p-value <0.001), and non-luminal (36% vs. 8%; p-value <0.001). In a model mutually-adjusted for age at diagnosis and clinical factors, all clinical factors were associated with moderate/high sTIL levels: node-positive (OR=2.15, 95% CI 1.28 – 3.58), high grade (OR=3.98, 95% CI 1.88 – 9.06), and non-luminal subtype (OR=3.65, 95% CI 2.00 – 6.59). Age at diagnosis was not associated with sTIL levels (per year: OR=1.01, 95% CI 0.97 – 1.05). Women with BBD were less likely to have moderate/high sTIL levels than minimal/none sTIL levels (38% vs. 54%; age-adjusted OR=0.50, 95% CI 0.31 – 0.79). Ever smokers also were less likely to have moderate/high sTIL levels (38% vs. 49%) with an OR=0.61 (95% 0.38 – 0.97). Other risk factors were not significantly associated with sTIL levels. In this large epidemiologic cohort, non-luminal cancers had more sTILs than luminal cancers. Women with a personal history of BBD and ever cigarette smokers had significant lower levels of sTILs. Our study is among the first to examine pre-diagnostic risk factors in relation to sTILs and provides the impetus for larger, population-based studies with phenotypic characterization of immune cells. Citation Format: Gaudet MM, Mellow MM, Puvanesarajah S, Gapstur SM, Sherman ME, Gansler T. Associations of epidemiologic and clinical features with intensity of immune infiltrates in postmenopausal breast cancer cases from the cancer prevention study-II cohort [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 P1-08-02.