Clinicopathologic predictors of outcomes in children with stage I testicular germ cell tumors: A pooled post hoc analysis of trials from the Children's Oncology Group.

BACKGROUND: Patients with clinical stage I (CS I: cN0M0) testicular germ cell tumors (TGCT) exhibit favorable oncologic outcomes. While prognostic features can help inform treatment in adults with CS I TGCT, we lack reliable means to predict relapse among pediatric and adolescent patients. OBJECTIVE: We sought to identify predictors of relapse in children with CS I TGCT. STUDY DESIGN: We performed a pooled post hoc analysis on pediatric and adolescent AJCC CS I TGCT patients enrolled in 3 prospective trials: INT-0097 (phase II), INT-0106 (phase III), and AGCT0132 (phase III). Pathology was centrally reviewed. Patient demographics, pT stage, serum tumor markers, margin status, histology, relapse, and survival were compiled. Cox regression analyses were used to identify predictors of events, defined as relapse, secondary malignant neoplasm, or death. RESULTS: 106 patients were identified with outcomes data available. Most patients were pT1-2 stage. Among patients with evaluable histopathology, yolk sac tumor elements were present in all patients and lymphovascular invasion in 51% of patients. Over a median follow-up of 56 months, no patients died, and 25 patients (24%) experienced an event (median event-free survival not reached). Independent predictors of events on multivariable analysis included age ≥12 years at diagnosis (HR 8.87, p < 0.001) and higher pT stage (pT2 HR 7.31, p = 0.0017; pT3 HR 13.5, p = 0.0043). DISCUSSION: Although our study population reflects the largest pooled prospective cohort of CS I pediatric and adolescent TGCT to our knowledge, the relatively low event rate limits our multivariable analysis, and longer follow-up duration would help further characterize the natural history of these patients. Centralized pathologic review was also unable to be performed for several patients. CONCLUSION: Pediatric and adolescent CS I TGCT patients exhibit remarkable 5-year survival. Using combined data from multiple prospective trials, our study identifies clinicopathologic features that predict relapse and inform personalized treatment for these patients by potentially guiding surveillance versus adjuvant treatment strategies.

Dietary intake from birth through adolescence in relation to risk of benign breast disease in young women.

PURPOSE: Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14 year and subsequent BBD. METHODS: A prospective cohort study of 9031 females, 9-15 year at baseline, completed questionnaires (including heights, weights) annually from 1996 to 2001, in 2003, 2005, 2007, 2010, 2013 and 2014. In 1996, mothers reported infant feeding practices during their daughters first year of life. Beginning in 1996, participants completed annual food frequency questionnaires. In 2005, participants (18 year +) began reporting whether they had ever been diagnosed with biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression models estimated associations between childhood nutrition and BBD, adjusted for maternal breast disease and childhood body size factors. RESULTS: Although no infant nutrition factors were associated with biopsy-confirmed BBD, certain adolescent dietary factors were. A multivariable model simultaneously included the most important diet and body size factors from different age periods: higher BBD risk was associated with greater age 10 year consumption of animal (non-dairy, energy-adjusted) fat (OR 2.27, p < .02, top vs. bottom quartiles) and with lower 14 year consumption of nuts/peanut butter (OR 0.60, p = .033, top vs. bottom quartiles). CONCLUSION: Greater intake of animal (non-dairy) fat at 10 year and lower intake of nuts/peanut butter at 14 year were independently associated with higher BBD risk. These dietary factors appeared to operate on BBD risk independent of childhood growth (gestational weight gain, childhood BMI and height, adolescent height growth velocity), young adult height and BMI, and family history.

Prenatal factors and infant feeding in relation to risk of benign breast disease in young women.

Benign breast disease (BBD) is a well-established risk factor for breast cancer, but little work has considered a girl's early life and her risk for BBD in adulthood. We investigated factors, from pre-conception through infant feeding practices, in relation to subsequent BBD risk in young women. The Growing Up Today Study (GUTS) includes 9032 females, born 1980-1987, who completed questionnaires annually from 1996 through 2001, then 2003, 2005, 2007, 2010, and 2013. In 1996, their mothers provided each participant's birth weight and length, gestational age, biological father's height, and infant feeding factors (e.g., breast-fed, type of formula). In 1999, their mothers reported maternal pre-pregnancy weight and weight gain during index pregnancy. Beginning in 2005, daughters (18 years+) reported whether they had ever been diagnosed with biopsy-confirmed BBD (n = 142 cases, through 2013). Logistic regression estimated associations between early life factors and biopsy-confirmed BBD. Girls whose mother's BMI prior to pregnancy was 20-25 kg/m(2) were at lower risk of BBD as young women (OR = 0.66, p = 0.04, vs. maternal pre-pregnancy BMI < 20). Girls whose mothers gained 20 + pounds (vs. <20 pounds) during pregnancy were at lower risk (among full-term singleton births: OR = 0.48, p = 0.007, if mother gained 20-35 pounds). However, neither birth weight nor BMI at birth were associated with subsequent BBD risk. We found no evidence that infant feeding practices were linked to BBD. A healthy maternal BMI before pregnancy and sufficient weight gain during pregnancy may produce daughters at lower risk for BBD as young women. Further examination of these findings is needed.

Adolescent physical activity and inactivity: a prospective study of risk of benign breast disease in young women.

In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9-15 years at study initiation (1996), who completed questionnaires annually through 2001, then in 2003, 2005, 2007, 2010 and 2013. Annual surveys (1996-2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18 years) reported whether they had ever been diagnosed with BBD confirmed by breast biopsy (n = 133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR = 0.61, ≥30 vs ≤15 min/day; p = .049). We observed no evidence that inactivity (≥3 vs <2 h/day OR = 1.02, p = .92) or METS (top vs bottom tertile OR = 1.19, p = .42) were associated with BBD. Accounting for factors including family history, childhood adiposity, and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed.