The effect of family history on screening procedures and prognosis in breast cancer patients - Results of a large population-based case-control study.

BACKGROUND: The potential benefit of additional breast cancer screening examinations in moderate risk patients (patients with a history of breast cancer in one or two family members) remains unclear. METHODS: A large population-based case-control study on breast cancer in postmenopausal women in Germany recruited 2002-2005 (3813 cases and 7341 age-matched controls) was used to assess the association of family history with breast cancer risk. Analysis of family history, participation in screening procedures, and tumor size regarding prognosis in patients was based on follow-up data until 2015. RESULTS: A first degree family history of breast cancer was associated with higher breast cancer risk (OR 1.39, p < 0.001). Patients with a first degree family history of breast cancer were more likely to have had >10 mammograms (MG) (42.7% vs. 24.9%, p < 0.001) and showed a higher rate of imaging-detected tumors (MG or ultrasound) (45.8% vs. 31.9%, p < 0.001). A smaller tumor size at initial diagnosis (below 2 cm) was more likely in patients with a positive family history (OR 1.45, p < 0.001) and a higher number of MG (≥10 MG: OR 2.29). After accounting for tumor characteristics, mammogram regularity (HR 0.72, p < 0.001) and imaging-assisted tumor detection (HR 0.66, p < 0.001) were associated with better overall survival but not with a positive family history. DISCUSSION: Patients with a positive family history had a higher rate of imaging detected tumors with smaller size at initial diagnosis compared to patients without affected family members. Screening was associated with improved survival after a breast cancer diagnosis, irrespective of a positive family history.

Pre- to postdiagnosis leisure-time physical activity and prognosis in postmenopausal breast cancer survivors.

BACKGROUND: Physical activity (PA) before and after breast cancer diagnosis has been reported to be associated with lower mortality. However, whether changes in the activity after diagnosis impact prognosis is unclear and has not received much attention. This study aimed to examine pre- to postdiagnosis leisure-time PA and breast cancer prognosis. METHODS: We used data from the MARIE study, a prospective population-based patient cohort study of 3813 postmenopausal breast cancer patients, aged 50-74 at diagnosis, recruited from 2002 to 2005, re-interviewed in 2009, and followed up until June 2015. Prediagnosis PA was assessed at recruitment; postdiagnosis PA was assessed at re-interview in 2009. To examine pre- to postdiagnosis change in PA, women were categorized by pre- and postdiagnosis PA using a cut-off of 7.5 MET-h/week for meeting PA recommendations and combined into four groups: insufficiently active, increasingly active, decreasingly active, and sufficiently active. Cox regression models with delayed entry were used to assess associations between pre- to postdiagnosis patterns of PA and overall mortality (OM), breast cancer mortality (BCM), and recurrence-free survival (RFS). Additional analyses of pre- and postdiagnosis PA (no activity (reference), low activity, sufficient activity) with cancer outcomes, such as using a time-dependent model, were performed. In total, 2042 patients were included in the analyses. RESULTS: There were 206 deaths (114 from breast cancer) after a median follow-up time of 6.0 years after the 2009 interview. Compared to insufficiently active women, increasingly active women were at lower risk of OM, BCM, and RFS (HR (95%CI) of 0.50 (0.31-0.82), 0.54 (0.30-1.00), 0.58 (0.40-0.84), respectively). In sufficiently active women, associations for OM (0.75 (0.48-1.15)), BCM (0.61 (0.33-1.13)), and RFS 0.80 (0.57-1.14)) were similar to increasingly active women but attenuated, and decreasingly active women were not at lower risk for OM (0.91 (0.61-1.36)), BCM (0.80 (0.45-1.42)), and RFS (1.04 (0.76-1.43)). In time-dependent analyses, sufficient activity vs. no activity was associated with better OM (0.73 (0.57-0.93)), BCM (0.64 (0.46-0.89)), and RFS (0.82 (0.68-0.99)). Low activity was not significantly associated with prognosis. CONCLUSION: Our data support benefits for breast cancer prognosis in being physically active pre- and postdiagnosis particularly for women who were insufficiently active prediagnosis.

Antioxidant supplementation and breast cancer prognosis in postmenopausal women undergoing chemotherapy and radiation therapy.

Background: There is a paucity of information on the prevalence of dietary supplement use in breast cancer survivors. Only a few studies have examined the impact of dietary supplements, particularly antioxidants, on breast cancer prognosis and the results are inconclusive. Objective: We examined pre- and postdiagnosis use of supplements in postmenopausal breast cancer survivors in Germany and investigated associations between postdiagnosis use of antioxidants and other supplements, and prognosis (total and breast cancer mortality, and recurrence-free survival) both overall and in women who received chemotherapy and radiation therapy. Design: Data from 2223 postmenopausal women diagnosed with nonmetastatic breast cancer from the population-based Mamma Carcinoma Risk Factor Investigation (MARIE) study were used. Women were interviewed at recruitment in 2002-2005 and again in 2009 and followed-up until 30 June 2015. Multivariate Cox regression analysis was used to estimate HRs and corresponding 95% CIs. Results: Pre- and postdiagnosis supplement use was reported by 36% and 45% of the women, respectively. There were 240 deaths (134 from breast cancer) and 200 breast cancer recurrences after a median follow-up time of 6.0 y after the 2009 re-interview. After adjusting for relevant confounders, concurrent antioxidant use with chemotherapy or radiation therapy among 1940 women was associated with increased risk of total mortality (HR: 1.64; 95% CI: 1.01, 2.66) and worsened recurrence-free survival (HR: 1.84; 95% CI: 1.26, 2.68). Overall postdiagnosis supplement use was not associated with breast cancer prognosis. Conclusions: Antioxidant use during chemotherapy or radiation therapy was associated with worsened breast cancer prognosis in postmenopausal women. There was no overall association between postdiagnosis supplement use and breast cancer prognosis. Results from our study align with the current recommendation to possibly avoid the use of antioxidants during chemotherapy or radiation therapy.

Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium.

Investigating the most likely causal variants identified by fine-mapping analyses may improve the power to detect gene-environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine-scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER-) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene-environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR-rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67-0.88, pint = 1.8 × 10-4 ). The interaction with the strongest statistical evidence was found between 5q14-rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16-1.59, pint = 1.9 × 10-5 ) in relation to ER- disease risk. The remaining two gene-environment interactions were also identified in relation to ER- breast cancer risk and were found between 3p21-rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12-1.43, pint =1.8 × 10-4 ) and between 8q23-rs13267382 and age at first full-term pregnancy (ORint = 0.89, 95% CI: 0.83-0.95, pint = 5.2 × 10-4 ). While these results do not suggest any strong gene-environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed.