BRCA2 Mutations and Triple-Negative Breast Cancer

Recently, BRCA1 germline mutations were found in a high proportion (14–34%) of patients with triple-negative breast cancer (TNBC). BRCA2 was either not analyzed or showed much lower mutation frequencies. Therefore, we screened a group of TNBC patients (n = 30) of white European descent for mutations in BRCA2 as well as in BRCA1. Cases were unselected for age of disease-onset (median age at breast cancer diagnosis was 58 years, ranging from 37 to 74 years), family history of cancer and BRCA1 and BRCA2 mutation status. Half of the patients (15/30) showed a family history of breast and/or ovarian cancer. A high frequency of deleterious germline mutations was observed in BRCA2 (5/30; 16.7%), and only one case showed a BRCA1 mutation (3.3%). Although the study group was small, these results point to BRCA2 mutations being important in TNBC

Increased prevalence of colorectal adenomas in women with breast cancer

Background: The frequency of colorectal adenomas and carcinomas was investigated in a large cohort of women with breast cancer in comparison with matched controls, since data on the occurrence of second tumors in women with breast cancer is controversial. Design: In a cohort study, 188 consecutive women (median age 57 years) with primary breast cancer and 376 age-matched women who served as controls were examined by total colonoscopy. Breast cancer patients and controls were compared for the frequency of colorectal adenomas and carcinomas. Results: Women with breast cancer showed a higher risk of colorectal adenomas than controls (14.9 vs. 9.3%, p = 0.047, OR 1.7, 95% Cl 1.0-2.9). This increased prevalence resulted primarily from an increased prevalence in the age group 65-85 (31 vs. 10%, p = 0.004, OR 3.8, 95% Cl 1.6-9.3). Colorectal carcinomas were found infrequently in both groups (2 in each group). Women with breast cancer receiving anti-estrogen therapy showed a trend towards a lower risk of adenomas compared to women without anti-estrogen therapy (3.7 vs. 17.2%, p = 0.053, OR 0.16, 95% Cl 0.0-1.1). Conclusions: Women with breast cancer above the age of 65 years have an increased risk of colorectal adenomas compared to women without breast cancer. Women with a diagnosis of breast cancer should especially be encouraged to participate in colorectal cancer-screening programs which, in most countries, call for screening of all average-risk individuals over the age of 50 years

PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs

Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer;PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances),or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%];P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%];P<0.001),but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier findings that PTK7 may be a prognostic and predictive marker associated with resistance to anthracycline-based chemotherapy. Further investigations are needed to validate these findings in breast cancer

The relationship between daily behavior, hormones, and a color dimorphism in a seabird under natural continuous light

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Elsevier in Hormones and Behavior on 08/02/2021.Available online: https://www.sciencedirect.com/science/article/pii/S0018506X2100009X?via%3DihubThe predictable oscillation between the light of day and the dark of night across the diel cycle is a powerful selective force that has resulted in anticipatory mechanisms in nearly all taxa. At polar latitude, however, this oscillation becomes highly attenuated during the continuous light of polar day during summer. A general understanding of how animals keep time under these conditions is poorly understood. We tested the hypothesis that the common murre (a seabird, Uria aalge) can use melatonin and corticosterone, hormones associated with timekeeping, to track the diel cycle despite continuous light. We also tested the assumption that common murres breeding during polar summer schedule their colony attendance by time of day and sex, as they do at subpolar latitude. In the Atlantic population, common murres have a plumage color dimorphism associated with fitnessrelated traits, and we investigated the relationship of this dimorphism with colony attendance, melatonin, and corticosterone. The common murres did not schedule their attendance behavior by time of day or sex, yet they had higher concentrations of melatonin and, to a more limited extent, corticosterone during “night” than “day”. Melatonin also linked to behavioral state. The two color morphs tended to have different colony-attendance behavior and melatonin concentrations, lending support for balancing selection maintaining the plumage dimorphism. In common murres, melatonin can signal time of day despite continuous light, and the limited diel variation of corticosterone contributes to the mounting evidence that polar-adapted birds and mammals require little or no diel variation in circulating glucocorticoids during polar day. Arctic Circadian rhythm Color dimorphism Continuous light Corticosterone profile Daily rhythm Glucocorticoid profile Melatonin profile Midnight sun Uria aalgeacceptedVersio

Zurich Consensus: German Expert Opinion on the St. Gallen Votes on 15 March 2009 (11th International Conference at St. Gallen: Primary Therapy of Early Breast Cancer)

A German working group of 23 breast cancer experts discussed the results from the vote at this year's St. Gallen Consensus Conference on Primary Therapy for Early Breast Cancer ( March 11-14, 2009) and came up with some concrete recommendations for day-to-day therapeutic decisions in Germany. Due the fact that the concept of the St. Gallen Consensus Conference merely allows for a minimal consensus, the objective of the working group was to provide practice-related recommendations for day-to-day clinical decisions in Germany. One area of emphasis at St. Gallen was tumor biology as a starting point for reaching individual therapeutic decisions. Intensive discussion was necessary with respect to the clinical relevance of predictive and prognostic factors. A new addition to the area of systemic therapy was a first-ever discussion of the adjuvant administration of bisphosponates and the fact that therapy with trastuzumab in HER2 overexpressing breast cancer has been defined as the standard for neoadjuvant therapy. The value of taxanes as a component of (neo) adjuvant chemotherapy as well as the value of aromatase inhibitors for the endocrine adjuvant treatment of postmenopausal patients were affirmed

Melatonin and corticosterone profiles under polar day in a seabird with sexually opposite activity-rhythms

The 24 h geophysical light-dark cycle is the main organizer of daily rhythms, scheduling physiology and behavior. This cycle attenuates greatly during the continuous light of summer at polar latitudes, resulting in species-specific and even individual-specific patterns of behavioral rhythmicity, but the physiological mechanisms underlying this variation are poorly understood. To address this knowledge gap and to better understand the roles of the hormones melatonin and corticosterone in rhythmic behavior during this ‘polar day’, we exploited the behavior of thick-billed murres (Uria lomvia), a charadriiform seabird with sexually opposite (‘antiphase’) activity-rhythms that have a duration of 24 h. Melatonin concentration in the plasma of inactive males was unexpectedly high around midday and subsequently fell during a sudden decrease in light intensity as the colony became shaded. Corticosterone concentration in plasma did not vary with time of day or activity in either sex. While the reasons for these unusual patterns remain unclear, we propose that a flexible melatonin response and little diel variation of corticosterone may be adaptive in thick-billed murres, and perhaps other polar birds and mammals, by stabilizing glucocorticoids’ role of modulating energy storage and mobilization across the diel cycle and facilitating the appropriate reaction to unexpected stimuli experienced across the diel cycle while attending the colony

Zurich Consensus: Statement of German Experts on St. Gallen Conference 2011 on Primary Breast Cancer (Zurich 2011)

Every 2 years, the International Consensus Conference on the Treatment of Primary Breast Cancer takes place in St. Gallen. Given that the concept of the St. Gallen Consensus Conference mainly reflects an international opinion, it appears useful to adapt the results of the vote for everyday therapy in Germany. A German working group comprising 28 breast cancer experts, amongst whom there are 3 members of the international St. Gallen panel, has therefore commented on this year's St. Gallen Consensus Conference (2011) from the German viewpoint. The focus of interest of this year's St. Gallen Conference was tumour biology as the starting point for decisions regarding individual therapy. There was an intensive discussion in relation to the clinical relevance of predictive and prognostic factors and possible consequences for decisions regarding therapy. Therefore, questions concerning the indication for adjuvant chemotherapy focused especially on the significance of the molecular phenotype of the tumour. In addition, important points for discussion were also the value of complete axillary dissection and the use of accelerated complete breast irradiation

Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics

BACKGROUND: Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor–positive (ER+) breast cancer. METHODS: Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer–specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. RESULTS: Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). CONCLUSIONS: Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherapy

Outcome Prediction for Estrogen Receptor-Positive Breast Cancer Based on Postneoadjuvant Endocrine Therapy Tumor Characteristics

Background Understanding how tumor response is related to relapse risk would help clinicians make decisions about additional treatment options for patients who have received neoadjuvant endocrine treatment for estrogen receptor-positive (ER+) breast cancer. Methods Tumors from 228 postmenopausal women with confirmed ER+ stage 2 and 3 breast cancers in the P024 neoadjuvant endocrine therapy trial, which compared letrozole and tamoxifen for 4 months before surgery, were analyzed for posttreatment ER status, Ki67 proliferation index, histological grade, pathological tumor size, node status, and treatment response. Cox proportional hazards were used to identify factors associated with relapse-free survival (RFS) and breast cancer-specific survival (BCSS) in 158 women. A preoperative endocrine prognostic index (PEPI) for RFS was developed from these data and validated in an independent study of 203 postmenopausal women in the IMPACT trial, which compared treatment with anastrozole, tamoxifen, or the combination 3 months before surgery. Statistical tests were two-sided. Results Median follow-up in P024 was 61.2 months. Patients with confirmed baseline ER+ clinical stage 2 and 3 tumors that were downstaged to stage 1 or 0 at surgery had 100% RFS (compared with higher stages, P < .001). Multivariable testing of posttreatment tumor characteristics revealed that pathological tumor size, node status, Ki67 level, and ER status were independently associated with both RFS and BCSS. The PEPI model based on these factors predicted RFS in the IMPACT trial (P = .002). Conclusions Breast cancer patients with pathological stage 1 or 0 disease after neoadjuvant endocrine therapy and a low-risk biomarker profile in the surgical specimen (PEPI score 0) have an extremely low risk of relapse and are therefore unlikely to benefit from adjuvant chemotherap