Christian F Singer

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

Are you Christian F Singer?

Claim your profile

Publications (252)1067.86 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the breast cancer screening efficacy of mammography, ultrasound, and magnetic resonance imaging (MRI) in a high-risk population and in various population subgroups. In a single-center, prospective, nonrandomized comparison study, BRCA mutation carriers and women with a high familial risk (> 20% lifetime risk) for breast cancer were offered screening with mammography, ultrasound, and MRI every 12 months. Diagnostic performance was compared between individual modalities and their combinations. Further comparisons were based on subpopulations dichotomized by screening rounds, mutation status, age, and breast density. There were 559 women with 1,365 complete imaging rounds included in this study. The sensitivity of MRI (90.0%) was significantly higher (P < .001) than that of mammography (37.5%) and ultrasound (37.5%). Of 40 cancers, 18 (45.0%) were detected by MRI alone. Two cancers were found by mammography alone (a ductal carcinoma in situ [DCIS] with microinvasion and a DCIS with < 10-mm invasive areas). This did not lead to a significant increase of sensitivity compared with using MRI alone (P = .15). No cancers were detected by ultrasound alone. Similarly, of 14 DCISs, all were detected by MRI, whereas mammography and ultrasound each detected five DCISs (35.7%). Age, mutation status, and breast density had no influence on the sensitivity of MRI and did not affect the superiority of MRI over mammography and ultrasound. MRI allows early detection of familial breast cancer regardless of patient age, breast density, or risk status. The added value of mammography is limited, and there is no added value of ultrasound in women undergoing MRI for screening. © 2015 by American Society of Clinical Oncology.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Specimen collection method and quality insurance is pivotal in biomarker discovery. Pre-analytical variables concerning blood collection and sample handling might affect analytical results and should be standardised prior application. In this study, we examine pre-analytical characteristics of blood samples using protein microarray. The influences of 1) standby times until centrifugation (1h, 4h, 24h and 48h), 2) four blood collection methods, and 3) IgG purified from those samples on differentially reactive antigens between samples ("DIRAGs") were investigated. Spearman correlation analyses of intra-individual arrays demonstrated remarkable differences (0.75-0.98 vs. 0.5-0.75) of antibody reactivities within and between serum and plasma samples. Class comparison showed that reactive antigen profiles were best preserved using IgG purified samples of serum tubes without separation gel as after 24hours 83% of the 1h baseline DIRAGs were re-found. Testing dilution series with protein microarrays and Luminex xMap® Technology, we found linear correlations (R(2)=0.94-0.99) between IgG concentration and read-out when using purified IgG instead of serum. Therefore, we highly recommend standardising pre-analytics and proposing the use of purified IgG for autoantibody immune-profiling with protein microarrays to reduce potential unspecific binding of matrix proteins abundant in serum and plasma samples. Although purified IgG cannot completely compensate the influence of pre-analytics, in highly parallel immune-profiling IgG enables reduction of unspecific effects, which occur when using serum or plasma for analysis on protein microarrays. Reproducibility problems due to pre-analytical processing of blood samples might explain discrepant results reported in various biomarker studies. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Immunological Methods 02/2015; DOI:10.1016/j.jim.2015.01.009 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Special focus and aim of our research activities at AIT, the Austrian Institute of Technology, is to define reliable biomarkers suitable for early and non-invasive disease diagnosis from body fluids such as serum/plasma and saliva. Along a selection of research projects, which are described in more detail underneath, we will present and introduce the broad portfolio of high throughput technologies we successfully apply for diagnostic biomarker discovery and validation. As a first show case of successful non-invasive disease biomarker discovery we will present a study where we investigated and compared the genome wide methylation levels of lung cancer patients, patients suffering from lung fibrosis, patients with COPD (chronic obstructive pulmonary disease), and DNA samples derived from healthy lungs. Along this study we could identify specific methylation patterns for each of these lung diseases. After quantitative PCR validation of 240 disease specific methylation markers in the discovery sample set, the 90 top markers were picked and applied for serum testing (n=204). When we applied gradient boosting classification for differential diagnosis of tested lung diseases and healthy controls an AUC value of 0.95 was reached here to separate cancer from all other non-cancer samples whereas in differential diagnosis of healthy-, COPD and fibrosis patients AUC values of 0.71 and 0.49 were obtained for fibrosis, respectively COPD. Thus in case of COPD the presented method may be used to monitor cancer risk within COPD patients. Our second show case comprises a study where we screened cancer patients’ sera for tumor-specific antibody profiles using an in-house developed 16k protein-microarray. This methodology, which will be described in detail, enabled us to define different tumor-associated antigen (TAA) classifier panels for the big 4 cancer entities (breast, colon, prostate and lung cancer) which all showed very promising classification successes in distinction of patients versus controls. We will further present preliminary data obtained when comparing serum and saliva autoantibody profiles of breast-cancer patients and healthy controls.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 6-15 % of breast cancer patients are diagnosed with primary ulcerated breast cancer (ULBC). ULBC is known to be associated with short recurrence free and poor overall survival. Therefore, the purpose of this study was to characterize ULBC and compare the histopathological findings with those of non-ulcerative breast cancer (NULBC). A total of 152 ULBCs were evaluated and compared to 304 consecutive non-ulcerated, age-matched breast malignancies. Patients mean age was 65 years (SD = 13.0 ULBC, SD = 14.0 NULBC). ULBC was associated with a higher rate of poorly differentiated tumors (p = <0.001), as well as larger tumor sizes (p = <0.001). As expected, the rate of axillary lymph node involvement was higher in ULBC patients (p = <0.001). In addition to that, ULBC was associated with a higher rate of triple negative breast cancer (p = 0.002), and higher Ki67 expression (p = <0.001). ULBC showed more aggressive histopathological features in comparison to NULBC which may contribute to the generally known poorer prognosis of women with ULBC.
    Tumor Biology 12/2014; DOI:10.1007/s13277-014-2977-7 · 2.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and non-genetic modifying factors. In this study we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n=3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed p-values of association ranged between 0.005-1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
    Cancer Epidemiology Biomarkers & Prevention 10/2014; 24:308-16. DOI:10.1158/1055-9965.EPI-14-0532 · 4.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan-Meier analyses. Use of RRSO was 45 % for BRCA1 and 34 % for BRCA2 by age 40, and 86 % for BRCA1 and 71 % for BRCA2 by age 50. RRM usage was estimated to be 46 % by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.
    Breast Cancer Research and Treatment 10/2014; 148(2). DOI:10.1007/s10549-014-3134-0 · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Men with a BRCA2 mutation face substantial lifetime risks for the development of both breast and prostate cancer.
    Clinical Genetics 08/2014; DOI:10.1111/cge.12478 · 3.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Women with a genetic predisposition to breast cancer may be at increased risk of cancer after exposure to ionizing radiation. It is unclear whether mammography screening increases the risk of breast cancer among BRCA1 and BRCA2 carriers. We identified 2,346 women with a BRCA1 (n = 1844) or BRCA2 (n = 502) mutation and no breast cancer, and we reviewed their history of mammography exposure. These women were followed for an average of 5.3 years and were observed for new breast cancer diagnoses. At study entry, 1808 women (77.1 %) reported ever having had a mammogram; of these, 204 women (11.2 %) reported having had a mammogram before age 30. We estimated the hazard ratios for the development of invasive breast cancer, conditional on the number of prior mammograms and on the age at first mammogram. Hazard ratios were estimated and stratified by gene (BRCA1 or BRCA2), relative to women with no exposure. We observed no significant association between prior mammography exposure and breast cancer risk for BRCA1 carriers (HR 0.79; 95 % CI 0.53-1.19; P = 0.26) or for BRCA2 carriers (HR 0.90; 95 % CI 0.35-2.34; P = 0.83). An early age at first mammogram (<30 years) did not increase breast cancer risk among BRCA1 carriers (HR 0.75; 95 % CI 0.41-1.37; P = 0.35) or among BRCA2 carriers (HR 0.69; 95 % CI 0.19-2.48; P = 0.57). Exposure to mammography in women with BRCA1 and BRCA2 mutations is not associated with an increased risk of breast cancer.
    Breast Cancer Research and Treatment 08/2014; 147(1). DOI:10.1007/s10549-014-3063-y · 4.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER(+), HER2(-) early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations.Methods:We prospectively recruited 75 ER(+), HER2(-) breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness.Results:The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective.Conclusions:The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy.British Journal of Cancer advance online publication, 8 July 2014; doi:10.1038/bjc.2014.339 www.bjcancer.com.
    British Journal of Cancer 07/2014; DOI:10.1038/bjc.2014.339 · 4.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite patient selection based on ERBB2-overexpression, not all patients benefit from trastuzumab therapy. We have investigated whether a ERBB2 gene dosage effect might provoke increased biological aggressiveness and altered trastuzumab sensitivity. Absolute ERBB2 copy numbers ("CN") and ERBB2/centromer 17 ratios ("R") were measured by FISH analysis in tumors of 127 patients receiving trastuzumab-based treatment for Her-2/neu over-expressing metastatic breast cancer. CN and R were both significantly associated with shorter time to first metastasis (TTM) (CN: OR: 1.099, 95% CI: 1.042-1.159; R: OR: 1.211, 95% CI: 1.080-1.357) and longer PFS (CN: OR: 0.917, 95% CI: 0.867-0.969; R: OR: 0.840, 95% CI: 0.743-0.949) in a continuous variable Cox Regression model. Tumors with ERBB2/centromer 17 ratios of <2.2 had a significantly shorter TTM (p=0.002) and significantly longer PFS (p=0.003) than tumors with low-level (R: 2.2-6) and high-level amplification (R:>6). Interestingly, when ERBB2 copy numbers were analysed, a significantly shorter TTM (p=0.001) and longer PFS (p=0.026) were observed in the group with high-level amplified CN (CN:>13), while no difference was observed between non- and low-level amplified CN. R, but not CN, was an independent predictor of complete (CR; OR: 1.685; 95%CI: 1.122-2.532) and partial (PR; OR: 1.704; 95% CI: 1.136-2.556) response in Logistic Regression analysis. CR (p=0.016) rates were significantly higher in the high-level amplification group (R>6), but no difference existed in response rates between non- and low-level amplified tumors in Chi-Square tests.High-level ERBB2 amplification is associated with shorter TTM but improved response to trastuzumab in metastatic breast cancer. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2014; 135(1). DOI:10.1002/ijc.28660 · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Women with a mutation in BRCA1 or BRCA2 face a lifetime risk of breast cancer of approximately 80 %. Tamoxifen treatment of the first cancer has been associated with a reduction in the risk of a subsequent contralateral cancer. We studied 1,504 women with a known BRCA1 or BRCA2 mutation, 411 women with bilateral breast cancer (cases) and 1,093 women with unilateral breast cancer (controls) in a matched case-control study. Control women were of similar age and had a similar age of diagnosis of first breast cancer as the cases. For each woman who used tamoxifen, the starting and stopping dates were abstracted and the duration of tamoxifen use was calculated. Three hundred and thirty-one women had used tamoxifen (22 %); of these 84 (25 %) had completed four or more years of tamoxifen, the remainder stopped prematurely or were current users. For women with up to 1 year of tamoxifen use, the odds ratio for contralateral breast cancer was 0.37 (95 % CI 0.20-0.69; p = 0.001) compared to women with no tamoxifen use. Among women with 1-4 years of tamoxifen use the odds ratio was 0.53 (95 % CI 0.32-0.87; p = 0.01). Among women with four or more years of tamoxifen use the odds ratio was 0.83 (95 % CI 0.44-1.55; p = 0.55). Short-term use of tamoxifen for chemoprevention in BRCA1 and BRCA2 mutation carriers may be as effective as a conventional 5-year course of treatment.
    Breast Cancer Research and Treatment 06/2014; 146(2). DOI:10.1007/s10549-014-3026-3 · 4.47 Impact Factor
  • Geburtshilfe und Frauenheilkunde 06/2014; 74(05). DOI:10.1055/s-0034-1374762 · 0.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
    PLoS Genetics 04/2014; 10(4):e1004256. DOI:10.1371/journal.pgen.1004256 · 8.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purposes of this study were to estimate the reduction in risk of ovarian, fallopian tube, or peritoneal cancer in women with a BRCA1 or BRCA2 mutation after oophorectomy, by age of oophorectomy; to estimate the impact of prophylactic oophorectomy on all-cause mortality; and to estimate 5-year survival associated with clinically detected ovarian, occult, and peritoneal cancers diagnosed in the cohort. Women with a BRCA1 or BRCA2 mutation were identified from an international registry; 5,783 women completed a baseline questionnaire and ≥ one follow-up questionnaires. Women were observed until either diagnosis of ovarian, fallopian tube, or peritoneal cancer, death, or date of most recent follow-up. Hazard ratios (HRs) for cancer incidence and all-cause mortality associated with oophorectomy were evaluated using time-dependent survival analyses. After an average follow-up period of 5.6 years, 186 women developed either ovarian (n = 132), fallopian (n = 22), or peritoneal (n = 32) cancer, of whom 68 have died. HR for ovarian, fallopian, or peritoneal cancer associated with bilateral oophorectomy was 0.20 (95% CI, 0.13 to 0.30; P < .001). Among women who had no history of cancer at baseline, HR for all-cause mortality to age 70 years associated with an oophorectomy was 0.23 (95% CI, 0.13 to 0.39; P < .001). Preventive oophorectomy was associated with an 80% reduction in the risk of ovarian, fallopian tube, or peritoneal cancer in BRCA1 or BRCA2 carriers and a 77% reduction in all-cause mortality.
    Journal of Clinical Oncology 02/2014; 32(15). DOI:10.1200/JCO.2013.53.2820 · 17.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: To assess the prognostic value of the PAM50 risk-of-recurrence (ROR) score on late distant recurrence (beyond 5 years after diagnosis and treatment) in a large cohort of postmenopausal, endocrine-responsive breast cancer patients.EXPERIMENTAL DESIGN: The PAM50 assay was performed on formalin-fixed paraffin-embedded whole-tumor sections of patients who had been enrolled in the Austrian Breast and Colorectal Cancer Study Group Trial 8 (ABCSG-8). RNA expression levels of the PAM50 genes were determined centrally using the nCounter Dx Analysis System. Late distant recurrence-free survival (DRFS) was analyzed using Cox models adjusted for clinical and pathologic parameters.RESULTS: PAM50 analysis was successfully performed in 1,246 ABCSG-8 patients. PAM50 ROR score and ROR-based risk groups provided significant additional prognostic information with respect to late DRFS compared with a combined score of clinical factors alone (ROR score: ΔLRχ2 15.32, P < 0.001; ROR-based risk groups: ΔLRχ2 14.83, P < 0.001). Between years 5 and 15, we observed an absolute risk of distant recurrence of 2.4% in the low ROR-based risk group, as compared with 17.5% in the high ROR-based risk group. The DRFS differences according to the PAM50 ROR score were observed for both node-positive and node-negative disease.CONCLUSION: PAM50 ROR score and ROR-based risk groups can differentiate patients with breast cancer with respect to their risk for late distant recurrence beyond what can be achieved with established clinicopathologic risk factors.
    Clinical Cancer Research 02/2014; 20(5). DOI:10.1158/1078-0432.CCR-13-1845 · 7.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories. One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables. In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P < 0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P < 0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups. The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment. ABCSG 8: NCT00291759.
    Annals of Oncology 02/2014; 25(2):339-45. DOI:10.1093/annonc/mdt494 · 6.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
    Breast Cancer Research and Treatment 02/2014; 143(3):579-86. DOI:10.1007/s10549-013-2823-4 · 4.47 Impact Factor
  • Breast Care 01/2014; 9(5):364-366. DOI:10.1159/000368876 · 0.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: This randomized phase III trial compared pathologic complete response (pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin–docetaxel (ED) ± capecitabine (C), and evaluated the addition of trastuzumab in HER2-positive tumors. Patients and methods: Patients with invasive breast cancer (except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75 mg/m2) ± C (1000 mg/m2, twice daily, days 1–14). Patients with HER2-positive disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg every 3 weeks) or not. Primary end point: pCR rate at the time of surgery. Results: Five hundred thirty-six patients were randomized to ED (n = 266) or EDC (n = 270); 93 patients were further randomized to trastuzumab (n = 44) or not (n = 49). pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P = 0.027), and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5% ED, P = 0.212). Rates of axillary node involvement at surgery and breast conservation were improved with EDC versus ED, but not significantly; the addition of trastuzumab had no further impact. Hormone receptor status, tumor size, grade, and C (all P ≤ 0.035) were independent prognostic factors for pCR. Trastuzumab added to ED ± C significantly increased the number of serious adverse events (35 versus 18; P = 0.020), mainly due to infusion-related reactions. Conclusion: These findings show that the integration of C into a neoadjuvant taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment option, with incorporation of trastuzumab in HER2-positive disease. Clinical trial number: NCT00309556, www.clinicaltrials.gov. Key words: capecitabine, docetaxel, early breast cancer, epirubicin, neoadjuvant treatment
    Annals of Oncology 12/2013; 25(2). DOI:10.1093/annonc/mdt508 · 6.58 Impact Factor

Publication Stats

3k Citations
1,067.86 Total Impact Points

Institutions

  • 2015
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 2002–2015
    • Medical University of Vienna
      • • Department of Obstetrics and Gynecology
      • • Comprehensive Cancer Center Vienna
      • • Universitätsklinik für Innere Medizin I
      Wien, Vienna, Austria
  • 2013
    • Mississippi University for Women
      Колумбус, Mississippi, United States
    • Peter MacCallum Cancer Centre
      • Department of Cancer Medicine
      Melbourne, Victoria, Australia
  • 2012
    • Treatment Research Institute, Philadelphia PA
      Philadelphia, Pennsylvania, United States
  • 2010–2012
    • Mayo Clinic - Rochester
      • • Department of Health Science Research
      • • Department of Laboratory Medicine & Pathology
      Рочестер, Minnesota, United States
    • Queensland Institute of Medical Research
      Brisbane, Queensland, Australia
  • 2009–2012
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
    • Pantarhei Bioscience
      Zeist, Utrecht, Netherlands
  • 1999–2011
    • University of Vienna
      • Department of Gynecology
      Wien, Vienna, Austria
  • 2008
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2002–2008
    • Ludwig Boltzmann Institute for Experimental and Clinical Traumatology
      Wien, Vienna, Austria
  • 2007
    • Ghent University
      Gand, Flemish, Belgium
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2000–2004
    • Ludwig Boltzmann-Cluster Oncology (LB-CO) | Medical University Vienna
      Wien, Vienna, Austria