Showing papers on "Breast cancer published in 2006"

American society of clinical oncology/college of american pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer

Abstract: Purpose To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. Methods The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. Results Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. Recommendations The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly...

Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.

Abstract: ContextGene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER–), luminal A, and luminal B.ObjectivesTo determine population-based distributions and clinical associations for breast cancer subtypes.Design, Setting, and ParticipantsImmunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2−), luminal B (ER+ and/or PR+, HER2+), basal-like (ER−, PR−, HER2−, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER− (ER−, PR−, and HER2+), and unclassified (negative for all 5 markers).Main Outcome MeasuresWe examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer–specific survival.ResultsThe basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non–African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER− subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer–specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER− and basal-like subtypes.ConclusionsBasal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non–African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.

Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer

Abstract: A b s t r ac t The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group. The hazard ratio for the independently assessed time to progression was 0.49 (95% confidence interval, 0.34 to 0.71; P<0.001), with 49 events in the combination-therapy group and 72 events in the monotherapy group. The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group. This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events. Conclusions Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2- positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572.)

Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer

Abstract: Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor‐positive, lymph node‐negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. Methods The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy‐ treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. Results A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P .038). Patients with high-RS ( 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS ( 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, 1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit.

Gene Expression Profiling in Breast Cancer: Understanding the Molecular Basis of Histologic Grade To Improve Prognosis

Abstract: Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30% – 60% of tumors are classifi ed as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profi les of breast cancers and whether such profi les could be used to improve histologic grading. Methods: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identifi ed differentially expressed genes in a training set of 64 estrogen receptor (ER) – positive tumor samples by comparing expression profi les between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to defi ne the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan – Meier analysis. All statistical tests were two-sided. Results: We identifi ed 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1 – 3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confi dence interval = 2.25 to 5.78; P <.001, log-rank test). Conclusions: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value. [J Natl Cancer Inst 2006;98:262 – 72]

Breast Density and Parenchymal Patterns as Markers of Breast Cancer Risk: A Meta-analysis

Abstract: Mammographic features are associated with breast cancer risk, but estimates of the strength of the association vary markedly between studies, and it is uncertain whether the association is modified by other risk factors. We conducted a systematic review and meta-analysis of publications on mammographic patterns in relation to breast cancer risk. Random effects models were used to combine study-specific relative risks. Aggregate data for > 14,000 cases and 226,000 noncases from 42 studies were included. Associations were consistent in studies conducted in the general population but were highly heterogeneous in symptomatic populations. They were much stronger for percentage density than for Wolfe grade or Breast Imaging Reporting and Data System classification and were 20% to 30% stronger in studies of incident than of prevalent cancer. No differences were observed by age/menopausal status at mammography or by ethnicity. For percentage density measured using prediagnostic mammograms, combined relative risks of incident breast cancer in the general population were 1.79 (95% confidence interval, 1.48-2.16), 2.11 (1.70-2.63), 2.92 (2.49-3.42), and 4.64 (3.64-5.91) for categories 5% to 24%, 25% to 49%, 50% to 74%, and > or = 75% relative to < 5%. This association remained strong after excluding cancers diagnosed in the first-year postmammography. This review explains some of the heterogeneity in associations of breast density with breast cancer risk and shows that, in well-conducted studies, this is one of the strongest risk factors for breast cancer. It also refutes the suggestion that the association is an artifact of masking bias or that it is only present in a restricted age range.

Estrogen carcinogenesis in breast cancer.

Abstract: n this article, we review recent findings related to estrogen exposure and the risk of breast cancer, the mechanisms that may be involved, and the clinical implications of these findings. The weight of evidence indicates that exposure to estrogen is an important determinant of the risk of breast cancer. The mechanisms of carcinogenesis in the breast caused by estrogen include the metabolism of estrogen to genotoxic, mutagenic metabolites and the stimulation of tissue growth. Together, these processes cause initiation, promotion, and progression of carcinogenesis. Insight into the mechanisms of the causation of cancer by estrogen will identify determinants of susceptibility to breast cancer and new targets for prevention and therapeutic intervention.

Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial.

Abstract: ContextTamoxifen is approved for the reduction of breast cancer risk, and raloxifene has demonstrated a reduced risk of breast cancer in trials of older women with osteoporosis.ObjectiveTo compare the relative effects and safety of raloxifene and tamoxifen on the risk of developing invasive breast cancer and other disease outcomes.Design, Setting, and PatientsThe National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene trial, a prospective, double-blind, randomized clinical trial conducted beginning July 1, 1999, in nearly 200 clinical centers throughout North America, with final analysis initiated after at least 327 incident invasive breast cancers were diagnosed. Patients were 19 747 postmenopausal women of mean age 58.5 years with increased 5-year breast cancer risk (mean risk, 4.03% [SD, 2.17%]). Data reported are based on a cutoff date of December 31, 2005.InterventionOral tamoxifen (20 mg/d) or raloxifene (60 mg/d) over 5 years.Main Outcome MeasuresIncidence of invasive breast cancer, uterine cancer, noninvasive breast cancer, bone fractures, thromboembolic events.ResultsThere were 163 cases of invasive breast cancer in women assigned to tamoxifen and 168 in those assigned to raloxifene (incidence, 4.30 per 1000 vs 4.41 per 1000; risk ratio [RR], 1.02; 95% confidence interval [CI], 0.82-1.28). There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). There were 36 cases of uterine cancer with tamoxifen and 23 with raloxifene (RR, 0.62; 95% CI, 0.35-1.08). No differences were found for other invasive cancer sites, for ischemic heart disease events, or for stroke. Thromboembolic events occurred less often in the raloxifene group (RR, 0.70; 95% CI, 0.54-0.91). The number of osteoporotic fractures in the groups was similar. There were fewer cataracts (RR, 0.79; 95% CI, 0.68-0.92) and cataract surgeries (RR, 0.82; 95% CI, 0.68-0.99) in the women taking raloxifene. There was no difference in the total number of deaths (101 vs 96 for tamoxifen vs raloxifene) or in causes of death.ConclusionsRaloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer and has a lower risk of thromboembolic events and cataracts but a nonstatistically significant higher risk of noninvasive breast cancer. The risk of other cancers, fractures, ischemic heart disease, and stroke is similar for both drugs.Trial Registrationclinicaltrials.gov Identifier: NCT00003906Published online June 5, 2006 (doi:10.1001/jama.295.23.joc60074).

Randomized Multicenter Trial of Sentinel Node Biopsy Versus Standard Axillary Treatment in Operable Breast Cancer: The ALMANAC Trial

Abstract: BACKGROUND: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. METHODS: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. RESULTS: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval [CI] = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P .05). CONCLUSION: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.

Concordance among Gene-Expression–Based Predictors for Breast Cancer

Abstract: BACKGROUND Gene-expression-profiling studies of primary breast tumors performed by different laboratories have resulted in the identification of a number of distinct prognostic profiles, or gene sets, with little overlap in terms of gene identity. METHODS To compare the predictions derived from these gene sets for individual samples, we obtained a single data set of 295 samples and applied five gene-expression-based models: intrinsic subtypes, 70-gene profile, wound response, recurrence score, and the two-gene ratio (for patients who had been treated with tamoxifen). RESULTS We found that most models had high rates of concordance in their outcome predictions for the individual samples. In particular, almost all tumors identified as having an intrinsic subtype of basal-like, HER2-positive and estrogen-receptor-negative, or luminal B (associated with a poor prognosis) were also classified as having a poor 70-gene profile, activated wound response, and high recurrence score. The 70-gene and recurrence-score models, which are beginning to be used in the clinical setting, showed 77 to 81 percent agreement in outcome classification. CONCLUSIONS Even though different gene sets were used for prognostication in patients with breast cancer, four of the five tested showed significant agreement in the outcome predictions for individual patients and are probably tracking a common set of biologic phenotypes.

Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer.

Abstract: Background We compared docetaxel with vinorelbine for the adjuvant treatment of early breast cancer. Women with tumors that overexpressed HER2/neu were also assigned to receive concomitant treatment with trastuzumab or no such treatment. Methods We randomly assigned 1010 women with axillary-node–positive or high-risk node-negative cancer to receive three cycles of docetaxel or vinorelbine, followed by (in both groups) three cycles of fluorouracil, epirubicin, and cyclophosphamide. The 232 women whose tumors had an amplified HER2/neu gene were further assigned to receive or not to receive nine weekly trastuzumab infusions. The primary end point was recurrence-free survival. Results Recurrence-free survival at three years was better with docetaxel than with vinorelbine (91 percent vs. 86 percent; hazard ratio for recurrence or death, 0.58; 95 percent confidence interval, 0.40 to 0.85; P=0.005), but overall survival did not differ between the groups (P=0.15). Within the subgroup of patients who had HER2/neu-...

Validation and Clinical Utility of a 70-Gene Prognostic Signature for Women With Node-Negative Breast Cancer

Abstract: Background: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. Methods: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from fi ve European centers were divided into high- and low-risk groups based on the gene signature classifi cation and on clinical risk classifi cations. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis – free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER] – positive patients) or 92% (for ERnegative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. Results: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confi dence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low – and high – clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. Conclusions: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer. [J Natl Cancer Inst 2006;98: 1183 – 92 ]

Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse

Abstract: Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (TR) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive TR were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue (n = 10) were determined. A median cutoff of ≥ 15 defined patients with high numbers of TR. Results TR numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive TR identified patients with DCIS at increased risk of relapse (P = .04) and patients with invasive tumors with both shorter relapse-free (P = .004) and overall survival (P = .007). High...

Lessons from phase III clinical trials on anti-VEGF therapy for cancer

Abstract: In randomized phase III trials two anti-vascular endothelial growth factor (VEGF) approaches have yielded survival benefit in patients with metastatic cancer. In one approach, the addition of bevacizumab, a VEGF-specific antibody, to standard chemotherapy improved overall survival in colorectal and lung cancer patients and progression-free survival in breast cancer patients. In the second approach, multitargeted tyrosine kinase inhibitors that block VEGF receptor and other kinases in both endothelial and cancer cells, demonstrated survival benefit in gastrointestinal stromal tumor and renal-cell-carcinoma patients. By contrast, adding bevacizumab to chemotherapy failed to increase survival in patients with previously treated and refractory metastatic breast cancer. Furthermore, addition of vatalanib, a kinase inhibitor developed as a VEGF receptor-selective agent, to chemotherapy did not show a similar benefit in metastatic colorectal cancer patients. These contrasting responses raise critical questions about how these agents work and how to combine them optimally. We summarize three of the many potential mechanisms of action of anti-VEGF agents, and also discuss progress relating to the identification of potential biomarkers for anti-VEGF-agent efficacy in humans.

Locoregional Relapse and Distant Metastasis in Conservatively Managed Triple Negative Early-Stage Breast Cancer

Abstract: Purpose To determine the prognostic significance of triple negative breast cancers with respect to locoregional relapse and distant metastasis in conservatively managed breast cancer patients. Patients and Methods A database of conservative managed (conservative surgery followed by radiation) patients, in whom all three markers (estrogen receptor, progesterone receptor, and HER2/neu) were available, was reviewed. Patients were classified as triple negative if they tested negative for all three markers. Of 482 patients with all three markers available, 117 were classified as triple negative. Results As of September 2005, with a median follow-up time of 7.9 years, of the 482 patients in the study, there have been 53 in-breast relapses, 10 nodal relapses, 77 distant relapses, and 69 deaths. At 5 years, the triple negative cohort had a poorer distant metastasis-free rate compared with the other subtypes (67% v 82%, respectively; P .002). Triple negative subtype was an independent predictor of distant metastasis (hazard ratio 2.14; 95% CI, 1.31 to 3.53; P .002) and cause-specific survival (hazard ratio 1.79; 95% CI, 1.03 to 3.22; P .047). There was no significant difference in local control between the triple negative and other subtypes (83% v 83%, respectively). Of 99 BRCA-tested patients in this cohort, 10 had deleterious mutations in BRCA1, and seven had mutations in BRCA2 .O f 10BRCA1 patients, eight were triple negative, whereas only one of seven BRCA2 patients was triple negative (P .001). Conclusion Patients classified as triple negative have a poor prognosis. However, there was no evidence that these patients are at higher risk for local relapse after conservative surgery and radiation. Patients with BRCA1 mutations develop predominantly triple negative tumors.

Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis

Abstract: Background: Physical exercise has been identified as a potential intervention to improve quality of life in women with breast cancer. We sought to summarize the available evidence concerning the effects of exercise on breast cancer patients and survivors. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsychINFO, CancerLit, PEDro and SportDiscus as well as conference proceedings, clinical practice guidelines and other unpublished literature resources. We included only randomized controlled trials that examined exercise interventions for breast cancer patients or survivors with quality of life, cardiorespiratory fitness or physical functioning as primary outcomes. We also extracted data on symptoms of fatigue, body composition and adverse effects. Results: Of 136 studies identified, 14 met all the inclusion criteria. Despite significant heterogeneity and relatively small samples, the point estimates in terms of the benefits of exercise for all outcomes were positive even when statistical significance was not achieved. Exercise led to statistically significant improvements in quality of life as assessed by the Functional Assessment of Cancer Therapy–General (weighted mean difference [WMD] 4.58, 95% confidence interval [CI] 0.35 to 8.80) and Functional Assessment of Cancer Therapy–Breast (WMD 6.62, 95% CI 1.21 to 12.03). Exercise also led to significant improvements in physical functioning and peak oxygen consumption and in reducing symptoms of fatigue. Interpretation: Exercise is an effective intervention to improve quality of life, cardiorespiratory fitness, physical functioning and fatigue in breast cancer patients and survivors. Larger trials that have a greater focus on study quality and adverse effects and that examine the long-term benefits of exercise are needed for this patient group.

Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival

Abstract: Purpose: We reported previously that ≥5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated. Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of ≥5 CTCs/7.5 mL at each blood draw. Results: Median PFS times for patients with 18.5 months. For patients with ≥5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different. Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.

Effect of Screening and Adjuvant Therapy on Mortality From Breast Cancer

Abstract: In several countries, a drop in mortality from breast cancer has been documented starting in 1975. Both early detection by mammographic screening and advances in management are plausible explanations. The National Institutes of Health have used a competitive peer review process to develop 7 independent statistical models of breast cancer incidence and mortality. A consortium of investigators used the same sources to obtain data on screening mammography, adjuvant treatment, and health benefits relating to the rate of death from breast cancer in the years 1975-2000. The use of mammographic screening in women age 40 and over increased markedly over the period 1985 to 2000. The use of adjuvant treatment depended on numerous factors beside the calendar year, including age, tumor stage, and estrogen-receptor status. The proportion of women given adjuvant treatment increased from virtually none in 1975 to approximately 80% in 2000. By 2000, half of all women were using tamoxifen. All 7 models predicted similar proportional reductions in mortality from a combination of screening and adjuvant therapy. The proportion of overall reduction in breast cancer deaths ascribed to screening ranged from 28% to 65% (median, 46%). The remaining decrease in mortality was associated with adjuvant treatment. Variation between models in the absolute contribution of screening was greater than for treatment. Combined screening and adjuvant therapy reduced breast cancer mortality by 25 to 38% (median, 30%). The proportion of decreased mortality ascribed to adjuvant treatment was 12 to 21% (median, 19%). For each of the 7 models, the combination of screening and adjuvant treatment lowered mortality slightly less than the sum of contributions from screening and adjuvant therapy alone. The investigators conclude from these findings that both mammographic screening and adjuvant treatment have helped to lower deaths from breast cancer in the United States.

Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women

Abstract: As compared with placebo, raloxifene had no significant effect on the risk of primary coronary events (533 vs. 553 events; hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.07), and it reduced the risk of invasive breast cancer (40 vs. 70 events; hazard ratio, 0.56; 95 percent confidence interval, 0.38 to 0.83; absolute risk reduction, 1.2 invasive breast cancers per 1000 women treated for one year); the benefit was primarily due to a reduced risk of estrogen-receptor–positive invasive breast cancers. There was no significant difference in the rates of death from any cause or total stroke according to group assignment, but raloxifene was associated with an increased risk of fatal stroke (59 vs. 39 events; hazard ratio, 1.49; 95 percent confidence interval, 1.00 to 2.24; absolute risk increase, 0.7 per 1000 woman-years) and venous thromboembolism (103 vs. 71 events; hazard ratio, 1.44; 95 percent confidence interval, 1.06 to 1.95; absolute risk increase, 1.2 per 1000 woman-years). Raloxifene reduced the risk of clinical vertebral fractures (64 vs. 97 events; hazard ratio, 0.65; 95 percent confidence interval, 0.47 to 0.89; absolute risk reduction, 1.3 per 1000). Conclusions Raloxifene did not significantly affect the risk of CHD. The benefits of raloxifene in reducing the risks of invasive breast cancer and vertebral fracture should be weighed against the increased risks of venous thromboembolism and fatal stroke. (ClinicalTrials.gov number, NCT00190593.)

Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer : National surgical adjuvant breast and bowel project protocol B-27

Abstract: Purpose This study was designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS). Patients and Methods Women with operable breast cancer (N = 2,411) were randomly assigned to receive preoperative AC followed by surgery, AC followed by T and surgery, or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9 months. Results Addition of T to AC did not significantly impact DFS or OS. There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events (P = .0034). Preoperative T, but not postoperative T, significantly improved DFS in patients who had a clinical partial response after AC (hazard ratio [HR] = 0.71; 95% CI, 0.55 to 0.91; P = .007). Pathologic complete response, which was doubled by addition ...

Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening

Abstract: Previous trials, limited in many respects, have not found digital mammography to be significantly more accurate than the standard film method. A total of 42,760 asymptomatic women seen at 33 sites in the United States and Canada requested screening mammography and underwent both film and digital examinations. Two radiologists independently interpreted the film and digital mammograms. All participants either had breast biopsy within 15 months after evaluation or had a follow-up mammogram 10 months or longer after entry to the study. The results were assessed by receiver operating characteristic analysis. Both digital and film mammograms were positive in 0.5% of women. Another 2.2% had only a positive digital study, whereas 1.9% had only a positive film study. In the remaining women, approximately 95% of the total, both imaging studies were negative. Of 335 breast cancers diagnosed within 455 days after entry to the study, approximately three fourths were found within a year after evaluation. There were no substantial differences between the digital and film findings with respect to histology or stage of disease. The area under the curve was similar for the 2 studies and was not influenced by race or the risk of breast cancer. Digital mammography did, however, perform significantly better than the film method in women less than 50 years of age, in those having heterogeneously dense or very dense breasts, and premenopausal or perimenopausal women. The digital and film methods performed equally well in women age 50 years and older, those with fatty breasts or scattered fibroglandular densities, and those who were postmenopausal.

Can Anesthetic Technique for Primary Breast Cancer Surgery Affect Recurrence or Metastasis

Abstract: Background: Regional anesthesia is known to prevent or attenuate the surgical stress response; thus, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. We hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. Methods: In this retrospective study, we examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Results: 50 patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32±5 months (mean±SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence and metastasis-free survival was 94% (95% CI 87,100) and 82% (74, 91) at 24 months and 94 (87, 100) and 77 (68, 87) at 36 months in the paravertebral and general anesthesia patients, respectively, P=0.012. Conclusions: This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.

Body image and sexual problems in young women with breast cancer

Abstract: Purpose: The purpose of this study was to determine the frequency of body image and sexual problems in the first months after treatment among women diagnosed with breast cancer at age 50 or younger. Background: Breast cancer treatment may have severe effects on the bodies of younger women. Surgical treatment may be disfiguring, chemotherapy may cause abrupt menopause, and hormone replacement is not recommended. Methods: A multi-ethnic population-based sample of 549 women aged 22–50 who were married or in a stable unmarried relationship were interviewed within seven months of diagnosis with in situ, local, or regional breast cancer. Results: Body image and sexual problems were experienced by a substantial proportion of women in the early months after diagnosis. Half of the 546 women experienced two or more body image problems some of the time (33%), or at least one problem much of the time (17%). Among sexually active women, greater body image problems were associated with mastectomy and possible reconstruction, hair loss from chemotherapy, concern with weight gain or loss, poorer mental health, lower self-esteem, and partner's difficulty understanding one's feelings. Among the 360 sexually active women, half (52%) reported having a little problem in two or more areas of sexual functioning (24%), or a definite or serious problem in at least one area (28%). Greater sexual problems were associated with vaginal dryness, poorer mental health, being married, partner's difficulty understanding one's feelings, and more body image problems, and there were significant ethnic differences in reported severity. Conclusions: Difficulties related to sexuality and sexual functioning were common and occurred soon after surgical and adjuvant treatment. Addressing these problems is essential to improve the quality of life of young women with breast cancer. Copyright © 2005 John Wiley & Sons, Ltd.

Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis.

Abstract: BACKGROUND Lymphatic mapping with sentinel lymph node biopsy has the potential for reducing the morbidity associated with breast carcinoma staging. It has become a widely used technology despite limited data from controlled clinical trials. METHODS A systematic review of the world's literature of sentinel lymph node (SLN) biopsy in patients with early-stage breast carcinoma was undertaken by using electronic and hand searching techniques. Only studies that incorporated full axillary lymph node dissection (ALND), regardless of SLN results, were included. Individual study results along with weighted summary measures were estimated using the Mantel–Haenszel method. The correlations of outcomes with the study size, the proportion of positive lymph nodes, the technique used, and the study quality were evaluated. RESULTS Between 1970 and 2003, 69 trials were reported that met eligibility criteria. Of the 8059 patients who were studied, 7765 patients (96%) had successfully mapped SLNs. The proportion of patients who had successfully mapped SLNs ranged from 41% to 100%, with > 50% of studies reporting a rate 10%. Significant inverse correlations were observed between the FNR and both the number of patients studied (r = − 0.42; P < 0.01) and the proportion of patients who had successfully mapped SLNs nodes (r = − 0.32; P = 0.009). CONCLUSIONS Lymphatic mapping with SLN biopsy is used widely to reduce the complications associated with ALND in patients with low-risk breast carcinoma. This systematic review revealed a wide variation in test performance. Cancer 2006. © 2005 American Cancer Society.

Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

Abstract: Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81); and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03); as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index). In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast and prostate cancer biopsies.

Low-Fat Dietary Pattern and Risk of Invasive Breast Cancer: The Women's Health Initiative Randomized Controlled Dietary Modification Trial

Abstract: ContextThe hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial.ObjectiveTo assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence.Design and SettingA randomized, controlled, primary prevention trial conducted at 40 US clinical centers from 1993 to 2005.ParticipantsA total of 48 835 postmenopausal women, aged 50 to 79 years, without prior breast cancer, including 18.6% of minority race/ethnicity, were enrolled.InterventionsWomen were randomly assigned to the dietary modification intervention group (40% [n = 19 541]) or the comparison group (60% [n = 29 294]). The intervention was designed to promote dietary change with the goals of reducing intake of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily. Comparison group participants were not asked to make dietary changes.Main Outcome MeasureInvasive breast cancer incidence.ResultsDietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group. The difference between groups in change from baseline for percentage of energy from fat varied from 10.7% at year 1 to 8.1% at year 6. Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller, more transient difference was found for grain consumption. The number of women who developed invasive breast cancer (annualized incidence rate) over the 8.1-year average follow-up period was 655 (0.42%) in the intervention group and 1072 (0.45%) in the comparison group (hazard ratio, 0.91; 95% confidence interval, 0.83-1.01 for the comparison between the 2 groups). Secondary analyses suggest a lower hazard ratio among adherent women, provide greater evidence of risk reduction among women having a high-fat diet at baseline, and suggest a dietary effect that varies by hormone receptor characteristics of the tumor.ConclusionsAmong postmenopausal women, a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period. However, the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer, planned, nonintervention follow-up may yield a more definitive comparison.Clinical Trials RegistrationClinicalTrials.gov Identifier: NCT00000611

Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome

Abstract: BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.