Showing papers on "Breast cancer published in 2007"
TL;DR: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.
Abstract: Purpose: To compare the clinical features, natural history, and outcomes for women with “triple-negative” breast cancer with women with other types of breast cancer. Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Women9s College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. Results: The median follow-up time of the 1,601 women was 8.1 years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P P Conclusions: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.
3,945 citations
TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.
3,766 citations
TL;DR: In this paper, the authors analyzed 13,023 genes in 11 breast and 11 colorectal cancers and found that individual tumors accumulate an average of 90 mutant genes but only a subset of these contribute to the neoplastic process.
Abstract: Analysis of 13,023 genes in 11 breast and 11 colorectal cancers revealed that individual tumors accumulate an average of ˜90 mutant genes but that only a subset of these contribute to the neoplastic process. Using stringent criteria to delineate this subset, we identified 189 genes (average of 11 per tumor) that were mutated at significant frequency. The vast majority of these genes were not known to be genetically altered in tumors and are predicted to affect a wide range of cellular functions, including transcription, adhesion, and invasion. These data define the genetic landscape of two human cancer types, provide new targets for diagnostic and therapeutic intervention and monitoring.
3,152 citations
American Cancer Society1, University of Washington2, University of Arkansas for Medical Sciences3, The Royal Marsden NHS Foundation Trust4, University of Washington Medical Center5, Memorial Sloan Kettering Cancer Center6, University of North Carolina at Chapel Hill7, University of Pennsylvania8, Northwestern University9, University of Toronto10, Sunnybrook Health Sciences Centre11, University of Southern California12
TL;DR: There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography.
Abstract: New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20-25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.
2,332 citations
TL;DR: Trastuzumab, a humanized monoclonal antibody that targets HER2, is approved by the Food and Drug Administration for patients with invasive breast cancers that overexpress HER2.
Abstract: Overexpression of human epidermal growth factor receptor type 2 (HER2) in breast cancer is associated with decreased overall survival. Trastuzumab, a humanized monoclonal antibody that targets HER2, is approved by the Food and Drug Administration for patients with invasive breast cancers that overexpress HER2. This review considers the mechanism of action and the use of this agent.
2,315 citations
University of Cambridge1, National Institutes of Health2, University of Southern California3, International Agency for Research on Cancer4, Academia Sinica5, Princess Anne Hospital6, St Mary's Hospital7, University of London8, The Breast Cancer Research Foundation9, Wellcome Trust Sanger Institute10, QIMR Berghofer Medical Research Institute11, Peter MacCallum Cancer Centre12, University of Copenhagen13, Curie Institute14, Nofer Institute of Occupational Medicine15, University of Helsinki16, Seoul National University17, University of Ulsan18, Harvard University19, Karolinska Institutet20, Agency for Science, Technology and Research21, Hannover Medical School22, Leiden University23, Erasmus University Rotterdam24, University of Minnesota25, University of Sheffield26, Mayo Clinic27, VU University Amsterdam28, Carlos III Health Institute29, University of Melbourne30, Cancer Council New South Wales31, University of Otago32, Cancer Council Victoria33, Bosch34, University of Tübingen35, German Cancer Research Center36, University of Eastern Finland37
TL;DR: To identify further susceptibility alleles, a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls was conducted, followed by a third stage in which 30 single nucleotide polymorphisms were tested for confirmation.
Abstract: Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2.0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P,1027). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P,0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.
2,288 citations
TL;DR: A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women, and this association might reflect a common cause for pre- eClampsia and cardiovascular disease, or an effect ofPre-e Clampsia on disease development, or both.
Abstract: Objective To quantify the risk of future cardiovascular diseases, cancer, and mortality after pre-eclampsia. Design Systematic review and meta-analysis. Data sources Embase and Medline without language restrictions, including papers published between 1960 and December 2006, and hand searching of reference lists of relevant articles and reviews for additional reports. Review methods Prospective and retrospective cohort studies were included, providing a dataset of 3 488 160 women, with 198 252 affected by pre-eclampsia (exposure group) and 29 495 episodes of cardiovascular disease and cancer (study outcomes). Results After pre-eclampsia women have an increased risk of vascular disease. The relative risks (95% confidence intervals) for hypertension were 3.70 (2.70 to 5.05) after 14.1 years weighted mean follow-up, for ischaemic heart disease 2.16 (1.86 to 2.52) after 11.7 years, for stroke 1.81 (1.45 to 2.27) after 10.4 years, and for venous thromboembolism 1.79 (1.37 to 2.33) after 4.7 years. No increase in risk of any cancer was found (0.96, 0.73 to 1.27), including breast cancer (1.04, 0.78 to 1.39) 17 years after pre-eclampsia. Overall mortality after pre-eclampsia was increased: 1.49 (1.05 to 2.14) after 14.5 years. Conclusions A history of pre-eclampsia should be considered when evaluating risk of cardiovascular disease in women. This association might reflect a common cause for pre-eclampsia and cardiovascular disease, or an effect of pre-eclampsia on disease development, or both. No association was found between pre-eclampsia and future cancer.
2,157 citations
TL;DR: Thirteen categories of breast tumor markers were considered, six of which were new for the guideline, and certain multiparameter gene expression assays not all applications for these markers were supported, however.
Abstract: Purpose To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer. Methods For the 2007 update, an Update Committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of MEDLINE and the Cochrane Collaboration Library were performed. The Update Committee’s literature review focused attention on available systematic reviews and metaanalyses of published tumor marker studies. In general, significant health outcomes (overall survival, disease-free survival, quality of life, lesser toxicity, and cost-effectiveness) were used for making recommendations. Recommendations and Conclusions
2,079 citations
TL;DR: Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests, and a substantial fraction of breast cancers can be attributed to this risk factor.
Abstract: Methods We carried out three nested case–control studies in screened populations with 1112 matched case–control pairs. We examined the association of the measured percentage of density in the baseline mammogram with risk of breast cancer, according to method of cancer detection, time since the initiation of screening, and age. Results As compared with women with density in less than 10% of the mammogram, women with density in 75% or more had an increased risk of breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4), whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than 12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8 to 65.9). Increased risk of breast cancer, whether detected by screening or other means, persisted for at least 8 years after study entry and was greater in younger than in older women. For women younger than the median age of 56 years, 26% of all breast cancers and 50% of cancers detected less than 12 months after a negative screening test were attributable to density in 50% or more of the mammogram. Conclusions Extensive mammographic density is strongly associated with the risk of breast cancer detected by screening or between screening tests. A substantial fraction of breast cancers can be attributed to this risk factor.
2,012 citations
TL;DR: Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers and could be explained by a higher likelihood of relapse in patients in whom pathologic complete response was not achieved.
Abstract: Purpose: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes. Experimental Design: We used immunohistochemical profiles [human epidermal growth factor receptor 2–positive (HER2+)/hormone receptor–negative for HER2+/estrogen receptor–negative (ER−), hormone receptor and HER2− for basal-like, hormone receptor–positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease–free survival and overall survival. Results: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ER−, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor–positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ER− (70%) and basal-like (85%) than the luminal subtypes (47%; P P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ER− subtypes had worse distant disease–free survival ( P = 0.04) and overall survival ( P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ER− subtypes was due to higher relapse among those with residual disease ( P = 0.003). Conclusions: Basal-like and HER2+/ER− subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ER− breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.
1,932 citations
TL;DR: In this article, the authors examined differences between triple-negative breast cancers compared with other breast cancers in relation to age, race/ethnicity, socioeconomic status (SES), stage at diagnosis, tumor grade, and relative survival.
Abstract: BACKGROUND.
Tumor markers are becoming increasingly important in breast cancer research because of their impact on prognosis, treatment, and survival, and because of their relation to breast cancer subtypes. The triple-negative phenotype is important because of its relation to the basal-like subtype of breast cancer.
METHODS.
Using the population-based California Cancer Registry data, we identified women diagnosed with triple-negative breast cancer between 1999 and 2003. We examined differences between triple-negative breast cancers compared with other breast cancers in relation to age, race/ethnicity, socioeconomic status (SES), stage at diagnosis, tumor grade, and relative survival.
RESULTS.
A total of 6370 women were identified as having triple-negative breast cancer and were compared with the 44,704 women with other breast cancers. Women with triple-negative breast cancers were significantly more likely to be under age 40 (odds ratio [OR], 1.53), and non-Hispanic black (OR, 1.77) or Hispanic (OR, 1.23). Regardless of stage at diagnosis, women with triple-negative breast cancers had poorer survival than those with other breast cancers, and non-Hispanic black women with late-stage triple-negative cancer had the poorest survival, with a 5-year relative survival of only 14%.
CONCLUSIONS.
Triple-negative breast cancers affect younger, non-Hispanic black and Hispanic women in areas of low SES. The tumors were diagnosed at later stage and were more aggressive, and these women had poorer survival regardless of stage. In addition, non-Hispanic black women with late-stage triple-negative breast cancer had the poorest survival of any comparable group. Cancer 2007. © 2007 American Cancer Society.
TL;DR: Four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer were identified and confirmed in 1,776 affected individuals and 2,072 controls from three additional studies.
Abstract: We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (Ptrend for the most strongly associated SNP (rs1219648) = 1.1 10-10; population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci
TL;DR: A protein‐network‐based approach is applied that identifies markers not as individual genes but as subnetworks extracted from protein interaction databases, which provide novel hypotheses for pathways involved in tumor progression.
Abstract: Mapping the pathways that give rise to metastasis is one of the key challenges of breast cancer research. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with metastasis. Here, we apply a protein-network-based approach that identifies markers not as individual genes but as subnetworks extracted from protein interaction databases. The resulting subnetworks provide novel hypotheses for pathways involved in tumor progression. Although genes with known breast cancer mutations are typically not detected through analysis of differential expression, they play a central role in the protein network by interconnecting many differentially expressed genes. We find that the subnetwork markers are more reproducible than individual marker genes selected without network information, and that they achieve higher accuracy in the classification of metastatic versus non-metastatic tumors.
The Royal Marsden NHS Foundation Trust1, Harvard University2, Université libre de Bruxelles3, Hoffmann-La Roche4, European Institute of Oncology5, Ludwig Maximilian University of Munich6, Hebron University7, Western General Hospital8, Geelong Hospital9, Karolinska Institutet10, Weston Park Hospital11, Westmead Hospital12
TL;DR: The results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a significant overall survival benefit after a median follow-up of 2 years, and the emergence of this benefit after only 2 years reinforces the importance of trastizumab in the treatment of women with HER2-positive early breast cancer.
Journal Article•
TL;DR: In this article, the authors compared mammography to MRI in detecting breast cancer in women with a familial or genetic predisposition to breast cancer, and found that MRI appears to be more sensitive than mammography.
Abstract: Question: In women with a familial or genetic predisposition for breast cancer is screening with MRI more effective than mammography or usual care? Design: Prospective cohort study Setting: Six familial cancer centers in the Netherlands Patients: One thousand and nine women aged 25 to 75 years with a cumulative lifetime risk of breast cancer of 15% or more owing to a familial or genetic predisposition based on a modified Clasus model were included. Description of Test and Diagnostic Standard: Two view mammography (oblique and craniocaudal views and if necessary, compression views or magnification) and dynamic breast MRI with gadolinium containing contrast medium using a standard protocol were performed yearly. Clinical breast examination was performed every 6 months. When possible, both imaging investigations were performed on the same day or same time period between day 5 & day 15 of the menstrual cycle. The results of both investigations, which were blinded were scored in a standardized way, according the Breast Imaging Reporting and Data Systems (BI-RADS) Classification. Main Outcomes Measure: Sensitivity and specificity of clinical examination, mammography and MRI. Main Results: The sensitivity of clinical breast examination, mammography and MRI for detecting invasive breast cancer was 17.9%, 33.3% and 79.5% respectively and the specificity was 98.1%, 95.0% and 89.8% respectively. Conclusion: MRI appears to be more sensitive than mammography in detecting tumors in females with a genetic or familial predisposition to breast cancer Commentary: Although Kriege et al, 1 address two questions in this study, the focus of this review is the comparison of mammography to MRI in detecting breast cancers in women with a familial or genetic predisposition to breast cancer.
TL;DR: Assessment of PI3K pathway activation may provide a biomarker to identify patients unlikely to respond to trastuzumab-based therapy, and the combined analysis of PTEN and PIK3CA identified twice as many patients at increased risk for progression compared to PTEN alone.
TL;DR: Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined, and for colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect ofBody mass index on risk differed significantly according to menopausal status.
Abstract: Objective To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Design Prospective cohort study. Participants 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Main outcome measures Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. Results 45 037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin9s lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Conclusions Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.
TL;DR: The CellSearch system enables the reliable detection of CTCs in blood and is suitable for the routine assessment of metastatic breast cancer patients in the clinical laboratory.
Abstract: Purpose: The CellSearch system (Veridex, Warren, NJ) is designed to enrich and enumerate circulating tumor cells (CTCs) from peripheral blood. Here, we validated the analytic performance of this system for clinical use in patients with metastatic breast cancer.
Experimental Design: This prospective multicenter study conducted at three independent laboratories involved samples from 92 patients with metastatic breast cancer. Intra- and inter-assay variability using controls containing defined numbers of cells (average, 50 and 1,000, respectively), cell stability based on varying storage and shipment conditions, recovery precision from samples spiked with 4 to 12 tumor cells, inter-instrument variability, and positivity of samples from metastatic breast cancer patients were tested.
Results: Intra- and inter-assay precision for two sites were high: All eight positive controls analyzed in the same run and >95% of the run to run control values ( n = 299) were within the specified ranges. Recovery rate of spiked samples averaged between 80% and 82%. CTCs were detected in ∼70% of metastatic breast cancer patients. CTC values of identical samples processed either immediately after blood drawing or after storage for 24, 48, or 72 h at room temperature or at 4°C did not differ significantly. Shipment of samples had no influence on CTC values. When analyzing identical samples in different centers, inter-instrument accordance was high.
Conclusions: The CellSearch system enables the reliable detection of CTCs in blood and is suitable for the routine assessment of metastatic breast cancer patients in the clinical laboratory. Blood samples should be shipped at room temperature and CTC counts are stable for at least 72 h.
TL;DR: Triple‐negative breast cancer (estrogen receptor‐ negative, progesterone receptor‐negative, and HER2‐negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins.
Abstract: BACKGROUND.
Triple-negative breast cancer (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is a high risk breast cancer that lacks the benefit of specific therapy that targets these proteins.
METHODS.
In this study, the authors examined a large and well characterized series of invasive breast carcinoma (n = 1944) with a long-term clinical follow-up (median, 56 months) by using tissue microarray. The series were also stained with concurrent immunohistochemical prognostic panels (estrogen receptor, progesterone receptor, HER-2, androgen receptor, epidermal growth factor receptor (EGFR), P-cadherin, E-cadherin, and basal (CK5/6, CK14), and p53), to characterize this specific subgroup of breast cancer and to identify prognostic markers that can identify tumors with more aggressive behavior.
RESULTS.
Of informative cases, 16.3% were of the triple-negative phenotype. The majority of these tumors were grade 3, ductal/no-specific-type carcinomas. There were positive associations with larger size, pushing margins, poorer Nottingham Prognostic Index, development of recurrence and distant metastasis, and poorer outcome. In addition, associations were found with loss of expression of androgen receptor and E-cadherin, and positive expression of basal cytokeratins (basal phenotype), P-cadherin, p53, and EGFR. In all tumors, tumor size, lymph node stage, and androgen receptor were the most useful prognostic markers. In the lymph node-positive subgroup, both size and androgen receptor retained their prognostic significance. However, in the lymph node-negative tumors, basal phenotype was the sole prognostic marker identified in this subgroup. Other parameters including age, histological grade, tumor size, vascular invasion or other biomarkers included in the current study were not significant.
CONCLUSIONS.
The authors concluded that assessment of androgen receptor and basal phenotype, in addition to the established pathologic variables, mainly lymph node status and tumor size, can be used to select high-risk and low-risk patients at the time of primary surgery and can provide valuable information on treatment options in these triple-negative tumors. Cancer 2007. © 2006 American Cancer Society
TL;DR: Residual cancer burden was calculated as a continuous index combining pathologic measurements of primary tumor and nodal metastases and was a significant predictor of distant relapse-free survival (DRFS) in multivariate Cox regression analyses.
Abstract: Purpose To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. Patients and Methods Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. Results RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio 2.50; 95% CI 1.70 to 3.69; P .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. Conclusion RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance. J Clin Oncol 25:4414-4422. © 2007 by American Society of Clinical Oncology
TL;DR: A large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe shows that the contrast in the microwave-frequency dielectrics properties betweenmalignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1.
Abstract: The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.
TL;DR: The gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium was compared to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer.
Abstract: BACKGROUND Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells. METHODS We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene "invasiveness" gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. RESULTS There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature. CONCLUSIONS The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.
TL;DR: Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.
Abstract: Purpose Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects. Patients and Methods We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy–Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema. Results The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. ...
TL;DR: This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer.
Abstract: MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression. Here we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed. This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.
TL;DR: The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia–DNA repair pathway and breast cancer predisposition.
Abstract: PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.
TL;DR: Age-adjusted 5-year period survival improved for patients diagnosed in 2000-02, especially for patients with colorectal, breast, prostate, and thyroid cancer, Hodgkin's disease, and non-Hodgkin lymphoma, although, patients in eastern European had the highest improvement in survival for major cancer sites during 1991-2002.
Abstract: BACKGROUND: Traditional cancer-survival analyses provide data on cancer management at the beginning of a study period, and are often not relevant to current practice because they refer to survival of patients treated with older regimens that might no longer be used. Therefore, shortening the delay in providing survival estimates is desirable. Period analysis can estimate cancer survival by the use of recent data. We aimed to apply the period-analysis method to data that were collected by European cancer registries to estimate recent survival by country and cancer site, and to assess survival changes in Europe. We also compared our findings with data on cancer survival in the USA from the US SEER (Surveillance, Epidemiology, and End Results) programme. METHODS: We analysed survival data for patients diagnosed with cancer in 2000-02, collected from 47 of the European cancer registries participating in the EUROCARE-4 study. 5-year period relative survival for patients diagnosed in 2000-02 was estimated as the product of interval-specific relative survival values of cohorts with different lengths of follow-up. 5-year survival profiles for patients diagnosed in 2000-02 were estimated for the European mean and for five European regions, and findings were compared with US SEER registry data for patients diagnosed in 2000-02. A 5-year survival profile for patients diagnosed in 1991-2002 and a 10-year survival profile for patients diagnosed in 1997-2002 were also estimated by the period method for all malignancies, by geographical area, and by cancer site. FINDINGS: For all cancers, age-adjusted 5-year period survival improved for patients diagnosed in 2000-02, especially for patients with colorectal, breast, prostate, and thyroid cancer, Hodgkin's disease, and non-Hodgkin lymphoma. The European mean age-adjusted 5-year survival calculated by the period method for 2000-02 was high for testicular cancer (97.3% [95% CI 96.4-98.2]), melanoma (86.1% [84.3-88.0]), thyroid cancer (83.2% [80.9-85.6]), Hodgkin's disease (81.4% [78.9-84.1]), female breast cancer (79.0% [78.1-80.0]), corpus uteri (78.0% [76.2-79.9]), and prostate cancer (77.5% [76.5-78.6]); and low for stomach cancer (24.9% [23.7-26.2]), chronic myeloid leukaemia (32.2% [29.0-35.7]), acute myeloid leukaemia (14.8% [13.4-16.4]), and lung cancer (10.9% [10.5-11.4]). Survival for patients diagnosed in 2000-02 was generally highest for those in northern European countries and lowest for those in eastern European countries, although, patients in eastern European had the highest improvement in survival for major cancer sites during 1991-2002 (colorectal cancer from 30.3% [28.3-32.5] to 44.7% [42.8-46.7]; breast cancer from 60% [57.2-63.0] to 73.9% [71.7-76.2]; for prostate cancer from 39.5% [35.0-44.6] to 68.0% [64.2-72.1]). For all solid tumours, with the exception of stomach, testicular, and soft-tissue cancers, survival for patients diagnosed in 2000-02 was higher in the US SEER registries than for the European mean. For haematological malignancies, data from US SEER registries and the European mean were comparable in 2000-02, except for non-Hodgkin lymphoma. INTERPRETATION: Cancer-service infrastructure, prevention and screening programmes, access to diagnostic and treatment facilities, tumour-site-specific protocols, multidisciplinary management, application of evidence-based clinical guidelines, and recruitment to clinical trials probably account for most of the differences that we noted in outcomes.
TL;DR: The absolute risk reduction at 10 years per age group was the largest and the largest, and the hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost.
Abstract: Purpose To investigate the long-term impact of a boost radiation dose of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy. Patients and Methods A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years. Results The median age was 55 years. Local recurrence was reported as the first treatment failure in 278 patients with no boost versus 165 patients with boost; at 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the no boost and the boost group, respectively (P < .0001). The hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost, with no statistically significant interaction per age group. The absolute risk reduction at 10 years per age group was the largest...
TL;DR: An expert Panel reaffirmed the primary importance of determining endocrine responsiveness of the cancer as a first approach to selecting systemic therapy and recommended the use of high-quality standard histopathological assessment for both risk allocation and target identification.
TL;DR: The present updated analysis, which was limited to patients on monotherapy arms in BIG 1-98, yields results similar to those from the previous primary analysis but more directly comparable with results from other trials of continuous therapy using a single endocrine agent.
Abstract: Purpose Previous analyses of the Breast International Group (BIG) 1-98 four-arm study compared initial therapy with letrozole or tamoxifen including patients randomly assigned to sequential treatment whose information was censored at the time of therapy change. Because this presentation may unduly reflect early events, the present analysis is limited to patients randomly assigned to the continuous therapy arms and includes protocol-defined updated results. Patients and Methods Four thousand nine hundred twenty-two of the 8,028 postmenopausal women with receptor-positive early breast cancer randomly assigned (double-blind) to the BIG 1-98 trial were assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen; the remainder of women were assigned to receive the agents in sequence. Disease-free survival (DFS) was the primary end point. Results At a median follow-up time of 51 months, we observed 352 DFS events among 2,463 women receiving letrozole and 418 events among 2,459 women re...
TL;DR: The characteristics of basal‐like and triple‐negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer are critically addressed.
Abstract: Breast cancer is a heterogeneous disease that encompasses several distinct entities with remarkably different biological characteristics and clinical behaviour. Currently, breast cancer patients are managed according to algorithms based on a constellation of clinical and histopathological parameters in conjunction with assessment of hormone receptor (oestrogen and progesterone receptor) status and HER2 overexpression/gene amplification. Although effective tailored therapies have been developed for patients with hormone receptor-positive or HER2+ disease, chemotherapy is the only modality of systemic therapy for patients with breast cancers lacking the expression of these markers (triple-negative cancers). Recent microarray expression profiling analyses have demonstrated that breast cancers can be systematically characterized into biologically and clinically meaningful groups. These studies have led to the re-discovery of basal-like breast cancers, which preferentially show a triple-negative phenotype. Both triple-negative and basal-like cancers preferentially affect young and African-American women, are of high histological grade and have more aggressive clinical behaviour. Furthermore, a significant overlap between the biological and clinical characteristics of sporadic triple-negative and basal-like cancers and breast carcinomas arising in BRCA1 mutation carriers has been repeatedly demonstrated. In this review, we critically address the characteristics of basal-like and triple-negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer. In addition, the possible mechanisms are discussed leading to BRCA1 pathway dysfunction in sporadic triple-negative and basal-like cancers and animal models for these tumour types.