Author
Larry Norton
Other affiliations: University of Chicago, Duke University, University of Western Ontario ...read more
Bio: Larry Norton is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: Breast cancer & Cancer. The author has an hindex of 118, co-authored 515 publications receiving 79541 citations. Previous affiliations of Larry Norton include University of Chicago & Duke University.
Papers published on a yearly basis
Papers
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TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
Abstract: Background The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. Methods We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide with (143 women) or without trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 ...
10,532 citations
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
6,309 citations
Journal Article•
TL;DR: The age-specific benefits of polychemotherapy appeared to be largely irrespective of menopausal status at presentation, oestrogen receptor status of the primary tumour, and of whether adjuvant tamoxifen had been given.
2,945 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: The Multiple Outcomes of Raloxifene Evaluation (MORE) as discussed by the authors was a multicenter, randomized, double-blind trial, in which women taking raloxion hydrochloride or placebo were followed up for a median of 40 months at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.
Abstract: ContextRaloxifene hydrochloride is a selective estrogen
receptor modulator that has antiestrogenic effects on breast and
endometrial tissue and estrogenic effects on bone, lipid metabolism,
and blood clotting.ObjectiveTo determine whether women taking raloxifene have a
lower risk of invasive breast cancer.Design and SettingThe Multiple Outcomes of Raloxifene Evaluation
(MORE), a multicenter, randomized, double-blind trial, in which women
taking raloxifene or placebo were followed up for a median of 40 months
(SD, 3 years), from 1994 through 1998, at 180 clinical centers composed
of community settings and medical practices in 25 countries, mainly in
the United States and Europe.ParticipantsA total of 7705 postmenopausal women, younger than 81
(mean age, 66.5) years, with osteoporosis, defined by the presence of
vertebral fractures or a femoral neck or spine T-score of at least 2.5
SDs below the mean for young healthy women. Almost all participants
(96%) were white. Women who had a history of breast cancer or who were
taking estrogen were excluded.InterventionRaloxifene, 60 mg, 2 tablets daily; or raloxifene, 60
mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome MeasuresNew cases of breast cancer, confirmed by
histopathology. Transvaginal ultrasonography was used to assess the
endometrial effects of raloxifene in 1781 women. Deep vein thrombosis
or pulmonary embolism were determined by chart review.ResultsThirteen cases of breast cancer were confirmed among the
5129 women assigned to raloxifene vs 27 among the 2576 women assigned
to placebo (relative risk [RR], 0.24; 95% confidence interval
[CI], 0.13-0.44; P<.001). To prevent 1 case of breast
cancer, 126 women would need to be treated. Raloxifene decreased the
risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10;
95% CI, 0.04-0.24), but not estrogen receptor–negative invasive
breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the
risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but
did not increase the risk of endometrial cancer (RR, 0.8; 95% CI,
0.2-2.7).ConclusionAmong postmenopausal women with osteoporosis, the
risk of invasive breast cancer was decreased by 76% during 3 years of
treatment with raloxifene.
1,692 citations
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TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
51,099 citations
TL;DR: The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression, a higher rate of objective response, a longer duration of response, and a lower rate of death at 1 year.
Abstract: Background The HER2 gene, which encodes the growth factor receptor HER2, is amplified and HER2 is overexpressed in 25 to 30 percent of breast cancers, increasing the aggressiveness of the tumor. Methods We evaluated the efficacy and safety of trastuzumab, a recombinant monoclonal antibody against HER2, in women with metastatic breast cancer that overexpressed HER2. We randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. Patients who had not previously received adjuvant (postoperative) therapy with an anthracycline were treated with doxorubicin (or epirubicin in the case of 36 women) and cyclophosphamide with (143 women) or without trastuzumab (138 women). Patients who had previously received adjuvant anthracycline were treated with paclitaxel alone (96 women) or paclitaxel with trastuzumab (92 women). Results The addition of trastuzumab to chemotherapy was associated with a longer time to disease progression (median, 7.4 ...
10,532 citations
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
Abstract: Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour. Chemotherapy or hormonal therapy reduces the risk of distant metastases by approximately one-third; however, 70-80% of patients receiving this treatment would have survived without it. None of the signatures of breast cancer gene expression reported to date allow for patient-tailored therapy strategies. Here we used DNA microarray analysis on primary breast tumours of 117 young patients, and applied supervised classification to identify a gene expression signature strongly predictive of a short interval to distant metastases ('poor prognosis' signature) in patients without tumour cells in local lymph nodes at diagnosis (lymph node negative). In addition, we established a signature that identifies tumours of BRCA1 carriers. The poor prognosis signature consists of genes regulating cell cycle, invasion, metastasis and angiogenesis. This gene expression profile will outperform all currently used clinical parameters in predicting disease outcome. Our findings provide a strategy to select patients who would benefit from adjuvant therapy.
9,664 citations
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
Abstract: Receptor tyrosine kinase genes were sequenced in nonsmall cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15 of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinibinsensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib. Protein kinase activation by somatic mutation or
9,265 citations
TL;DR: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion.
Abstract: When epidermal growth factor and its relatives bind the ErbB family of receptors, they trigger a rich network of signalling pathways, culminating in responses ranging from cell division to death, motility to adhesion. The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit: over 25,000 women with breast cancer have now been treated with trastuzumab (Herceptin), a recombinant antibody designed to block the receptor ErbB2. Likewise, small-molecule enzyme inhibitors and monoclonal antibodies to ErbB1 are in advanced phases of clinical testing. What can this pathway teach us about translating basic science into clinical use?
6,462 citations