المؤلفون: Clark, Amy S, Yau, Christina, Wolf, Denise M, Petricoin, Emanuel F, van 't Veer, Laura J, Yee, Douglas, Moulder, Stacy L, Wallace, Anne M, Chien, A Jo, Isaacs, Claudine, Boughey, Judy C, Albain, Kathy S, Kemmer, Kathleen, Haley, Barbara B, Han, Hyo S, Forero-Torres, Andres, Elias, Anthony, Lang, Julie E, Ellis, Erin D, Yung, Rachel, Tripathy, Debu, Nanda, Rita, Wulfkuhle, Julia D, Brown-Swigart, Lamorna, Gallagher, Rosa I, Helsten, Teresa, Roesch, Erin, Ewing, Cheryl A, Alvarado, Michael, Crane, Erin P, Buxton, Meredith, Clennell, Julia L, Paoloni, Melissa, Asare, Smita M, Wilson, Amy, Hirst, Gillian L, Singhrao, Ruby, Steeg, Katherine, Asare, Adam, Matthews, Jeffrey B, Berry, Scott, Sanil, Ashish, Melisko, Michelle, Perlmutter, Jane, Rugo, Hope S, Schwab, Richard B, Symmans, W Fraser, Hylton, Nola M, Berry, Donald A, Esserman, Laura J, DeMichele, Angela M

المصدر: Nature communications. 12(1)

مصطلحات موضوعية: Humans, Breast Neoplasms, Paclitaxel, Maytansine, Receptor, erbB-2, Neoadjuvant Therapy, Adult, Aged, Middle Aged, Antibodies, Monoclonal, Humanized, Biomarkers, Tumor, Trastuzumab, Ado-Trastuzumab Emtansine, Receptor, ErbB-2, Clinical Trials and Supportive Activities, Clinical Research, Breast Cancer, Cancer, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals

الوصف: HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1sh0p1q6Test

المؤلفون: Yee, Douglas, Isaacs, Claudine, Wolf, Denise M, Yau, Christina, Haluska, Paul, Giridhar, Karthik V, Forero-Torres, Andres, Jo Chien, A, Wallace, Anne M, Pusztai, Lajos, Albain, Kathy S, Ellis, Erin D, Beckwith, Heather, Haley, Barbara B, Elias, Anthony D, Boughey, Judy C, Kemmer, Kathleen, Yung, Rachel L, Pohlmann, Paula R, Tripathy, Debu, Clark, Amy S, Han, Hyo S, Nanda, Rita, Khan, Qamar J, Edmiston, Kristen K, Petricoin, Emanuel F, Stringer-Reasor, Erica, Falkson, Carla I, Majure, Melanie, Mukhtar, Rita A, Helsten, Teresa L, Moulder, Stacy L, Robinson, Patricia A, Wulfkuhle, Julia D, Brown-Swigart, Lamorna, Buxton, Meredith, Clennell, Julia L, Paoloni, Melissa, Sanil, Ashish, Berry, Scott, Asare, Smita M, Wilson, Amy, Hirst, Gillian L, Singhrao, Ruby, Asare, Adam L, Matthews, Jeffrey B, Hylton, Nola M, DeMichele, Angela, Melisko, Michelle, Perlmutter, Jane, Rugo, Hope S, Fraser Symmans, W, Van't Veer, Laura J, Berry, Donald A, Esserman, Laura J

المصدر: NPJ breast cancer. 7(1)

مصطلحات موضوعية: Diabetes, Cancer, Breast Cancer, 6.1 Pharmaceuticals

الوصف: I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone. While pathologic complete response (pCR) rates were numerically higher in the PGM treatment arm for hormone receptor-negative, HER2-negative breast cancer (32% versus 21%), this small increase did not meet I-SPY's prespecified threshold for graduation. PGM was associated with increased hyperglycemia and elevated hemoglobin A1c (HbA1c), despite the use of metformin in combination with ganitumab. We evaluated several putative predictive biomarkers of ganitumab response (e.g., IGF-1 ligand score, IGF-1R signature, IGFBP5 expression, baseline HbA1c). None were specific predictors of response to PGM, although several signatures were associated with pCR in both arms. Any further development of anti-IGF-1R therapy will require better control of anti-IGF-1R drug-induced hyperglycemia and the development of more predictive biomarkers.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0qx0g4qbTest

المؤلفون: Pusztai, Lajos, Yau, Christina, Han, Hyo, Du, Lili, Wallace, Anne, String-Reasor, Erica, Boughey, Judy, Chien, A, Elias, Anthony, Beckwith, Heather, Nanda, Rita, Albain, Kathy, Clark, Amy, Kemmer, Kathleen, Kalinsky, Kevin, Isaacs, Claudine, Thomas, Alexandra, Helsten, Theresa, Forero-Torres, Andres, Liu, Minetta, Brown-Swigart, Lamorna, Petricoin, Emmanuel, Wulfkuhle, Julia, Asare, Smita, Wilson, Amy, Singhrao, Ruby, Sit, Laura, Berry, Scott, Sanil, Ashish, Asare, Adam, Matthews, Jeffrey, Perlmutter, Jane, Melisko, Michelle, Rugo, Hope, Schwab, Richard, Symmans, W, Yee, Doug, Vant Veer, Laura, DeMichele, Angela, Berry, Donald, Esserman, Laura, Hylton, Nola, Wolf, Denise, Shatsky, Rebecca, Hirst, Gillian

المصدر: Cancer Cell. 39(7)

مصطلحات موضوعية: DNA repair inhibitor, breast cancer, clinical trial, immunotherapy, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Follow-Up Studies, Humans, Middle Aged, Neoadjuvant Therapy, Paclitaxel, Phthalazines, Piperazines, Prognosis, Receptor, ErbB-2, Survival Rate, Young Adult

الوصف: The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%-37%), hormone receptor (HR)-positive/HER2-negative (14%-28%), and triple-negative breast cancer (TNBC) (27%-47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP (pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR 9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3r25p13vTest

المؤلفون: Chien, A Jo, Tripathy, Debasish, Albain, Kathy S, Symmans, W Fraser, Rugo, Hope S, Melisko, Michelle E, Wallace, Anne M, Schwab, Richard, Helsten, Teresa, Forero-Torres, Andres, Stringer-Reasor, Erica, Ellis, Erin D, Kaplan, Henry G, Nanda, Rita, Jaskowiak, Nora, Murthy, Rashmi, Godellas, Constantine, Boughey, Judy C, Elias, Anthony D, Haley, Barbara B, Kemmer, Kathleen, Isaacs, Claudine, Clark, Amy S, Lang, Julie E, Lu, Janice, Korde, Larissa, Edmiston, Kirsten K, Northfelt, Donald W, Viscusi, Rebecca K, Yee, Douglas, Perlmutter, Jane, Hylton, Nola M, Van't Veer, Laura J, DeMichele, Angela, Wilson, Amy, Peterson, Garry, Buxton, Meredith B, Paoloni, Melissa, Clennell, Julia, Berry, Scott, Matthews, Jeffrey B, Steeg, Katherine, Singhrao, Ruby, Hirst, Gillian L, Sanil, Ashish, Yau, Christina, Asare, Smita M, Berry, Donald A, Esserman, Laura J

المصدر: Journal of Clinical Oncology. 38(10)

مصطلحات موضوعية: Clinical Research, Clinical Trials and Supportive Activities, Cancer, Prevention, Breast Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Doxorubicin, Female, Heterocyclic Compounds, 3-Ring, Humans, Middle Aged, Neoadjuvant Therapy, Paclitaxel, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Receptor, ErbB-2, Receptors, Steroid, Trastuzumab, I-SPY 2 Consortium, Receptor, erbB-2, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: PurposeThe phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer.Patients and methodsI-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and MammaPrint statuses in a 2 × 2 × 2 layout. Patients within each of these 8 biomarker subtypes are adaptively randomly assigned to one of several experimental therapies, including MK-2206, or control. Therapies are evaluated for 10 biomarker signatures, each of which is a combination of these subtypes. The primary end point is pathologic complete response (pCR). A therapy graduates with one or more of these signatures if and when it has an 85% Bayesian predictive probability of success in a hypothetical phase III trial, adjusting for biomarker covariates. Patients in the current report received standard taxane- and anthracycline-based neoadjuvant therapy without (control) or with oral MK-2206 135 mg/week.ResultsMK-2206 graduated with 94 patients and 57 concurrently randomly assigned controls in 3 graduation signatures: HR-negative/HER2-positive, HR-negative, and HER2-positive. Respective Bayesian mean covariate-adjusted pCR rates and percentage probability that MK-2206 is superior to control were 0.48:0.29 (97%), 0.62:0.36 (99%), and 0.46:0.26 (94%). In exploratory analyses, MK-2206 evinced a numerical improvement in event-free survival in its graduating signatures. The most significant grade 3-4 toxicity was rash (14% maculopapular, 8.6% acneiform).ConclusionThe Akt inhibitor MK-2206 combined with standard neoadjuvant therapy resulted in higher estimated pCR rates in HR-negative and HER2-positive breast cancer. Although MK-2206 is not being further developed at this time, this class of agents remains of clinical interest.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/98s7h5kgTest

المؤلفون: Park, John W, Liu, Minetta C, Yee, Douglas, Yau, Christina, van 't Veer, Laura J, Symmans, W Fraser, Paoloni, Melissa, Perlmutter, Jane, Hylton, Nola M, Hogarth, Michael, DeMichele, Angela, Buxton, Meredith B, Chien, A Jo, Wallace, Anne M, Boughey, Judy C, Haddad, Tufia C, Chui, Stephen Y, Kemmer, Kathleen A, Kaplan, Henry G, Isaacs, Claudine, Nanda, Rita, Tripathy, Debasish, Albain, Kathy S, Edmiston, Kirsten K, Elias, Anthony D, Northfelt, Donald W, Pusztai, Lajos, Moulder, Stacy L, Lang, Julie E, Viscusi, Rebecca K, Euhus, David M, Haley, Barbara B, Khan, Qamar J, Wood, William C, Melisko, Michelle, Schwab, Richard, Helsten, Teresa, Lyandres, Julia, Davis, Sarah E, Hirst, Gillian L, Sanil, Ashish, Esserman, Laura J, Berry, Donald A

المصدر: New England Journal of Medicine. 375(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Breast Cancer, Clinical Research, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Bayes Theorem, Biomarkers, Tumor, Breast Neoplasms, Female, Humans, Middle Aged, Neoadjuvant Therapy, Paclitaxel, Quinolines, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Trastuzumab, I-SPY 2 Investigators, Receptor, erbB-2, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences

الوصف: BackgroundThe heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery).MethodsWe used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature.ResultsNeratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%.ConclusionsNeratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4xs2222bTest

المؤلفون: Rugo, Hope S, Olopade, Olufunmilayo I, DeMichele, Angela, Yau, Christina, van 't Veer, Laura J, Buxton, Meredith B, Hogarth, Michael, Hylton, Nola M, Paoloni, Melissa, Perlmutter, Jane, Symmans, W Fraser, Yee, Douglas, Chien, A Jo, Wallace, Anne M, Kaplan, Henry G, Boughey, Judy C, Haddad, Tufia C, Albain, Kathy S, Liu, Minetta C, Isaacs, Claudine, Khan, Qamar J, Lang, Julie E, Viscusi, Rebecca K, Pusztai, Lajos, Moulder, Stacy L, Chui, Stephen Y, Kemmer, Kathleen A, Elias, Anthony D, Edmiston, Kirsten K, Euhus, David M, Haley, Barbara B, Nanda, Rita, Northfelt, Donald W, Tripathy, Debasish, Wood, William C, Ewing, Cheryl, Schwab, Richard, Lyandres, Julia, Davis, Sarah E, Hirst, Gillian L, Sanil, Ashish, Berry, Donald A, Esserman, Laura J

المصدر: New England Journal of Medicine. 375(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Genetics, Breast Cancer, Clinical Research, Cancer, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Bayes Theorem, Benzimidazoles, Carboplatin, Female, Humans, Middle Aged, Neoadjuvant Therapy, Paclitaxel, Poly(ADP-ribose) Polymerase Inhibitors, Triple Negative Breast Neoplasms, I-SPY 2 Investigators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences

الوصف: BackgroundThe genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin.MethodsIn this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well.ResultsWith regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control.ConclusionsThe process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1039w857Test

المؤلفون: Yee, Douglas, DeMichele, Angela M., Yau, Christina, Isaacs, Claudine, Symmans, W. Fraser, Albain, Kathy S., Chen, Yunn-Yi, Krings, Gregor, Wei, Shi, Harada, Shuko, Datnow, Brian, Fadare, Oluwole, Klein, Molly, Pambuccian, Stefan, Chen, Beiyun, Adamson, Kathi, Sams, Sharon, Mhawech-Fauceglia, Paulette, Magliocco, Anthony, Feldman, Mike, Rendi, Mara, Sattar, Husain, Zeck, Jay, Ocal, Idris T., Tawfik, Ossama, LeBeau, Lauren Grasso, Sahoo, Sunati, Vinh, Tuyethoa, Chien, A. Jo, Forero-Torres, Andres, Stringer-Reasor, Erica, Wallace, Anne M., Pusztai, Lajos, Boughey, Judy C., Ellis, Erin D., Elias, Anthony D., Lu, Janice, Lang, Julie E., Han, Hyo S., Clark, Amy S., Nanda, Rita, Northfelt, Donald W., Khan, Qamar J., Viscusi, Rebecca K., Euhus, David M., Edmiston, Kirsten K., Chui, Stephen Y., Kemmer, Kathleen, Park, John W., Liu, Minetta C.

المصدر: JAMA Oncology ; volume 6, issue 9, page 1355 ; ISSN 2374-2437

الإتاحة: https://doi.org/10.1001/jamaoncol.2020.2535Test
https://jamanetwork.com/journals/jamaoncology/articlepdf/2768226/jamaoncology_yee_2020_oi_200035_1599155066.86542.pdfTest

المؤلفون: Nanda, Rita, Liu, Minetta C., Yau, Christina, Shatsky, Rebecca, Pusztai, Lajos, Wallace, Anne, Chien, A. Jo, Forero-Torres, Andres, Ellis, Erin, Han, Heather, Clark, Amy, Albain, Kathy, Boughey, Judy C., Jaskowiak, Nora T., Elias, Anthony, Isaacs, Claudine, Kemmer, Kathleen, Helsten, Teresa, Majure, Melanie, Stringer-Reasor, Erica, Parker, Catherine, Lee, Marie C., Haddad, Tufia, Cohen, Ronald N., Asare, Smita, Wilson, Amy, Hirst, Gillian L., Singhrao, Ruby, Steeg, Katherine, Asare, Adam, Matthews, Jeffrey B., Berry, Scott, Sanil, Ashish, Schwab, Richard, Symmans, W. Fraser, van ‘t Veer, Laura, Yee, Douglas, DeMichele, Angela, Hylton, Nola M., Melisko, Michelle, Perlmutter, Jane, Rugo, Hope S., Berry, Donald A., Esserman, Laura J.

المصدر: JAMA Oncology ; volume 6, issue 5, page 676 ; ISSN 2374-2437

الإتاحة: https://doi.org/10.1001/jamaoncol.2019.6650Test
https://jamanetwork.com/journals/jamaoncology/articlepdf/2761193/jamaoncology_nanda_2020_oi_190112.pdfTest

المؤلفون: Boughey, Judy C., Alvarado, Michael D., Lancaster, Rachael B., Symmans, W. Fraser, Mukhtar, Rita, Wong, Jasmine M., Ewing, Cheryl A., Potter, David A., Tuttle, Todd M., Hieken, Tina J., Carter, Jodi M., Jakub, James W., Kaplan, Henry G., Buchanan, Claire L., Jaskowiak, Nora T., Sattar, Husain A., Mueller, Jeffrey, Nanda, Rita, Isaacs, Claudine J., Pohlmann, Paula R., Lynce, Filipa, Tousimis, Eleni A., Zeck, Jay C., Lee, M. Catherine, Lang, Julie E., Mhawech-Fauceglia, Paulette, Rao, Roshni, Taback, Bret, Goodellas, Constantine, Chen, Margaret, Kalinsky, Kevin M., Hibshoosh, Hanina, Killelea, Brigid, Sanft, Tara, Hirst, Gillian L., Asare, Smita, Matthews, Jeffrey B., Perlmutter, Jane, Esserman, Laura J., Chien, A. Jo, Forero-Torres, Andres, Yee, Douglas, Ellis, Erin D., Han, Heather S., Lu, Janice, Wallace, Anne M., Albain, Kathy S., Elias, Anthony D., Clark, Amy S., Kemmer, Kathleen

المصدر: npj Breast Cancer ; volume 5, issue 1 ; ISSN 2374-4677

مصطلحات موضوعية: Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Oncology

الوصف: In the original version of the published article, Constantine Godellas was mistakenly omitted from the Author list and Author Contributions statement. Constantine Godellas has been added as the 29th Author, and is affiliated with Loyola University Medical Center, Maywood, IL, United States. The author contributions statement has been updated as follows: “Author Contributions Statement: Judy C. Boughey conducted the review of current protocols, led the effort to establish new I-SPY standards and was the principal author of the manuscript. Laura Esserman co-led the review and standardization processes. Michael D. Alvarado, Rachael B. Lancaster, Fraser Symmans, W, Rita Mukhtar, Jasmine Wong, Cheryl Ewing, David Potter, Todd Tuttle, Tina Hieken, Jodi Carter, James Jakub, Henry Kaplan, Claire Buchanan, Nora Jaskowiak, Husain Sattar, Jeffrey Mueller, Rita Nanda, Claudine Isaacs, Paula Pohlmann, Filipa Lynce, Eleni Tousimis, Jay Zeck, M. Catherine Lee, Julie Lang, Paulette Mhawech-Fauceglia, Roshni Rao, Bret Taback, Margaret Chen, Kevin Kalinsky, Hanina Hibshoosh, Brigid Killelea, Constantine Godellas, and Tara Sanft provided medical and scientific expertise/opinion towards the development of I-SPY standards. Jane Perlmutter provided the patient advocate’s perspective in these discussions. All I-SPY2 trial investigators participated in the review of current standards, had the opportunity to participate in and comment on proposed standards and the final manuscript. Gill Hirst and Smita Asare provided expertise on, conducted and analyzed surveys of I-SPY trial sites. Jeffrey B. Matthews provided significant input and editing throughout the manuscript development process. All authors reviewed manuscript drafts and signed off on the final manuscript. This has been corrected in the HTML and PDF version of the article.

الإتاحة: https://doi.org/10.1038/s41523-018-0096-0Test
https://www.nature.com/articles/s41523-018-0096-0.pdfTest
https://www.nature.com/articles/s41523-018-0096-0Test

المؤلفون: Boughey, Judy C., Alvarado, Michael D., Lancaster, Rachael B., Fraser Symmans, W., Mukhtar, Rita, Wong, Jasmine M., Ewing, Cheryl A., Potter, David A., Tuttle, Todd M., Hieken, Tina J., Carter, Jodi M., Jakub, James W., Kaplan, Henry G., Buchanan, Claire L., Jaskowiak, Nora T., Sattar, Husain A., Mueller, Jeffrey, Nanda, Rita, Isaacs, Claudine J., Pohlmann, Paula R., Lynce, Filipa, Tousimis, Eleni A., Zeck, Jay C., Lee, M. Catherine, Lang, Julie E., Mhawech-Fauceglia, Paulette, Rao, Roshni, Taback, Bret, Godellas, Constantine, Chen, Margaret, Kalinsky, Kevin M., Hibshoosh, Hanina, Killelea, Brigid, Sanft, Tara, Hirst, Gillian L., Asare, Smita, Matthews, Jeffrey B., Perlmutter, Jane, Esserman, Laura J., Chien, A. Jo, Forero-Torres, Andres, Yee, Douglas, Ellis, Erin D., Han, Heather S., Lu, Janice, Wallace, Anne M., Albain, Kathy S., Elias, Anthony D., Clark, Amy S., Kemmer, Kathleen

المصدر: npj Breast Cancer ; volume 4, issue 1 ; ISSN 2374-4677

مصطلحات موضوعية: Pharmacology (medical), Radiology, Nuclear Medicine and imaging, Oncology

الوصف: Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease—the primary endpoint of many drug therapy trials in the neoadjuvant setting—is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice.

الإتاحة: https://doi.org/10.1038/s41523-018-0074-6Test
https://www.nature.com/articles/s41523-018-0074-6Test
https://www.nature.com/articles/s41523-018-0074-6.pdfTest