252 results on '"Moy, B."'
Search Results
2. Neratinib and ado-trastuzumab emtansine for pretreated and untreated human epidermal growth factor receptor 2 (HER2)-positive breast cancer brain metastases: Translational Breast Cancer Research Consortium trial 022
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Freedman, R.A., Heiling, H.M., Li, T., Trapani, D., Tayob, N., Smith, K.L., Davis, R., Pereslete, A.M., DeMeo, M.K., Cotter, C., Chen, W.Y., Parsons, H.A., Santa-Maria, C.A., Van Poznak, C., Moy, B., Brufsky, A.M., Melisko, M.E., O’Sullivan, C.C., Ashai, N., Rauf, Y., Nangia, J.R., Burns, R.T., Savoie, J., Wolff, A.C., Winer, E.P., Rimawi, M.F., Krop, I.E., and Lin, N.U.
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- 2024
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3. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
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Barroso-Sousa, R., Barry, W.T., Guo, H., Dillon, D., Tan, Y.B., Fuhrman, K., Osmani, W., Getz, A., Baltay, M., Dang, C., Yardley, D., Moy, B., Marcom, P.K., Mittendorf, E.A., Krop, I.E., Winer, E.P., and Tolaney, S.M.
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- 2019
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4. Effects of neratinib on health-related quality of life in women with HER2-positive early-stage breast cancer: longitudinal analyses from the randomized phase III ExteNET trial
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Delaloge, S., Cella, D., Ye, Y., Buyse, M., Chan, A., Barrios, C.H., Holmes, F.A., Mansi, J., Iwata, H., Ejlertsen, B., Moy, B., Chia, S.K.L., Gnant, M., Smichkoska, S., Ciceniene, A., Martinez, N., Filipović, S., Ben-Baruch, N.E., Joy, A.A., Langkjer, S.T., Senecal, F., de Boer, R.H., Moran, S., Yao, B., Bryce, R., Auerbach, A., Fallowfield, L., and Martin, M.
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- 2019
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5. Real world patterns of care in HER2-overexpressing breast cancer: Results of a survey of TEACH clinical trial investigators in 2011
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Chavarri-Guerra, Y., St. Louis, J., Bukowski, A., Soto-Perez-de-Celis, E., Liedke, P.E.R., Symecko, H., Moy, B., Higgins, M., Finkelstein, D.M., and Goss, P.E.
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- 2017
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6. Impact of treatment duration of extended adjuvant therapy with neratinib in early stage HER2+HR+ breast cancer after trastuzumab-based therapy on patient outcomes
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Martin Jimenez, M., Gnant, M. I., Ejlertsen, B., Mansi, J. L., Ruiz-Borrego, M., Jakobsen, E. H., Osborne, C. K., Birhiray, R., Zhang, B., Wong, A., Moy, B., and Holmes, F. A.
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- 2020
7. Size-effect on the physical characteristics of the aerobic granule in a SBR
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Toh, S., Tay, J., Moy, B., Ivanov, V., and Tay, S.
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- 2003
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8. 'Sport and smoking - you've got to be joking.'
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Moy, R, Moy, B, Tickner, B, and Gilmour, W
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- 1997
9. Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer
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Moy, B., Tu, D., Pater, J.L., Ingle, J.N., Shepherd, L.E., Whelan, T.J., and Goss, P.E.
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- 2006
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10. CO168 Adaptive Behaviors Over Time in Children and Young Adults With Classic Galactosemia
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Fridovich-Keil, JL, Qian, C, Wells, C, Szabo, S, Paull, N, Moy, B, Jayasinghe, P, and Gallo, D
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- 2022
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11. A Phase I Study of Adjuvant Niraparib Administered Concurrently with Postoperative Radiation Therapy in Patients with Localized Triple Negative Breast Cancer
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Keenan, J.C., Dunn, S.A., Collins, M.E., Taghian, A.G., Spring, L.M., Moy, B., Bardia, A., Kuter, I., Cho, H.L., Gadd, M.A., Vidula, N., Shin, J.A., Peppercorn, J.M., Bellon, J.R., Wong, J.S., Punglia, R.S., Tolaney, S., Isakoff, S.J., and Ho, A.Y.
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- 2022
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12. Local���regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)
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Partridge, A.H., Ellis, M., Albain, K.S., Winer, E.P., Overmoyer, B.A., Carey, L.A., Rugo, H.S., Yardley, D.A., Krop, I., Wolff, A.C., Hudis, C.A., Guo, H., Moy, B., Marcom, P.K., Dang, C.T., Bellon, J.R., Burstein, H.J., Tolaney, S.M., and Barry, W.T.
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skin and connective tissue diseases - Abstract
Purpose: Women with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local���regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T). Methods: Patients with HER2-positive tumors ��� 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan���Meier method. Results: Of the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4���96.2), and LRR-free survival was 98.6% (95% CI 97.4���99.8). Conclusion: LRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy.
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- 2019
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13. PIK3CA alterations and benefit with neratinib after trastuzumab-based adjuvant therapy in early- stage HER2+ breast cancer: Correlative analyses of the phase III ExteNET trial
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Chia, S.K.L., Martin, M., Holmes, F.A., Ejlertsen, B., Delaloge, S., Moy, B., Iwata, H., von Minckwitz, G., Mansi, J., Barrios, C.H., Gnant, M., Tomašević, Z., Denduluri, N., Šeparović, Robert, Kim, Jakobsen, E.H., Harvey, V., Robert, N., Smith, J.I.I., Harker, G., Lalani, A.S., Zhang, B., Eli, L.D., Chan, A., and Van Dang, Chi
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neratinib ,trastuzumab ,ExteNET studija ,rani HER2 pozitivni karcinom dojke ,skin and connective tissue diseases ,neoplasms - Abstract
One year of neratinib treatment after trastuzumab- based adjuvant therapy significantly improves iDFS after 5 years in patients with early-stage HER2+ breast cancer. From this modest-sized exploratory cohort, it appears that PIK3CA may be a biomarker for differential sensitivity to neratinib after 1 year of trastuzumab in the adjuvant setting.These exploratory results should be validated in a larger subset.
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- 2018
14. Leptomeningeal Disease in Breast Cancer: Pre-Treatment Prognostic Factors and Outcomes
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Milligan, M.G., Aitelli, A., Mehan, W.A., Shi, D.D., Cagney, D.N., Oh, K.S., Wang, N., Brastianos, P., Moy, B., Lin, N.U., and Shih, H.A.
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- 2021
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15. 161P Population effectiveness model of the consequences of recurrence after trastuzumab emtansine (T-DM1) treatment among U.S. patients with high-risk HER2+ early-stage breast cancer (ESBC)
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Veenstra, D.L., Hendrix, N., Dolan, C.M., Fisher, K.A., Lalla, D., Oestreicher, N., and Moy, B.
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- 2021
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16. 45P Long-term efficacy of neratinib in HER2-positive early-stage breast cancer: Overall survival and central nervous system outcomes from the phase III ExteNET trial
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Chan, A., Moy, B., Mansi, J.L., Gnant, M.I., Barrios, C.H., Separovic, R., Guerrero-Zotano, A., Gore, I., Smith, J., Bryce, R.P., Xu, F., Wong, A., Martin, M., and Holmes, F.A.
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- 2021
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17. P005 - Continued efficacy of neratinib in patients with HER2-positive (HER2+) early-stage breast cancer: final overall survival (OS) analysis from the randomized phase 3 ExteNET trial
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Martin, M., Holmes, F.A., Moy, B., Mansi, J., Gnant, M., Buyse, M., Barrios, C., Bryce, R., Wong, A., and Chan, A.
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- 2021
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18. Neratinib after trastuzumab (T)-based adjuvant therapy in early- stage HER2+ breast cancer (BC): 5-year analysis of the phase III ExteNET trial
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Martin Jimenez, M, Holmes, FA, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Kim, SB, Jakobsen, EH, Bryce, RP, Xu, F, Buyse, M, Chan, A, and Andre, Fabrice
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macromolecular substances ,neratinib ,trastuzumab ,rani rak dojke ,ExteNET studija - Abstract
1 y of neratinib after T-based adjuvant therapy significantly improves iDFS at 5 y in pts with early-stage HER2+ BC, with a long-term sustained effect. A protocol-specified subgroup analysis suggested greater benefit in HR+ pts. Overall survival data are not yet mature.
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- 2017
19. 358TiP Phase Ib/II study of antibody-drug conjugate, sacituzumab govitecan, in combination with the PARP inhibitor, talazoparib, in metastatic triple-negative breast cancer
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Bardia, A., Spring, L.M., Juric, D., Partridge, A., Ligibel, J., Kuter, I., Peppercorn, J., Parsons, H., Ryan, P., Chawla, D., Attaya, V., Fitzgerald, D.M., Viscosi, E., Lormill, B., Shellock, M., Moy, B., Tolaney, S.M., and Ellisen, L.W.
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- 2020
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20. 1O Neratinib + capecitabine vs lapatinib + capecitabine in HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: Exploratory biomarker analyses from phase III NALA trial
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Saura, C., Vivancos, A., Matito, J., Wildiers, H., Brufsky, A.M., Oliveira, M., Waters, S., Hurvitz, S.A., Moy, B., Kim, S-B., Gradishar, W.J., Queiroz, G.S., Cronemberger, E., Bebchuk, J., Keyvanjah, K., Lalani, A.S., Eli, L.D., and Delaloge, S.
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- 2020
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21. 83P Impact of treatment duration of extended adjuvant therapy with neratinib in early stage HER2+ HR+ breast cancer after trastuzumab-based therapy on patient outcomes
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Martin Jimenez, M., Gnant, M.I., Ejlertsen, B., Mansi, J.L., Ruiz-Borrego, M., Jakobsen, E.H., Osborne, C.K., Birhiray, R., Zhang, B., Wong, A., Moy, B., and Holmes, F.A.
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- 2020
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22. 318P - Association between PIK3CA mutation status and development of brain metastases in HR+/HER2- metastatic breast cancer
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Fitzgerald, D.M., Muzikansky, A., Pinto, C., Henderson, L., Walmsley, C., Allen, R., Ferraro, G.B., Isakoff, S., Moy, B., Oh, K., Shih, H.A., Dias-Santagata, D., Iafrate, A.J., Bardia, A., Brastianos, P.K., and Juric, D.
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- 2019
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23. P012 - Population effectiveness model of the consequences of recurrences following treatment with trastuzumab among women with HER2+ early stage breast cancer in the United States
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Doan, Q., Martin, M., Lalla, D., Halperin, M., Barnett, B., Bryce, R., Danese, M., and Moy, B.
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- 2019
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24. P011 - Efficacy of neratinib in hormone receptor-positive (HR+) patients who initiated treatment within 1 year of completing trastuzumab-based adjuvant therapy in HER2+ early-stage breast cancer (BC): subgroup analyses from the phase III ExteNET trial
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Ejlertsen, B., Holmes, F.A., Chia, S.K.L., Iwata, H., Moy, B., Delaloge, S., Xu, F., Barnett, B., Chan, A., and Martin, M.
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- 2019
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25. Measuring decision quality: Psychometric evaluation of a new instrument for breast cancer chemotherapy
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Belkora, Jeffrey, Lee, CN, Wetschler, MH, Chang, Y, Belkora, JK, Moy, B, Partridge, A, and Sepucha, KR
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© 2014 Lee et al.; licensee BioMed Central Ltd.Background: Women diagnosed with early stage (I or II) breast cancer face a highly challenging decision - whether or not to undergo adjuvant chemotherapy. We developed a decision quality instrument for chemoth
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- 2014
26. 177P - Effects of neratinib (N) on health-related quality of life (HRQoL) in early-stage HER2+ breast cancer (BC): longitudinal analyses from the phase III ExteNET trial
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Delaloge, S., Ye, Y., Cella, D., Buyse, M., Chan, A., Barrios, C., Holmes, F.A., Mansi, J., Iwata, H., Ejlertsen, B., Moy, B., von Minckwitz, G., Chia, S., Gnant, M., Smichkoska, S., Ciceniene, A., Moran, S., Auerbach, A.H., Fallowfield, L., and Martin Jimenez, M.
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- 2017
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27. 149O - Neratinib after trastuzumab (T)-based adjuvant therapy in early-stage HER2+ breast cancer (BC): 5-year analysis of the phase III ExteNET trial
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Martin Jimenez, M., Holmes, F.A., Ejlertsen, B., Delaloge, S., Moy, B., Iwata, H., von Minckwitz, G., Chia, S., Mansi, J., Barrios, C., Gnant, M., Tomasevic, Z., Denduluri, N., Separovic, R., Kim, S-B., Jakobsen, E.H., Bryce, R.P., Xu, F., Buyse, M., and Chan, A.
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- 2017
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28. Association Between the 21-Gene Recurrence Score and Isolated Local-Regional Recurrence in Hormone Receptor-Positive Breast Cancer
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Buscariollo, D., Cronin, A., Bleicher, R.J., Cohen, A., Hassett, M.J., Javid, S., Kumar, S., Moy, B., Niland, J., Wolff, A., and Punglia, R.S.
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- 2016
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29. A radiation monitor and data acquisition system with multiple access possibilities
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Moy, B, Rau, G, and Tausch, Lothar A
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Health Physics and Radiation Effects - Published
- 1994
30. Association Between Breast Cancer Biological Subtype and Risk of Locoregional Recurrence A Mastectomy in Node-Negative Patients
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Tseng, Y.D., Uno, H., Hughes, M.E., Niland, J.C., Wong, Y., Theriault, R., Marcom, P.K., Moy, B., Breslin, T., Edge, S.B., Wilson, J.L., and Punglia, R.S.
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- 2014
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31. American society of clinical oncology policy statement: opportunities in the patient protection and affordable care act to reduce cancer care disparities.
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Moy B, Polite BN, Halpern MT, Stranne SK, Winer EP, Wollins DS, and Newman LA
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- 2011
32. Doctor-patient communication about advance directives in metastatic breast cancer.
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Ozanne EM, Partridge A, Moy B, Ellis KJ, and Sepucha KR
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PURPOSE: Oncology providers often find it difficult to discuss end-of-life issues with patients and assume that patients are reluctant to think about the issues involved. This study examined whether or not patients with metastatic breast cancer had advance directives, and if so, with whom they discussed written plans for end-of-life decisions. PATIENTS AND METHODS: A cross-sectional sample of 32 women with metastatic breast cancer and their providers from two academic medical centers in the United States were surveyed at baseline and again 3 months later about advance directives, decision-making goals, and their expectations. After the baseline assessment, patients viewed a decision aid that discussed choices for treatment of metastatic disease. The patients' experience with advance directives in addition to associations between advance directives and patient preferences regarding end-of-life care, demographics, and clinical characteristics were analyzed. RESULTS: At baseline, the majority of women had gathered information (75%) about or had written (66%) advance directives. These percentages increased at 3 months. Providers were only aware of the presence of an advance directive in a minority of cases (14%). Patients were more than three times as likely to talk to and share written plans with family and friends than with their providers. CONCLUSIONS: The majority of patients gathered information about advance directives and had made written plans, yet few discussed these plans with their providers. Explicit discussion of advance directives and patient preferences regarding end-of-life care are lacking in this setting. Facilitation of doctor-patient communication about end-of-life care is needed in order to provide quality patient care at this difficult time. [ABSTRACT FROM AUTHOR]
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- 2009
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33. Institutional academic industry relationships.
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Campbell EG, Weissman JS, Ehringhaus S, Rao SR, Moy B, Feibelmann S, Goold SD, Campbell, Eric G, Weissman, Joel S, Ehringhaus, Susan, Rao, Sowmya R, Moy, Beverly, Feibelmann, Sandra, and Goold, Susan Dorr
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Context: Institutional academic-industry relationships have the potential of creating institutional conflicts of interest. To date there are no empirical data to support the establishment and evaluation of institutional policies and practices related to managing these relationships.Objective: To conduct a national survey of department chairs about the nature, extent, and consequences of institutional-academic industry relationships for medical schools and teaching hospitals.Design, Setting, and Participants: National survey of department chairs in the 125 accredited allopathic medical schools and the 15 largest independent teaching hospitals in the United States, administered between February 2006 and October 2006.Main Outcome Measure: Types of relationships with industry.Results: A total of 459 of 688 eligible department chairs completed the survey, yielding an overall response rate of 67%. Almost two-thirds (60%) of department chairs had some form of personal relationship with industry, including serving as a consultant (27%), a member of a scientific advisory board (27%), a paid speaker (14%), an officer (7%), a founder (9%), or a member of the board of directors (11%). Two-thirds (67%) of departments as administrative units had relationships with industry. Clinical departments were more likely than nonclinical departments to receive research equipment (17% vs 10%, P = .04), unrestricted funds (19% vs 3%, P < .001), residency or fellowship training support (37% vs 2%, P < .001), and continuing medial education support (65% vs 3%, P < .001). However, nonclinical departments were more likely to receive funding from intellectual property licensing (27% vs 16%, P = .01). More than two-thirds of chairs perceived that having a relationship with industry had no effect on their professional activities, 72% viewed a chair's engaging in more than 1 industry-related activity (substantial role in a start-up company, consulting, or serving on a company's board) as having a negative impact on a department's ability to conduct independent unbiased research.Conclusion: Overall, institutional academic-industry relationships are highly prevalent and underscore the need for their active disclosure and management. [ABSTRACT FROM AUTHOR]- Published
- 2007
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34. Long-term psychosocial adjustment of older vs younger survivors of breast and endometrial cancer.
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Kornblith AB, Powell M, Regan MM, Bennett S, Krasner C, Moy B, Younger J, Goodman A, Berkowitz R, and Winer E
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Background: The study's objective was to test whether there were signfiicant differences in adjustment between younger and older breast and endometrial cancer survivors.Methods: Two hundred and fifty-two breast and endometrial cancer survivors participated in this study, ranging in age from either 18 to 55 years old or 65 years old or older. Survivors were interviewed by telephone at study entry and 12 months, using a battery of measures to assess their adjustment, physical functioning, and treatment-related physical problems.Results: With an average of 3.7 years since treatment completion, almost all survivors reported good adjustment to having had cancer. While most differences in psychosocial adjustment between groups were small, younger survivors reported significantly worse adaptation than older survivors, as measured by the Hospital Anxiety and Depression Scale (HADS, p<0.0001), Appearance-Orientation Scale (AOS, body image; p=0.02), Fear of Recurrence (p<0.0001), Distress about Long-term Treatment-Related Cancer Problems (p=0.01), and Number of Sexual Problems Attributed to Cancer (p<0.0001).Conclusion: Survivors reported few cancer-related problems with only a small subset reporting problems in adjustment. Although differences were small, younger cancer survivors reported significantly worse adaptation than older survivors. Much of the adaptation to having had cancer may have already occurred in long-term survivors. Copyright (c) 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2007
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35. P388 leukaemia cells resistant to the anthracycline menogaril lack multidrug resistant phenotype.
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Badiner, GJ, Moy, BC, Smith, KS, Tarpley, WG, Groppi, VE, Bhuyan, BK, Badiner, G J, Moy, B C, Smith, K S, Tarpley, W G, Groppi, V E, and Bhuyan, B K
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- 1990
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36. 0154 TEACH: Phase III study of lapatinib after completion of adjuvant chemotherapy in trastuzumab-naive women with HER2-positive breast cancer
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Moy, B., Maltzman, J.D., Rappold, E., Nicolodi, L., Williams, L.S., and Goss, P.E.
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- 2009
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37. 5034 Troponin I and C-reactive protein as biomarkers for changes in left ventricular ejection fraction in patients with early stage breast cancer treated with dose-dense doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel with trastuzumab and lapatinib
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Morris, P.G., Chen, C., Lin, N., Moy, B., Come, S., Abbruzzi, A., Winer, E., Norton, L., Hudis, C.A., and Dang, C.T.
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- 2009
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38. P119 Phase III study of lapatinib after completion of adjuvant chemotherapy in trastuzumab-naive women with ErbB2-overexpressing breast cancer: Tykerb evaluation after chemotherapy (TEACH) study
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Moy, B., Maltzman, J.D., and Goss, P.E.
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- 2007
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39. immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.
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Barroso-Sousa, R, Barry, W T, Guo, H, Dillon, D, Tan, Y B, Fuhrman, K, Osmani, W, Getz, A, Baltay, M, Dang, C, Yardley, D, Moy, B, Marcom, P K, Mittendorf, E A, Krop, I E, Winer, E P, and Tolaney, S M
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HORMONE receptor positive breast cancer , *BREAST cancer , *EPIDERMAL growth factor receptors , *CLINICAL trial registries , *SECONDARY analysis , *BIOMARKERS - Abstract
Background Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. Patients and methods The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. Results Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. Conclusion Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. Clinical trial registration clinicaltrials.gov identifier: NCT00542451. [ABSTRACT FROM AUTHOR]
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- 2019
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40. Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial
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Sara A. Hurvitz, Maureen E. Trudeau, William J. Gradishar, Larisa Ryvo, Ming-Shen Dai, Sujith Kalmadi, Cristiano Souza, Eduardo Cronemberger, Suzette Delaloge, Adam Brufsky, Mafalda Oliveira, Vladimir Milovanov, Beverly Moy, Sung Bae Kim, Kiana Keyvanjah, J. Alarcón, Fairooz F. Kabbinavar, Ron Bose, Richard A. Bryce, Cristina Saura, Judith Bebchuk, Barbara Haley, Luciana Landeiro, Institut Català de la Salut, [Hurvitz SA] University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, California, USA. [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Cooperative Group, Barcelona, Spain. [Trudeau ME] Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. [Moy B] Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA. [Delaloge S] Gustave Roussy, Villejuif, France, and Vall d'Hebron Barcelona Hospital Campus
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0301 basic medicine ,Oncology ,Central Nervous System ,Cancer Research ,Receptor, ErbB-2 ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Neratinib ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,ErbB-2 ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Cumulative incidence ,Other subheadings::/therapeutic use [Other subheadings] ,Receptor, ErbB‐2 ,skin and connective tissue diseases ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Hazard ratio ,terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Metastatic breast cancer ,Treatment Outcome ,030220 oncology & carcinogenesis ,Quinolines ,Female ,medicine.symptom ,Receptor ,medicine.drug ,medicine.medical_specialty ,Oncology and Carcinogenesis ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Breast Neoplasms ,Lapatinib ,Asymptomatic ,Quimioteràpia combinada ,Capecitabine ,03 medical and health sciences ,Breast cancer ,Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Internal medicine ,Breast Cancer ,medicine ,Humans ,Oncology & Carcinogenesis ,Otros calificadores::/uso terapéutico [Otros calificadores] ,business.industry ,medicine.disease ,030104 developmental biology ,Central nervous system neoplasms ,Mama - Càncer - Tractament ,Avaluació de resultats (Assistència sanitària) ,business - Abstract
Background Neratinib has efficacy in central nervous system (CNS) metastases from HER2‐positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C). Materials and Methods NALA was a randomized, active‐controlled trial in patients who received two or more previous HER2‐directed regimens for HER2‐positive MBC. Patients with asymptomatic/stable brain metastases (treated or untreated) were eligible. Patients were assigned to N + C (neratinib 240 mg per day, capecitabine 750 mg/m2 twice daily) or L + C (lapatinib 1,250 mg per day, capecitabine 1,000 mg/m2 twice daily) orally. Independently adjudicated progression‐free survival (PFS), overall survival (OS), and CNS endpoints were considered. Results Of 621 patients enrolled, 101 (16.3%) had known CNS metastases at baseline (N + C, n = 51; L + C, n = 50); 81 had received prior CNS‐directed radiotherapy and/or surgery. In the CNS subgroup, mean PFS through 24 months was 7.8 months with N + C versus 5.5 months with L + C (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.41–1.05), and mean OS through 48 months was 16.4 versus 15.4 months (HR, 0.90; 95% CI, 0.59–1.38). At 12 months, cumulative incidence of interventions for CNS disease was 25.5% for N + C versus 36.0% for L + C, and cumulative incidence of progressive CNS disease was 26.2% versus 41.6%, respectively. In patients with target CNS lesions at baseline (n = 32), confirmed intracranial objective response rates were 26.3% and 15.4%, respectively. No new safety signals were observed. Conclusion These analyses suggest improved PFS and CNS outcomes with N + C versus L + C in patients with CNS metastases from HER2‐positive MBC. Implications for Practice In a subgroup of patients with central nervous system (CNS) metastases from HER2‐positive breast cancer after two or more previous HER2‐directed regimens, the combination of neratinib plus capecitabine was associated with improved progression‐free survival and CNS outcomes compared with lapatinib plus capecitabine. These findings build on previous phase II and III studies describing efficacy of neratinib in the prevention and treatment of CNS metastases, and support a role for neratinib as a systemic treatment option in the management of patients with HER2‐positive brain metastases following antibody‐based HER2‐directed therapies., This article reports outcomes among HER2‐positive breast cancer patients with central nervous system metastases at baseline from the phase III NALA trial of neratinib plus capecitabine versus lapatinib plus capecitabine.
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- 2021
41. Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial
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Cristina Saura, Suzette Delaloge, Sung Bae Kim, Mafalda Oliveira, Yen-Shen Lu, Bin Yao, John Crown, Ming-Shen Dai, Hong-Tai Chang, Thomas Yau, Takaaki Fujii, Nala Investigators, Daniele Fagnani, Maureen E. Trudeau, Ming-Feng Hou, William J. Gradishar, Johanna Mattson, Marketa Palacova, Barbara Haley, Masato Takahashi, Beverly Moy, Yu-Min Yeh, Richard Bryce, Kiana Keyvanjah, Miki Yamaguchi, Shang Wen Chen, Judith Bebchuk, Adam Brufsky, Norikazu Masuda, Michelino De Laurentiis, Yin-Hsun Feng, Johnson Lin, Toshimi Takano, Sara A. Hurvitz, Hans Wildiers, Yoon Sim Yap, Institut Català de la Salut, [Saura C, Oliveira M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. SOLTI Breast Cancer Cooperative Group, Barcelona, Spain. [Feng YH, Dai MS, Chen SW] Chi Mei Medical Centre, Liouying, Tainan, Taiwan and Tri-Service General Hospital, Taipei, Taiwan. [Hurvitz SA] University of California Los Angeles/Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA, Vall d'Hebron Barcelona Hospital Campus, Saura, C., Oliveira, M., Feng, Y. -H., Dai, M. -S., Chen, S. -W., Hurvitz, S. A., Kim, S. -B., Moy, B., Delaloge, S., Gradishar, W., Masuda, N., Palacova, M., Trudeau, M. E., Mattson, J., Yap, Y. S., Hou, M. -F., De Laurentiis, M., Yeh, Y. -M., Chang, H. -T., Yau, T., Wildiers, H., Haley, B., Fagnani, D., Lu, Y. -S., Crown, J., Lin, J., Takahashi, M., Takano, T., Yamaguchi, M., Fujii, T., Yao, B., Bebchuk, J., Keyvanjah, K., Bryce, R., and Brufsky, A.
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Receptor, ErbB-2 ,Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] ,Quinoline ,Medicaments antineoplàstics - Ús terapèutic ,Kaplan-Meier Estimate ,THERAPY ,Tyrosine-kinase inhibitor ,law.invention ,chemistry.chemical_compound ,ErbB-2 ,0302 clinical medicine ,Randomized controlled trial ,Mama - Càncer ,law ,Antineoplastic Combined Chemotherapy Protocols ,Other subheadings::/therapeutic use [Other subheadings] ,neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES] ,Brain Neoplasms ,Nausea ,ORIGINAL REPORTS ,Middle Aged ,OPEN-LABEL ,Metastatic breast cancer ,Progression-Free Survival ,3. Good health ,Survival Rate ,TRASTUZUMAB EMTANSINE ,030220 oncology & carcinogenesis ,Neratinib ,Retreatment ,Quinolines ,Female ,Life Sciences & Biomedicine ,Breast Neoplasm ,medicine.drug ,Human ,Diarrhea ,medicine.medical_specialty ,medicine.drug_class ,Clinical Sciences ,Oncology and Carcinogenesis ,Breast Neoplasms ,Lapatinib ,Breast Neoplasms, Male ,Capecitabine ,Brain Neoplasm ,03 medical and health sciences ,Internal medicine ,Breast Cancer ,medicine ,Humans ,Oncology & Carcinogenesis ,Progression-free survival ,COMBINATION ,terapéutica::protocolos clínicos::protocolos antineoplásicos::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Aged ,Science & Technology ,Antineoplastic Combined Chemotherapy Protocol ,RECEPTOR ,business.industry ,Otros calificadores::/uso terapéutico [Otros calificadores] ,Therapeutics::Clinical Protocols::Antineoplastic Protocols::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,medicine.disease ,030104 developmental biology ,chemistry ,Trastuzumab emtansine ,Quality of Life ,NALA Investigators ,business - Abstract
PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .0004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.
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- 2020
42. FGFR1 gene amplification mediates endocrine resistance but retains TORC sensitivity in metastatic hormone receptor positive (HR+) breast cancer
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Megan Yuen, Carlos L. Arteaga, Andrzej Niemierko, Luigi Formisano, Neelima Vidula, Jerry Younger, Steven J. Isakoff, Alberto Servetto, Dennis C. Sgroi, Jeffrey Peppercorn, Laura Spring, Joshua Z. Drago, Aditya Bardia, Seth A. Wander, Leif W. Ellisen, Dejan Juric, Beverly Moy, A. John Iafrate, Giuliana Malvarosa, Formisano, L, Drago, Jz, Juric, D, Niemierko, A, Servetto, A, Wander, Sa, Spring, Lm, Vidula, N, Younger, J, Peppercorn, J, Yuen, M, Malvarosa, G, Sgroi, D, Isakoff, Sj, Moy, B, Ellisen, Lw, Iafrate, Aj, Arteaga, Cl, and Bardia, A
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0301 basic medicine ,Cancer Research ,medicine.drug_class ,medicine.medical_treatment ,Palbociclib ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Progesterone receptor ,medicine ,biological marker circulating tumor DNA cyclin dependent kinase 4 cyclin dependent kinase 6cyclin dependent kinase inhibitor cyclin dependent kinase inhibitor 4cyclin dependent kinase inhibitor 6epidermal growth factor receptor 2estrogen receptor everolimus fibroblast growth factor receptor 1fulvestranthormone receptor letrozole paclitaxel palbociclib phosphatidylinositol 3 kinase progesterone receptor unclassified drug ,skin and connective tissue diseases ,Everolimus ,Fulvestrant ,business.industry ,medicine.disease ,Metastatic breast cancer ,stomatognathic diseases ,030104 developmental biology ,Oncology ,Estrogen ,030220 oncology & carcinogenesis ,Cancer research ,Hormone therapy ,business ,medicine.drug - Abstract
Purpose: While FGFR1 amplification has been described in breast cancer, the optimal treatment approach for FGFR1-amplified (FGFR1+) metastatic breast cancer (MBC) remains undefined. Experimental Design: We evaluated clinical response to endocrine and targeted therapies in a cohort of patients with hormone receptor–positive (HR+)/HER2− MBC and validated the functional role of FGFR1-amplification in mediating response/resistance to hormone therapy in vitro. Results: In the clinical cohort (N = 110), we identified that patients with FGFR1+ tumors were more likely to have progesterone receptor (PR)-negative disease (47% vs. 20%; P = 0.005), coexisting TP53 mutations (41% vs. 21%; P = 0.05), and exhibited shorter time to progression with endocrine therapy alone and in combination with CDK4/6 inhibitor, but not with a mTOR inhibitor (everolimus), adjusting for key prognostic variables in multivariate analysis. Furthermore, mTOR-based therapy resulted in a sustained radiological and molecular response in an index case of FGFR1+ HR+/HER2− MBC. In preclinical models, estrogen receptor–positive (ER+)/FGFR1-amplified CAMA1 human breast cancer cells were only partially sensitive to fulvestrant, palbociclib, and alpelisib, but highly sensitive to everolimus. In addition, transduction of an FGFR1 expression vector into ER+ T47D cells induced resistance to fulvestrant that could be overcome by added TORC1 inhibition, but not PI3K or CDK4/6 inhibition. Conclusions: Collectively, these findings suggest that while FGFR1 amplification confers broad resistance to ER, PI3K, and CDK4/6 inhibitors, mTOR inhibitors might have a unique therapeutic role in the treatment of patients with ER+/FGFR1+ MBC.
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- 2019
43. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial
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Miguel Martin, Frankie A Holmes, Bent Ejlertsen, Suzette Delaloge, Beverly Moy, Hiroji Iwata, Gunter von Minckwitz, Stephen K L Chia, Janine Mansi, Carlos H Barrios, Michael Gnant, Zorica Tomašević, Neelima Denduluri, Robert Šeparović, Erhan Gokmen, Anna Bashford, Manuel Ruiz Borrego, Sung-Bae Kim, Erik Hugger Jakobsen, Audrone Ciceniene, Kenichi Inoue, Friedrich Overkamp, Joan B Heijns, Anne C Armstrong, John S Link, Anil Abraham Joy, Richard Bryce, Alvin Wong, Susan Moran, Bin Yao, Feng Xu, Alan Auerbach, Marc Buyse, Arlene Chan, Vernon Harvey, Rudolf Tomek, Nicholas J. Robert, Ira Gore, John W. Smith, Norikazu Masuda, S. Di Sean Kendall, William Graydon Harker, Katarina Petrakova, Angel Guerrero Zotano, Amparo Ruiz Simon, Zora Neskovic Konstantinovic, Nicholas O. Iannotti, Pierfrancesco Tassone, Gladys I. Rodriguez, Noelia Jáñez Martinez, Carmen Crespo Massieu, Snezana Smickoska, Isil Somali, Ugur Yilmaz, Mirta Garcia Alonso, Adolfo Murias Rosales, Soeren Cold, Ann Soegaard Knoop, Debra Patt, Beth A. Hellerstedt, Serafin Morales Murillo, Ingrid A. Mayer, Julie Ann Means-Powell, Rina Hui, Francis M. Senecal, Richard Hendry De Boer, Zhenzhou Shen, Adam Andrzej Luczak, Joanna W.Y. Chui, Janice Wing-hang Tsang, Istvan Lang, Yoshiaki Rai, Yasuo Hozumi, Albert J. Ten Tije, Manish Bhandari, Cynthia R.C. Osborne, Shoichiro Ohtani, Kenji Higaki, Kenichi Watanabe, Kazunori Taguchi, Masato Takahashi, Sladjana Filipovic, Vincent L. Hansen, Vijayarama Phooshkooru Rao, Manish Gupta, Petar Petrov, Bruno Coudert, Zeljko Vojnovic, Zsofia Polya, Toshiko Miyaki, Naohito Yamamoto, Stephen Brincat, Krzysztof Lesniewski-Kmak, Ewa Chmielowska, Ruemu E. Birhiray, Marc L. Citron, Steven William Papish, William R. Berry, Sven Tyge Langkjer, José Angel Garcia Sáenz, Ana Maria Arance, Noa Efrat, Tomasz Sarosiek, Lukasz Grzeda, Yvonne Manalo, Julie C. Smith, Irfan Vaziri, Tabitha Healey, Yasmin Rahim, Cynthia Luk, Brian Dingle, Sandra Franco, Peter Grundtvig Sorensen, Anjana Anand, Sarah Khan, George Fountzilas, Kenjiro Aogi, Satoru Shimizu, Milada Mikulova, Stanislav Spanik, Robert A. Somer, Patrick J. Flynn, Jermaine Coward, Paul Mainwaring, Guy Jerusalem, Carine Segura-Ojezzar, Christelle Levy, Thierry Delozier, David Khayat, Robert E. Coleman, Martin J. Rolles, Robert Maisano, Mario Nardi, Yoshinori Ito, Perran Fulden Yumuk, Gul Basaran, Nazim Serdar Turhal, Mary J. Wilkinson, Nathan B. Green, Algis P. Sidrys, Sigrun Hallmeyer, Douglas J. Testori, Srikala Sridhar, Jose Chang, Qiang Sun, Carlos Jara-Sanchez, Xabier Rubio, Maria Lomas Garrido, Juan Rafael De La Haba Rodriguez, Antonia Perello Martorell, Antoni Avelia Mestre, Julio Rifa Ferrer, Sonia del Barco Berron, Zsuzsanna Nagy, Maki Tanaka, Young-Hyuck Im, Robert R. Carroll, Laura C. Dickerson, Joseph R. Mace, Ragene Rivera, Leonard M. Klein, Robert Ruxer, Sharon T. Wilks, Dusan Kotasek, Vasil Popov, Violina Taskova, Violetka Marinova-Venkova, Constanta Timcheva, Christine Desbiens, Jean-Pierre Ayoub, Debjani Grenier, Norbert Marschner, Hans Tesch, Hans-Joachim Lueck, Jan Janssen, Ingo Schwaner, Stine Wahlstrom, Eva Harder Brix, Susanne Vallentin, Dan Kristensen, Anna Andreeva, Vesna Glavicic, Isabel Calvo Plaza, Antonio Anton Torres, Corinne Veyret, Jean-Pierre Bergerat, Emmanuelle Bourbouloux, Wendy Ann Ella, Hafiz Algurafi, Anne Robinson, Seung Jin Kim, Tetsuya Taguchi, Elona Juozaityte, Stanley Madretsma, Sandra Radema, Malgorzata Czerniawska-Meier, Wojciech Rogowski, Maria Wagnerova, Donald A. Richards, Elizabeth Tan-Chiu, Asskikis Vasileios, Charles Arthur Henderson, Viran Roger Holden, Xiaojia Wang, Zhongsheng Tong, Junlan Yang, Manuel Enrique Gonzalez, Mahdi Rezai, John Hackmann, Eduardo Martinez de Dueñas, Begoña Bermejo de las Heras, Louis Marie Dourthe, Dorothee Chocteau-Bouju, Philippe Bougnoux, Stylianos Kakolyris, Haralabos Kalofonos, Dimitrios Pectasidis, Ting Ying Ng, Gabor Pajkos, Eva Ezer Somogyine, Giuseppe Tonini, Dario Giuffrida, Shintaro Takao, Makoto Ishitobi, Hideo Inaji, Yutaka Tokuda, Katarzyna Wozniak, Dan Lungulescu, Yen-Shen Lu, King-Jen Chang, Julian Hill, Christopher Charles Croot, Albert Dekker, Neil D. Belman, Miguel Conde, Richard A. Michaelson, Kathleen Kemmer, Stephen Chui, Shiuh-Wen Luoh, Kenneth Nahum, Andrew R. Greenspan, Joni C. Nichols, Carlos A. Encarnacion, Thomas M.J. Niederman, Theresa Lee, Roland Alexander, Robert Gordon, Antoanet Tomova, Daniel Rauch, Razvan Andrei Popescu, Gustavo Adolfo Rojas, Jaroslav Vanasek, Tanja Neunhoeffer, Jana Barinoff, Gerd Graffunder, Abenhardt Wolfgang, Peter Bojko, Bernhard Heinrich, Albert von der Assen, Bogovic Jurij Antonovic, Lene Adrian, Manuel Ramos Vazquez, Santiago Gonzalez Santiago, Veronique Dieras, Jill Mercia Bishop, Timothy John Perren, Ioannis Varthalitis, Dimitris Mavroudis, Vassilis Georgoulias, Louis W.C. Chow, Chung Cheung Thomas Yau, Raymond Hin-Suen Liang, Béla Pikó, Agnes Wéber, Bella Kaufman, Karen Drumea, Francesco Nuzzo, Andrea De Matteis, Giacomo Carteni, Eriko Tokunaga, Mayumi Ishida, Shinji Ohno, Nobuaki Sato, Katsumasa Kuroi, Reiki Nishimura, Junichiro Watanabe, Yoon Ji Choi, Kyong Hwa Park, Marek Wojtukiewicz, Jacek Jassem, Niklas Loman, Sercan Askoy, Mustafa Kadri Altundag, Pinar Saip, Muhammad Amjad Ali, James Lloyd Wade, Amy Jo Chien, Debra Brandt, Yelena Novik, Chirag Jani, Robert L. Rice, Yousuf A. R Gaffar, Mark R. Keaton, Rajesh Bajaj, Gretchen Kimmick, David Campbell, Theodore Turnquest, Sideras Lucas, Pierre Dube, Binghe Xu, Joerg Schilling, Klaus Apel, Peter Michael Vestlev, Brita Bjerregaard Jensen, Vera Haahr, Alvaro Rodriguez Lescure, Begona Grana Suarez, Cristina Saura Manich, Jean-Philippe Jacquin, Ahmed Samreen, Ion Boiangiu, Magdolna Dank, Cristina Falci, Antonio Jirillo, Saverio Cinieri, Takayuki Ueno, Fumiaki Sato, Hiroyasu Yamashiro, Tomoharu Sugie, Keun Seok Lee, Jung Sil Ro, In Hae Park, Anita Zarina Bustam, Malgorzata Suszko-Kazarnowicz, Artur Piktel, Krzysztof Krzemieniecki, Polizenia Georgeta Iorga, Yoon Sim Yap, Marian Kakalejcik, Alper Sevinc, Mustafa Ozguroglu, Shin-Cheh Chen, Richard H. Greenberg, Allan Daniel Eisemann, Robert Droder, M. Rashid Abbasi, Marina Vaysburd, Humberto Jose Caldera, Barbara Bacsik Haley, Erwin Robin, Roger C. Inhorn, David Hufnagel, Peter D. Kenyon, Ellen Spremulli, Paula Silverman, Sharad Jain, Robert Weigand, Jeroen Mebis, Tatyana Koynova, Bernard Lesperance, Jana Prausova, Claus-Henning Kohne, Andreas Schneeweiss, Christian Jackisch, Stefan Fuxius, Ricardo Cubedo Cervera, Ander Urruticoechea Ribate, Sonia Pernas Simon, Jose Valero Gallego, Angels Arcusa Lanza, Maria del Pilar Alvarez, Jesus Florian Gerico, Laurent Cany, Justin Stebbing, Dejan Labudovic, Damir Gugic, Damir Vrbanec, Fausto Roila, Sandro Barni, Paolo Bidoli, Hirofumi Mukai, Vanessa Bermudez, Alexandru Eniu, Barry C. Mirtsching, Emad Ibrahim, Joan Trey, Paul Francis Hergenroeder, Aftab Mahmood, Anneliese Gonzalez, Edward H. Kaplan, Stacy Ban, Dhimant Patel, Billy Clowney, Karen Hoelzer, Garry H. Schwartz, Mohamed Salkeni, Jame Abraham, Sunil Narula, Khaled Jabboury, Robert Scott Mocharnuk, Richard H. McDonough, David H. Sikes, Ronald H. Kawanchi, Larry Schlabach, Samuel Spence McCachren, Thomas M. Cosgriff, Luke Dreisbach, Angela DeMichele, Lawrence Pawl, Jennifer Lucas, Lowell C. Shinn, Nabiel Alkhouri, Manish Monga, Deborah L. Lindquist, Thomas C. Anderson, Humera Khurshid, Sabrina Witherby, Nicholette Erickson, Ann Traynor, Ron Bose, Timothy J. Pluard, Michael C. Jones, Sucharu Prakash, Fabio Volterra, Gerardo Capo, Lawrence E. Flaherty, Elaina Gartner, Said Baidas, Ian Okazaki, Bichlien Nguyen, Thomas Rakowski, Ira Oliff, Joseph W. Leach, Daniel Anderson, Kendra Kubiak, Michaela Tsai, Philippe Vroman, Ines Deleu, Willem Lybaert, Marleen Borms, Felix Couture, Jonathan J. Wilson, Gordon Hunt, David R. Holland, Walter Mingrone, Shusen Wang, Donggeng Liu, Zefei Jiang, Vera Benesova, Martin Smakal, Petra Garnolova, Anne-Sophie Vesper, Monika Neumann, Wolfgang Janni, Cornelia Liedtke, Dorothea Fischer, Eva-Maria Grischke, Dietmar Seeger, Volker Moebus, Anita Prechtl, Juan Carlos Camara Toral, Alfonso Sanchez Munoz, Sonia Gonzalez Jimenez, Javier Cassinello Espinosa, Beatriz Cirauqui, Mireia Margeli Vila, Norberto Batista Lopez, Jose Ignacio Chacon Lopez-Muniz, Miguel Angel de la Cruz Mora, Audrey Mailliez, Laurence Vanlemmens, Damien Pouessel, Marc Espie, John Conibear, Rebecca Roylance, Adrian Harnett, David Geffen, Enzo Maria Ruggeri, Teresa Gamucci, Cees J. Van Groeningen, Renata Banas, Necati Alkis, Ming-Feng Hou, Amy K. Krie, Nandagopal S. Vrindavanam, Orion M. Howard, Dennis Citrin, Mark S. Morginstin, Ajit Desai, Ines J. Sanchez, David Allen Nixon, Patrick G. Beatty, Kathryn Edmiston, Marilyn McLaughlin, Jonathan D. Eneman, Cynthia A. Lynch, Edward O'Brien, Justin A. Call, Keith S. Lanier, Alison Conlin, Donald J. Brooks, Kristi McIntyre, Marc A. Saltzman, Michael J. Castine, Gregory L. Ortega, Young M. Choi, Craig H. Reynolds, Frankie Ann Brescia, Rita Kramer, Aimee D. Kohn, John P. Micha, Jessica M. Rhee, Satish Shah, David A. Riseberg, William Kevin Patterson, Jean-Paul Salmon, Chantal Andre, Alain Bols, Randal D'hondt, Sylvie Luce, Claire Nouwynck, Gino Pelgrims, Vincent Richard, Johan Verschuere, Kurt Geldhof, Clemens Caspar, Rongcheng Luo, Otakar Bednarik, Kathrin Schwedler, Marcus Schmidt, Romy Neumeister, Joachim Bischoff, Brigitte Rack, Roland Repp, Stefan Fries, Ralf Adrion, Volker Schulz, Peter Klare, Mahmoud Danei, Dirk Ossenbuhl, Jakob Manfred Kusche, Frank Griesinger, Jose Manuel Baena Canada, Purificacion Martinez del Prado, David Machover, Didier Mayeur, Nathalie Trufflandier, Valerie Delecroix, Mireille Mousseau, Marie-Ange Mouret-Reynier, Jean-Marc Nabholtz, Anula D. Chetiyawardana, Christos Papandreou, Lajos Hornyak, Zsolt Faluhelyi, Erzsebet Simo, Mario Di Palma, Francesco Cognetti, Gabriella Gorzegno, Luigi Dogliotti, Cesare Gridelli, Alfredo Falcone, Hector Soto Parra, Calogero Buscarino, Seock-Ah Im, Benito Sanchez Llamas, Wouter Dercksen, Franciscus Erdkamp, Jan B. Ruit, Hans Braun, Joanneke E.A. Portielje, Aydin Ciltas, Suleyman Buyukberber, Mustafa Benekli, Andrew J. Zahalsky, Rebecca Jaslow, Gary W. Thomas, Archana Maini, Israel Wiznitzer, Ali Khojasteh, Manuel Francisco Gonzalez, Lynn R. Kong, Aruna Padmanabhan, William A. Conkright, Sandra M. Swain, Douglas E. Faig, Kirti Jain, Ronald H. Yanagihara, Yvonne Ottaviano, Andrew Delmas, Heather A. Steele, Gordon K. Rainey, Penelope J. Harris, Jason K. Burris, Erik J. Rupard, Esther Tan, Pat W. Whitworth, Abby R. Bova, Ian C. Anderson, Mihran Shirinian, Caesar Tin-u, Timothy J. O'Rourke, Michael S. Roberts, Michael Francisco, A. Scott Pierson, Peter D. Byeff, Peter A. Kovach, John R. Caton, Mark Urban Rarick, William G. Schimidt, Alison T. Stopeck, Rachel Swart, Maria Regina Carrillo Flores, Carlos A. Alemany, Brennely Lozada, Paul L. Weinstein, Wei Wang, Michael Porubcin, David M. Ellison, George F. Geils, Edgardo Rivera, Mahmoud Charif, Martin, M, Holmes, F, Ejlertsen, B, Delaloge, S, Moy, B, Iwata, H, von Minckwitz, G, Chia, S, Mansi, J, Barrios, C, Gnant, M, Tomasevic, Z, Denduluri, N, Separovic, R, Gokmen, E, Bashford, A, Borrego, M, Kim, S, Jakobsen, E, Ciceniene, A, Inoue, K, Overkamp, F, Heijns, J, Armstrong, A, Link, J, Abraham, A, Bryce, J, Wong, A, Moran, S, Yao, B, Xu, F, Auerbach, A, Buyse, M, Chan, A, and Bidoli, P
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0301 basic medicine ,Time Factors ,Receptor, ErbB-2 ,Clinical Trial, Phase III ,Receptor, ErbB-2/metabolism ,Administration, Oral ,Kaplan-Meier Estimate ,exteNET ,0302 clinical medicine ,Japan ,Trastuzumab ,Antineoplastic Combined Chemotherapy Protocols ,pan-HER tyrosine kinase inhibitor ,Mastectomy ,Antineoplastic Combined Chemotherapy Protocols/administration & dosage ,Middle Aged ,neratinib ,trastuzumab ,breast cancer ,adjuvant ,Multicenter Study ,Treatment Outcome ,Oncology ,Antibodies, Monoclonal, Humanized/adverse effects ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Randomized Controlled Trial ,Neratinib ,Quinolines ,Neoplasm Invasiveness/pathology ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Quinolines/administration & dosage ,Breast Neoplasms ,Placebo ,Antibodies, Monoclonal, Humanized ,Risk Assessment ,Disease-Free Survival ,Drug Administration Schedule ,Trastuzumab/administration & dosage ,03 medical and health sciences ,Breast cancer ,Breast Neoplasms/drug therapy ,Double-Blind Method ,Internal medicine ,Journal Article ,medicine ,Adjuvant therapy ,Humans ,Comparative Study ,Neoplasm Invasiveness ,HER2-positive breast cancer ,Neoplasm Staging ,Proportional Hazards Models ,Intention-to-treat analysis ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,Survival Analysis ,Mastectomy/methods ,Surgery ,Clinical trial ,Regimen ,030104 developmental biology ,business ,Follow-Up Studies - Abstract
BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [INTERPRETATION: At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.FUNDING: Wyeth, Pfizer, and Puma Biotechnology.
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- 2017
44. Myelodysplatic syndrome and/or acute myelogenous leukemia (MDS and/or AML) after a breast cancer diagnosis: the National Comprehensive Cancer Network (NCCN) experience.
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Karp, J. E., Blackford, A., Visvanathan, K., Rugo, H. S., Moy, B., Goldstein, L. J., Goldstein, K. Stockerl, Neumayer, L., Langbaum, T. S., Hughes, M. E., Weeks, J. C., and Wolff, A. C.
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DRUG therapy , *BREAST cancer patients , *MORTALITY , *CANCER treatment , *THERAPEUTICS - Abstract
BACKGROUND: Cooperative group trials and institutional series reported the risk of MDS and/or AML after adjuvant chemotherapy for early stage breast cancer (eg, NSABP 0.21%, Smith JCO 2003; ECOG 2197 0.5%, Goldstein ASCO 2012). We examined the incidence of MDS and/or AML in breast cancer survivors that are part of the NCCN Breast Cancer Outcomes Database. METHODS: The NCCN Database prospectively identifies all incident breast cancers diagnosed at participating cancer centers, and patients that continue their care at an NCCN site are followed annually with information collected on subsequent treatment, recurrence, and new cancers. Mortality is also ascertained for all diagnosed patients every 2 years through the National Death Index. Women with stages 1-3 breast cancer (BC) diagnosed between 1997- 2008 were included in this analysis. Univariate chi square analyses were used to compare characteristics between patients with BC and BC&MDS and/or AML. Time from BC to MDS and/or AML and 5-/10-year cumulative incidence rates were analyzed using proportional subdistribution hazards regression models that account for death as a competing risk to MDS and/or AML. RESULTS: Among 21563 stage 1-3 BC patients from 8 NCCN sites, 39 (0.18%) subsequently developed MDS and/or AML. Median overall follow-up was 4.7 years and median time from BC to MDS and/or AML was 2.8 years (range, 0.6 to 8.3 years). Cumulative MDS and/or AML incidence was 0.19% at 5y and 0.27% at 10y. Overall, cancer characteristics at BC diagnosis within BC&MDS and/or AML and within BC groups were similar (Caucasian 82%v82%, AA 8% v8%; ER+ 79%v75%, HER2+ 14%v21%, TNBC 15%v14%; contralateral BC 3%v2%; pancreas or ovarian cancer 0%v1%). 13191 had adjuvant chemo (75%v67%; anthracycline 89%v91%, AC-taxane 46%v35%, dose-dense 6%v5%). Trends observed included more patients in BC&MDS and/or AML group with prior radiation (85%v70%, p = 0.06) and older age at BC diagnosis (median age 59v54 years, p = 0.09). Risk for developing MDS and/or AML after BC (adjusted for age at BC and race) was increased in those receiving any chemotherapy versus no chemotherapy (HR 2.16, 95% CI 0.98-4.77, p = 0.06), any RT versus no RT (HR 2.44, 95% CI 1.01-5.88, p = 0.04), and if chemo/RT given versus just chemo or just RT (HR 2.2, 95% CI 1.05-4.59, p = 0.04). No increased risk was observed if a taxane was added to an anthracycline regimen (HR 1.27, 95% CI 0.57-2.81, p = 0.56). CONCLUSIONS: In a large national prospective registry across NCCN sites, risk of MDS and/or AML is increased after adjuvant chemotherapy and/or adjuvant radiation therapy for stages 1-3 breast cancer, especially if both are used. Specific population subsets will be further examined. These rates are similar to those observed in clinical trials, but may underestimate actual numbers due to patients lost to follow-up. In addition, an MDS diagnosis was routinely under-reported in population databases until recently. Strategies to limit risk of subsequent cancers in patients likely to survive early stage breast cancer should be considered at the time of initial diagnosis. Predictors of MDS and/or AML in breast cancer survivors are needed. [ABSTRACT FROM AUTHOR]
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- 2012
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45. Dynamic tomographic optical breast imaging (TOBI) to monitor response to neoadjuvant therapy in breast cancer.
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Carp, S. A., Wanyo, C. M., Specht, M., Schapira, L., Moy, B., Finkelstein, D. M., Boas, D. A., and Isakoff, S. J.
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ADJUVANT treatment of cancer , *BREAST cancer research , *MAMMOGRAMS , *DRUG therapy , *HEMOGLOBIN polymorphisms - Abstract
Background: Near-infrared optical measurements have been recently shown to offer a promising non-invasive way for monitoring breast neoadjuvant chemotherapy (NAC) and predicting outcome. In particular, snapshots of tissue oxy and deoxy-hemoglobin concentration as well as water and lipid content have been demonstrated to be sensitive to therapy-induced changes. In this study, we extend optical measurements to capture additional hemodynamic and metabolic biomarkers revealed by dynamically imaging breast tissue during fractional mammographic compression. Using our dynamic tomographic optical breast imaging (TOBI) system we evaluate the early prediction performance of this advanced technology. Methods: We are conducting a pilot feasibility study in female patients with unilateral locally advanced breast cancer undergoing standard-of-care NAC. Pre-treatment and day 7 post-treatment TOBI scans are obtained, with additional (optional) scans on day 1 of each subsequent chemotherapy cycle. Both breasts are compressed in turn to 4-8 lbs of force, and optical images are acquired once every 2 seconds over two minutes. Time-resolved oxy-(HbO), deoxy-(HbR), and total-(HbT) hemoglobin concentration and hemoglobin oxygen saturation (SO2) are calculated. The compression-induced rate of change of HbT correlates with changes in tissue blood volume indicative of biomechanical properties. The evolution of tissue SO2 is modeled to obtain an index of the ratio of oxygen metabolism to blood flow. Therapy induced changes are quantified, and comparisons between changes in responders vs. non-responders are performed (response is defined here as >50% reduction in the largest tumor diameter). Results: We have enrolled 20 patients so far, of which 90% (N = 18) completed both the day 0 and day 7 scans. 17 patients have undergone surgery at this point. We focused our initial analysis on 5 HER2+ patients, of which two were non-responders, and three were responders according to our criteria. Four patients received taxol+herceptin+lapatinib, while the other received taxol+lapatinib only. In this small subgroup, the non-responders had an average increase of 1% in total hemoglobin concentration (HbT) from day 0 to day 7, while the responders had an average 12% decrease in HbT, respectively. We also noted different trends in the evolution of the tissue oxygen consumption to blood flow ratio, which increased 32% in non-responders from day 0 to day 7, while decreasing 11% in responders. Conclusions: The large percentage of enrolled patients that completed both initial scans demonstrates the feasibility of using dynamic optical breast tomography for breast neoadjuvant chemotherapy monitoring. Results in a small cohort of 5 HER2+ patients suggested a decreasing trend in HbT for responders as observed by previous studies. We also report for the first time an increase in the metabolic ratio of oxygen consumption to blood flow in non-responders vs. a decrease in responders. These initial results of our on- going study suggest that dynamic TOBI can detect changes due to treatment and may have predictive value for the treatment outcome and supports further studies of this non- invasive and portable tool for chemotherapy monitoring. [ABSTRACT FROM AUTHOR]
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- 2012
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46. The association between timing in adjuvant chemotherapy administration and overall survival for women with breast cancer within the National Comprehensive Cancer Network (NCCN).
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Vandergrift, J. L., Breslin, T. M., Niland, J. C., Edge, S. B., Wolff, A. C., Marcom, P. K., Rugo, H. S., Moy, B., Wilson, J. L., Ottesen, R. A., Weeks, J. C., and Wong, Y.-N.
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ADJUVANT treatment of cancer , *SURVIVAL , *BREAST surgery , *CANCER in women , *CANCER prognosis - Abstract
Introduction: Population based studies (eg, Hershman et al. BCRT 2006 and Lohrisch et al. JCO 2006) showed poorer survival associated with long delays in adjuvant chemotherapy (CTX) initiation following definitive surgery (DS) for women with breast cancer (BC). Delays in CTX following diagnosis (DX) have not been evaluated. The ASCO/NCCN quality measures (QMs) recommend CTX <=120 days after DX for patients with stage II/III ER/PR negative disease. We sought to examine the impact of delayed CTX on survival overall and stratified by disease-specific prognostic factors. Methods: 4,608 women with stage I-III HER2 negative breast cancer diagnosed between 2000 and 2006 at 8 NCCN centers were identified using the NCCN outcomes database. Patients with T3/4 disease or who received neoadjuvant therapy were excluded. The association between CTX timing and OS was evaluated using multivariate Cox models adjusted for CTX type, age, race, BMI, residential distance, insurance, SES, comorbidity, ER/PR, LVI, grade, T stage, and N stage. The impact of CTX timing was evaluated using a >90-day (d) DS-to-CTX threshold, based on poor outcomes observed in prior studies, and a >120d DX-to-CTX threshold, based on the ASCO/NCCN QMs. Results: Median follow-up was 7.2 years and OS at 7 years was 89%. Overall, 401 (8.7%) patients received CTX >120d after DX and 113 (2.4%) patients received CTX >90d after DS. The DX-to-CTX interval was more strongly correlated with the DX-to-DS (r = 0.74) interval than DS-to-CTX (r = 0.54) interval. A >90d DS-to-CTX interval was significantly associated with poorer survival (HR: 1.65, 95% CI 1.04-2.60, p = 0.03) in adjusted analyses. Shorter DS-to-CTX thresholds of >60d (n = 636, HR: 1.13, 95% CI: 0.89-1.43, p = 0.319) or >75d (n = 273, HR: 1.05, 95% CI 0.74-1.49, p = 0.76) were not associated with OS. The association between a >120d DX-to-CTX interval and OS was not statistically significant (HR: 1.32, 95% CI 0.99-1.76, p = 0.06). Patients who received CTX >135d(n = 231, HR1.25, 95% CI: 0.87-1.81, p = 0.22)or>150d(n = 128, HR1.15, 95% CI: 0.59-2.24, p = 0.69) after DX did not display an increased risk of death. Excluding pathological staging factors from the model had no effect on the results. In subgroup analyses stratified by ER/PR, LVI, grade, T stage or N stage, a >120d delay in CTX did not display significant associations with OS. Among ER/PR negative patients, the association between a >120d delay and OS was borderline non-significant after adjusting the p-value for multiple hypothesis testing using the false discovery rate method (HR: 1.80, 95% CI: 1.16-2.79, p = 0.09). Conclusion: Consistent with previous studies, CTX delays of >90 days following surgery were associated with poorer survival. OS was not significantly compromised in patients with DX-to-CTX intervals >120 days although this analysis may have limited power to detect small effects. More variation in the DX-to-CTX interval was attributed to pre-surgery time which may explain the differences observed between the DX-to-CTX and DS-to-CTX intervals. Among patients with ER/PR negative disease, a non-significant association between OS and a >120 day DX-to -CTX interval was observed that warrants further examination. [ABSTRACT FROM AUTHOR]
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- 2012
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47. Patterns of definitive axillary management in the era prior to reporting ACOSOG Z0011: comparison between NCCN Centers and hospitals in Michigan.
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Breslin, T., Hwang, S., Mamet, R., Hughes, M., Otteson, R., Edge, S., Moy, B., Rugo, H., Wong, Y.-N., Wilson, J., Laronga, C., Weeks, J., Silver, S., and Marcom, P.
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BREAST cancer research , *SENTINEL lymph nodes , *LUMPECTOMY , *BREAST surgery , *MASTECTOMY , *HORMONE receptors - Abstract
Background: The results of the ACOSOG- Z0011 trial have had potential practice changing implications for the management of patients with positive sentinel lymph node (SLN) undergoing lumpectomy and radiation for breast cancer. However, some evidence suggests a shift in axillary management even prior to the initial report of data supporting sentinel lymph node biopsy (SLNB) alone in mid-2010. We analyzed data in the National Comprehensive Cancer Network (NCCN) outcomes database from NCCN centers and the Michigan Breast Oncology Quality Initiative (MiBOQI) hospitals to examine institutional practice patterns with respect to use of completion axillary dissection (CALND) for SLN positive breast cancer in the years leading up to publication of these trial results. We hypothesized that CALND would be omitted more frequently in women treated at NCCN centers compared to those treated at MiBOQI programs. Methods: We identified 2,172 women with clinical T1/T2 N0 breast cancer who underwent breast surgery and SLNB and had a positive SLN from 2007 through 2010 at one of 12 participating NCCN centers or 12 MiBOQI sites. Patient and tumor characteristics, definitive breast procedure, year of diagnosis, and institutional affiliation were analyzed as predictors of use of SLNB alone in univariate Chi-Square and multivariable logistic regression models. Results: CALND was omitted in 314 (14.5%) of the 2,172 patients. Over time, there was a dramatic increase in the use of SLNB alone (12% in 2007 to 23% in 2010). In the univariate analyses, increased patient age, later year of diagnosis, lower T stage, and lower pathologic N stage were significant predictors of use of SLNB alone (all p < .0001). There was no association between definitive breast surgery type, hormone receptor status, Her-2 Neu status, or institutional affiliation and use of SLNB alone. In the multivariable model, older age at diagnosis, later year of diagnosis, and lower pathologic N stage remained significant independent predictors of SLNB alone. There were no significant differences in rates of omission of CALND between NCCN and MIBOQI sites. Conclusions: Omission of CALND occurred frequently in women with SLN positive breast cancer cared for in both NCCN and MiBOQI institutions in advance of reporting results of ACOSOG-Z0011. This shift was seen in management of patients undergoing lumpectomy as well as mastectomy. Further study is warranted to determine the extent of durable practice changes as well as any impact on survival and local-regional control. [ABSTRACT FROM AUTHOR]
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- 2012
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48. Functional decline in older breast cancer survivors treated with and without chemotherapy and non-cancer controls: results from the Hurria Older PatiEnts (HOPE) prospective study.
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Sedrak MS, Sun CL, Bae M, Freedman RA, Magnuson A, O'Connor T, Moy B, Wildes TM, Klepin HD, Chapman AE, Tew WP, Dotan E, Fenton MA, Kim H, Katheria V, Muss HB, Cohen HJ, Gross CP, and Ji J
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- Aged, Aged, 80 and over, Female, Humans, Case-Control Studies, Prospective Studies, Quality of Life, Breast Neoplasms drug therapy, Cancer Survivors
- Abstract
Purpose: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both., Methods: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference)., Results: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001)., Conclusion: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy., Implications for Cancer Survivors: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes., Clinical Trial: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2024
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49. Community collaboration to advance racial/ethnic equity in colorectal Cancer screening: Protocol for a multilevel intervention to improve screening and follow-up in community Health centers.
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May FP, Brodney S, Tuan JJ, Syngal S, Chan AT, Glenn B, Johnson G, Chang Y, Drew DA, Moy B, Rodriguez NJ, Warner ET, Anyane-Yeboa A, Ukaegbu C, Davis AQ, Schoolcraft K, Regan S, Yoguez N, Kuney S, Le Beaux K, Jeffries C, Lee ET, Bhat R, and Haas JS
- Abstract
Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings., Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment., Results: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings., Conclusions: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities., Trial Registration: NCT05714644., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Folasade P. May: Exact Sciences: Advisory Board Sapna Syngal: inventor of the PREMM model (the intellectual property of which is owned by Dana-Farber Cancer Institute); research funding by Exact Sciences, Biological Dynamics, Inc.; consultant for Natera, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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50. Antibody-Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients with Breast Cancer.
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Bardia A, Sun S, Thimmiah N, Coates JT, Wu B, Abelman RO, Spring L, Moy B, Ryan P, Melkonyan MN, Partridge A, Juric D, Peppercorn J, Parsons H, Wander SA, Attaya V, Lormil B, Shellock M, Nagayama A, Bossuyt V, Isakoff SJ, Tolaney SM, and Ellisen LW
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- Humans, Female, Middle Aged, Aged, Adult, Triple Negative Breast Neoplasms drug therapy, Triple Negative Breast Neoplasms pathology, Phthalazines administration & dosage, Cell Line, Tumor, DNA Topoisomerases, Type I metabolism, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Antigens, Neoplasm immunology, Cell Adhesion Molecules, Immunoconjugates administration & dosage, Immunoconjugates therapeutic use, Immunoconjugates pharmacology, Poly(ADP-ribose) Polymerase Inhibitors administration & dosage, Antibodies, Monoclonal, Humanized administration & dosage, Camptothecin analogs & derivatives, Camptothecin administration & dosage, Camptothecin therapeutic use, Topoisomerase I Inhibitors administration & dosage, Topoisomerase I Inhibitors therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology
- Abstract
Purpose: The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule., Patients and Methods: In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or sequential (N = 23) schedule. Outcome measures included safety, tolerability, preliminary efficacy, and establishment of a recommended phase 2 dose., Results: We hypothesized that tumor-selective delivery of TOP1i via SG would reduce nontumor toxicity and create a temporal window, enabling sequential dosing of SG and PARP inhibition. In vitro, sequential SG followed by TZP delayed TOP1 cleavage complex clearance, increased DNA damage, and promoted apoptosis. In the clinical trial, sequential SG/TZP successfully met primary objectives and demonstrated median progression-free survival (PFS) of 7.6 months without dose-limiting toxicities (DLT), while concurrent dosing yielded 2.3 months PFS and multiple DLTs including severe myelosuppression., Conclusions: While SG dosed concurrently with TZP is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG followed by TZP proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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