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Adjuvant bevacizumab- containing therapy in triple- negat\ ive breast cancer \(BEATRICE\): primary results of a randomised, phase 3 trial. \nLancet Oncol. 14, 933 942 \(2013\).\r:87)/F 4/H/N/Rect[468.578 312.855 473.566 300.444]/Subtype/Link/Type/Annot>> endobj 27 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:20. Piccart- Gebhart, M. etal. Adjuvant lapatinib and trastuzumab for early hum\ an epidermal growth factor receptor 2-positive breast cancer: results from the randomized phase III adjuvant lapatinib and/or tr\ astuzumab treatment optimization trial.:88)/F 4/H/N/Rect[519.195 312.855 524.183 300.444]/Subtype/Link/Type/Annot>> endobj 28 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:20. Piccart- Gebhart, M. etal. 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Գĝљmցr0igv|`%1ؼ{L*jeTg(U+<[XrM@oDo=%J]('`Zr{LivȠM%[+֎jrn/@ mŴ{Z!S[f,|n.c<1dW;'6@;PoΨF=cTɥ^ÈqiDq n9I:|d qy<$#6i0rJ{>"L4b,ʦ]3%WdBVw"lff 2zDr&@?OnF,wO> endobj 36 0 obj <> endobj 37 0 obj [36 0 R] endobj 38 0 obj <>stream HN yŒ Y.;i%i@kJ;1!p>Qf[ oMfWnd1kP;Dr88# lanZo;#7H<Nk6MUWsDzXj@_AC4e(śyBAQTZNј9D;NA4K}8. ,';;ypPug&H,ca$:z0EgmQhZc܎7DgRz\-踮,)lacxԯ:KS)>AI!X2Rv.m]97- XccۍO_ȗ$ endstream endobj 39 0 obj <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/XObject<<>>>> endobj 40 0 obj <>stream x%O@ SL'ǽmA؅ b?Jy /a4Tcatvq&ڬ2Ɍ:bۏm$/9$3 endstream endobj 41 0 obj <> endobj 42 0 obj [43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R] endobj 43 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:22. Holmes, E. M. etal. Are we assuming too much with our statistical assumptio\ ns? Lessons learned from the ALTTO trial. Ann. Oncol. 30, 1507 1513 \(2019\).\r:93)/F 4/H/N/Rect[274.261 719.855 279.356 707.444]/Subtype/Link/Type/Annot>> endobj 44 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:23. Ragaz, J. etal. Preoperative adjuvant chemotherapy \(neoadjuvant\) for carci\ noma of the breast: rationale and safety report. Recent. Results Cancer Res. 98, 99 105 \(1985\).\r:94)/F 4/H/N/Rect[208.359 598.855 213.454 586.444]/Subtype/Link/Type/Annot>> endobj 45 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:24. Wolmark, N., Wang, J., Mamounas, E., Bryant, J. \n& Fisher, B. Preoperative c\ hemotherapy in patients with operable breast cancer: nine- year results from National Surgical Adjuvant Breast and Bowel Projec\ t B-18. J. Natl Cancer Inst. Monogr. :95)/F 4/H/N/Rect[241.541 554.855 246.637 542.444]/Subtype/Link/Type/Annot>> endobj 46 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:25. Fumagalli, D. etal. A common language in neoadjuvant breast cancer clinical\ trials: proposals for standard definitions and endpoints. Lancet Oncol. 13, e240 e248 \(2012\).\r:96)/F 4/H/N/Rect[212.261 433.855 217.356 421.444]/Subtype/Link/Type/Annot>> endobj 47 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:Table 1 | Evolution of neoadjuvant chemotherapy and endocrine therapy for pati\ ents with breast cancer\r:97)/F 4/H/N/Rect[243.527 433.855 247.937 421.444]/Subtype/Link/Type/Annot>> endobj 48 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:26. FDA. Pathological Complete Response in Neoadjuvant Treatment of High- Risk Earl\ y- Stage Breast Cancer: \nUse as an Endpoint to Support Accelerated Approval. https://www.fda.gov/drugs/guidance- compliance-\n\ regulatory- information/guidances- drugs:98)/F 4/H/N/Rect[191.447 345.855 196.73 333.444]/Subtype/Link/Type/Annot>> endobj 49 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:27. Cortazar, P. etal. Pathological complete response \nand long- term clinical \ benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164 172 \(2014\).\r:99)/F 4/H/N/Rect[290.047 224.855 295.36 212.444]/Subtype/Link/Type/Annot>> endobj 50 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:28. Conforti, F. etal. Evaluation of pathological complete response as surrogat\ e endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta- analysis. BMJ \ 375, e066381 \(2021\).\r:100)/F 4/H/N/Rect[219.197 202.855 224.405 190.444]/Subtype/Link/Type/Annot>> endobj 51 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:29. Collins, F. S., Morgan, M. & Patrinos, A. The human genome project: lessons \ from large- scale biology. Science 300, 286 290 \(2003\).\r:101)/F 4/H/N/Rect[262.334 81.8547 267.985 69.4439]/Subtype/Link/Type/Annot>> endobj 52 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:30. Meystre, S. M., Narus, S. P. & Mitchell, J. A. \nIn: Clinical Research Informat\ ics \(eds Richesson, R. L. \n& Andrews, J. E.\). 113 131. \(Springer, 2012\).\r:102)/F 4/H/N/Rect[512.895 708.855 517.99 696.444]/Subtype/Link/Type/Annot>> endobj 53 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:31. Heys, S. D. etal. Neoadjuvant docetaxel in breast cancer: 3-year survival r\ esults from the Aberdeen trial. Clin. Breast Cancer 3, S69 S74 \(2002\).\r:103)/F 4/H/N/Rect[529.288 598.855 534.814 586.444]/Subtype/Link/Type/Annot>> endobj 54 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:32. Green, M. C. etal. Weekly paclitaxel improves pathologic complete remission\ in operable breast cancer when compared with paclitaxel once every \n3 weeks. J. Clin. 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Res. 35, 5179 5184 \(2015\).\r:109)/F 4/H/N/Rect[386.646 444.855 391.742 432.444]/Subtype/Link/Type/Annot>> endobj 60 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:33. Ellis, M. J. etal. Letrozole is more effective neoadjuvant endocrine thera\ py than tamoxifen for ErbB-1  and/or ErbB-2 positive, estrogen receptor positive primary breast cancer: evidence from a phase II\ I randomized trial. J. Clin. Oncol. :110)/F 4/H/N/Rect[494.559 444.855 499.654 432.444]/Subtype/Link/Type/Annot>> endobj 61 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:37. Bartlett, J. M. S. etal. HER2 status predicts for upfront AI benefit: a TRA\ NS- AIOG meta- analysis \nof 12,129 patients from ATAC, BIG 1-98 and TEAM with centrally determined HER2. Eur. J. 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Gianni, L. etal. Efficacy and safety of neoadjuvant pertuzumab and trastuzu\ mab in women with locally advanced, inflammatory, or early HER2-positive \nbreast cancer \(NeoSphere\): a randomised multicentre,\ open- label, phase 2 trial. Lancet Onco:119)/F 4/H/N/Rect[334.661 389.974 339.761 377.444]/Subtype/Link/Type/Annot>> endobj 70 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:21. von Minckwitz, G. etal. Adjuvant pertuzumab and trastuzumab in early HER2-\ positive breast cancer. \nN. Engl. J. Med. 377, 122 131 \(2017\).\r:120)/F 4/H/N/Rect[194.146 356.855 199.53 344.444]/Subtype/Link/Type/Annot>> endobj 71 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:39. Schmid, P. etal. Pembrolizumab for early triple- negative breast cancer. N\ . Engl. J. Med. 382, 810 821 \(2020\).\r:121)/F 4/H/N/Rect[165.57 257.855 170.774 245.444]/Subtype/Link/Type/Annot>> endobj 72 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:40. Schmid, P. etal. Event- free survival with pembrolizumab in early triple- n\ egative breast cancer. N. Engl. J. Med. 386, 556 567 \(2022\).\r:122)/F 4/H/N/Rect[172.024 257.855 177.228 245.444]/Subtype/Link/Type/Annot>> endobj 73 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:41. Fisher, B., Saffer, E., Rudock, C., Coyle, J. & Gunduz, N. Effect of local o\ r systemic treatment prior to primary tumor removal on the production and response to a serum growth- stimulating factor in mice\ . Cancer Res. 49, 2002 2004 \(1989\).:123)/F 4/H/N/Rect[233.441 92.8547 238.65 80.4439]/Subtype/Link/Type/Annot>> endobj 74 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:42. Smith, I. E. etal. Neoadjuvant treatment of postmenopausal breast cancer w\ ith anastrozole, tamoxifen, or both in combination: the Immediate Preoperative Anastrozole, Tamoxifen, or Combined \nwith Tamoxi\ fen \(IMPACT\) multicenter double- blind r:124)/F 4/H/N/Rect[336.645 59.8547 341.858 47.4439]/Subtype/Link/Type/Annot>> endobj 75 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:43. Ellis, M. J. etal. Ki67 proliferation index as a tool \nfor chemotherapy dec\ isions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results from the American College of Surgeo\ ns Oncology Group Z1031 trial \(Alliance\):125)/F 4/H/N/Rect[413.227 422.855 418.61 410.444]/Subtype/Link/Type/Annot>> endobj 76 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:44. Smith, I. etal. Long- term outcome and prognostic value of Ki67 after perio\ perative endocrine therapy \nin postmenopausal women with hormone- sensitive early breast cancer \(POETIC\): an open- label, mult\ icentre, parallel- group, randomised, pha:126)/F 4/H/N/Rect[368.249 378.855 373.358 366.444]/Subtype/Link/Type/Annot>> endobj 77 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:44. Smith, I. etal. Long- term outcome and prognostic value of Ki67 after peri\ operative endocrine therapy \nin postmenopausal women with hormone- sensitive early breast cancer \(POETIC\): an open- label, mul\ ticentre, parallel- group, randomised, ph:127)/F 4/H/N/Rect[391.596 268.855 396.854 256.444]/Subtype/Link/Type/Annot>> endobj 78 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:43. Ellis, M. J. etal. Ki67 proliferation index as a tool \nfor chemotherapy de\ cisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results from the American College of Surge\ ons Oncology Group Z1031 trial \(Alliance:128)/F 4/H/N/Rect[493.366 169.855 498.678 157.444]/Subtype/Link/Type/Annot>> endobj 79 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:45. Nitz, U. etal. The run- in phase of the prospective WSG- ADAPT HR+/HER2- tr\ ial demonstrates the feasibility of a study design combining static and dynamic biomarker assessments for individualized therapy\ in early breast cancer. Ther. Adv. Me:129)/F 4/H/N/Rect[483.414 147.855 488.987 135.444]/Subtype/Link/Type/Annot>> endobj 80 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:31. Heys, S. D. etal. Neoadjuvant docetaxel in breast cancer: 3-year survival \ results from the Aberdeen trial. Clin. Breast Cancer 3, S69 S74 \(2002\).\r:112)/F 4/H/N/Rect[152.536 697.175 157.462 687.655]/Subtype/Link/Type/Annot>> endobj 81 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:32. Green, M. C. etal. Weekly paclitaxel improves pathologic complete remissio\ n in operable breast cancer when compared with paclitaxel once every \n3 weeks. J. Clin. Oncol. 23, 5983 5992 \(2005\).\r:113\ )/F 4/H/N/Rect[174.784 611.276 179.71 601.756]/Subtype/Link/Type/Annot>> endobj 82 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:116. Sparano, J. A. etal. Long- term follow- up of the \nE1199 phase III trial e\ valuating the role of taxane \nand schedule in operable breast cancer. J. Clin. Oncol. 33, 2353 2360 \(2015\).\r:114)/F 4/H/N/Rect[534.816 566.276 542.209 556.756]/Subtype/Link/Type/Annot>> endobj 83 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:33. Ellis, M. J. etal. Letrozole is more effective neoadjuvant endocrine ther\ apy than tamoxifen for ErbB-1  and/or ErbB-2 positive, estrogen receptor positive primary breast cancer: evidence from a phase I\ II randomized trial. J. Clin. Oncol. :115)/F 4/H/N/Rect[166.955 552.377 171.881 542.857]/Subtype/Link/Type/Annot>> endobj 84 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:16. Early Breast Cancer Trialists  Collaborative Group \(EBCTCG\).Aromatase inh\ ibitors versus tamoxifen in early breast cancer: patient- level meta- analysis of the randomised trials. Lancet 386, 1341 13\ 52 \(2015\).\r:116)/F 4/H/N/Rect[435.959 489.377 440.959 479.857]/Subtype/Link/Type/Annot>> endobj 85 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:34. Dowsett, M. etal. Short- term changes in Ki-67 during neoadjuvant treatmen\ t of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence- free survival. Clin. 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Gnant, M. etal. Adjuvant palbociclib for early breast cancer: the PALLAS tr\ ial results \(ABCSG-42/AFT-05/BIG-14-03\). J. Clin. Oncol. 40, 282 293 \(2022\).\r:130)/F 4/H/N/Rect[273.021 730.855 278.191 718.444]/Subtype/Link/Type/Annot>> endobj 92 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:47. Johnston, S. R. D. etal. Abemaciclib combined with endocrine therapy for th\ e adjuvant treatment of HR+, HER2-, node- positive, high- risk, early breast cancer \(monarchE\). J. Clin. Oncol. 38, 3987 39\ 98 \(2020\).\r:131)/F 4/H/N/Rect[334.59 730.855 339.761 718.444]/Subtype/Link/Type/Annot>> endobj 93 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:48. Cottu, P. etal. Letrozole and palbociclib versus chemotherapy as neoadjuvan\ t therapy of high- risk luminal breast cancer. Ann. Oncol. 29, 2334 2340 \(2018\).\r:132)/F 4/H/N/Rect[265.097 609.855 270.193 597.444]/Subtype/Link/Type/Annot>> endobj 94 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:53. Prat, A. etal. Ribociclib plus letrozole versus chemotherapy for postmenopa\ usal women with hormone receptor- positive, HER2-negative, luminal B breast cancer \(CORALLEEN\): an open- label, multicentre, ra\ ndomised, phase 2 trial. Lancet Oncol.:133)/F 4/H/N/Rect[272.955 609.855 278.05 597.444]/Subtype/Link/Type/Annot>> endobj 95 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:54. Ellis, M. J. etal. Outcome prediction for estrogen receptor positive breast\ cancer based on postneoadjuvant endocrine therapy tumor characteristics. J. Natl Cancer Inst. 100, 1380 1388 \(2008\).\r:13\ 4)/F 4/H/N/Rect[193.174 510.855 198.306 498.444]/Subtype/Link/Type/Annot>> endobj 96 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:55. Suman, V. J., Ellis, M. J. & Ma, C. X. The ALTERNATE trial: assessing a biom\ arker driven strategy for the treatment of post- menopausal women with ER+/Her2- invasive breast cancer. Chin. Clin. Oncol.\ 4, 34 \(2015\).\r:135)/F 4/H/N/Rect[298.922 510.855 304.055 498.444]/Subtype/Link/Type/Annot>> endobj 97 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:56. Ma, C. X. etal. ALTERNATE: Neoadjuvant endocrine treatment \(NET\) approache\ s for clinical stage II or III estrogen receptor- positive HER2-negative breast cancer \(ER+HER2- BC\) in postmenopausal \(PM\ \) women: alliance A011106. J. Clin. Oncol:136)/F 4/H/N/Rect[305.27 510.855 310.402 498.444]/Subtype/Link/Type/Annot>> endobj 98 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:56. Ma, C. X. etal. ALTERNATE: Neoadjuvant endocrine treatment \(NET\) approach\ es for clinical stage II or III estrogen receptor- positive HER2-negative breast cancer \(ER+HER2- BC\) in postmenopausal \(P\ M\) women: alliance A011106. J. Clin. Onco:137)/F 4/H/N/Rect[161.968 378.855 167.064 366.444]/Subtype/Link/Type/Annot>> endobj 99 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:57. Kalinsky, K. etal. 21-Gene assay to inform chemotherapy benefit in node- po\ sitive breast cancer. N. Engl. J. Med. 385, 2336 2347 \(2021\).\r:138)/F 4/H/N/Rect[311.919 257.855 317.014 245.444]/Subtype/Link/Type/Annot>> endobj 100 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:59. Piccart, M. etal. 70-gene signature as an aid for treatment decisions in ea\ rly breast cancer: updated results of the phase 3 randomised MINDACT trial \nwith an exploratory analysis by age. Lancet Oncol.\ 22, 476 488 \(2021\).\r:139)/F 4/H/N/Rect[319.777 257.855 324.872 245.444]/Subtype/Link/Type/Annot>> endobj 101 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:60. Prat, A. etal. Correlative biomarker analysis of intrinsic subtypes and eff\ icacy across the MONALEESA phase III studies. J. Clin. Oncol. https://doi.org/10.1200/JCO.20.\n02977 \(2021\).\r:140)/F 4/H/N/Rect[211.377 169.855 216.701 157.444]/Subtype/Link/Type/Annot>> endobj 102 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:61. Dieci, M. V. etal. Impact of estrogen receptor levels \non outcome in non- m\ etastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy. NPJ Breast Cancer 7, 101 \(\ 2021\).\r:141)/F 4/H/N/Rect[330.342 59.8547 335.405 47.4439]/Subtype/Link/Type/Annot>> endobj 103 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:62. Gingras, I., Gebhart, G., de Azambuja, E. \n& Piccart- Gebhart, M. HER2-posit\ ive breast cancer \nis lost in translation: time for patient- centered research. Nat. Rev. Clin. Oncol. 14, 669 681 \(2017\).\ \r:142)/F 4/H/N/Rect[377.53 675.855 382.625 663.444]/Subtype/Link/Type/Annot>> endobj 104 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:62. Gingras, I., Gebhart, G., de Azambuja, E. \n& Piccart- Gebhart, M. HER2-posi\ tive breast cancer \nis lost in translation: time for patient- centered research. Nat. Rev. Clin. Oncol. 14, 669 681 \(2017\)\ .\r:143)/F 4/H/N/Rect[467.99 499.855 473.229 487.444]/Subtype/Link/Type/Annot>> endobj 105 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:63. Nitz, U. A. etal. De- escalation strategies in HER2-positive early breast c\ ancer \(EBC\): final analysis of the WSG- ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 wee\ ks of neoadjuvant dual blockade with tra:144)/F 4/H/N/Rect[422.56 477.855 427.655 465.444]/Subtype/Link/Type/Annot>> endobj 106 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:64. Graeser, M. LBA2  Impact of RNA expression signatures and tumor infiltratin\ g lymphocytes \(TILs\) for pathological complete response \(pCR\) and survival after 12 week de- escalated neoadjuvant pertuzumab \ + trastuzumab paclitaxel in the WSG- HE:145)/F 4/H/N/Rect[428.852 477.855 433.947 465.444]/Subtype/Link/Type/Annot>> endobj 107 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:65. Schettini, F. etal. PAM50 HER2-enriched subtype and pathological complete r\ esponse in HER2-positive early breast cancer: a meta- analysis. Ann. Oncol. 30, v82 \(2019\).\r:146)/F 4/H/N/Rect[486.7 411.855 491.927 399.444]/Subtype/Link/Type/Annot>> endobj 108 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:66. Prat, A. etal. A multivariable prognostic score to guide systemic therapy i\ n early- stage HER2-positive breast cancer: a retrospective study with an external evaluation. Lancet Oncol. 21, 1455 1464 \(\ 2020\).\r:147)/F 4/H/N/Rect[457.835 367.855 462.931 355.444]/Subtype/Link/Type/Annot>> endobj 109 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:67. Agostinetto, E., Eiger, D., Punie, K. & de Azambuja, E. Emerging therapeutic\ s for patients with triple- negative breast cancer. Curr. Oncol. 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Bianchini, G. etal. LBA13 Tumour infiltrating lymphocytes \(TILs\), PD- L1 e\ xpression and their dynamics in the NeoTRIPaPDL1 trial. Ann. Oncol. \n31 \(Suppl. 4\), S1145 S1146 \(2020\).\r:149)/F 4/H/N/Rect[281.599 675.855 286.702 663.444]/Subtype/Link/Type/Annot>> endobj 115 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:68. Bianchini, G. etal. LBA13 Tumour infiltrating lymphocytes \(TILs\), PD- L1 \ expression and their dynamics in the NeoTRIPaPDL1 trial. Ann. Oncol. \n31 \(Suppl. 4\), S1145 S1146 \(2020\).\r:150)/F 4/H/N/Rect[309.848 675.855 314.951 663.444]/Subtype/Link/Type/Annot>> endobj 116 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:69. Loibl, S. etal. A randomised phase II study investigating durvalumab in add\ ition to an anthracycline taxane- based neoadjuvant therapy \nin early triple- negative breast cancer: clinical results and biom\ arker analysis of GeparNuevo study. \nAn:151)/F 4/H/N/Rect[194.751 653.855 199.846 641.444]/Subtype/Link/Type/Annot>> endobj 117 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:70. Ren, X.-Y. etal. Mismatch repair deficiency and microsatellite instability \ in triple- negative breast cancer: a retrospective study of 440 patients. \nFront. Oncol. 11, 570623 \(2021\).\r:152)/F 4/H/N/Rect[301.966 653.855 307.061 641.444]/Subtype/Link/Type/Annot>> endobj 118 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:71. Emens, L. A. etal. The tumor microenvironment \(TME\) and atezolizumab + nab\ - paclitaxel \(A+nP\) activity in metastatic triple- negative breast cancer \(mTNBC\): IMpassion130. J. Clin. Oncol. 39 \(Supp\ l. 15\), 1006 \(2021\).\r:153)/F 4/H/N/Rect[201.737 642.855 207.089 630.444]/Subtype/Link/Type/Annot>> endobj 119 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:71. Emens, L. A. etal. The tumor microenvironment \(TME\) and atezolizumab + na\ b- paclitaxel \(A+nP\) activity in metastatic triple- negative breast cancer \(mTNBC\): IMpassion130. J. Clin. Oncol. 39 \(Sup\ pl. 15\), 1006 \(2021\).\r:154)/F 4/H/N/Rect[336.608 642.855 341.858 630.444]/Subtype/Link/Type/Annot>> endobj 120 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:72. Doroshow, D. B. etal. PD- L1 as a biomarker of response to immune- checkpoi\ nt inhibitors. Nat. Rev. Clin. Oncol. 18, 345 362 \(2021\).\r:155)/F 4/H/N/Rect[225.891 554.855 230.981 542.444]/Subtype/Link/Type/Annot>> endobj 121 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:73. Agostinetto, E. etal. Progress and pitfalls in the use \nof immunotherapy fo\ r patients with triple negative breast cancer. Expert Opin. Investig. Drugs 31, \n567 591 \(2022\).\r:156)/F 4/H/N/Rect[177.86 521.855 182.973 509.444]/Subtype/Link/Type/Annot>> endobj 122 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:74. Savas, P. etal. Clinical relevance of host immunity \nin breast cancer: from\ TILs to the clinic. Nat. Rev. \nClin. Oncol. 13, 228 241 \(2016\).\r:157)/F 4/H/N/Rect[274.546 510.855 279.667 498.444]/Subtype/Link/Type/Annot>> endobj 123 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:75. Murphy, W. J. & Longo, D. L. The surprisingly positive association between o\ besity and cancer immunotherapy efficacy. JAMA 321, 1247 1248 \(2019\).\r:158)/F 4/H/N/Rect[309.84 510.855 314.961 498.444]/Subtype/Link/Type/Annot>> endobj 124 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:76. Routy, B. etal. Gut microbiome influences efficacy of PD-1-based immunother\ apy against epithelial tumors. Science 359, 91 97 \(2018\).\r:159)/F 4/H/N/Rect[195.226 499.855 200.305 487.444]/Subtype/Link/Type/Annot>> endobj 125 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:77. Eiger, D., Agostinetto, E., Sade- Conde, R. & \nde Azambuja, E. The exciting\ new field of HER2-low breast cancer treatment. Cancers 13, 1015 \(2021\).\r:160)/F 4/H/N/Rect[287.795 411.855 293.115 399.444]/Subtype/Link/Type/Annot>> endobj 126 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:78. Modi, S. etal. Trastuzumab deruxtecan in previously treated her2-low advanc\ ed breast cancer. N. Engl. \nJ. Med. https://doi.org/10.1056/NEJMoa2203690 \(2022\).\r:161)/F 4/H/N/Rect[194.195 378.855 199.471 366.444]/Subtype/Link/Type/Annot>> endobj 127 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:79. Lenzer, J. & Brownlee, S. 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A randomised phase II study investigating durvalumab in ad\ dition to an anthracycline taxane- based neoadjuvant therapy \nin early triple- negative breast cancer: clinical results and bio\ marker analysis of GeparNuevo study. \nA:167)/F 4/H/N/Rect[315.532 59.8547 320.551 47.4439]/Subtype/Link/Type/Annot>> endobj 133 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:83. Loibl, S. etal. Durvalumab improves long- term outcome in TNBC: results fro\ m the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoa\ djuvant chemotherapy in early triple- n:168)/F 4/H/N/Rect[321.709 59.8547 326.728 47.4439]/Subtype/Link/Type/Annot>> endobj 134 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:69. Loibl, S. etal. A randomised phase II study investigating durvalumab in a\ ddition to an anthracycline taxane- based neoadjuvant therapy \nin early triple- negative breast cancer: clinical results and bi\ omarker analysis of GeparNuevo study. \n:169)/F 4/H/N/Rect[418.231 697.855 423.357 685.444]/Subtype/Link/Type/Annot>> endobj 135 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:83. Loibl, S. etal. Durvalumab improves long- term outcome in TNBC: results fr\ om the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neo\ adjuvant chemotherapy in early triple- :170)/F 4/H/N/Rect[432.581 653.974 437.705 641.444]/Subtype/Link/Type/Annot>> endobj 136 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:84. Wolchok, J. D. etal. Guidelines for the evaluation \nof immune therapy activ\ ity in solid tumors: immune- related response criteria. Clin. 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Replacing pathological complete response \(pCR\) with a residual cancer burden \(RCB\) profile and event- free survival \(E\ FS\) is likely to improve the accuracy \nof :174)/F 4/H/N/Rect[370.491 345.855 375.055 333.444]/Subtype/Link/Type/Annot>> endobj 140 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:88. Symmans, W. F. etal. Long- term prognostic risk after neoadjuvant chemother\ apy associated with residual cancer burden and breast cancer subtype. J. Clin. Oncol. 35, 1049 1060 \(2017\).\r:175)/F 4/H/N/Rect[492.534 301.855 497.629 289.444]/Subtype/Link/Type/Annot>> endobj 141 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:89. FDA. 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Schnipper, L. E. etal. Updating the American Society of Clinical Oncology v\ alue framework: revisions and reflections in response to comments received. J. Clin. Oncol. 34, 2925 2934 \(2016\).\r:180)/F 4/H/N/Rect[230.031 466.855 235.032 454.444]/Subtype/Link/Type/Annot>> endobj 148 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:92. Dafni, U. etal. Detailed statistical assessment of the characteristics of t\ he ESMO magnitude of clinical benefit scale \(ESMO- MCBS\) threshold rules. \nESMO Open 2, e000216 \(2017\).\r:181)/F 4/H/N/Rect[173.416 444.855 178.711 432.444]/Subtype/Link/Type/Annot>> endobj 149 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:93. Wolf, I. etal. Implementation of the ESMO- magnitude of clinical benefit sc\ ale: real world example from the 2022 Israeli National Reimbursement Process. \nESMO Open 7, 100379 \(2022\).\r:182)/F 4/H/N/Rect[262.959 323.855 268.036 311.444]/Subtype/Link/Type/Annot>> endobj 150 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:27. Cortazar, P. etal. Pathological complete response \nand long- term clinical\ benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164 172 \(2014\).\r:183)/F 4/H/N/Rect[226.861 180.855 231.989 168.444]/Subtype/Link/Type/Annot>> endobj 151 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:Fig. 2 | The post-neoadjuvant setting: an attractive scenario for future clini\ cal trials. The post- neoadjuvant setting offers the possibility of selecting patients with residual invasive disease at sur\ gery who might benefit from additional :184)/F 4/H/N/Rect[189.753 103.855 194.266 91.4439]/Subtype/Link/Type/Annot>> endobj 152 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:94. Masuda, N. etal. Adjuvant capecitabine for breast cancer after preoperative\ chemotherapy. N. Engl. \nJ. Med. 376, 2147 2159 \(2017\).\r:185)/F 4/H/N/Rect[268.898 59.8547 274.131 47.4439]/Subtype/Link/Type/Annot>> endobj 153 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:95. von Minckwitz, G. etal. Trastuzumab emtansine \nfor residual invasive HER2-p\ ositive breast cancer. \nN. Engl. J. Med. 380, 617 628 \(2019\).\r:186)/F 4/H/N/Rect[515.416 477.855 520.512 465.444]/Subtype/Link/Type/Annot>> endobj 154 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:94. Masuda, N. etal. Adjuvant capecitabine for breast cancer after preoperativ\ e chemotherapy. N. Engl. \nJ. Med. 376, 2147 2159 \(2017\).\r:187)/F 4/H/N/Rect[471.733 334.855 476.758 322.444]/Subtype/Link/Type/Annot>> endobj 155 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:95. von Minckwitz, G. etal. Trastuzumab emtansine \nfor residual invasive HER2-\ positive breast cancer. \nN. Engl. J. Med. 380, 617 628 \(2019\).\r:188)/F 4/H/N/Rect[439.233 257.855 444.329 245.444]/Subtype/Link/Type/Annot>> endobj 156 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:96. Tutt, A. N. J. etal. Adjuvant olaparib for patients \nwith BRCA1- or BRCA2-m\ utated breast cancer. \nN. Engl. J. Med. 384, 2394 2405 \(2021\).\r:189)/F 4/H/N/Rect[491.827 246.855 497.029 234.444]/Subtype/Link/Type/Annot>> endobj 157 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:Fig. 2 | The post-neoadjuvant setting: an attractive scenario for future clin\ ical trials. 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Gebhart, G. etal. 18F- FDG PET/CT for early prediction of response to neoa\ djuvant lapatinib, trastuzumab, and their combination in HER2-positive breast \ncancer: results from Neo- ALTTO. J. Nucl. Med.\ 54, 1862 1868 \(2013\).\r:206)/F 4/H/N/Rect[272.124 642.855 279.487 630.444]/Subtype/Link/Type/Annot>> endobj 1175 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:109. Connolly, R. M. etal. TBCRC 008: early change \nin 18F- FDG uptake on PET p\ redicts response to preoperative systemic therapy in human epidermal growth factor receptor 2-negative primary operable breast \ cancer. J. Nucl. Med. 56, 31 37 \(201:207)/F 4/H/N/Rect[280.589 642.855 287.952 630.444]/Subtype/Link/Type/Annot>> endobj 1176 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:110. Connolly, R. M. etal. Updated results of TBCRC026: phase II trial correlat\ ing standardized uptake value with pathological complete response to pertuzumab and trastuzumab in breast cancer. J. Clin. Onco\ l. 39, 2247 2256 \(2021\).\r:208)/F 4/H/N/Rect[232.196 510.855 239.922 498.444]/Subtype/Link/Type/Annot>> endobj 1177 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:110. Connolly, R. M. etal. Updated results of TBCRC026: phase II trial correla\ ting standardized uptake value with pathological complete response to pertuzumab and trastuzumab in breast cancer. J. Clin. Onc\ ol. 39, 2247 2256 \(2021\).\r:209)/F 4/H/N/Rect[173.118 411.855 180.969 399.444]/Subtype/Link/Type/Annot>> endobj 1178 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:111. Prez- Garca, J. M. etal. 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Genet. 22, 627 644 \(2021\).\r:212)/F 4/H/N/Rect[331.711 81.8547 339.761 69.4439]/Subtype/Link/Type/Annot>> endobj 1181 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:113. Taichman, D. B. etal. Sharing clinical trial data: \na proposal from the in\ ternational committee of medical journal editors. Ann. Intern. Med. 164, 505 506 \(2016\).\r:213)/F 4/H/N/Rect[389.886 532.855 397.529 520.444]/Subtype/Link/Type/Annot>> endobj 1182 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:114. Collyar, D. An essential partnership: patient advocates and cooperative gro\ ups. Semin. Oncol. 35, 553 555 \(2008\).\r:214)/F 4/H/N/Rect[503.049 400.855 510.692 388.444]/Subtype/Link/Type/Annot>> endobj 1183 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatRevClinOnc_687.indd:115. Katz, M. L. etal. Patient advocates  role in clinical trials: perspectives\ from Cancer and Leukemia \nGroup B investigators and advocates. 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