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Published in: Annals of Surgical Oncology 10/2016

01-10-2016 | Breast Oncology

Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes

Authors: Henry M. Kuerer, MD, PhD, FACS, Raquel F. D. van la Parra, MD, PhD

Published in: Annals of Surgical Oncology | Issue 10/2016

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Abstract

Clinical trials in breast cancer have contributed immensely to the advancements of modern multimodal breast cancer treatment. Due to improved screening methods and more effective biologic-based tailored systemic therapies, the extent of surgery necessary for local and systemic control of disease is decreasing. Sequential trials for ductal carcinoma in situ (DCIS) have changed the management of this disease and are culminating in randomized active surveillance studies in an effort potentially to prevent overtreatment of low- and intermediate-grade disease. For patients with initial node-positive disease, clipping and marking of the biopsy-proven nodal metastases before the start of neoadjuvant chemotherapy can allow for selective node dissection based on the axillary response. With the current advances in primary systemic therapy, feasibility trials are beginning to investigate the potential of nonoperative therapy for invasive cancers with percutaneously documented pathologic complete response. This article presents a review and update on landmark clinical trials related to DCIS, the extent of axillary surgery in node-positive disease, and the integration of systemic therapy with local therapy.
Literature
2.
go back to reference Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–41.CrossRefPubMed Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347:1233–41.CrossRefPubMed
3.
go back to reference Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.CrossRefPubMed Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med. 2002;347:567–75.CrossRefPubMed
4.
go back to reference Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of l-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986;4:929–41.PubMed Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of l-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986;4:929–41.PubMed
8.
go back to reference Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674–81.CrossRefPubMed Fisher B, Redmond C, Fisher ER, et al. Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation. N Engl J Med. 1985;312:674–81.CrossRefPubMed
9.
go back to reference Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305:6–11.CrossRefPubMed Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med. 1981;305:6–11.CrossRefPubMed
10.
go back to reference Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer. 1999;86:429–38.CrossRefPubMed Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer. 1999;86:429–38.CrossRefPubMed
11.
go back to reference Houghton J, George WD, Cuzick J, et al. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet. 2003;362:95–102.CrossRefPubMed Houghton J, George WD, Cuzick J, et al. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet. 2003;362:95–102.CrossRefPubMed
12.
go back to reference Group EBCC, Group ER, Bijker N, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853: a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24:3381–7.CrossRef Group EBCC, Group ER, Bijker N, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853: a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24:3381–7.CrossRef
13.
go back to reference Early Breast Cancer Trialists’ Collaborative G, Darby S, McGale P, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–16. Early Breast Cancer Trialists’ Collaborative G, Darby S, McGale P, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–16.
14.
go back to reference Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast. J Clin Oncol. 2008;26:1247–52.CrossRefPubMed Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast. J Clin Oncol. 2008;26:1247–52.CrossRefPubMed
15.
go back to reference McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33:709–15.CrossRefPubMedPubMedCentral McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33:709–15.CrossRefPubMedPubMedCentral
16.
go back to reference Wapnir IL, Dignam JJ, Fisher B, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103:478–88.CrossRefPubMedPubMedCentral Wapnir IL, Dignam JJ, Fisher B, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103:478–88.CrossRefPubMedPubMedCentral
17.
go back to reference Solin LJ, Gray R, Hughes LL, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 study. J Clin Oncol. 2015;33:3938–44.CrossRefPubMed Solin LJ, Gray R, Hughes LL, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 study. J Clin Oncol. 2015;33:3938–44.CrossRefPubMed
18.
go back to reference Margolese RG, Cecchini RS, Julian TB, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet. 2016;387:849–56.CrossRefPubMed Margolese RG, Cecchini RS, Julian TB, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. Lancet. 2016;387:849–56.CrossRefPubMed
19.
go back to reference Forbes JF, Sestak I, Howell A, et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet. 2016;387:866–73.CrossRefPubMedPubMedCentral Forbes JF, Sestak I, Howell A, et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet. 2016;387:866–73.CrossRefPubMedPubMedCentral
20.
go back to reference Silverstein MJ, Buchanan C. Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status. Breast. 2003;12:457–71.CrossRefPubMed Silverstein MJ, Buchanan C. Ductal carcinoma in situ: USC/Van Nuys Prognostic Index and the impact of margin status. Breast. 2003;12:457–71.CrossRefPubMed
21.
go back to reference Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med. 1999;340:1455–61.CrossRefPubMed Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med. 1999;340:1455–61.CrossRefPubMed
22.
go back to reference Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002;184:383–93.CrossRefPubMed Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002;184:383–93.CrossRefPubMed
23.
go back to reference Houssami N, Macaskill P, Marinovich ML, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 2010;46:3219–32.CrossRefPubMed Houssami N, Macaskill P, Marinovich ML, et al. Meta-analysis of the impact of surgical margins on local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 2010;46:3219–32.CrossRefPubMed
24.
go back to reference Bartelink H, Horiot JC, Poortmans PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007;25:3259–65.CrossRefPubMed Bartelink H, Horiot JC, Poortmans PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007;25:3259–65.CrossRefPubMed
25.
go back to reference Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28:1677–83.CrossRefPubMedPubMedCentral Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol. 2010;28:1677–83.CrossRefPubMedPubMedCentral
26.
go back to reference Solin LJ, Gray R, Goldstein LJ, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early-stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012;134:683–92.CrossRefPubMedPubMedCentral Solin LJ, Gray R, Goldstein LJ, et al. Prognostic value of biologic subtype and the 21-gene recurrence score relative to local recurrence after breast conservation treatment with radiation for early-stage breast carcinoma: results from the Eastern Cooperative Oncology Group E2197 study. Breast Cancer Res Treat. 2012;134:683–92.CrossRefPubMedPubMedCentral
27.
go back to reference Rakovitch E, Nofech-Mozes S, Hanna W, et al. A population-based validation study of the DCIS score predicting recurrence risk in individuals treated by breast-conserving surgery alone. Breast Cancer Res Treat. 2015;152:389–98.CrossRefPubMedPubMedCentral Rakovitch E, Nofech-Mozes S, Hanna W, et al. A population-based validation study of the DCIS score predicting recurrence risk in individuals treated by breast-conserving surgery alone. Breast Cancer Res Treat. 2015;152:389–98.CrossRefPubMedPubMedCentral
28.
go back to reference Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013;105:701–10.CrossRefPubMedPubMedCentral Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst. 2013;105:701–10.CrossRefPubMedPubMedCentral
29.
go back to reference Kuerer HM. Ductal carcinoma in situ: treatment or active surveillance? Expert Rev Anticancer Ther. 2015;15:777–85.CrossRefPubMed Kuerer HM. Ductal carcinoma in situ: treatment or active surveillance? Expert Rev Anticancer Ther. 2015;15:777–85.CrossRefPubMed
30.
go back to reference Francis A, Thomas J, Fallowfield L, et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer. 2015;51:2296–303.CrossRefPubMed Francis A, Thomas J, Fallowfield L, et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer. 2015;51:2296–303.CrossRefPubMed
31.
go back to reference Elshof LE, Tryfonidis K, Slaets L, et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low-risk ductal carcinoma in situ: The LORD study. Eur J Cancer. 2015;51:1497–510.CrossRefPubMed Elshof LE, Tryfonidis K, Slaets L, et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low-risk ductal carcinoma in situ: The LORD study. Eur J Cancer. 2015;51:1497–510.CrossRefPubMed
33.
go back to reference Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–8; discussion 398–401. Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg. 1994;220:391–8; discussion 398–401.
34.
go back to reference Anderson BO. Sentinel lymphadenectomy in breast cancer: an update on the NCCN clinical practice guidelines. J Natl Compr Canc Netw. 2003;1(Suppl 1):S64–70.PubMed Anderson BO. Sentinel lymphadenectomy in breast cancer: an update on the NCCN clinical practice guidelines. J Natl Compr Canc Netw. 2003;1(Suppl 1):S64–70.PubMed
35.
go back to reference American Society of Breast Surgeons. Guidelines for Performing Sentinel Lymph Node Biopsy in Breast Cancer. 2nd rev. American Society of Breast Surgeons, Columbia, MD, 2002. American Society of Breast Surgeons. Guidelines for Performing Sentinel Lymph Node Biopsy in Breast Cancer. 2nd rev. American Society of Breast Surgeons, Columbia, MD, 2002.
36.
go back to reference Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.CrossRefPubMed Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003;349:546–53.CrossRefPubMed
37.
go back to reference Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98:599–609.CrossRefPubMed Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006;98:599–609.CrossRefPubMed
38.
go back to reference Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11:927–33.CrossRefPubMedPubMedCentral Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010;11:927–33.CrossRefPubMedPubMedCentral
39.
go back to reference Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252:426–32; discussion 432–423. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010;252:426–32; discussion 432–423.
40.
go back to reference Giuliano AE, Hawes D, Ballman KV, et al. Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA. 2011;306:385–93.CrossRefPubMed Giuliano AE, Hawes D, Ballman KV, et al. Association of occult metastases in sentinel lymph nodes and bone marrow with survival among women with early-stage invasive breast cancer. JAMA. 2011;306:385–93.CrossRefPubMed
41.
go back to reference Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–75.CrossRefPubMed Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569–75.CrossRefPubMed
42.
go back to reference Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14:297–305.CrossRefPubMedPubMedCentral Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14:297–305.CrossRefPubMedPubMedCentral
43.
go back to reference Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15:1303–10.CrossRefPubMedPubMedCentral Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15:1303–10.CrossRefPubMedPubMedCentral
44.
go back to reference Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.CrossRefPubMed Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165–74.CrossRefPubMed
45.
go back to reference Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8:1483–96.PubMed Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8:1483–96.PubMed
46.
go back to reference Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672–85.PubMed Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672–85.PubMed
47.
go back to reference Fisher B, Glass A, Redmond C, et al. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977;39(6 Suppl):2883–903.CrossRefPubMed Fisher B, Glass A, Redmond C, et al. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977;39(6 Suppl):2883–903.CrossRefPubMed
48.
go back to reference Fisher B, Redmond C, Brown A, et al. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981;305:1–6.CrossRefPubMed Fisher B, Redmond C, Brown A, et al. Treatment of primary breast cancer with chemotherapy and tamoxifen. N Engl J Med. 1981;305:1–6.CrossRefPubMed
49.
go back to reference Fisher B, Redmond C, Legault-Poisson S, et al. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990;8:1005–18.PubMed Fisher B, Redmond C, Legault-Poisson S, et al. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. J Clin Oncol. 1990;8:1005–18.PubMed
50.
go back to reference Huang L, Johnson KA, Mariotto AB, Dignam JJ, Feuer EJ. Population-based survival-cure analysis of ER-negative breast cancer. Breast Cancer Res Treat. 2010;123:257–64.CrossRefPubMed Huang L, Johnson KA, Mariotto AB, Dignam JJ, Feuer EJ. Population-based survival-cure analysis of ER-negative breast cancer. Breast Cancer Res Treat. 2010;123:257–64.CrossRefPubMed
51.
go back to reference Jatoi I, Bandos H, Jeong JH, et al. Time-varying effects of breast cancer adjuvant systemic therapy. J Natl Cancer Inst. 2016;108:djv304CrossRefPubMed Jatoi I, Bandos H, Jeong JH, et al. Time-varying effects of breast cancer adjuvant systemic therapy. J Natl Cancer Inst. 2016;108:djv304CrossRefPubMed
52.
go back to reference Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–96.CrossRefPubMed Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–96.CrossRefPubMed
53.
go back to reference Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998;90:1361–70.CrossRefPubMed Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst. 1998;90:1361–70.CrossRefPubMed
54.
go back to reference Rastogi P, Buyse ME, Swain SM, et al. Concurrent bevacizumab with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy for HER2– locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group. Clin Breast Cancer. 2011;11:228–34.CrossRefPubMed Rastogi P, Buyse ME, Swain SM, et al. Concurrent bevacizumab with a sequential regimen of doxorubicin and cyclophosphamide followed by docetaxel and capecitabine as neoadjuvant therapy for HER2– locally advanced breast cancer: a phase II trial of the NSABP Foundation Research Group. Clin Breast Cancer. 2011;11:228–34.CrossRefPubMed
55.
go back to reference Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.CrossRefPubMed Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353:1673–84.CrossRefPubMed
56.
go back to reference Smith RE, Anderson SJ, Brown A, et al. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. Clin Breast Cancer. 2002;3:333–40.CrossRefPubMed Smith RE, Anderson SJ, Brown A, et al. Phase II trial of doxorubicin/docetaxel/cyclophosphamide for locally advanced and metastatic breast cancer: results from NSABP trial BP-58. Clin Breast Cancer. 2002;3:333–40.CrossRefPubMed
57.
go back to reference Swain SM, Tang G, Geyer CE Jr, et al. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013;31:3197–204.CrossRefPubMedPubMedCentral Swain SM, Tang G, Geyer CE Jr, et al. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013;31:3197–204.CrossRefPubMedPubMedCentral
58.
go back to reference Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol. 2006;24:2028–37.CrossRefPubMed Wapnir IL, Anderson SJ, Mamounas EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol. 2006;24:2028–37.CrossRefPubMed
59.
go back to reference Yang SX, Costantino JP, Kim C, et al. Akt phosphorylation at Ser473 predicts benefit of paclitaxel chemotherapy in node-positive breast cancer. J Clin Oncol. 2010;28:2974–81.CrossRefPubMedPubMedCentral Yang SX, Costantino JP, Kim C, et al. Akt phosphorylation at Ser473 predicts benefit of paclitaxel chemotherapy in node-positive breast cancer. J Clin Oncol. 2010;28:2974–81.CrossRefPubMedPubMedCentral
60.
go back to reference Fisher B WD, Redmond C, Wolmark N, Glass A, Bowman D, Jochimsen P, Poisson S. Increased benefit from addition of adriamycin to adjuvant therapy for stage II breast cancer: results from NSABP protocols B-11 and B-12. Proc Am Soc Clin Oncol. 1987;6. Fisher B WD, Redmond C, Wolmark N, Glass A, Bowman D, Jochimsen P, Poisson S. Increased benefit from addition of adriamycin to adjuvant therapy for stage II breast cancer: results from NSABP protocols B-11 and B-12. Proc Am Soc Clin Oncol. 1987;6.
61.
go back to reference Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.PubMed Kuerer HM, Newman LA, Smith TL, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17:460–9.PubMed
62.
go back to reference Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116:2884–9.CrossRefPubMedPubMedCentral Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116:2884–9.CrossRefPubMedPubMedCentral
63.
go back to reference Kuerer HM, Sahin AA, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230:72–8.CrossRefPubMedPubMedCentral Kuerer HM, Sahin AA, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230:72–8.CrossRefPubMedPubMedCentral
64.
go back to reference Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33:258–64.CrossRefPubMed Boileau JF, Poirier B, Basik M, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;33:258–64.CrossRefPubMed
65.
go back to reference Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455–61.CrossRefPubMedPubMedCentral Boughey JC, Suman VJ, Mittendorf EA, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455–61.CrossRefPubMedPubMedCentral
67.
go back to reference Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–18.CrossRefPubMed Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–18.CrossRefPubMed
68.
go back to reference Caudle AS, Yang WT, Mittendorf EA, et al. Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surg. 2015;150:137–43.CrossRefPubMedPubMedCentral Caudle AS, Yang WT, Mittendorf EA, et al. Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial. JAMA Surg. 2015;150:137–43.CrossRefPubMedPubMedCentral
69.
go back to reference Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261:378–82.CrossRefPubMed Donker M, Straver ME, Wesseling J, et al. Marking axillary lymph nodes with radioactive iodine seeds for axillary staging after neoadjuvant systemic treatment in breast cancer patients: the MARI procedure. Ann Surg. 2015;261:378–82.CrossRefPubMed
70.
go back to reference Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016. doi:10.1200/JCO.2015.64.0094 PubMed Caudle AS, Yang WT, Krishnamurthy S, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016. doi:10.​1200/​JCO.​2015.​64.​0094 PubMed
71.
go back to reference van la Parra RF, Kuerer HM. Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials. Breast Cancer Res. 2016;18:28. van la Parra RF, Kuerer HM. Selective elimination of breast cancer surgery in exceptional responders: historical perspective and current trials. Breast Cancer Res. 2016;18:28.
73.
go back to reference Heil J, Kummel S, Schaefgen B, et al. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565–70.CrossRefPubMed Heil J, Kummel S, Schaefgen B, et al. Diagnosis of pathological complete response to neoadjuvant chemotherapy in breast cancer by minimal invasive biopsy techniques. Br J Cancer. 2015;113:1565–70.CrossRefPubMed
Metadata
Title
Breast Cancer Clinical Trials: Past Half Century Moving Forward Advancing Patient Outcomes
Authors
Henry M. Kuerer, MD, PhD, FACS
Raquel F. D. van la Parra, MD, PhD
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 10/2016
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5326-9

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