Skip to main content
Top
Published in: Annals of Surgical Oncology 3/2021

01-03-2021 | Mastectomy | Breast Oncology

Does Failure to Achieve Pathologic Complete Response with Neoadjuvant Chemotherapy Identify Node-Negative Patients Who Would Benefit from Postmastectomy Radiation or Regional Nodal Irradiation?

Authors: Angelena Crown, MD, Mithat Gonen, PhD, Tiana Le, BA, Monica Morrow, MD

Published in: Annals of Surgical Oncology | Issue 3/2021

Login to get access

Abstract

Background

Postmastectomy radiation (PMRT) and regional nodal irradiation (RNI) improve outcomes for patients at high risk of locoregional recurrence (LRR). Node-negative patients with the triple-negative (TN) subtype and those who do not have a pCR with neoadjuvant chemotherapy (NAC) are at increased risk for LRR, but whether the absolute risk for LRR is high enough to justify PMRT/RNI is uncertain.

Methods

Patients with cT1-T3N0 and pN0 disease treated with NAC who had residual disease in the breast were identified from a prospective database. Patients were eligible for the study if they had mastectomy or breast-conserving therapy with negative margins and whole-breast radiation. Those receiving PMRT or RNI were excluded. Actuarial rates were estimated using the cumulative incidence function.

Results

The 227 patients in this study had a mean age was 51.4 ± 12.6 years, and 82 (36.1%) were TN. During a median follow-up period of 35 months, nine LRR events occurred. The overall crude and actuarial 3-year LRR rates were 4.4% and 5.9%, respectively. The crude LRR rate for the TN patients was 7.4%, and the 3-year actuarial rate was 10.1%. The hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2−) patients had a crude LRR rate of 2.8% and a 3-year actuarial rate of 3.2%. The HER2+ patients had a crude LRR rate of 2.7% and a 3-year actuarial rate of 3.3%.

Conclusions

Locoregional recurrence is uncommon for patients with node-negative HR+/HER2− and HER2+ tumors who have residual disease in the breast; however, TN patients have LRR rates that approach 10% at 3 years, suggesting a possible role for PMRT/RNI for node-negative TN patients. Additional follow-up with more patients is needed for definitive conclusions.
Literature
1.
go back to reference Recht A, Gray R, Davidson NE, et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol. 1999;17:1689–700.CrossRef Recht A, Gray R, Davidson NE, et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol. 1999;17:1689–700.CrossRef
2.
go back to reference Katz A, Strom EA, Buchholz TA, et al. Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol. 2000;18:2817–27.CrossRef Katz A, Strom EA, Buchholz TA, et al. Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol. 2000;18:2817–27.CrossRef
3.
go back to reference Wallgren A, Bonetti M, Gelber RD, et al. Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII. J Clin Oncol. 2003;21:1205–13.CrossRef Wallgren A, Bonetti M, Gelber RD, et al. Risk factors for locoregional recurrence among breast cancer patients: results from International Breast Cancer Study Group Trials I through VII. J Clin Oncol. 2003;21:1205–13.CrossRef
4.
go back to reference Taghian A, Jeong JH, Mamounas E, et al. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004;22:4247–54.CrossRef Taghian A, Jeong JH, Mamounas E, et al. Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol. 2004;22:4247–54.CrossRef
5.
go back to reference EBCTCG, McGale P, Taylor C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–35.CrossRef EBCTCG, McGale P, Taylor C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–35.CrossRef
6.
go back to reference Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337:949–55.CrossRef Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997;337:949–55.CrossRef
7.
go back to reference Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641–8.CrossRef Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999;353:1641–8.CrossRef
8.
go back to reference Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97:116–26.CrossRef Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005;97:116–26.CrossRef
9.
go back to reference Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Eng J Med. 2015;373:317–27.CrossRef Poortmans PM, Collette S, Kirkove C, et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N Eng J Med. 2015;373:317–27.CrossRef
10.
go back to reference Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307–16.CrossRef Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015;373:307–16.CrossRef
11.
go back to reference Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30:3960–6.CrossRef Mamounas EP, Anderson SJ, Dignam JJ, et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of National Surgical Adjuvant Breast and Bowel Project B-18 and B-27. J Clin Oncol. 2012;30:3960–6.CrossRef
12.
go back to reference A randomized phase III clinical trial evaluating post-mastectomy chestwall and regional nodal XRT and post-lumpectomy regional nodal XRT in patients with positive axillary nodes before neoadjuvant chemotherapy who convert to pathologically negative axillary nodes after neoadjuvant chemotherapy. ClinicicalTrials.gov Identifier: NCT01872975. Retrieved 30 April 2020 at https://clinicaltrials.gov/ct2/show/NCT01872975. 2013. A randomized phase III clinical trial evaluating post-mastectomy chestwall and regional nodal XRT and post-lumpectomy regional nodal XRT in patients with positive axillary nodes before neoadjuvant chemotherapy who convert to pathologically negative axillary nodes after neoadjuvant chemotherapy. ClinicicalTrials.gov Identifier: NCT01872975. Retrieved 30 April 2020 at https://​clinicaltrials.​gov/​ct2/​show/​NCT01872975. 2013.
13.
go back to reference Swisher SK, Vila J, Tucker SL, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23:749–56.CrossRef Swisher SK, Vila J, Tucker SL, et al. Locoregional control according to breast cancer subtype and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Ann Surg Oncol. 2016;23:749–56.CrossRef
14.
go back to reference Yang TJ, Morrow M, Modi S, et al. The effect of molecular subtype and residual disease on locoregional recurrence in breast cancer patients treated with neoadjuvant chemotherapy and postmastectomy radiation. Ann Surg Oncol. 2015;22(Suppl 3):S495–501.CrossRef Yang TJ, Morrow M, Modi S, et al. The effect of molecular subtype and residual disease on locoregional recurrence in breast cancer patients treated with neoadjuvant chemotherapy and postmastectomy radiation. Ann Surg Oncol. 2015;22(Suppl 3):S495–501.CrossRef
15.
go back to reference Caudle AS, Yu TK, Tucker SL, et al. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Breast Cancer Res. 2012;14:R83.CrossRef Caudle AS, Yu TK, Tucker SL, et al. Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast-conserving therapy. Breast Cancer Res. 2012;14:R83.CrossRef
16.
go back to reference Meyers MO, Klauber-Demore N, Ollila DW, et al. Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol. 2011;18:2851–7.CrossRef Meyers MO, Klauber-Demore N, Ollila DW, et al. Impact of breast cancer molecular subtypes on locoregional recurrence in patients treated with neoadjuvant chemotherapy for locally advanced breast cancer. Ann Surg Oncol. 2011;18:2851–7.CrossRef
17.
go back to reference Wright JL, Takita C, Reis IM, et al. Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation. Cancer. 2013;119:16–25.CrossRef Wright JL, Takita C, Reis IM, et al. Predictors of locoregional outcome in patients receiving neoadjuvant therapy and postmastectomy radiation. Cancer. 2013;119:16–25.CrossRef
18.
go back to reference Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRef Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRef
19.
go back to reference Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRef Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72.CrossRef
20.
go back to reference von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30:1796–804.CrossRef
21.
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.CrossRef 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.CrossRef
22.
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;17:460–469.CrossRef 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;17:460–469.CrossRef
23.
go back to reference Mamounas EP, Cortazar P, Zhang L, et al. Locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC): pooled-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC). J Clin Oncol. 2014;32(26 Suppl):61.CrossRef Mamounas EP, Cortazar P, Zhang L, et al. Locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC): pooled-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC). J Clin Oncol. 2014;32(26 Suppl):61.CrossRef
24.
go back to reference Edge SB CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. Berlin: Springer; 2010. Edge SB CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. Berlin: Springer; 2010.
25.
go back to reference Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.CrossRef Hammond ME, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28:2784–95.CrossRef
26.
go back to reference Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res. 2008;14:8019–26.CrossRef Dowsett M, Dunbier AK. Emerging biomarkers and new understanding of traditional markers in personalized therapy for breast cancer. Clin Cancer Res. 2008;14:8019–26.CrossRef
27.
go back to reference Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003;88:406–12.CrossRef Faneyte IF, Schrama JG, Peterse JL, Remijnse PL, Rodenhuis S, van de Vijver MJ. Breast cancer response to neoadjuvant chemotherapy: predictive markers and relation with outcome. Br J Cancer. 2003;88:406–12.CrossRef
28.
go back to reference Guarneri V, Broglio K, Kau SW, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24:1037–44.CrossRef Guarneri V, Broglio K, Kau SW, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24:1037–44.CrossRef
29.
go back to reference Bonnefoi H, Litiere S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014;25:1128–36.CrossRef Bonnefoi H, Litiere S, Piccart M, et al. Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial. Ann Oncol. 2014;25:1128–36.CrossRef
30.
go back to reference Valachis A, Mamounas EP, Mittendorf EA, et al. Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: an international collaboration and individual patient meta-analysis. Cancer. 2018;124(14):2923–2930.CrossRef Valachis A, Mamounas EP, Mittendorf EA, et al. Risk factors for locoregional disease recurrence after breast-conserving therapy in patients with breast cancer treated with neoadjuvant chemotherapy: an international collaboration and individual patient meta-analysis. Cancer. 2018;124(14):2923–2930.CrossRef
31.
go back to reference Dominici LS, Mittendorf EA, Wang X, et al. Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy. Breast Cancer Res. 2012;14:R82.CrossRef Dominici LS, Mittendorf EA, Wang X, et al. Implications of constructed biologic subtype and its relationship to locoregional recurrence following mastectomy. Breast Cancer Res. 2012;14:R82.CrossRef
32.
go back to reference Chen VE, Gillespie EF, Zakeri K, et al. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer. Adv Radiat Oncol. 2017;2:105–9.CrossRef Chen VE, Gillespie EF, Zakeri K, et al. Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer. Adv Radiat Oncol. 2017;2:105–9.CrossRef
33.
go back to reference von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380:617–28.CrossRef von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380:617–28.CrossRef
34.
go back to reference Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147–59.CrossRef Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017;376:2147–59.CrossRef
35.
go back to reference Mazouni C, Peintinger F, Wan-Kau S, et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25:2650–5.CrossRef Mazouni C, Peintinger F, Wan-Kau S, et al. Residual ductal carcinoma in situ in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy does not adversely affect patient outcome. J Clin Oncol. 2007;25:2650–5.CrossRef
36.
go back to reference Choi MK, Park YH, Kil WH, et al. Clinicopathological features of early failure of neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Chemother Pharmacol. 2014;74:521–9.CrossRef Choi MK, Park YH, Kil WH, et al. Clinicopathological features of early failure of neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Chemother Pharmacol. 2014;74:521–9.CrossRef
37.
go back to reference Hamy AS, Lam GT, Laas E, et al. Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma. Breast Cancer Res Treat. 2018;169:295–304.CrossRef Hamy AS, Lam GT, Laas E, et al. Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated with poor prognosis in breast carcinoma. Breast Cancer Res Treat. 2018;169:295–304.CrossRef
38.
go back to reference Pagani O, Price KN, Gelber RD, et al. Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century. Breast Cancer Res Treat. 2009;117:319–24.CrossRef Pagani O, Price KN, Gelber RD, et al. Patterns of recurrence of early breast cancer according to estrogen receptor status: a therapeutic target for a quarter of a century. Breast Cancer Res Treat. 2009;117:319–24.CrossRef
39.
go back to reference Colleoni M, Sun Z, Price KN, et al. Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the international breast cancer study group trials I to V. J Clin Oncol. 2016;34:927–35.CrossRef Colleoni M, Sun Z, Price KN, et al. Annual hazard rates of recurrence for breast cancer during 24 years of follow-up: results from the international breast cancer study group trials I to V. J Clin Oncol. 2016;34:927–35.CrossRef
Metadata
Title
Does Failure to Achieve Pathologic Complete Response with Neoadjuvant Chemotherapy Identify Node-Negative Patients Who Would Benefit from Postmastectomy Radiation or Regional Nodal Irradiation?
Authors
Angelena Crown, MD
Mithat Gonen, PhD
Tiana Le, BA
Monica Morrow, MD
Publication date
01-03-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-09136-8

Other articles of this Issue 3/2021

Annals of Surgical Oncology 3/2021 Go to the issue