Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis from the ALTTO Trial

Isabelle Gingras, Eileen Holmes, Evandro De Azambuja, David H.A. Nguyen, Miguel Izquierdo, Jo Anne Zujewski, Moshe Inbar, Bjorn Naume, Gianluca Tomasello, Julie R. Gralow, Antonio C Wolff, Lyndsay Harris, Michael Gnant, Alvaro Moreno-Aspitia, Martine J. Piccart, Hatem A. Azim

Research output: Contribution to journalArticle

Abstract

Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randmized clinical trials.

Original languageEnglish (US)
Article numberdjw331
JournalJournal of the National Cancer Institute
Volume109
Issue number8
DOIs
StatePublished - Aug 1 2017

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Segmental Mastectomy
Disease-Free Survival
Breast Neoplasms
Lymph Nodes
Recurrence
Therapeutics
human ERBB2 protein
Neoplasms
Breast
Regression Analysis
Clinical Trials
Hormones
Confidence Intervals
Drug Therapy
Survival

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer : Results of a Subanalysis from the ALTTO Trial. / Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H.A.; Izquierdo, Miguel; Zujewski, Jo Anne; Inbar, Moshe; Naume, Bjorn; Tomasello, Gianluca; Gralow, Julie R.; Wolff, Antonio C; Harris, Lyndsay; Gnant, Michael; Moreno-Aspitia, Alvaro; Piccart, Martine J.; Azim, Hatem A.

In: Journal of the National Cancer Institute, Vol. 109, No. 8, djw331, 01.08.2017.

Research output: Contribution to journalArticle

Gingras, I, Holmes, E, De Azambuja, E, Nguyen, DHA, Izquierdo, M, Zujewski, JA, Inbar, M, Naume, B, Tomasello, G, Gralow, JR, Wolff, AC, Harris, L, Gnant, M, Moreno-Aspitia, A, Piccart, MJ & Azim, HA 2017, 'Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis from the ALTTO Trial', Journal of the National Cancer Institute, vol. 109, no. 8, djw331. https://doi.org/10.1093/jnci/djw331
Gingras, Isabelle ; Holmes, Eileen ; De Azambuja, Evandro ; Nguyen, David H.A. ; Izquierdo, Miguel ; Zujewski, Jo Anne ; Inbar, Moshe ; Naume, Bjorn ; Tomasello, Gianluca ; Gralow, Julie R. ; Wolff, Antonio C ; Harris, Lyndsay ; Gnant, Michael ; Moreno-Aspitia, Alvaro ; Piccart, Martine J. ; Azim, Hatem A. / Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer : Results of a Subanalysis from the ALTTO Trial. In: Journal of the National Cancer Institute. 2017 ; Vol. 109, No. 8.
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abstract = "Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8{\%}) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3{\%} in the RNI group and 88.3{\%} in the non-RNI group. No differences in regional recurrence (0.9 {\%} vs 0.6 {\%}) or in overall survival (93.6{\%} vs 95.3{\%}) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95{\%} confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randmized clinical trials.",
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T1 - Regional Nodal Irradiation after Breast Conserving Surgery for Early HER2-Positive Breast Cancer

T2 - Results of a Subanalysis from the ALTTO Trial

AU - Gingras, Isabelle

AU - Holmes, Eileen

AU - De Azambuja, Evandro

AU - Nguyen, David H.A.

AU - Izquierdo, Miguel

AU - Zujewski, Jo Anne

AU - Inbar, Moshe

AU - Naume, Bjorn

AU - Tomasello, Gianluca

AU - Gralow, Julie R.

AU - Wolff, Antonio C

AU - Harris, Lyndsay

AU - Gnant, Michael

AU - Moreno-Aspitia, Alvaro

AU - Piccart, Martine J.

AU - Azim, Hatem A.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randmized clinical trials.

AB - Background: Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. Methods: This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. Results: One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Conclusions: Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randmized clinical trials.

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