Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial

Matteo Lambertini, Christine Campbell, Richard D. Gelber, Giuseppe Viale, Ann McCullough, Florentine Hilbers, Larissa A. Korde, Olena Werner, Saranya Chumsri, Christian Jackisch, Antonio C Wolff, Ines Vaz-Luis, Arlindo R. Ferreira, Aleix Prat, Alvaro Moreno-Aspitia, Martine Piccart, Sherene Loi, Evandro de Azambuja

Research output: Contribution to journalArticle

Abstract

Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. Methods: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0–5 and 6–8. Results: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0–5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6–8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6–8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0–5, and 6–8 were different in patients with HR-positive and HR-negative tumors. Conclusions: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalBreast Cancer Research and Treatment
Volume177
Issue number1
DOIs
StatePublished - Aug 30 2019

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Randomized Controlled Trials
Hormones
Breast Neoplasms
Disease-Free Survival
Neoplasms
Recurrence
Progesterone Receptors
Natural History
Estrogen Receptors
Clinical Trials

Keywords

  • Breast cancer
  • Estrogen receptor
  • HER2
  • Progesterone receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer : exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial. / Lambertini, Matteo; Campbell, Christine; Gelber, Richard D.; Viale, Giuseppe; McCullough, Ann; Hilbers, Florentine; Korde, Larissa A.; Werner, Olena; Chumsri, Saranya; Jackisch, Christian; Wolff, Antonio C; Vaz-Luis, Ines; Ferreira, Arlindo R.; Prat, Aleix; Moreno-Aspitia, Alvaro; Piccart, Martine; Loi, Sherene; de Azambuja, Evandro.

In: Breast Cancer Research and Treatment, Vol. 177, No. 1, 30.08.2019, p. 103-114.

Research output: Contribution to journalArticle

Lambertini, M, Campbell, C, Gelber, RD, Viale, G, McCullough, A, Hilbers, F, Korde, LA, Werner, O, Chumsri, S, Jackisch, C, Wolff, AC, Vaz-Luis, I, Ferreira, AR, Prat, A, Moreno-Aspitia, A, Piccart, M, Loi, S & de Azambuja, E 2019, 'Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer: exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial', Breast Cancer Research and Treatment, vol. 177, no. 1, pp. 103-114. https://doi.org/10.1007/s10549-019-05284-y
Lambertini, Matteo ; Campbell, Christine ; Gelber, Richard D. ; Viale, Giuseppe ; McCullough, Ann ; Hilbers, Florentine ; Korde, Larissa A. ; Werner, Olena ; Chumsri, Saranya ; Jackisch, Christian ; Wolff, Antonio C ; Vaz-Luis, Ines ; Ferreira, Arlindo R. ; Prat, Aleix ; Moreno-Aspitia, Alvaro ; Piccart, Martine ; Loi, Sherene ; de Azambuja, Evandro. / Dissecting the effect of hormone receptor status in patients with HER2-positive early breast cancer : exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial. In: Breast Cancer Research and Treatment. 2019 ; Vol. 177, No. 1. pp. 103-114.
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abstract = "Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. Methods: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0–5 and 6–8. Results: Out of 6273 patients included in this analysis, 3603 (57.4{\%}) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86{\%} and 80{\%} in patients with HR-positive disease, and 83{\%} and 79{\%} in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0–5 were 3{\%} in patients with HR-positive disease and 4{\%} in those with HR-negative tumors, while in years 6–8 they were 3{\%} and 2{\%}, respectively. Distribution of first DFS event in years 6–8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0–5, and 6–8 were different in patients with HR-positive and HR-negative tumors. Conclusions: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.",
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T2 - exploratory analysis from the ALTTO (BIG 2-06) randomized clinical trial

AU - Lambertini, Matteo

AU - Campbell, Christine

AU - Gelber, Richard D.

AU - Viale, Giuseppe

AU - McCullough, Ann

AU - Hilbers, Florentine

AU - Korde, Larissa A.

AU - Werner, Olena

AU - Chumsri, Saranya

AU - Jackisch, Christian

AU - Wolff, Antonio C

AU - Vaz-Luis, Ines

AU - Ferreira, Arlindo R.

AU - Prat, Aleix

AU - Moreno-Aspitia, Alvaro

AU - Piccart, Martine

AU - Loi, Sherene

AU - de Azambuja, Evandro

PY - 2019/8/30

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N2 - Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. Methods: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0–5 and 6–8. Results: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0–5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6–8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6–8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0–5, and 6–8 were different in patients with HR-positive and HR-negative tumors. Conclusions: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.

AB - Purpose: Limited evidence exists on the impact of hormone receptor (HR) status to counsel HER2-positive early breast cancer patients receiving adjuvant anti-HER2 therapy. Methods: ALTTO (BIG 2-06) was an international, intergroup, open-label, randomized phase III trial in HER2-positive early breast cancer patients randomized to receive 1 year of trastuzumab and/or lapatinib. HER2, estrogen and progesterone receptors were centrally tested for all patients. We investigated the impact of HR status on prognosis, risk of disease-free survival (DFS) events over time, patterns of first DFS events, and factors associated with risk of DFS events overall, in years 0–5 and 6–8. Results: Out of 6273 patients included in this analysis, 3603 (57.4%) had HR-positive tumors. Median follow-up was 6.93 years. Five-year and 8-year DFS were 86% and 80% in patients with HR-positive disease, and 83% and 79% in those with HR-negative tumors, respectively. Mean annual hazards of recurrence in years 0–5 were 3% in patients with HR-positive disease and 4% in those with HR-negative tumors, while in years 6–8 they were 3% and 2%, respectively. Distribution of first DFS event in years 6–8 (P = 0.005) and type of first distant recurrence (P < 0.001) were significantly different between the two groups. Risk factors for DFS events overall, in years 0–5, and 6–8 were different in patients with HR-positive and HR-negative tumors. Conclusions: HER2-positive early breast cancer is characterized by the presence of two diseases with distinct natural history based on HR status requiring the development of different follow-up strategies and future de-escalation and escalation clinical trials.

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