Breast cancer, ER and HER2 co-expressing

Section editor transclusions Note: these are regimens tested in patients with hormone receptor-positive, HER2-positive breast cancer. Please see the main breast cancer page, ER+ breast cancer page, and HER2+ breast cancer page for other regimens.

19 regimens on this page 21 variants on this page

Neoadjuvant chemotherapy

Ado-trastuzumab emtansine monotherapy

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T-DM1: Trastuzumab-DM1 (Ado-trastuzumab emtansine)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-switch-ic)	1. T-DM1 & ET	Not reported
			2. Trastuzumab & ET	Superior pCR rate

Antibody-drug conjugate therapy

• Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

21-day cycle for 4 cycles

Subsequent treatment

• Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

T-DM1 & ET

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T-DM1 & ET: Trastuzumab-DM1 (Ado-trastuzumab emtansine) & Endocrine Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (E-esc)	1. T-DM1	Not reported
			2. Trastuzumab & ET	Superior pCR rate

Antibody-drug conjugate therapy

• Ado-trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

Endocrine therapy

• One of the following:
  • Premenopausal women: Tamoxifen (Nolvadex) recommended
  • GnRH analogs were also allowed
  • Postmenopausal women: Aromatase inhibitor recommended

21-day cycle for 4 cycles

Subsequent treatment

• Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

Trastuzumab & ET

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Trastuzumab & ET: Trastuzumab & Endocrine Therapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Harbeck et al. 2017 (WGSG ADAPT)	2012-2015	Randomized Phase 2 (C)	1. T-DM1 2. T-DM1 & ET	Inferior pCR rate

Targeted therapy

• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycles 2 to 4: 6 mg/kg IV once on day 1

Endocrine therapy

• Endocrine therapy by the following criteria:
  • Premenopausal women: Tamoxifen (Nolvadex) recommended
    • GnRH analogs were also allowed
  • Postmenopausal women: Aromatase inhibitor recommended

21-day cycle for 4 cycles

Subsequent treatment

• Surgery was performed within 3 weeks of the end of therapy. Adjuvant therapy consisted of EC, then TH (Taxol), unless the patient had pCR in which case adjuvant therapy was optional

References

1. WGSG ADAPT: Harbeck N, Gluz O, Christgen M, Kates RE, Braun M, Küemmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, von Schumann R, Liedtke C, Grischke EM, Schumacher J, Wuerstlein R, Kreipe HH, Nitz UA; West German Study Group. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (BC): Final analysis of the West German Study Group Adjuvant Dynamic marker-Adjusted Personalized Therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor-positive phase II randomized trial-efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Sep 10;35(26):3046-3054. Epub 2017 Jul 6. link to original article contains verified protocol PubMed NCT01817452

Adjuvant therapy

Anastrozole monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (eMonarcHER)	2021-ongoing	Phase 3 (C)	ET & Abemaciclib	In progress

Preceding treatment

• HER2-targeted therapy

Endocrine therapy

• Anastrozole (Arimidex) 1 mg PO once per day

Continued for up to 10 years

References

1. eMonarcHER: NCT04752332

Metastatic disease, first-line therapy

Anastrozole monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (C)	Anastrozole & Trastuzumab	Inferior PFS

Endocrine therapy

• Anastrozole (Arimidex) 1 mg PO once per day

28-day cycles

References

1. TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00022672

Anastrozole & Trastuzumab

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Regimen variant #1, weekly trastuzumab

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kaufman et al. 2009 (TAnDEM)	2001-2004	Phase 3 (E-esc)	Anastrozole	Superior PFS Median PFS: 4.8 vs 2.4 mo (HR 0.63, 95% CI 0.47-0.84)

Endocrine therapy

• Anastrozole (Arimidex) 1 mg PO once per day

Targeted therapy

• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 4 mg/kg IV once on day 1, then 2 mg/kg IV once per day on days 8, 15, 22
  • Cycle 2 onwards: 2 mg/kg IV once per day on days 1, 8, 15, 22

28-day cycles

Regimen variant #2, q3wk trastuzumab

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Anastrozole (Arimidex) 1 mg PO once per day

21-day cycles

References

1. TAnDEM: Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Révil C, Jones A. Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol. 2009 Nov 20;27(33):5529-37. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00022672
2. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211
3. SYSUCC-002: NCT01950182

Anastrozole, Lapatinib, Trastuzumab

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Lapatinib (Tykerb) 1000 mg PO once per day
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Anastrozole (Arimidex) 1 mg PO once per day

21-day cycles

References

1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Exemestane & Trastuzumab

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Exemestane (Aromasin) 1 mg PO once per day

21-day cycles

References

1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211
2. SYSUCC-002: NCT01950182

Exemestane, Lapatinib, Trastuzumab

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Lapatinib (Tykerb) 1000 mg PO once per day
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Exemestane (Aromasin) 25 mg PO once per day

21-day cycles

References

1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Lapatinib & Letrozole

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (E-RT-esc)	Letrozole	Seems to have superior PFS Median PFS: 8.2 vs 3 mo (HR 0.71, 95% CI 0.53-0.96)

Targeted therapy

• Lapatinib (Tykerb) 1500 mg PO once per day

Endocrine therapy

• Letrozole (Femara) 2.5 mg PO once per day

Continued indefinitely

References

1. EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00073528

Lapatinib, Letrozole, Trastuzumab

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (E-esc)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole & Trastuzumab 5. Exemestane & Trastuzumab 6. Letrozole & Trastuzumab	Superior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Lapatinib (Tykerb) 1000 mg PO once per day
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Letrozole (Femara) 2.5 mg PO once per day

21-day cycles

References

1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211

Letrozole monotherapy

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2009 (EGF30008)	2003-2006	Phase 3 (C)	Lapatinib & Letrozole	Seems to have inferior PFS

Endocrine therapy

• Letrozole (Femara) 2.5 mg PO once per day

28-day cycles

References

1. EGF30008: Johnston S, Pippen J Jr, Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, Press MF, Maltzman J, Florance A, O'Rourke L, Oliva C, Stein S, Pegram M. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009 Nov 20;27(33):5538-46. Epub 2009 Sep 28. link to original article contains protocol PubMed NCT00073528

Letrozole & Trastuzumab

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Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Johnston et al. 2020 (ALTERNATIVE)	2011-2016	Phase 3 (C)	1. Anastrozole & Lapatinib 2. Exemestane & Lapatinib 3. Lapatinib & Letrozole	Not reported
			4. Anastrozole, Lapatinib, Trastuzumab 5. Exemestane, Lapatinib, Trastuzumab 6. Lapatinib, Letrozole, Trastuzumab	Inferior PFS

Note: the original article published in 2018 was retracted due to numeric errors in the analysis, and an update has been published.

Targeted therapy

• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

Endocrine therapy

• Letrozole (Femara) 2.5 mg PO once per day

21-day cycles

References

1. ALTERNATIVE: Johnston SRD, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021 Jan 1;39(1):79-89. Epub 2020 Aug 21. link to original article contains verified protocol PubMed NCT01160211
2. SYSUCC-002: NCT01950182