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Dr. Roesch scans the journals, so you don't have to!
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Erin Roesch, MD

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [18F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.[6,7]

Additional References:

  1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
  2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
  3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
  4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
  5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
  6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
  7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source
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Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

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Clinical Edge Journal Scan
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Author(s)
Erin Roesch, MD
Author(s)
Erin Roesch, MD
Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Author and Disclosure Information

Erin E. Roesch, MD, Associate Staff, Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio
Erin E. Roesch, MD, has disclosed the following relevant financial relationships:
Serve(d) as a speaker or a member of a speakers bureau for: Puma Biotechnology

Dr. Roesch scans the journals, so you don't have to!
Dr. Roesch scans the journals, so you don't have to!

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [18F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.[6,7]

Additional References:

  1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
  2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
  3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
  4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
  5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
  6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
  7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source

Erin Roesch, MD
Support for de-escalation of axillary surgery for select patients, specifically those with cT1-2, node-negative breast cancer and a positive sentinel lymph node (SLN) biopsy, has been demonstrated in prior studies, including the ACOSOG Z0011 and AMAROS trials.[1,2] Both of these trials showed no benefit of completion axillary-node dissection (ALND) after 10 years of follow-up for these patients, and higher rates of lymphedema for ALND were observed in AMAROS. The phase 3 noninferiority SENOMAC trial aimed to validate findings from prior studies and to include groups of patients that were underrepresented (patients undergoing mastectomy, SLN with extracapsular extension, T3 tumors, and males). A total of 2540 patients with cT1-3cN0 primary breast cancer and one to two SLN macrometastases were randomly assigned to SLNB or completion ALND. The majority of patients received radiation, including nodal target volumes, as well as adjuvant systemic therapy. The estimated 5-year recurrence-free survival after SLNB only was noninferior to that seen with complete ALND (89.7%, 95% CI 87.5%-91.9%; vs 88.7%, 95% CI 86.3%-91.1%) with a hazard ratio for recurrence or death of 0.89, which was significantly (P < .001) below the noninferiority margin. These results add to the growing body of data indicating that certain patient populations can be spared more aggressive axillary surgery while maintaining excellent survival outcomes and reducing side effects.

The class of CDK 4/6 inhibitors represents a significant advance in the treatment of hormone receptor (HR)-positive breast cancer. All three CDK 4/6 inhibitors (palbociclib, abemaciclib, and ribociclib) are approved in combination with endocrine therapy in the metastatic setting. As drugs show promise in later-stage disease, they are then often studied in the curative space. Presently, abemaciclib is the only CDK 4/6 inhibitor that has been approved by the US Food and Drug Administration for the treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, high-risk early breast cancer, based on results from the monarchE trial, which demonstrated invasive disease-free survival benefit with the addition of 2 years of abemaciclib to endocrine therapy. At 4 years, the absolute difference in invasive disease-free survival (IDFS) between the groups was 6.4% (85.8% in the abemaciclib + endocrine therapy group vs 79.4% in the endocrine therapy–alone group).[3] In contrast, the PENELOPE-B and PALLAS trials did not show benefit with the addition of palbociclib to endocrine therapy in the adjuvant setting.[4,5] The phase 3 NATALEE trial randomly assigned patients with HR-positive, HER2-negative early breast cancer to ribociclib (400 mg daily for 3 weeks followed by 1 week off for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI) or an NSAI alone. At the time of prespecified interim analysis, among 5101 patients, ribociclib + NSAI led to a significant improvement in IDFS compared with endocrine therapy alone (3-year IDFS was 90.4% vs 87.1%; hazard ratio 0.75; 95% CI 0.62-0.91; P = .003). It is certainly noteworthy that the trial design, endocrine therapies, and patient populations differed between these adjuvant studies; for example, NATALEE included a lower-risk population, and all patients received an NSAI (in monarchE approximately 30% received tamoxifen). The current results of NATALEE are encouraging; an absolute benefit of 3.3% should be considered and weighed against toxicities and cost, and longer follow-up is needed to further elucidate the role of ribociclib in the adjuvant space.

The meaningful impact of achieving a pathologic complete response (pCR) has been demonstrated in various prior studies. Response to neoadjuvant chemotherapy informs prognosis and helps tailor adjuvant therapy, the latter of which is particularly relevant for the HER2-positive subtype. Strategies to identify patients who are more likely to achieve pCR and predictors of early responders may aid in improving efficacy outcomes and limiting toxicities. TRAIN-3 is a single-arm, phase 2 study that included 235 and 232 patients with stage II/III HR-/HER2+ and HR+/HER2+ breast cancer, respectively, undergoing neoadjuvant chemotherapy (weekly paclitaxel D1 and D8/carboplatin AUC 6 D1/trastuzumab D1/pertuzumab D1 every 3 weeks for up to nine cycles), and was designed to evaluate radiologic and pathologic response rates and event-free survival. Response was monitored by breast MRI every 3 cycles and lymph node biopsy. Among patients with HR-/HER2+ tumors, 84 (36%; 95% CI 30-43) achieved a radiologic complete response after one to three cycles, of whom the majority (88%; 95% CI 79-94) had pCR. Patients with HR+/HER2+ tumors did not show the same degree of benefit with an MRI-based monitoring strategy; among the 138 patients (59%; 95% CI 53-66) who had a complete radiologic response after one to nine cycles, 73 (53%; 95% CI 44-61) had pCR. Additional imaging-guided modalities being studied to tailor and optimize treatment include [18F]fluorodeoxyglucose-PET-CT and volumetric MRI, in the PHERGain and I-SPY trials, respectively.[6,7]

Additional References:

  1. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 Source
  2. Bartels SAL, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565 Source
  3. Johnston SRD, Toi M, O'Shaughnessy J, et al, on behalf of the monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): Results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24:77-90. doi: 10.1016/S1470-2045(22)00694-5 Source
  4. Loibl S, Marmé F, Martin M, et al. Palbociclib for residual high-risk invasive HR-positive and HER2-negative early breast cancer—The Penelope-B trial. J Clin Oncol. 2021;39:1518-1530. doi: 10.1200/JCO.20.03639 Source
  5. Gnant M, Dueck AC, Frantal S, et al, on behalf of the PALLAS groups and investigators. Adjuvant palbociclib for early breast cancer: The PALLAS trial results (ABCSG-42/AFT-05/BIG-14-03). J Clin Oncol. 2022;40:282-293. doi: 10.1200/JCO.21.02554 Source
  6. Pérez-García JM, Cortés J, Ruiz-Borrego M, et al, on behalf of the PHERGain trial investigators. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): A randomised, open-label, phase 2 trial. Lancet. 2024;403:1649-1659. doi: 10.1016/S0140-6736(24)00054-0 Source
  7. Hylton NM, Gatsonis CA, Rosen MA, et al, for the ACRIN 6657 trial team and I-SPY 1 trial investigators. Neoadjuvant chemotherapy for breast cancer: Functional tumor volume by MR imaging predicts recurrence-free survival-results from the ACRIN 6657/CALGB 150007 I-SPY 1 trial. Radiology. 2016;279:44-55. doi: 10.1148/radiol.2015150013 Source
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