Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival

Voort, Anna van der; Liefaard, Marte C.; Ramshorst, Mette S. van; Werkhoven, Erik van; Sanders, Joyce; Wesseling, Jelle; Scholten, Astrid N.; Peeters, M; Munck, Linda de; Siesling, Sabine; Sonke, Gabe S.

doi:10.1016/j.breast.2022.07.005

Cited by 11 publications

(9 citation statements)

References 28 publications

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“…For example, Pertuzumab received FDA approval in 2013 for HER2-positive patients based on pCR criteria, in the absence of long-term data in the neoadjuvant setting. 15 In our study, it has been shown that among patients who achieved a pCR, patients with stage III or more or those who have undergone mastectomy as opposed to breast conservation are at an increased risk of developing metastasis after a pathological complete response. Also, patients with T1 tumors had more recurrence than T2 and T3, the reason being that in our data, 81% of patients with T1 tumors had aggressive biology, Her2 positive and triple negative (Table 2 and Table 3).…”

Section: Discussionmentioning

confidence: 61%

Impact of Pathological Complete Response in Breast Cancer Following Neoadjuvant Therapy on Patient’s Outcome

Soomro,

Zehra

2023

Arch Breast Cancer

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Background: Patients who achieve a pathological complete response (pCR) after neoadjuvant therapy have better outcomes than patients with residual disease. Despite the excellent prognosis associated with achieving a pCR, recurrence still occurs. The study was conducted with the intent to evaluate factors associated with tumor recurrence and survival among patients achieving pCR after neoadjuvant therapy. Methods: We evaluated the medical records of patients with breast cancer who received neoadjuvant therapy and achieved pCR in our academic institute. The survival curve was estimated with the Kaplan-Meier method in patients who developed recurrence. Results: In our retrospective study 2,360 received neoadjuvant therapy out of which 315 (13.3%) who achieved pCR were included in this study. The mean age was 45.85 (range 21-92 years) and the mean duration of follow-up was 41.2 months. The clinical tumor stage T1-T2 represented 55%, T3-T4 was 44.1%, and node-positive was 54%. The primary endpoint was the correlation between pCR achieved after neoadjuvant therapy and disease-free survival or overall survival. . Predictors of pCR were clinical T-stage and receiving appropriate chemotherapy. We observed that patients who had an increased risk of recurrence after achieving pCR were those with clinical stage III-IV, patients with mastectomy, and those with triple-negative tumor subtype. Conclusion: Achieving pCR after neoadjuvant therapy is distinctly related to the improvement of survival, however patients who achieved a pCR, women younger than 50 years of age and those with stage III/IV disease have a higher risk of developing distant metastasis.

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Section: Discussionmentioning

confidence: 61%

Impact of Pathological Complete Response in Breast Cancer Following Neoadjuvant Therapy on Patient’s Outcome

Soomro,

Zehra

2023

Arch Breast Cancer

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“…Despite taking measures to ensure adequate matching, cases and controls differed with respect to chemotherapy regimens, tumor grade and nodal stage. Given that anthracycline-based treatment was preferred as a chemotherapy regimen in the Netherlands during the study period, the majority of control patients had received anthracyclines, which made perfect matching impossible, and also affected the matching of the other clinical variables [ 36 ]. In addition, tumor grade was only available after case–control selection and thus not accounted for during matching.…”

Section: Discussionmentioning

confidence: 99%

BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer

et al. 2023

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Background The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab. Methods From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups. Results BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36–4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25–0.80) and BCSS (aHR 0.46, 95% CI 0.24–0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes. Conclusions In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.

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“…The TPC combination is also associated with an improvement of clinical and societal outcomes. In particular, TPC is associated with a reduction of days of work lost due to progressive disease, because of the estimated reduction in the rate of distant recurrences and improved prognosis with an increase of QALY [ 9 , 42 , 43 ]. In addition, the estimated higher rate of pCR with use of neadjuvant TPC will derive a limited use of T-DM1, as escalating treatment in the adjuvant setting, with a substantial benefit for the quality of life of the patients [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

A cost-consequence analysis of adding pertuzumab to the neoadjuvant combination therapy in HER2-positive high-risk early breast cancer in Italy

Zambelli¹,

Cazzaniga²,

Verde³

et al. 2023

The Breast

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Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: a nationwide cohort analysis of pathologic response and 5-year survival

Cited by 11 publications

References 28 publications

Impact of Pathological Complete Response in Breast Cancer Following Neoadjuvant Therapy on Patient’s Outcome

Impact of Pathological Complete Response in Breast Cancer Following Neoadjuvant Therapy on Patient’s Outcome

BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer

A cost-consequence analysis of adding pertuzumab to the neoadjuvant combination therapy in HER2-positive high-risk early breast cancer in Italy

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