Dataset Information

Incidence and prognostic impact of HER2-positivity loss after dual HER2-directed neoadjuvant therapy for HER2+ breast cancer.

ABSTRACT:

Background

Loss of HER2 "positivity" can occur in patients with residual disease after neoadjuvant treatment, but the incidence of HER2-positivity loss after neoadjuvant dual HER2-targeted treatment plus chemotherapy, the current standard-of-care for most early stage HER2-positive breast cancers, is not well described. Previous studies that report the HER2 discordance rate after neoadjuvant treatment also do not include the novel HER2-low category. In this retrospective study, we determine the incidence and prognostic impact of HER2-positivity loss, including the evolution to HER2-low disease, after neoadjuvant dual HER2-targeted therapy with chemotherapy.

Methods

Clinicopathologic data for patients with stage I-III HER2+ breast cancer diagnosed between 2015 and 2019 were reviewed in this single institution retrospective study. Patients who received dual HER2-targeted treatment with chemotherapy were included, and HER2 status before and after neoadjuvant therapy was interrogated.

Results

A total of 163 female patients were included in the analysis with a median age of 50 years. A pathologic complete response (pCR as defined by ypT0/is) was achieved in 102 (62.5%) of 163 evaluable patients. Among the 61 patients with residual disease after neoadjuvant therapy, 36 (59.0%) had HER2-positive and 25 (41.0%) had HER2-negative residual disease. Of the 25 patients with HER2-negative residual disease, 22 (88%) of patients were classified as HER2-low. After a median follow-up of 3.3 years, patients who retained HER2-positivity after neoadjuvant treatment had a 3-year IDFS rate of 91% (95% CI, 91%-100%), while patients who lost HER2-positivity had a 3-year IDFS rate of 82% (95% CI, 67%-100%).

Conclusion

Almost half of patients with residual disease following neoadjuvant dual HER2-targeted therapy plus chemotherapy lost HER2-positivity. The loss of HER2-positivity may not confer negative prognostic impact, although the results were limited by short follow-up time. Further research on the HER2 status after neoadjuvant treatment may help guide treatment decisions in the adjuvant setting.

SUBMITTER: LeVee A

PROVIDER: S-EPMC10225224 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Incidence and prognostic impact of HER2-positivity loss after dual HER2-directed neoadjuvant therapy for HER2+ breast cancer.

LeVee Alexis A Spector Kellie K Larkin Brigid B Dezem Felipe F Plummer Jasmine J Dadmanesh Farnaz F Patil Sujata S McArthur Heather L HL

Cancer medicine 20230327 9

<h4>Background</h4>Loss of HER2 "positivity" can occur in patients with residual disease after neoadjuvant treatment, but the incidence of HER2-positivity loss after neoadjuvant dual HER2-targeted treatment plus chemotherapy, the current standard-of-care for most early stage HER2-positive breast cancers, is not well described. Previous studies that report the HER2 discordance rate after neoadjuvant treatment also do not include the novel HER2-low category. In this retrospective study, we determi ...[more]

PMID: 36971049

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Project description:BackgroundTrastuzumab and pertuzumab are approved for the neoadjuvant treatment of human epidermal growth receptor 2 (HER2)-positive breast cancer, but cardiac safety data is limited. We report the cardiac safety of dose-dense doxorubicin and cyclophosphamide (AC) followed by paclitaxel, trastuzumab, and pertuzumab (THP) in the neoadjuvant setting followed by adjuvant trastuzumab-based therapy.MethodsFifty-seven patients treated with neoadjuvant dose-dense AC-THP followed by adjuvant trastuzumab-based therapy between September 1, 2013, and March 1, 2015, were identified. The primary outcome was cardiac event rate, defined by heart failure (New York Heart Association [NYHA] class III/IV) or cardiac death. Patients underwent left ventricular ejection fraction (LVEF) monitoring at baseline, after AC, and serially during 1 year of anti-HER2 therapy.ResultsThe median age was 46 years (range 26-68). Two (3.5%) patients developed NYHA class III/IV heart failure 5 and 9 months after initiation of trastuzumab-based therapy, leading to permanent discontinuation of anti-HER2 treatment. Seven (12.3%) patients developed a significant LVEF decline (without NYHA class III/IV symptoms). The median LVEF was 65% (range 55%-75%) at baseline and 64% (range 53%-72%) after AC, and decreased to 60% (range 35%-70%), 60% (range 23%-73%), 61% (range 25%-73%), and 58% (range 28%-66%) after 3, 6, 9, and 12 months (± 6 weeks) of trastuzumab-based therapy.ConclusionThe incidence of NYHA class III/IV heart failure after neoadjuvant AC-THP (followed by adjuvant trastuzumab-based therapy) is comparable to rates reported in trials of sequential doxorubicin and trastuzumab. Our findings do not suggest an increased risk of cardiotoxicity from trastuzumab plus pertuzumab following a doxorubicin-based regimen.Implications for practiceDual anti-human epidermal growth receptor 2 (HER2) therapy with trastuzumab and pertuzumab combined with standard chemotherapy has received accelerated approval for the neoadjuvant treatment of stage II-III HER2-positive breast cancer. Cardiac safety data for trastuzumab and pertuzumab in this setting are limited to clinical trials that utilized epirubicin-based chemotherapy. Formalized investigations into the cardiac safety of trastuzumab and pertuzumab with doxorubicin- (rather than epirubicin) based regimens are important because these regimens are widely used for the adjuvant and neoadjuvant treatment of breast cancer. The known role of HER2 signaling in the physiological adaptive responses of the heart provides further rationale for study on the potential cardiotoxicity of dual anti-HER2 blockade. Findings from this retrospective study provide favorable preliminary data on the cardiac safety of trastuzumab and pertuzumab in combination with a regimen of neoadjuvant doxorubicin and cyclophosphamide followed by paclitaxel, one of the preferred breast cancer treatment regimens, according to the National Comprehensive Cancer Network.

Dataset Information

Incidence and prognostic impact of HER2-positivity loss after dual HER2-directed neoadjuvant therapy for HER2+ breast cancer.

Background

Methods

Results

Conclusion

Publications

Incidence and prognostic impact of HER2-positivity loss after dual HER2-directed neoadjuvant therapy for HER2+ breast cancer.

Similar Datasets

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