Dataset Information

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

ABSTRACT:

Background

Neoadjuvant Chemotherapy (NC) including trastuzumab induces a high rate of pathological Complete Responses (pCR) in patients with locally advanced HER2-overexpressing Breast Cancer (BC), but is penalized by a severe cardiotoxicity when combined with anthracyclines. A phase II study was designed to assess whether an anthracycline-free NC regimen based on the early addition of trastuzumab to paclitaxel may increase the pCR rate without inducing severe cardiotoxicity in patients with locally advanced HER2-overexpressing BC. Immunomonitoring was performed to assess the contribution of patients' immunological background to the induction of clinical responses.

Methods

Stage II-III HER2-positive BC patients received 24 weeks paclitaxel and trastuzumab NC, followed by 1 year adjuvant trastuzumab ± hormonal and/or radio-therapy. Assessment of pCR rate was the primary endpoint. A group of HER2-negative BC patients treated with neoadjuvant taxanes and anthracyclines was included. Serum levels of 10 cytokines and the efficiency of trastuzumab-mediated antibody-dependent cell cytotoxicity (ADCC) were monitored in vitro every 3 months.

Results

From July 2006 to February 2013, we enrolled 109 patients including 46 evaluable HER2-positive cases. A pCR rate of 50% was reached and no severe cardiotoxicity occurred. Serum cytokine profiling revealed only an IL-10 decrease (P = 0.02) in patients achieving a partial response, while HER2-negative patients disclosed marked cytokines changes. Compared to the unfavourable F/F genotype, patients carrying the V allele in the FcγRIIIa-158 polymorphism showed a higher efficacy of trastuzumab-ADCC throughout treatment (P ≤0.05).

Conclusions

In the absence of anthracyclines, trastuzumab and paclitaxel induced a high rate of pCR, exploiting the synergy between the immunomodulating properties of these drugs and the retained immunological proficiency of patients with HER2-overexpressing BC.

Trial registration

Trial registration number: NCT02307227, registered on ClinicalTrials.gov (http://www.clinicaltrials.gov, November 26, 2014).

SUBMITTER: Miolo G

PROVIDER: S-EPMC4302069 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

Miolo Gianmaria G Muraro Elena E Martorelli Debora D Lombardi Davide D Scalone Simona S Spazzapan Simon S Massarut Samuele S Perin Tiziana T Viel Elda E Comaro Elisa E Talamini Renato R Bidoli Ettore E Turchet Elisa E Crivellari Diana D Dolcetti Riccardo R

BMC cancer 20141215

<h4>Background</h4>Neoadjuvant Chemotherapy (NC) including trastuzumab induces a high rate of pathological Complete Responses (pCR) in patients with locally advanced HER2-overexpressing Breast Cancer (BC), but is penalized by a severe cardiotoxicity when combined with anthracyclines. A phase II study was designed to assess whether an anthracycline-free NC regimen based on the early addition of trastuzumab to paclitaxel may increase the pCR rate without inducing severe cardiotoxicity in patients ...[more]

PMID: 25512030

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Project description:BackgroundThe aim of this study was to compare the efficacy, cardiotoxicity and factors affecting pathologic complete response (pCR) of neoadjuvant chemotherapy (NACT) regimen TCbHP (docetaxel/nab-paclitaxel, carboplatin, trastuzumab and pertuzumab) and AC-THP (doxorubicin, cyclophosphamide followed by docetaxel/nab-paclitaxel, trastuzumab and pertuzumab) for human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer at a retrospective cohort.MethodsThis retrospective study included the patients with HER2+ early-stage breast cancer who received NACT with the regimen TCbHP or AC-THP and then underwent surgery from 2019 to 2022. pCR rate and breast-conserving rate were calculated to evaluate the efficacy of the regimens. Left ventricular ejection fraction (LVEF) from echocardiograms and abnormal electrocardiographs (ECGs) were collected to evaluate the cardiotoxicity of the two regimens. Association between the characteristics of the breast cancer lesions by magnetic resonance imaging (MRI) and the pCR rate were also explored.ResultsA total of 159 patients were enrolled, including 48 patients in the AC-THP group and 111 patients in the TCbHP group. The pCR rate of the TCbHP group 64.0% (71/111) was significantly higher than that of for the the AC-THP group 37.5% (18/48) (P=0.002). Estrogen receptor (ER) status (P=0.011, OR: 0.437, 95% CI: 0.231-0.829), progesterone receptor (PR) status (P=0.001, OR: 0.309, 95% CI: 0.157-0.608) and IHC HER2 status (P=0.003, OR: 7.167, 95% CI: 1.970-26.076) were significantly correlated with the pCR rate. LVEF decreased at 6 and 12 months after treatment in the AC-THP group (P=0.024 and 0.040), which only decreased after 6 months of treatment in the TCbHP group (P=0.048). Post-NACT MRI characteristics including mass features (P<0.001) and enhancement type (P<0.001) were significantly associated with pCR rate.ConclusionsEarly-stage HER2+ breast cancer treated with the TCbHP regimen has a higher pCR rate than the AC-THP group. The TCbHP regimen appears to have lower cardiotoxicity than the AC-THP regimen in terms of LVEF. Mass features and enhancement type at post-NACT MRI significantly associated with the pCR rate of breast cancer patients.

Project description:BackgroundDual-targeted therapy is the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and effective biomarkers to predict the response to neoadjuvant trastuzumab and pertuzumab treatment need further investigation. Here, we developed a predictive model to evaluate the dual-targeted neoadjuvant treatment efficacy in HER2 gene-amplified breast cancer.MethodThis retrospective study included 159 HER2-amplified patients with locally advanced breast cancer who received neoadjuvant trastuzumab, pertuzumab, and chemotherapy. The correlation between clinicopathological factors and pathological complete response (pCR, in the breast and axilla) was evaluated. Patients were randomly assigned into the training set (n=110) and the testing set (n=49). We used an independent cohort (n=65) for external validation. We constructed our predictive nomogram model with the results of risk variables associated with pCR identified in the multivariate logistic analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration curves were employed to assess the nomogram's performance.ResultsWe revealed that the HER2/CEP17 ratio (p=0.001), CD8 levels (p=0.005), and histological grade (p=0.007) were independent indicators for pCR in dual-targeted neoadjuvant treatment after multivariate adjustment. The combined prediction efficacy of the three indicators was significantly higher than that of each single indicator alone. The AUCs were 0.819, 0.773, and 0.744 in the training, testing, and external validation sets, respectively.ConclusionsThe HER2/CEP17 ratio, CD8 levels, and histological grade were significantly correlated with pCR in dual-targeted neoadjuvant treatment. The combined model using these three markers provided a better predictive value for pCR than the HER2/CEP17 ratio, CD8 levels, and the histological grade alone, which showed that an immunological effect partially mediates the predictive impact of neoadjuvant treatment.

Dataset Information

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

Background

Methods

Results

Conclusions

Trial registration

Publications

Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients.

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