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Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer: latest evidence and clinical implications.

ABSTRACT: Neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer is exactly the paradigm of targeted therapy and a suitable setting to develop and test rapidly novel therapies in early stages. Moreover, neoadjuvant approaches provide a significant source of tumour tissue to identify molecular heterogeneity and potential predictive biomarkers of response. The addition of trastuzumab to primary chemotherapy revolutionized the treatment of this tumour subtype, increasing pathological complete response rate (pCR) that, even with its limitations, has also been shown to be an early marker of survival in HER2-positive disease. HER2-positive breast cancer is a biological heterogeneous disease with different characteristics and clinical outcomes. Multiple promising anti-HER2 drugs with nonoverlapping mechanisms of action have recently been developed. Combined administration of two different HER2-targeted agents, that is, trastuzumab with lapatinib or pertuzumab, and primary chemotherapy shows enhanced antitumour activity, with an increase in pCR to values never reached in the past. Moreover, results of recent studies show that the combination of targeted therapy alone (dual HER2 blockade with or without endocrine therapy) also has activity in a substantial percentage of patients, eradicating HER2-positive tumours without chemotherapy and with a favourable toxicity profile. It is still necessary to be able to select the appropriate group of patients who can avoid chemotherapy (approximately 25%), and to establish robust predictive biomarkers of response or resistance to the anti-HER2 approach. Neoadjuvant therapy represents an enormous step forward in HER2-positive breast cancer. The results of the most relevant neoadjuvant studies and latest evidence are described in this review, though new questions have emerged.

SUBMITTER: Pernas Simon S

PROVIDER: S-EPMC4206611 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer: latest evidence and clinical implications.

Pernas Simon Sonia S

Therapeutic advances in medical oncology 20140901 5

Neoadjuvant therapy in human epidermal growth factor receptor 2 (HER2)-positive breast cancer is exactly the paradigm of targeted therapy and a suitable setting to develop and test rapidly novel therapies in early stages. Moreover, neoadjuvant approaches provide a significant source of tumour tissue to identify molecular heterogeneity and potential predictive biomarkers of response. The addition of trastuzumab to primary chemotherapy revolutionized the treatment of this tumour subtype, increasin ...[more]

PMID: 25342988

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Project description:IntroductionHR+/HER2- breast cancer (BC) has a much lower pathological complete response (pCR) rate to neoadjuvant chemotherapy (NAC). Therefore, to better stratify the relapse risk for HR+/HER2- non-pCR populations, it is essential to accurate identification new prognostic markers.Materials and methodsThe study retrospectively analyzed 105 stage II-III patients who were diagnosed with HR+/HER2- BC and received NAC followed by breast and axilla surgery between 2013 and 2019 in Sun Yat-Sen University Cancer Center. The Miller-Payne (MP) grading system was used to evaluate pathological responses to NAC. The 70-gene signature was used to classify the prognosis signatures.ResultsAmong the 105 patients, the study demonstrated that larger tumor size and lower progesterone receptor level at baseline and larger tumor size postoperative were statistically significantly associated with worse disease-free survival (DFS) (p = 0.004, p = 0.021, and p = 0.001, respectively). Among 54 patients who underwent the 70-gene assays, 26 (48.1%) had a low-risk signature; 28 (51.9%) patients had a high-risk signature. Patients with poor response (MP grades 1-2) were more likely to with a high-risk 70-gene signature than those with good response (MP grades 4-5). The final analysis showed that DFS was longer in the low-risk group than in the high-risk group [52.4 vs. 36.1 months of the median DFS, hazard ratio (HR) for recurrence, 0.29; 95% confidence interval (CI), 0.10-0.80; p = 0.018]. DFS was longer in the good response (MP grades 3-4) group than in the poor response (MP grades 1-2) group (94.7% vs. 60% of the patients free from recurrence; HR, 0.16; 95% CI, 0.05-0.47; p = 0.037). When stratified by MP grades combined with the 70-gene signature, subgroup analyses showed the good-response low-risk group with the best DFS, whereas the poor-response high-risk group showed the worst DFS (p = 0.048). Due to the short median follow-up time of 34.5 months (5.9-75.1 months), MP grades and the 70-gene signature did not show significant prognostic value for overall survival.ConclusionThe study showed that analysis of MP grades combined with the 70-gene signature with residual NAC-resistant breast samples has a significant correlation with DFS.

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Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer: latest evidence and clinical implications.

Publications

Neoadjuvant therapy of early stage human epidermal growth factor receptor 2 positive breast cancer: latest evidence and clinical implications.

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