A single-arm confirmatory study to evaluate the efficacy of nonsurgical therapy for HER2-positive early breast cancer with clinical complete response after primary systemic therapy (JCOG1806: AMATERAS-BC study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS601-TPS601
Author(s):  
Tomomi Fujisawa ◽  
Tadahiko Shien ◽  
Hiroji Iwata ◽  
Hideo Shigematsu ◽  
Taro Shibata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Physical Examination ◽  
Early Breast Cancer ◽  
Surgical Therapy ◽  
Systemic Therapy ◽  
Complete Response ◽  
Breast Mass ◽  
Her2 Positive ◽  
Primary Systemic Therapy

TPS601 Background: The surgical treatment is a standard therapy for early breast cancer (EBC) after primary systemic therapy (PST). In more than half of HER2 positive (HER2(+)) breast cancer, pathological complete response (pCR) is achieved by PST with HER2 inhibitors and chemotherapy. In addition, hormone receptor (HR) negative HER2(+) (HR(-)HER2(+)) subtype has higher concordance between pCR and clinical complete response (cCR) before surgery than other subtypes, especially in EBC. However, non-surgical therapy is not an option for EBC with cCR after PST because of few evidence. We planned single arm confirmatory study to evaluate the efficacy and safety of the non-surgical therapy for HR(-)HER2(+) EBC with cCR after PST. Methods: The key eligibility criteria are as follows: 1) Histologically confirmed as invasive ductal carcinoma of breast, HR(-)HER2(+). 2) cT1-2, N0, M0 (UICC 8th). 3) No ipsilateral BC. 4) Women aged 20-74 years. 5) ECOG performance status 0 or 1. 6) Written informed consent. HER2 inhibitors (trastuzumab and pertuzumab) and cytotoxic drugs as PST are administered for all patients (pts). After completion of PST, cCR is diagnosed by breast imaging and physical examination. cCR is defined as 1) Not palpable breast mass by physical examination, 2) No enhanced breast mass by enhanced MRI, 3) No breast mass by sonography. After diagnosis of cCR, conventional radiotherapy for whole breast and boost radiation for tumor bed are mandatory, followed by pertuzumab and trastuzumab every 3 weeks during 9 months. In non-cCR cases, surgical resection is performed and adjuvant therapy are not specified. The primary endpoint is a distant metastasis-free survival (DMFS) at 3 year, the secondary endpoints are DFS, OS, RFS, proportion of local recurrence, and cosmetics outcome. Given that the threshold and expected of DMFS at 3-year is 93% and 98% with a significance level 2.5% (one sided) and 80% power, 170 cCR cases are required. Assuming half of HER2 pts reach to cCR, 350 pts are required as sample size started PST. Enrollment launched January, 2020 and 57 pts are enrolled as of January 12, 2021. Recent reports found that HR positive HER2(+) subtype has higher concordance between pCR and cCR by adding needle biopsy in the diagnosis, so we are planning to include HR positive subtype in this trial. This clinical trial has been registered at Japan Registry of Clinical Trials as jRCTs031190129 and conducted by the Japan Clinical Oncology Group (JCOG) Breast Cancer Study Group under public fund (National Cancer Center Research and Development Fund). Clinical trial information: jRCTs031190129.

scholarly journals Omitting surgery for early breast cancer showing clinical complete response to primary systemic therapy

2020 ◽  
Vol 50 (6) ◽  
pp. 629-634
Author(s):  
Hideo Shigematsu ◽  
Tomomi Fujisawa ◽  
Tadahiko Shien ◽  
Hiroji Iwata
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Local Control ◽  
Systemic Therapy ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Local Control Rate ◽  
Primary Systemic Therapy ◽  
Primary Tumor Site ◽  
Clinical Complete Response

Abstract Breast cancer is highly sensitive to systemic therapy. High probability of pathological complete response suggests a clinical question that omitting surgery is an effective alternative to surgery in breast cancer showing clinical complete response to primary systemic therapy. However, the validity of omitting surgery for early breast cancer after primary systemic therapy has not been sufficiently established; thus, even if pathological complete response is expected in patients showing clinical complete response, excision of the primary tumor site remains the standard treatment of breast cancer. Inappropriate omitting surgery increases the incidence of local recurrence, which can be the risk of a subsequent distant metastasis and reduced overall survival. To achieve acceptable local control rate, omitting surgery should be investigated in patients with early breast cancer where a high percentage of pathological complete response, a high concordance rate between clinical complete response and pathological complete response and an acceptable local control rate are expected. This review presents concept and ongoing clinical trials for omitting surgery for patients with breast cancer showing clinical complete response to primary systemic therapy.

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

scholarly journals Minimally Invasive Complete Response Assessment of the Breast After Neoadjuvant Systemic Therapy for Early Breast Cancer (MICRA trial): Interim Analysis of a Multicenter Observational Cohort Study

2020 ◽  
Author(s):  
Ariane A. van Loevezijn ◽  
Marieke E.M. van der Noordaa ◽  
Erik D. van Werkhoven ◽  
Claudette E. Loo ◽  
Gonneke A. O. Winter-Warnars ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Triple Negative ◽  
False Negative ◽  
False Negative Rate ◽  
Complete Response ◽  
Ultrasound Guided ◽  
Her2 Positive ◽  
Surgical Specimen ◽  
Neoadjuvant Systemic Therapy

Abstract Background The added value of surgery in breast cancer patients with pathological complete response (pCR) after neoadjuvant systemic therapy (NST) is uncertain. The accuracy of imaging identifying pCR for omission of surgery, however, is insufficient. We investigated the accuracy of ultrasound-guided biopsies identifying breast pCR (ypT0) after NST in patients with radiological partial (rPR) or complete response (rCR) on MRI. Methods We performed a multicenter, prospective single-arm study in three Dutch hospitals. Patients with T1–4(N0 or N +) breast cancer with MRI rPR and enhancement ≤ 2.0 cm or MRI rCR after NST were enrolled. Eight ultrasound-guided 14-G core biopsies were obtained in the operating room before surgery close to the marker placed centrally in the tumor area at diagnosis (no attempt was made to remove the marker), and compared with the surgical specimen of the breast. Primary outcome was the false-negative rate (FNR). Results Between April 2016 and June 2019, 202 patients fulfilled eligibility criteria. Pre-surgical biopsies were obtained in 167 patients, of whom 136 had rCR and 31 had rPR on MRI. Forty-three (26%) tumors were hormone receptor (HR)-positive/HER2-negative, 64 (38%) were HER2-positive, and 60 (36%) were triple-negative. Eighty-nine patients had pCR (53%; 95% CI 45–61) and 78 had residual disease. Biopsies were false-negative in 29 (37%; 95% CI 27–49) of 78 patients. The multivariable associated with false-negative biopsies was rCR (FNR 47%; OR 9.81, 95% CI 1.72–55.89; p = 0.01); a trend was observed for HR-negative tumors (FNR 71% in HER2-positive and 55% in triple-negative tumors; OR 4.55, 95% CI 0.95–21.73; p = 0.058) and smaller pathological lesions (6 mm vs 15 mm; OR 0.93, 95% CI 0.87–1.00; p = 0.051). Conclusion The MICRA trial showed that ultrasound-guided core biopsies are not accurate enough to identify breast pCR in patients with good response on MRI after NST. Therefore, breast surgery cannot safely be omitted relying on the results of core biopsies in these patients.

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