Preoperative Systemic Therapy vs Upfront Surgery in HER2 Positive Early Breast Cancer

Preoperative Systemic Therapy Versus Upfront Surgery in HER2 Positive Early Breast Cancer: a Prospective Nested Case-control Study in Real World

Preoperative systemic treatment can make patients getting more opportunity for breast-conserving surgery, down-staging and new drugs developing. It is particularly common in human epidermal growth factor receptor 2 (HER2)-over expressing subtype for as high as 40%~60% pCR rate of such a population. Even though, in NSABP B18/27 trials, it had been proved that PST could not improve either disease-free survival (DFS) or overall survival (OS) comparing with postoperatively systemic treatment in total population. We designed a real-world study to investigate the prognosis of anti-HER2 treatment combined with chemotherapy preoperatively versus postoperatively in HER2-positive early breast cancer

Study Overview

• Status: Completed
• Conditions: Breast Cancer; HER2; Preoperative Systemic Treatment
• Intervention / Treatment: Procedure: Preoperative systemic treatment

Detailed Description

Patients with a diagnosis of HER2 positive early invasive breast cancer (cT1-3N0-1M0), from January 2012 to December 2014 were identified and enrolled continuously. The conditions of HER2-positive expression of primary breast cancer were defined as follows: HER2 3+ by immunohistochemical (IHC) method or HER2 2+ by IHC with a further positive result by fluorescence in situ hybridization (FISH). According to the real upfront treatment, all eligible patients were classified as PST group and surgery group. All the patients accepted standard one-year trastuzumab as anti-HER2 treatment combined with chemotherapy. In the PST group, the effect was evaluated according to RECIST1.1 every two cycles, the patients with clinical complete response (cCR) or partial response (PR) would receive the whole course of chemotherapy, those with stable disease (SD) or progressive disease (PD) would receive surgery promptly. After surgery, all patients underwent irradiation and endocrine therapies if necessary. The pCR was defined as the absence of infiltrating residual invasive disease in the breast and axillary nodes. For those non-pCR patients after PST, intensive adjuvant chemotherapy was not routine treatment except patients with progressive disease.The primary endpoint was DFS defined as the time from enrollment to local, regional, or distant recurrences; the occurrence of contralateral breast cancer; or death without evidence of breast cancer. Patients suffered disease progress becoming inoperable before surgery were counted as local treatment failures. The second endpoint was OS defined as the time from study entry to death from any cause. All the endpoints were compared between PST group and upfront surgery group, also further analysis according to pathological response status stratified in PST group.

• Study Type: Observational
• Enrollment (Actual): 1067

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

HER2 positive early invasive breast cancer, using trastuzumab for one year both in neoadjuvant or adjuvant setting.

Description

Inclusion Criteria:

1. HER2 positive
2. early invasive breast cancer (cT1-3N0-1M0)
3. using one-year trastuzumab as anti-HER2 treatment

Exclusion Criteria:

1. Exclude metastasis and recurrent breast cancer
2. using trastuzumab less than a year

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PST; patient accepts preoperative systemic treatment as upfront strategy	Procedure: Preoperative systemic treatment; neoadjuvant chemotherapy combined with trastuzumab as preoperative systemic treatment; Other Names: neoadjuvant treatment
upfront surgery; patient accepts upfront surgery and run postoperative systemic treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival	as the time from enrollment to local, regional, or distant recurrences; the occurrence of contralateral breast cancer; or death without evidence of breast cancer	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	the time from study entry to death from any cause	5 years

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Publications and helpful links

General Publications

• Yu X, Wang C, Zheng Y, Miao B, Hu J, Shao X, Sheng L, Lin J, Ding Y, Xuan H, Ding Y, Gong L, Feng W, Qin C, Chen D, Yu Y, Yang H. Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World. Front Oncol. 2021 Jul 28;11:704842. doi: 10.3389/fonc.2021.704842. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2012
• Primary Completion (ACTUAL): December 30, 2019
• Study Completion (ACTUAL): March 30, 2020

Study Registration Dates

• First Submitted: January 29, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (ACTUAL): January 31, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2020
• Last Update Submitted That Met QC Criteria: September 23, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: breast cancer; HER2; preoperative systemic treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HER2-RWSNeo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data available to others

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No