Prophylactic Irradiation to the Contralateral Breast for BCAs Patients (PICB)

Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for Breast Cancer Patients With BRCA1, BRCA2 and PALB2 Deleterious Mutation

Breast cancer is the most common cancer in women worldwide, with high mortality. About 5% to 10% of breast cancers are hereditary. Most inherited cases of breast cancer are associated with germline mutations in genes, such as BRCA1, BRCA2 and PALB2. The cumulative breast cancer risk for BRCA1, BRCA2 or PALB2 mutation carriers was high.

Besides the increased breast cancer risk for the inherited mutation carriers, the risk of subsequent contralateral breast cancer for the mutation carriers with breast cancer was also significantly increased. Contralateral prophylactic mastectomy was usually recommended to the breast cancer patients with BRCA mutation. However, many breast cancer patients refused the contralateral prophylactic mastectomy, due to the surgical injury, potential surgical complications, deleteriously affected body image and sexuality.

Solid evidence validated that radiotherapy after surgery resulted in a reduced local recurrence for three times lower than surgery alone. It is thought that radiation would eliminate the microscopic tumors which may already exist in the breast. Thus, we proposed that for the breast cancer patients with BRCA1, BRCA2 or PALB2 deleterious germline mutations, prophylactic irradiation to the contralateral breast may reduce the risk of subsequent contralateral breast cancer. And we would like to further compare the effect of prophylactic irradiation to the published data from traditional prophylactic contralateral mastectomy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Prophylactic contralateral breast irradiation

Detailed Description

Breast cancer is the most common cancer in women worldwide, with high mortality. In the US in 2018, the number of estimated new cases of breast cancer accounted for 30% of all the new cancer cases in women, while the estimated deaths of breast cancer accounted for 14% of all new cancer deaths. In Chinese females, the most commonly diagnosed cancer was breast cancer, accounting for 19% of total cases. And breast cancer was the main 5 most common causes of cancer-related deaths in China.

About 5% to 10% of breast cancers are hereditary. Most inherited cases of breast cancer are associated with germline mutations in two genes: BRCA1 (BRCA1 DNA repair associated) and BRCA2 (BRCA2 DNA repair associated). The cumulative breast cancer risk for BRCA1 or BRCA2 mutation carriers at age 70 years reached as high as 50% in US population and 37% in Chinese population. Benefiting from the next generation sequencing technology, more inherited gene mutations were discovered. Among these new discovered susceptibility genes, PALB2 (Partner and localizer of BRCA2) was associated with high increased risks of breast cancer in both Chinese and US population.

Besides the increased breast cancer risk for the inherited mutation carriers, the risk of subsequent contralateral breast cancer for the mutation carriers with breast cancer was also significantly increased. For contralateral breast cancer in BRCA mutation carriers, the cumulative risk for 10 years after breast cancer diagnosis was as high as 25% and for 20 years reached to 40%, as compared 3% and 12% respectively in non-carriers. Contralateral prophylactic mastectomy was usually recommended to the breast cancer patients with BRCA mutation, as it can absolutely reduce the risk of contralateral primary cancer. However, many breast cancer patients refused the contralateral prophylactic mastectomy, due to the surgical injury, potential surgical complications, deleteriously affected body image and sexuality.

Solid evidence validated that radiotherapy after surgery resulted in a reduced local recurrence for three times lower than surgery alone. It is thought that radiation would eliminate the microscopic tumors which may already exist in the breast. Thus, we proposed that for the breast cancer patients with BRCA1, BRCA2 or PALB2 deleterious germline mutations, prophylactic irradiation to the contralateral breast may reduce the risk of subsequent contralateral breast cancer. And we would like to further compare the effect of prophylactic irradiation to the published data from traditional prophylactic contralateral mastectomy.

• Study Type: Interventional
• Enrollment (Anticipated): 323
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yiding Chen, M.D.; Phone Number: +86-571-87784527; Email: ydchen@zju.edu.cn
• Study Contact Backup: Name: Jiaojiao Zhou; Phone Number: +86-571-87214404; Email: zhoujj@zju.edu.cn

Study Locations

• China
  • Jiangxi
    • Jiangxi, Jiangxi, China
      • Not yet recruiting
      • Department of Breast Surgery, Jiangxi Provincial Cancer Hospital
      • Contact: Zhengkui Sun, M.D.
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Department of Breast Surgery, Obestrics and Gynecology Hospital of Fudan University
      • Contact: Kejin Wu, M.D.
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences
      • Contact: Xiaowen Ding, M.D.
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Department of Breast Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University
      • Contact: Peifen Fu, M.D.
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine
      • Contact: Yiding Chen, M.D.
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University
      • Contact: Weijun Cjen, M.D.
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Department of Oncology, Zhejiang Hospital
      • Contact: Zhibing Wu
• Singapore
  • Singapore, Singapore
    • Not yet recruiting
    • Department of Breast Surgery, Yong Loo Lin School of Medicine, National University of Singapore
    • Contact: Mikael Hartman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Female patients, aged 30-70yrs, diagnosed with stage 0-III breast cancer (NCCN-Breast Cancer V2.2019), undergoing the lumpectomy or mastectomy no more than 1 year. ALND or SLNB should be carried out and the lymph node status should be known.
• Patients with a deleterious germline mutation of BRCA 1/2 or PALB2.
• The patients with no contraindictation for irradiation.
• The patients consent for prophylactic irradiation to the contralateral breast.
• The patient may receive any regimen of adjuvant, neoadjuvant chemotherapy, according to the treating physician. The radiation therapy should start at least 2 weeks after the completion of all the chemotherapy cycles.
• The patient may receive endocrine therapy before, during or after study entry.
• The patient may receive target therapy (Trastuzumab) before, during or after study entry.
• The patient must be eligible for MRI examination of the contralateral breast.
• The patient refused prophylactic contralateral mastectomy and oophorectomy.

Exclusion Criteria:

• Metastatic breast cancer.
• Past history of other cancer besides breast cancer
• Previous irradiation of the breast or chest wall, but not for breast cancer treatment
• Synchronous bilateral breast cancer
• Patients with active connective tissue diseases, pneumonia are excluded due to the potential risk of significant radiotherapeutic toxicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard group; Standard loco-regional treatment without prophylactic contralateral breast irradiation
Experimental: Prophylactic irradiation group; Standard loco-regional treatment with prophylactic contralateral breast irradiation	Radiation: Prophylactic contralateral breast irradiation; The whole contralateral breast will be irradiated once daily, 5 days a week, for 5-6 weeks, using 1.8-2 Gy/fx to a total dose of 45-50 Gy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Contralateral breast cancer	The recurrence rate of contralateral breast cancer	up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overal survival	The length of time from either the date of diagnosis or the start of lumpectomy or mastectomy for primary breast cancer with or without prophylactic irradiation to the contralateral breast	up to 10 years
Ipsilateral loco-regional recurrence	Reappearance of cancer in the ipsilateral preserved breast, chest wall, axillary or supraclavicular lymph nodes.	Every 3-6 months. Follow up will be continued until 10 years after lumpectomy or mastectomy for primary breast cancer.
Distant metastasis	Breast cancer that has spread from the original (primary) breast cancer to distant organs or distant lymph nodes.	up to 10 years
Short time adverse effects	Any short term adverse effects that related to prophylactic irradiation	3 months since radiation treatment start
Long time adverse effects	Any long term adverse effects that related to prophylactic irradiation	up to 10 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Peifen Fu, M.D., Department of Breast Surgery, the First Affiliated Hospital, College of Medicine, Zhejiang University; Principal Investigator: Wenjun Chen, M.D., Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University; Principal Investigator: Kejin Wu, M.D., Department of Breast Surgery, Obsterics and Gynecology Hospital of Fudan University; Principal Investigator: Xiaowen Ding, M.D., Department of Breast Surgery, Cancer Hospital of University of Chinese Academy of Sciences; Principal Investigator: Zhengkui Sun, Department of Breast Surgery, Jiangxi Provincial Cancer Hospital; Principal Investigator: Mikael Hartman, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore; Principal Investigator: Yiding Chen, Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine; Principal Investigator: Jiaojiao Zhou, Departmen of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine; Principal Investigator: Kun Zhang, Departmen of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine; Principal Investigator: Wenhong Xu, Departmen of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine; Principal Investigator: Zhibing Wu, Department of Oncology, Zhejiang Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): December 1, 2029
• Study Completion (Anticipated): December 1, 2029

Study Registration Dates

• First Submitted: May 12, 2020
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: BRCA2; BRCA1; PALB2; Deleterious mutation; Prophylactic irradiation; Contralateral breast cancer risk
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2019-228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No