Prophylactic Irradiation to the Contralateral Breast for BRCA Mutation Carriers Undergoing Treatment for Breast Cancer

NCT00496288 | Unknown Phase 2 DMC

• 1 other identifier: 102/07 (HT4351)
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Women with BRCA germline mutations face a very high risk of developing breast cancer during their lives. It was shown that for carrier patients, breast conservation, comprising of lumpectomy followed by whole breast radiation, was not associated with increased risk of ipsilateral breast cancer recurrence as compared with non carriers (10-15% over 10 years), especially if they also underwent prophylactic oophorectomy. Yet their risk of subsequent contralateral breast cancer was significantly increased, reported as high as 25-30% over 10 years and 40% over 15 years, as compared to 3% and 7% respectively in non carriers. The reduction in ipsilateral disease was attributed to radiation of the affected breast. We propose that for breast cancer patients with BRCA germline mutation that choose to have breast-conserving therapy and refuse prophylactic contralateral mastectomy, prophylactic radiation to the contralateral breast may reduce the rate of subsequent contralateral breast cancer and offer an option for risk reduction.

Conditions

Breast Cancer

Keywords

BRCA mutation; Breast cancer; Prophylactic breast irradiation; Prevention of contralateral breast cancer

Outcome Measures

Primary Outcomes (1)

• Rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast compared with carrier patients that did not receive that treatment.

  To compare the rate of contralateral breast cancer in carrier patients that received prophylactic radiation to the contralateral breast to the rate in carrier patients that did not receive that treatment

  15 years

Secondary Outcomes (2)

• Short and long term adverse effects of prophylactic contralateral breast irradiation.

  15 years

• factors that influence patient's choice of treatment

  15 years

Study Arms (2)

prophylactic irradiation

EXPERIMENTAL

prophylactic contralateral breast irradiation

Radiation: Prophylactic radiation to the contralateral breast

controls

NO INTERVENTION

Those that do not opt for prophylactic irradiation or mastectomy

Interventions

Prophylactic radiation to the contralateral breast RADIATION

The contralateral breast will be treated with 2 tangent fields, using 1.8-2 Gy/fx to a total dose of 50-50.4 Gy. The whole breast will be treated according to traditional guidelines and as described in the RTOG/NSABP B39 study. The heart should be maximally blocked for left sided breasts, included lung tissue should be reduced to minimum. No overlapping field is allowed on the skin between the two breast fields in the midline. Maximal dose should not exceed 110%

prophylactic irradiation

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patient diagnosed with stage I-III breast cancer (AJCC 6), undergoing breast irradiation as part of her adjuvant therapy.
• The patient must be a carrier of a deleterious mutation in BRCA 1/2.
• Age above 30 years.
• The patient may receive any regimen of adjuvant chemotherapy, according to the treating physician. All cycles of chemotherapy must be completed at least 3 weeks prior to the start of radiation therapy.
• The patient may be treated with hormonal therapy before, during or after study entry, according to the guidelines of her treating center.
• The patient must have negative gadolinium based MRI of the contralateral breast, no more than 6 months prior to study entry.
• The patient refused prophylactic contralateral mastectomy.
• The patient is aware that subsequent breast cancer in the irradiated breast will probably mandate mastectomy.
• The patient consent for contralateral prophylactic irradiation. -

You may not qualify if:

• Metastatic breast cancer.
• Previous irradiation of the breast or chest wall.
• Pregnancy.
• No concurrent chemotherapy is allowed
• Patients with active connective tissue diseases are excluded due to the potential risk of significant radiotherapy toxicity.
• Patients who are unable to lie on their back and raise their arms above their heads in the treatment planning position for radiotherapy are excluded -

Sponsors & Collaborators

• Assaf-Harofeh Medical Center: lead
• Rambam Health Care Campus: collaborator
• Tel-Aviv Sourasky Medical Center: collaborator
• Sheba Medical Center: collaborator
• Soroka University Medical Center: collaborator
• Western Galilee Hospital-Nahariya: collaborator
• Rabin Medical Center: collaborator

Study Sites (1)

Assaf-Harofeh Medical Center

Zerrifin, 70300, Israel

RECRUITING

Related Publications (4)

• Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, Harris EE, Gaffney DK, Haffty BG, Dawson LA, Narod SA, Olivotto IA, Eisen A, Whelan TJ, Olopade OI, Isaacs C, Merajver SD, Wong JS, Garber JE, Weber BL. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006 Jun 1;24(16):2437-43. doi: 10.1200/JCO.2005.02.7888. Epub 2006 Apr 24.

  PMID: 16636335 BACKGROUND

• Metcalfe K, Lynch HT, Ghadirian P, Tung N, Olivotto I, Warner E, Olopade OI, Eisen A, Weber B, McLennan J, Sun P, Foulkes WD, Narod SA. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004 Jun 15;22(12):2328-35. doi: 10.1200/JCO.2004.04.033.

  PMID: 15197194 BACKGROUND

• Evron E, Goldberg H, Ben-David MA, Corn BW. Participation in a Novel Trial Assessing Prophylactic Breast Irradiation: The Importance of Input From the Radiation Oncologist. Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):792-794. doi: 10.1016/j.ijrobp.2019.08.004. Epub 2019 Aug 10. No abstract available.

  PMID: 31408668 DERIVED

• Evron E, Ben-David AM, Goldberg H, Fried G, Kaufman B, Catane R, Pfeffer MR, Geffen DB, Chernobelsky P, Karni T, Abdah-Bortnyak R, Rosengarten O, Matceyevsky D, Inbar M, Kuten A, Corn BW. Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer. Ann Oncol. 2019 Mar 1;30(3):412-417. doi: 10.1093/annonc/mdy515.

  PMID: 30475942 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Ella Evron, MD

  Assaf-Harofeh Medical Center

  STUDY DIRECTOR

Central Study Contacts

Ella Evron, MD

CONTACT

972-8-9778144; alaa@asaf.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: July 3, 2007
• First Posted: July 4, 2007
• Study Start: March 1, 2008
• Primary Completion: March 1, 2023
• Last Updated: April 5, 2011

Record last verified: 2008-06

Locations

IL (1)