Breast-Conserving Surgery and Radiation Therapy in Patients With Multiple Ipsilateral Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer

• Registration Number: NCT01556243
• Lead Sponsor: Alliance for Clinical Trials in Oncology

Brief Summary

RATIONALE: Breast-conserving surgery is a less invasive type of surgery for breast cancer and may have fewer side effects and improve recovery. Radiation therapy uses high-energy x rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial studies how well breast-conserving surgery and radiation therapy work in treating patients with multiple ipsilateral breast cancer

Detailed Description

OBJECTIVES:

Primary

* To assess the local recurrence (LR) rate with breast-conservation in patients with multiple ipsilateral primary breast cancer (MIBC).

Secondary

* To examine the conversion rate to mastectomy secondary to persistent positive margins; poor cosmesis within the first year of attempting breast-conservation surgery (BCS) or inability to satisfy the radiation dose constraints on the boost to the lumpectomy bed of each site of disease.

* To assess whether patients who did not undergo re-excision for close margins (\< 2 mm) have a higher local recurrence (LR) rate than patients for whom negative margins were achieved.

* To assess patient's perception of cosmesis and incidence of breast lymphedema.

* To assess incidence of breast lymphedema

* To examine the type and severity of adverse effects of breast conserving surgery and radiation for women with multiple ipsilateral primary breast cancer (MIBC).

* To examine the radiation-related side effects of whole-breast radiation with a boost to 1 large or \> 1 lumpectomy site.

OUTLINE: This is a multicenter study.

Patients undergo breast-conserving surgery (BCS) with all lesions resected to negative margins using 1 lumpectomy or 2-3 separate lumpectomy incisions at the discretion of the surgeon. Patients receive adjuvant chemotherapy and/or endocrine therapy at the discretion of the treating medical oncologist based on tumor characteristics.

Study Timeline

• Study First Submitted: 2012-03-15
• Study First Submitted QC: 2012-03-15
• Study First Posted: 2012-03-16
• Study Start: 2012-07
• Primary Completion: 2022-06-01
• Study Completion: 2023-04-15
• Results First Submitted: 2023-08-03
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-07
• Last Update Submitted: 2023-11-07
• Results First Posted: 2023-11-30
• Last Update Posted: 2023-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 270

Inclusion Criteria

1. Age ≥ 40 years per National Comprehensive Cancer Network (NCCN) recommendations for breast conservation.

2. Life Expectancy of at least 5 years, excluding diagnosis of breast cancer (Comorbid conditions should be taken into consideration, but breast cancer diagnosis is not a consideration)

3. Female Gender - Men are excluded from this study. Male breast cancer is a rare event.

   Men are rarely candidates for breast conservation surgery due to small breast size. Men are less likely to be candidates for breast conservation surgery if found to have MIBC.

   Men are rarely candidates for breast conservation surgery due to small breast size. Men are less likely to be candidates for breast conservation surgery if found to have MIBC.

4. Foci of Breast Cancer

   4.1 Upon clinical exam and pre-operative imaging by mammogram +/- MRI, two or three foci of biopsy proven breast cancer separated by > 2 cm of normal breast tissue.

   4.2 Foci must include at least one focus of invasive breast carcinoma with another focus of either invasive breast carcinoma or ductal carcinoma in situ (DCIS).

   No more than 2 quadrants with biopsy proven breast cancer.

   4.3 Note: The shortest distance between lesions must be reported on mammogram +/- MRI and eligibility criteria must be met on both, if both are obtained.

   4.4 Note: Patient is eligible for study if lesion is not visualized on all imaging modalities (i.e., any of the lesion(s) is/are visualized on MRI but not on mammogram OR visualized on mammogram but not on MRI).

   4.5 Ultrasound cannot be used to determine patient eligibility; eligibility to be determined by bilateral mammogram +/- MRI only.

   4.6 Fine needle aspirate of the second or third lesion to document malignancy is allowed if the first focus is shown to be invasive by core needle biopsy.

   4.7 Patient may remain on study if, upon pathological assessment, two or three lesions identified on pre-operative imaging represent one contiguous lesion.

5. Patients may be registered AFTER surgery and PRIOR TO radiation therapy if either of the criteria is met:

   5.1 An area of atypia > 2cm from the index lesion excised at the time of cancer operation is upgraded to DCIS or invasive carcinoma thereby identifying MIBC. OR

   5.2 Patient underwent resection of two or three foci of malignancy by breast conservation surgery with a minimum of one invasive focus of breast cancer and a minimum of 2 cm of normal breast tissue between the lesions on final pathology.

6. Mammogram Imaging - Bilateral mammogram ≤ 90 days prior to date of surgery.

   6.1 Note: For patients undergoing more than 1 breast operation, this is the date of the first breast surgery for breast cancer treatment.

7. Staging of Cancer - cN0 or cN1 disease

8. ECOG Performance Status (PS) - 0, 1, or 2.

9. Ability to Complete Questionnaires - Ability to complete questionnaire(s) by themselves or with assistance

10. Ability to Provide Written Informed Consent

11. Willing to Return to Enrolling Institution - Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (the active treatment and observation portions) of the study. Patients are encouraged to return to the enrolling institution; however, patients may receive radiation therapy at a different institution other than the enrolling institution.

Registration

Exclusion Criteria

1. Pregnancy, Nursing and Requirement for Contraception - Pregnant women, nursing women and women of childbearing potential who are unwilling to employ adequate contraception (as determined by the treating physician) are excluded from participation.

   This study involves radiation therapy (WBI) that has known genotoxic, mutagenic and teratogenic effects.

2. Size of Single Focus of Disease on Preoperative Imaging - Largest single focus of disease > 5 centimeters by either mammogram or MRI or both. Note: Measurement of the largest single focus should include any satellite lesions within 1 centimeter of the index lesion.

3. Prior Staging Procedure - Surgical axillary staging procedure prior to first definitive breast operation. Note: FNA or core needle biopsy of axillary node is permitted.

4. Evidence of Metastatic Disease - Clinical or radiographic evidence of metastatic disease

5. Prior History of Breast Cancer - Prior history of ipsilateral breast cancer [DCIS, LCIS (lobular cancer in situ) or invasive]

6. Staging of Cancer - cNX, cN2, or cN3 disease

7. Breast Implants - Breast implants at time of diagnosis. Note: Patients who have had implants previously removed prior to diagnosis are eligible.

8. Systemic Illnesses or Concurrent Disease - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would interfere significantly with whole breast irradiation (such as connective tissue disorders, lupus, scleroderma).

9. Uncontrolled Intercurrent Illness - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

10. Bilateral Breast Cancer - Prior or current LCIS, DCIS or invasive breast cancer in the opposite breast (i.e., bilateral disease is not allowed).

11. Disallowed Prior Treatments - Treatment including radiation therapy, chemotherapy, biotherapy, hormonal therapy for this cancer prior to surgery (i.e., any neoadjuvant chemotherapy or endocrine therapy is not allowed). Patients who undergo surgical resection with breast conservation and then are treated with adjuvant systemic therapy are eligible to enroll prior to the start of radiotherapy.

12. Partial Breast Radiation - Planned partial breast radiation.

13. Known BRCA Mutations - Patients with known BRCA mutations. Patients who are not tested or whose testing result is not returned at the time of registration are not excluded from registering to this study.

14. Other Active Malignancies - Other active malignancy ≤ 5 years prior to registration.

14.1 Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.

14.2 Note: If there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Local Recurrence	5 years	Local recurrence(LR) defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall assessed up to 5 years. The estimated 5-year cumulative incidence of LR will be reported as a percentage of patients expected to experience a LR at 5 years.

Secondary Outcome Measures

Name	Time	Method
Type and Severity of Adverse Effects of Breast-conserving Surgery and Radiation as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0	Up to 30 days post-treatment
Radiation-related Side Effects	17 months	Radiation-related side effects of whole-breast radiation with a boost to 1 large or \> 1 lumpectomy site as assessed by NCI CTCAE version 4.0.
Conversion Rate to Mastectomy	5 years	The conversion rate to mastectomy secondary to persistent positive margins; poor cosmesis within the first year of attempting BCS; or inability to satisfy the radiation dose constraints on the boost to the lumpectomy bed of each site of disease.
Patient's Perception of Cosmesis	24 months	Patient's perception of cosmesis will be assessed at their initial post-operative visit as well as 24 months following completion of WBI using the BREAST-Q subscales: satisfaction with breasts, satisfaction with overall outcome, and physical well-being. Patients registered after surgery will not partake in the pre-operative assessment but will be asked to complete subsequent cosmesis surveys. The total score for each of these subscales will be determined using the BREAST-Q scoring module (http://www.mskcc.org/mskcc/shared/Breast-Q/scoreBQ.html). The BREAST-Q has multiple domains, and each domain score is obtained by transforming the raw scale item responses with the Q-Score software program. Each domain results in an independent score from 0 to 100 (higher scores indicate greater satisfaction or quality of life).

Trial Locations

Locations (350)

CHI Saint Vincent Cancer Center Hot Springs; 🇺🇸 Hot Springs, Arkansas, United States

Epic Care-Dublin; 🇺🇸 Dublin, California, United States

Bay Area Breast Surgeons, Incorporated; 🇺🇸 Emeryville, California, United States

Epic Care Partners in Cancer Care; 🇺🇸 Emeryville, California, United States

UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Contra Costa Regional Medical Center; 🇺🇸 Martinez, California, United States

Alta Bates Summit Medical Center-Summit Campus; 🇺🇸 Oakland, California, United States

Bay Area Tumor Institute; 🇺🇸 Oakland, California, United States

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