Sentinel Node Biopsy in Breast Cancer Patients

Breast Cancer Clinical Trial

Official title:

Cohort Study of Axillary Recurrences and Survival After Negative Negative Sentinel Node Biopsy Without Completion Axillary Clearance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01351974
• Other study ID #: 00-053
• Status: Completed
• Phase: N/A
• First received: May 10, 2011
• Last updated: May 27, 2011
• Start date: September 2000
• Est. completion date: January 2004

Study information

• Verified date: June 2000
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: The National Board of Health and Welfare
• Study type: Observational

Clinical Trial Summary

Axillary lymph node dissection (ALND) was previously the standard axillary staging procedure in breast cancer patients. However, ALND is accompanied by a considerable morbidity, and sentinel lymph node biopsy (SLNB) evolved as a mean to decrease this morbidity. Between September 2000 and January 2004 breast cancer patients were included in the Swedish Sentinel Node Multicenter Cohort Study with the intent of studying axillary recurrence after negative SLNB for patients in which completion ALND were omitted. The patients were followed prospectively and events (local, regional and distant recurrences and deaths) were registered. The primary endpoint was axillary recurrence and secondary endpoints were disease-free, cancer-specific and overall survival.

Description:

Axillary lymph node dissection (ALND) was previously the standard axillary staging procedure in breast cancer patients. However, ALND is accompanied by a considerable morbidity, including seroma formation, lymphedema, neuropathy of the arm with numbness, stiffness, impaired shoulder movement and pain. Sentinel lymph node biopsy (SLNB) has evolved as a mean to decrease this morbidity, and validation studies have demonstrated the accuracy of the method.

With the intent of studying axillary recurrence after negative SLNB for patients in which completion ALND were omitted, consecutive breast cancer patients were included in the Swedish Sentinel Node Multicenter Cohort Study between September 2000 and January 2004.

Patients with a unifocal, invasive breast cancer less than 3 cm in diameter were eligible for enrollment. Exclusion criteria were palpable regional lymph nodes, neoadjuvant chemo- or radiotherapy, pregnancy, known allergic reactions to blue dye or isotope, previous surgery in the ipsilateral breast, and preoperatively diagnosed tumor multifocality.

Surgical procedure:

After the preoperative injection of 40-60 mBq Technetium-99 nanocolloid (Solco Nanocoll®) and 1 ml blue dye (Patent Blue V®), sentinel lymph node (SLN) biopsy was performed. If no sentinel node could be identified, ALND of levels I and II was performed. A completion ALND was also performed in the event of a positive SLN biopsy, if lymph nodes clearly suspicious of metastasis were detected during surgery, or if the primary tumor in the breast was found to be multifocal on pathological examination.

Pathological assessment:

Frozen sections were obtained from each SLN and examined peroperatively. If a sentinel lymph node was smaller than 4 mm, two sections were analyzed separately. Nodes larger than 4 mm were bisected, and two sections from each half analyzed. According to the study protocol, at least three sections were prepared from the sentinel node or each part of a bisected node for definitive histopathology. Sections were stained with haematoxylin and eosin (HE). If no cancer cells were detected, immunohistochemistry (IHC) with cytokeratin antibodies was also performed.

Non-sentinel lymph nodes were examined by routine staining (HE) according to the protocol of each pathology department.

Treatment and follow-up:

Adjuvant treatment combinations were given according to national and regional treatment guidelines, based on tumor characteristics, lymph node status, and surgical treatment. Patients with isolated tumor cells were regarded as lymph node-negative. If breast-conserving surgery had been performed, radiation therapy to the breast was given, which was extended to include the regional lymph nodes in case of axillary lymph node metastases.

Chemotherapy was offered to all patients with lymph node metastases or those with a combination of unfavorable primary tumor characteristics (large tumor, high Elston score, progesterone receptor negativity), after consideration of their general health. Endocrine therapy was offered to all patients with estrogen or progesterone receptor-positive tumors larger than 10 mm. The actual reported adjuvant treatment is controlled for in the analyses.

Patients were followed prospectively. The research protocol postulated an annual follow-up with mammography and clinical examination.

After enrollment, data sheets, including information on primary tumor characteristics, number of sentinel and non-sentinel lymph nodes with and without metastasis, and given adjuvant treatment, were computerized. The study was approved by the ethics committee of Karolinska Institutet, Stockholm, and each region's local ethics committee. All patients gave written informed consent.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3369
• Est. completion date: January 2004
• Est. primary completion date: January 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Primary invasive breast cancer

Exclusion Criteria:

• Preoperatively diagnosed axillary metastases

• Multifocal tumors

• Tumors > 3 cm

• Impalpable tumors

• Earlier resection of the tumor

• Neoadjuvant treatment

• Pregnancy

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Recurrence

Locations

Country	Name	City	State
Sweden	Centre for Clinical Research, Uppsala University	Västerås

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Swedish Cancer Society

Country where clinical trial is conducted

Sweden, 

References & Publications (2)

Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L. Breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. J Clin Oncol. 2010 Jun 10;28(17):2868-73. doi: 10.1200/JCO.2009.24.5001. Epub 2010 May 10. — View Citation

Bergkvist L, de Boniface J, Jönsson PE, Ingvar C, Liljegren G, Frisell J; Swedish Society of Breast Surgeons. Axillary recurrence rate after negative sentinel node biopsy in breast cancer: three-year follow-up of the Swedish Multicenter Cohort Study. Ann — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Axillary recurrence after negative sentinel node biopsy	Prospective follow-up of axillary recurrences in patients with negative sentinel lymph node biopsy in which completion axillary lymph node dissection were omitted	5 years	Yes
Secondary	Survival	Survival (disease-free, cancer-specific and overall) in the sentinel lymph node biopsy cohort	5 years	Yes