3. Sentinel Node Biopsy, Axillary Dissection

3.1 Phase III Randomized Study of Sentinal Node Dissection with or without Conventional Axillary Dissection in Women with Clinically Node Negative Breast Cancer

Objectives

I. Compare the long term control of regional disease by sentinal node resection vs sentinal node resection followed by conventional axillary dissection in women with breast cancer who are clinically node negative and pathologically sentinal node negative.

II. Compare the effect of these two regimens on the overall and disease free survival of these patients.

III. Compare the morbidity associated with these two regimens in these patients.

IV. Compare the prognostic value of these two regimens in patients who are sentinal node negative or positive by pathology.

V. Determine the potentially increased risk of systemic recurrence in patients who are node negative by pathology.

VI. Determine the technical success rate of sentinal node dissection and the variability of technical success rate in a broad population of surgeons.

VII. Determine the sensitivity of the sentinal node to determine the presence of nodal metastases in these patients.

Participation Criteria

• Resectable invasive adenocarcinoma of the breast.
  
  
• Clinically negative lymph nodes.
  
  
• No positive ipsilateral axillary lymph nodes.
  
  
• No prior removal of ipsilateral axillary lymph nodes.
  
  
• No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven nonmalignant by biopsy.
  
  
• No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude. Tethering or dimpling of the skin or nipple inversion allowed.
  
  
• No bilateral malignancy or mass in the opposite breast that is suspicious for malignancy, unless proven nonmalignant by biopsy.
  
  
• No diffuse tumors or multiple malignant tumors in different quadrants of the breast.
  
  
• No other prior breast malignancy except lobular carcinoma in situ.
  
  
• No breast implants.

All patients receive technetium Tc 99m sulfur colloid injected into normal breast tissue within 1 cm of the primary tumor or biopsy cavity, approximately 0.5-8 hours before surgery. Patients also receive an injection of isosulfan blue dye around the tumor or biopsy cavity after a hot spot is identified with a gamma detector.

Participating Organizations/Investigators
David N. Krag, Chair, Ph: 802-656-5830 National Surgical Adjuvant Breast and Bowel Project

3.2 Phase III Prognostic Study of Sentinel Node and Bone Marrow Micrometastases in Women with Stage I or IIA Breast Cancer (Summary Last Modified 09/2000)

Objectives I.

Estimate the prevalence and evaluate the prognostic significance of sentinel lymph node micrometastases detected by immunohistochemistry in women with stage I or IIA breast cancer.

II. Estimate the prevalence and evaluate the prognostic significance of bone marrow micrometastases detected by immunocytochemistry for the first 3600 women in this patient population.

III. Evaluate the hazard rate for regional recurrence in women whose sentinel nodes are negative by hematoxylin and eosin (H&E) staining.

IV. Provide a mechanism for identifying women whose sentinel nodes contain metastases detected by H&E so that these women can be considered as candidates for ACOSOG-Z0011.

Participation Criteria

• Histologically or cytologically confirmed stage I or IIA (T1 or T2 N0 M0) breast carcinoma diagnosed within 60 days of planned sentinel lymph node dissection.
  
  
• Evidence of noninvasive breast carcinoma by biopsy allowed if final diagnosis is invasive/infiltrating carcinoma.
  
  
• Tumor must not be attached to the skin, underlying muscle or chest wall.
  
  
• No contralateral, supraclavicular, or infraclavicular node involvement.
  
  
• No bilateral breast malignancies.
  
  
• No more than 1 malignant tumor mass present in the same breast.
  
  
• Tumor must be amenable to segmental mastectomy (lumpectomy).
  
  
• Patients with a medial quadrant lesion must have axillary drainage demonstrated by lymphoscintigraphy or intraoperative gamma counting.
  
  
• Surgery:
  
  • No prior ipsilateral axillary surgery (e.g., excisional biopsy of lymph nodes, treatment of hidradenitis).
    
    
  • No prior excisional biopsy cavity exceeding 6 cm in diameter.
    
    
  • No pre-pectoral breast implant. l Subpectoral implant allowed.

Protocol

Patients undergo breast conserving therapy consisting of a segmental mastectomy with planned postoperative whole breast radiotherapy and systemic adjuvant therapy.

Following segmental mastectomy, patients undergo sentinel lymph node dissection (SLND) consisting of ipsilateral axillary sentinel node identification and histopathology.

Patients may undergo bilateral iliac crest bone marrow aspiration to test for presence of micrometastases.

Patients with no sentinel node identified intraoperatively and patients with sentinel node metastasis identified by hematoxylin and eosin (H&E) who choose not to be registered to ACOSOG-Z0011 undergo axillary lymph node dissection involving removal of at least level I and II nodes.

All patients receive whole breast radiotherapy (exclusive of a supraclavicular field) 5 days a week for a maximum of 7 weeks.

Principal Investigator

Armando E. Giuliano, Ph: 310-829-8089 John Wayne Cancer Institute Santa Monica, California

3.3 Phase III Randomized Study of Axillary Lymph Node Dissection in Women with Stage I or IIA Breast Cancer Who Have a Positive Sentinel Node

Objectives

I. Determine whether axillary lymph node dissection (ALND) improves overall survival in patients with stage I or IIA breast cancer.

II. Quantify and compare surgical morbidities associated with sentinel lymph node dissection with or without ALND in these patients.

Participation Criteria

• Must have been registered to and treated under study ACOSOG-Z0010
  
  
• Histologically or cytologically confirmed stage I or IIA breast carcinoma.
  
  
• Tumor must not have been attached to the skin, underlying muscle or chest wall.
  
  
• No contralateral, supraclavicular, or infraclavicular node involvement.
  
  
• No bilateral breast malignancies.
  
  
• No more than 1 malignant tumor mass present in the same breast.
  
  
• No primary malignant breast tumor other than carcinoma.
  
  
• No more than 2 positive lymph nodes.
  
  
• Lumpectomy margins must be free of disease.
  
  
• Relevant lymph nodes must meet the following criteria:
  
  
  • Sentinel node must have been identified and found to contain metastatic disease in protocol ACOSOG-Z0010.
    
    
  • No sentinel or nonsentinel node demonstrating extracapsular tumor extension.
    
    
  • No matted lymph nodes or gross extranodal disease.

• Surgery:
  
  
  • No pre-pectoral breast implant.
    
    
  • Subpectoral implant allowed.
    
    
  • No prior axillary surgery except sentinel node biopsy.

Randomization

3.4 Phase II Study of Sentinel Node Biopsy to Assess Axillary Nodal Status in Patients with Resectable Stage I or II Breast Cancer

Objectives

Compare sentinel node biopsy vs axillary dissection in determining axillary nodal status in patients with resectable stage I or II breast cancer.

Participation Criteria

• Diagnosis of stage I or II invasive breast cancer by triple assessment:
  
  
  • Clinically l Mammogram and/or ultrasound
    
    
  • Fine needle cytology

• No ductal carcinoma in situ.
  
  
• Resectable disease by either wide local excision or mastectomy with axillary dissection.

Protocol

Patients undergo lymphoscintigraphy, which consists of technetium Tc 99m human serum albumin colloid being injected near the tumor. Dynamic imaging using a gamma camera is performed for 20 minutes postinjection and static images are obtained for up to 3 hours postinjection.

Surgery is performed within 24 hours of lymphoscintigraphy. Patients are injected with patent blue V dye near the tumor and a gamma detection probe is used to measure radioactive counts in the sentinel node. Surgery begins within 5 minutes of the patent blue V dye injection.

All lymph nodes that stain blue or have a high radioactive count are removed. The primary breast lump is removed by either wide local excision or mastectomy and the axilla are cleared by standard axillary dissection.

Some patients may only receive patent blue V dye injected as a pilot study. Sentinel lymph node biopsy and axillary dissection proceed as above.

Participating Organizations/Investigators
Gerald Gui, Chair Ph: +44-020-808-2383 Royal Marsden NHS Trust London, England, United Kingdom

3.5 Phase III Randomized Trial of Quadrantectomy with vs without Axillary Lymph Node Dissection in Women Over 65 Years Old with Stage I Breast Cancer

Objectives

I. Assess the efficacy of quadrantectomy vs quadrantectomy with axillary lymph node dissection in patients over age 65 with stage I breast cancer, with efficacy measured by local and distant relapse rates and by overall survival.

II. Study the relationship between biological variables, such as hormone receptor status, cell proliferation, and DNA ploidy, and the clinical outcome of the disease in these patients.

Participation Criteria

Age Range: 65 to 80. n Menopausal status: Postmenopausal. n Histologically confirmed invasive breast cancer. n Clinical stage I (T1, N0, M0) n Hormone receptor status: l Estrogen receptor-positive l Progesterone receptor-positive or -negative

Randomization

Principal Investigator
Ph: 39-2-2390-324 Istituto Nazionale per lo Studio e la Cura dei Tumori Milano (Milan), Italy

3.6 Phase III Randomized Study of Surgery with or without Axillary Node Clearance Followed by Adjuvant Tamoxifen in Elderly Women with Breast Cancer

Objectives

I. Determine local and systemic disease-free survival, ipsilateral axillary relapse, occurrence of postmastectomy syndrome, overall survival, and toxicity of breast surgery with vs. without axillary node dissection in elderly women with clinically operable stage I or IIA breast cancer who subsequently receive adjuvant tamoxifen.

II. Compare the quality of life in patients treated with the two regimens.

Participation Criteria

• Age: 60 and over.
  
  
• Menopausal status: Postmenopausal.
  
  
• Histologically or cytologically diagnosed stage I or IIA breast carcinoma that is considered operable.
  
  
• No prior axillary clearance or biopsy allowed.
  
  
• Complete excisional biopsy without axillary clearance or biopsy allowed.

Randomization

Patients in both arms who undergo breast- conserving surgery may receive optional radiotherapy for 5-6 weeks to the remaining breast tissue, chest, and lung. Upon recurrence in the conserved breast, patients undergo total mastectomy; those in Arm II who experience ipsilateral axillary recurrence undergo surgical excision. Adjuvant tamoxifen and follow up are continued.

Participating Organizations/Investigators
Diana Crivellari, Chair International Breast Cancer Study Group Principal Investigator Ph: 39-434-659206 Centro di Riferimento Oncologico - Aviano Aviano, Italy

3.7 Randomized Study of Drainage of the Axilla after Lymph Node Dissection in Women with Stage I or II Breast Cancer

Objectives

I. Compare high vacuum drainage vs low vacuum drainage vs simple tube drainage in patients undergoing axillary surgery for stage I or II breast cancer.

Participation Criteria

• Diagnosis of resectable stage I or II breast cancer.
  
  
• Planned primary surgery of level II or III axillary dissection in association with one of the following:
  
  
  • Wide local excision (may be done through separate incision).
    
    
  • No breast surgery.
    
    
  • No immediate breast reconstruction using implants, latissimus dorsi, or rectus abdominus myocutaneous flaps at primary operation.

• No prior axillary surgery.

Randomization

Patients undergo axillary dissection, then are randomized to one of three axillary drainage systems.

All drains are removed when daily volumes are below 30 mL or at 5 days after surgery, regardless of drain volume.

Gerald Gui, Chair
Ph: +44-020-808-2383 Royal Marsden NHS Trust

Anthony G. Nash, Principal Investigator
Ph: 0181-642-6011 Royal Marsden Hospital Sutton, England, United Kingdom

N.P.M. Sacks, Principal Investigator
Ph: 0207-808-2782 Royal Marsden NHS Trust London, England, United Kingdom

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