Immunohistochemistry Not Effective in Early Breast Cancer Survival

From Medscape Education Clinical Briefs

News Author: Nick Mulcahy
CME Author: Désirée Lie, MD, MSEd

08/01/2011;JAMA. 2011;306:385-393 and 436-437.

Study Highlights

• The study involved 126 US centers between 1999 and 2003.
• Included were women with clinical T1 to T2N0M0 invasive breast carcinoma planning to undergo breast-conserving therapy. These women were not pregnant and had a functional status score of 2 or less.
• Excluded were those who required neoadjuvant therapy, those with prepectoral breast implants, women with concurrent bilateral disease, those with previous axillary dissection, and those with breast cancer not amenable to lumpectomy.
• Bilateral bone marrow aspiration biopsy of the anterior iliac crest was performed immediately before SLN dissection and lumpectomy.
• SLN dissection technique was left at the discretion of individual surgeons.
• Whole-breast irradiation specified in the protocol excluded a third supraclavicular field.
• Total dose for the breast was 45 to 50 Gy administered in tangential fields with coplanar posterior borders.
• IHC for both SLN and bone marrow was performed at a central laboratory on H&E-negative SLNs.
• Pathologists blinded to patient status assessed both specimens for occult metastases.
• Of 5210 patients enrolled between 1999 and 2003, SLNs were identified in 5119 (98.3%).
• 69% of patients were older than 50 years, 83.3% had clinical stage I disease, and 80.1% had invasive ductal carcinoma.
• Median duration of follow-up was 6.3 years, and median tumor size was 1.4 cm.
• 81.2% of patients had estrogen-receptor–positive tumors, and axillary lymph node dissection was performed in 107 (2.1%) with H&E-negative SLNs.
• Of 5119 patients in whom an SLN specimen was identified, 1215 (23.7%) had nodes that were H&E-negative, and 3326 (85.2%) had specimens assessed by IHC.
• Of those patients, 349 (10.5%) had occult metastases.
• Of 3413 patients who underwent bone marrow biopsy, 104 (3.0%) had occult metastases by ICC.
• Increasing tumor size was associated with SLN metastases but not with occult bone marrow metastases.
• At follow-up of 6.3 years, there were 435 deaths and 376 women with disease recurrence.
• Less than 10% of women had overdue follow-up.
• The 5-year overall survival rate was 95.7% among women with immunohistochemical-negative SLNs and 95.1% among women with immunohistochemical-positive SLNs, with no significant difference in overall survival benefit (P = .64).
• Rates of disease-free survival were 92.2% and 90.4%, respectively, for women with negative and positive occult SLN metastases, with no significant differences.
• Immunochemically detected metastases in SLNs were not associated with overall survival or disease-free survival benefit.
• Occult bone marrow metastases were positively associated with overall survival rate (mortality rates were 5.0% for ICC-negative bone marrow specimens and 9.9% for ICC-positive bone marrow specimens; P = .01).
• Overall survival rates were 95.0% in women with ICC-negative bone marrow specimens and 90.1% in women with ICC-positive occult bone marrow metastases (P = .01).
• The 5-year disease-free survival rates were 90.8% for ICC-negative occult bone marrow metastases and 86.7% for ICC-positive occult bone marrow metastases.
• However, when multivariate analysis was applied, the difference in mortality was significant only for women older than 50 years and for those with a tumor size greater than 1.0 cm.
• For the 2 groups, the unadjusted HR for overall survival benefit was 1.94, and the adjusted HR was 1.83.
• Adjuvant systemic therapy did not affect the association between occult SLN or bone marrow metastases.
• The authors concluded that among women with breast-conserving therapy for early-stage breast cancer, immunochemical evidence of SLN metastases was not useful in the prediction of overall survival benefit, but occult bone marrow metastases was associated with overall survival benefit.

Clinical Implications

• In women with breast-conserving therapy for early-stage breast cancer, occult metastases in SLNs are not associated with overall survival or disease-free survival benefit.
• In women with breast-conserving therapy for early-stage breast cancer, occult metastases in bone marrow are associated with overall survival benefit for women older than 50 years with a tumor size of 1.0 cm or greater.