HER2/neu, Topoisomerase 2a, Estrogen and Progesterone Receptors: Discordance between Primary Breast Cancer and Metastatic Axillary Lymph Node in Expression and Amplification Characteristics

20106 Background: Adjuvant hormonal therapy and trastuzumab are known to be associated with a significant reduction in cancer-related mortality in a subset of women with breast cancer. The treatment decision is usually based on immunohistochemistry (IHC) staining of the primary tumor. We reported here a case of discordance of HER-2/neu overexpression and estrogen receptor status between the primary breast cancer and axillary lymph node with metastasis. Methods: IHC and fluorescence in situ hybridization (FISH) analysis was perfromed for the assessment of HER-2/neu. E-cadherin staining was done on the primary tumor and lymph node with metastasis. Results: A 52 year old woman presented with right breast lump. The imaging studies showed a 5 × 5 cm speculated mass. No other abnormalities were noted. An excision biopsy revealed 3 cm moderately differentiated invasive lobular carcinoma. Subsequently a wider excision and axillary lymph node dissection was done. 2/20 lymph nodes were involved by the cancer. IHC was done in the primary tumor and the lymph node with metastasis. IHC of the primary tumor revealed less than 1% nuclei positive for estrogen receptor (ER), 0% nuclei positive for progesterone receptor (PR), and no HER-2/neu overexpression. IHC of the lymph nodes with metastasis revealed 80% nuclei positive for ER, less than 1% nuclei positive for PR, and equivocal HER-2/neu overexpression. FISH analysis for HER-2/neu gene was done on the primary tumor which revealed no amplification in the tumor nuclei (Her2/CEP17 ratio was 3.6/2.7 = 1.3) whereas FISH analysis on the lymph node section revealed amplification in tumor nuclei (Her2/CEP 17 ratio of 7.3/1.9 = 3.9). E-cadherin staining of the primary breast tumor as well as the lymph node with metastasis revealed no membrane staining of the malignant cells in either section. Conclusions: The unusual occurrence of a divergent IHC profile and FISH analysis results between the primary carcinoma and metastatic carcinoma may be due to a subselection of a malignant clone which were not represented in the section of primary tumor chosen for IHC. Future studies are required to determine the utility of IHC staining of metastatic cells involving the lymph nodes if primary tumor is negative for HER-2/neu & ER. No significant financial relationships to disclose.

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Meta-analysis to determine the clinical effectiveness of axillary lymph node dissection in the treatment of operable primary breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1112 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1112-1112

Author(s):

Doireann Joyce ◽

Aidan Manning ◽

Arnold D. Hill ◽

Malcolm R. Kell ◽

Mitchel Barry

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Lymph Node ◽

Axillary Lymph Node Dissection ◽

Axillary Lymph Node ◽

Primary Breast Cancer ◽

Meta Analysis ◽

Axillary Lymph ◽

Node Dissection ◽

Axillary Surgery

1112 Background: The optimum surgical management of the axilla is controversial. Guidelines mandate axillary surgery in the setting of positive sentinel nodes. However, recent studies have questioned the oncological benefits of this potentially morbid procedure. Therefore a meta-analysis of relevant randomised trials was performed to clarify this issue. Methods: A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without axillary lymph node dissection (ALND) was performed using MEDLINE and available data was cross referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. Results: A total of 4,759 patients with operable primary breast cancer were identified from 13 randomised controlled trials comparing patients with/without ALND. Overall survival favours patients not having ALND (OR = 1.38 (95% CI = 1.12 TO 1.69, p=0.002)) however patients undergoing ALND had similar disease free survival (OR=1.04 (95% CI= 083-1.31, p=0.7). However, though axillary recurrence was uncommon it was significantly less so following ALND (1% vs. 5 %, p<0.05, ALND vs. No ALND). Conclusions: Based on this meta-analysis, ALND does not appear to positively impact on breast cancer survival. Enhanced and targeted adjuvant treatment strategies may facilitate less aggressive axillary surgery. The management and implications of a positive sentinel node need to be re-evaluated in this regard.

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