Axillary lymph node nanometastases are prognostic factors for metastatic relapse in breast cancer patients
Reviewer: John P. Plastaras, MD, PhD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 16, 2006
Presenter: S. Alberti Affiliation: University of Chieti, Chieti, Italy
There is a wide range of outcomes after diagnosis and treatment for early stage breast cancer. The unexplained heterogeneity of outcomes may be a result of inaccurately under staged axillary lymph node metastases
Routine pathologic analysis of axillary lymph nodes may miss very small tumor deposits. Undetected, microscopic lymph node tumor deposits may account for a fraction the observed prognostic diversity.
702 single institution, consecutive patients with 8 years of median follow-up were carefully evaluated for "nanometastases"
whole-axilla dissections from 1989-1993 were examined
pathologic N0 cases were reexamined systematically using step sectioning and cytokeratin immunohistochemistry to reveal pN0(i+) cases
6676 lymph nodes from 377 pN0 whole axillary dissections
250 sections per LN, resulting in 90,000 data points
risk of first adverse events, distant relapse
compare "bona fide" pN0 with pN0(i+), pN1mi, and pN1
Cox regression analysis was used to determine prognostic significance of various factors, including pathologic lymph node status
Sensitivity should be ~90% using 50-150 micron interval with at least 10 lymph nodes dissected
They found 24 patients with previously undetected of nanometastases (pN0(i+))
There was a disproportionate number of lobular carcinoma with nanometastases compared to ductal carcinomas. Lobular carcinoma was associated with isolated tumor cells.
total population: 70% ductal, 16% lobular
nanometastases: 67% ductal, 24% lobular
pN0(i+) status was a strong risk factor for event free survival (p<0.0005) and metastatic relapse using univariate and multivariate analysis
Adverse events were rare in the first 36 months, however, after this point, events started occurring in the pN0(i+) patients, suggesting that the small size of these deposits took time to become clinically evident
Nanometastasis in early stage breast cancer as detected by systematic sectioning and immunohistochemical analysis is a significant negative prognostic factor
The lack of a size threshold for an impact on prognosis indicates that even tiny lymph node deposits are bona fide metastases
Late relapse in patients with nanometastases indicates that long follow-up is required to really assess impact on relapse
These results support inclusion of procedures for nanometastasis detection in TNM pathological staging.
Some have argued that the use of ultra sensitive methods of detection of tumors only reveals clinically insignificant tumor burdens. This paper suggests that any size of metastatic tumor deposit is an indicator of worse prognosis, and that pN0(i+) can not be ignored.
The serial sectioning and immunohistochemical processing of these specimens was painstaking. If this method became standard for all axillary lymph node dissections, there would be a significant impact on the cost of pathologic evaluation for breast cancer treatment
With the rise of sentinel lymph node sampling, the impact of this study is unclear. It supports the thorough systematic sectioning and immunohistochemical analysis of sentinel lymph nodes.
Feb 9, 2011 - Patients who have limited sentinel lymph node metastatic breast cancer have similar survival rates when treated with sentinel lymph node dissection or axillary lymph node dissection, according to a study published in the Feb. 9 issue of the Journal of the American Medical Association.