The prognostic relevance of sentinel lymph node micrometastases and how they should influence treatment decisions has not been firmly established. Recent studies have concluded that early-stage patients with sentinel lymph node micrometastases who do not undergo axillary node dissection have similar survival rates as those who do.
Micrometastases usually are defined as metastases of 2 mm or less in diameter. Now a new study has reported that removing sentinel lymph nodes appears to be sufficient in early breast cancer patients with sentinel node micrometastasis, with no significant negative effects on survival.
Sentinel and axillary lymph node dissection
In sentinel lymph node dissection, the first lymph nodes to which cancer is likely to spread from the primary tumor are removed for biopsy. Axillary lymph node dissection, which is surgery to remove the remaining lymph nodes in the armpit, is recommended for breast cancer patients with positive sentinel lymph nodes. Omitting axillary node dissection greatly reduces the likelihood of lymphedema.
Significance of lymph node micrometastases
Unfortunately, the role of the lymph nodes in facilitating the spread of breast cancer is not fully understood. Are lymph nodes an effective first line of defense against metastasis or merely a way station through which cancer cells and small metastases easily pass? How long do micrometastases remain in the lymph nodes? Is the presence of tumor cells and micrometastases simply a marker of disease stage (implying that other cancer cells and micrometastases have already passed through the same lymph node)? Or does removing micrometastases stop the spread of disease?
Isolated tumor cells
Micrometastases consist either of isolated tumor cells or tiny metastases. The majority of studies that have examined the issue have reported that the existence of undetected isolated tumor cells in sentinel lymph nodes have no impact on survival. This suggests that most isolated tumor cells are not able to survive.
However, there is evidence that, in the case of lobular breast cancer, diffuse single cancer cells or small clusters in sentinel lymph nodes should not be interpreted as isolated tumor cells. This is because lobular breast cancer tends to infiltrate in small linear groups ("Indian file"). Experienced pathologists take this characteristics into account, thereby preventing the inappropriate downstaging of lobular micrometastases to isolated tumor cells.
While there is disagreement on this topic, several studies have reported that true micrometastases (i.e., not isolated tumor cells) have the potential to increase the risk of local recurrence. One 2012 study reported that, among women who did not undergo axillary lymph node dissection, the five-year regional recurrence rates were 2.3% for women with negative sentinel lymph nodes, 2.0% for those with isolated tumor cells, and 5.6% for those with micrometastases. Other factors that increased the likelihood of recurrence were high tumor growth rate, grade 3 tumor (fast growing, proliferative, and aggressive) and negative hormone receptor (ER-/PR-) status. The authors concluded that axillary dissection should be performed in patients with sentinel lymph node micrometastases and unfavorable tumor characteristics.
However, most studies have reported that five-year survival rates are similar for women with sentinel node micrometastases who do and do not undergo axillary node dissection. This suggests that as long as aggressive early-stage disease is treated appropriately with a combination of surgery, radiotherapy and systemic treatment, axillary node dissection is not necessary. In other words, the presence of sentinel micrometastases should be used primarily to stage the disease and inform treatment decisions and not as a trigger for axillary node dissection.
Latest research finds axillary node dissection unnecessary for sentinel node micrometastases
The prospective study referenced at the beginning of this news article was designed to investigate whether omitting axillary lymph node dissection produces similar prognostic information and disease control as proceeding with completion axillary lymph node dissection in early breast cancer patients with micrometastasis at sentinel lymph node biopsy. The study included 233 early-stage breast cancer patients (tumor size < 3.5 cm, clinically lymph node negative, no distance metastases) who were found to have micrometastatic sentinel lymph nodes. The women were randomly assigned either to complete axillary lymph node dissection (control arm) or clinical follow-up only (experimental arm). Participants were followed for a median of five years.
A total of 15 (13.4%) of the 112 women in the completion axillary lymph node dissection group were found to have positive lymph nodes, however with a low tumor burden. One (0.9%) of these women experienced disease recurrence during follow up, compared to 3 (2.5%) of the 119 patients who did not have axillary node dissection. However, there were no statistically significant differences in disease-free survival between the two study groups and no cancer-related deaths. The authors conclude that selective sentinel node excision appears to be sufficient to control locoregional and distant disease in early breast cancer patients with sentinel lymph node micrometastasis, with no significant effects on survival.
Partial breast irradiation might not be ideal in this case
Recent trends that reduce the rate of axillary node dissection while at the same time localizing radiation treatment (e.g., with partial breast irradiation or partial breast brachytherapy) could result in undertreatment of women with lymph node micrometastases. Some observers have even suggested that it is not necessary to attempt to detect lymph node micrometastases. Presumably, radiation to the armpit is effective in eliminating micrometastases and should be undertaken in most such cases. However, this requires good coordination between a patient's surgical and radiation oncologists.
Selected breast cancer studies
Effectiveness of Sentinel Lymph Node Intraoperative Examination in 753 Women With Breast Cancer
Taffurelli M, Montroni I, Santini D, Fiacchi M, Zanotti S, Ugolini G, et al. Effectiveness of Sentinel Lymph Node Intraoperative Examination in 753 Women With Breast Cancer. Annals of Surgery. Ovid Technologies (Wolters Kluwer Health); 2012; 255:976-980 10.1097/sla.0b013e31824def4e
Prognostic impact of isolated tumor cells in breast cancer axillary nodes: single tumor cell(s) versus tumor cell cluster(s) and microanatomic location
Vestjens JH, de Boer M, van Diest PJ, van Deurzen CH, van Dijck JA, Borm GF, et al. Prognostic impact of isolated tumor cells in breast cancer axillary nodes: single tumor cell(s) versus tumor cell cluster(s) and microanatomic location. Breast Cancer Research and Treatment. Springer Science and Business Media LLC; 2011; 131:645-651 10.1007/s10549-011-1771-0
Axillary node staging for microinvasive breast cancer: Is it justified?
Lyons JM, Stempel M, Van Zee KJ, Cody HS. Axillary node staging for microinvasive breast cancer: Is it justified?. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2011; 29:7-7 10.1200/jco.2011.29.27_suppl.7
Effect of axillary dissection for occult detected sentinel nodes metastases on survival: NSABP B-32.
Julian TB, Anderson SJ, Mamounas EP, Krag DN, Weaver D, Ashikaga T, et al. Effect of axillary dissection for occult detected sentinel nodes metastases on survival: NSABP B-32.. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2011; 29:80-80 10.1200/jco.2011.29.27_suppl.80
Iatrogenic displacement of tumor cells to the sentinel node after surgical excision in primary breast cancer
Tvedskov TF, Jensen M, Kroman N, Balslev E. Iatrogenic displacement of tumor cells to the sentinel node after surgical excision in primary breast cancer. Breast Cancer Research and Treatment. Springer Science and Business Media LLC; 2011; 131:223-229 10.1007/s10549-011-1720-y
Occult axillary lymph node metastases do not have prognostic significance in early stage breast cancer
Wu Y, Mittendorf EA, Kelten C, Tucker SL, Wei W, Middleton LP, et al. Occult axillary lymph node metastases do not have prognostic significance in early stage breast cancer. Cancer. Wiley; 2011; 118:1507-1514 10.1002/cncr.26458
Effect of Occult Metastases on Survival in Node-Negative Breast Cancer
Weaver DL, Ashikaga T, Krag DN, Skelly JM, Anderson SJ, Harlow SP, et al. Effect of Occult Metastases on Survival in Node-Negative Breast Cancer. New England Journal of Medicine. Massachusetts Medical Society; 2011; 364:412-421 10.1056/nejmoa1008108
Accurate classification of sentinel lymph node metastases in patients with lobular breast carcinoma
Apple SK, Moatamed NA, Finck RH, Sullivan PS. Accurate classification of sentinel lymph node metastases in patients with lobular breast carcinoma. The Breast. Elsevier BV; 2010; 19:360-364 10.1016/j.breast.2010.02.010