Micrometastases of breast cancer

Micrometastases of breast cancer is a subject of some controversy in breast cancer staging and treatment. In fact, the term ‘micro metastasis‘ is not in common use among all breast cancer physicians. It refers to the detection of a tiny amount of malignant breast cancer cells in the axillary lymph nodes and/or the sentinel node.

This page still has great information, I would still use it, however we have created a newer version with more up-to-date information on micro metastasis.

breast-cancer-micrometastasis

In this lymph node, the dark big cells, two side-by-side, are cancer cells.

They won’t survive the normal cancer treatment, or, the immune system might kill those cells anyway.

The prognostic relevance of breast cancer micrometastases remains unclear

The crux of the issue regarding micro metastasis of breast cancer is what to do next if tiny amounts of malignant breast cancer cells are found in a sentinel node following a sentinel lymph node biopsy procedure. The ‘prognostic relevance‘ of the detection of micro metastases and small, isolated breast tumor cells in lymph nodes remains unclear. The presence of breast cancer micro-metastasis in the sentinel lymph node has been associated with less positive disease free and overall survival rates, but these findings are generally too inconsistent to lead to any definitive conclusions.

This page is old. New conclusions might have been made, but whether they stand the test of time, is an open question.

Sentinel lymph node biopsy determines lymph node status with about 95% accuracy

Statistically, the histological status of the sentinel lymph node can predict the status of the axillary lymph nodes with over 95% certainty. Still, micrometastasis of breast cancer in the sentinel lymph is sometimes missed by histological analysis, even with serial sectioning techniques.

breast-cancer-nodal-micrometastasis

The darker purple cells are normal lymph node, the lighter purple cells are the cancer in the node

Adjuvant treatments to lower risk of further breast cancer metastasis do show benefits

Should women in whom a micrometastasis of breast cancer to the sentinel lymph node receive pro-active treatment to limit the possibility of further spread? Some studies now show that women who do receive adjuvant breast cancer therapy when a micrometastasis is detected in a sentinel lymph node do have an increased five-year survival rate. But, with the chances of axillary node metastasis already very low, and considering the ‘morbidity‘ associated with adjuvant treatments, it truly presents a ‘grey area‘ in terms of the best course of action to take.

Adjuvant treatment may include completion axillary lymph node dissection

Typical ‘follow-up‘ treatments after the detection of micrometastasis in the sentinel node might include axillary radiation or completion axillary lymph node dissection. With no followup treatments the rate of axillary lymph node metastasis for women who show micrometastasis in the sentinel node is perhaps 5%, but for women who undergo adjuvant therapy, that rate drops to about 1%. So the question remains, is it worth it? Axillary node radiation can cause skin tightness and other effects in the axilla region, and axillary lymph node dissection surgery can have the risk of causing lymphedema swelling in the arm.

Breast cancer micro-metastasis may be detected by PCR

Another method for detecting micro metastasis, not only in the sentinel node but also in bone marrow and within the blood stream, is through the use of molecular assays. For example, the polymerase chain reaction technique is now being used, where available resources warrant, as another means of detecting micro metastasis of breast cancer undetected by immunohistochemical staining. Essentially, the polymerase chain reaction is a localized ‘cloning‘ technique, which amplifies a few copies of a particular piece of DNA, and then staining these cells with markers such as MUCi, CK19, and CEA. A very tiny metastasis of breast cancer may be undetected in just a small sample, but many thousands of copies of a few cells are then stained, the presence of breast cancer metastasis may become clear.

A parallel issue to the use of breast MRI

The concern over micro metastasis of breast cancer staging in some ways has parallels to the use of MRI in breast cancer screening. As diagnostic tools become more sensitive, leading to findings of smaller and smaller quantities of suspicious abnormalities or finding them in areas which are hidden from other views, these in turn require follow-up procedures, leading in many cases to false positive findings, increased anxiety, and un-needed waste of time and expense. Of course, the goal is to find malignant or potentially malignant cancer cells at the earliest possible time in order to improve treatment and ultimately save more lives. But, many findings are unclear or ‘non-obligate‘, which means that even though a suspicious feature or even malignant cancer cells are found in one location, it does not necessarily mean that it will progress or be found to have metastasized somewhere else. And, even if it did, these changes are usually discovered in follow-up examinations, treated, and cured.

All you pretty much need to know about micro metastasis of the breast is listed above. For further reading, visit this breast cancer staging page.

References

Cao, Q. Wang, S., Liu, X. Lin, L., Zhao, J. Sentinel lymph node micrometastasis detection using immunohistochemistry and reverse transcription-polymerase chain reaction for cytokeratin 19 in breast cancer. Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 11074
Bear. HD. Sentinel node micrometastases and non-sentinel nodes in breast cancer: how much do we need to know? J Clin Oncol. (April 2006);24(12):1788-90.
Houvenaeghel G, Nos C, Mignotte H, et al: Micrometastases in sentinel lymph node in a multicentric study: Predictive factors of non-sentinel lymph node involvement. J Clin Oncol (2006) 24:1814-1822.
Chagpar A, Middleton LP, Sahin AA, et al: Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry. Cancer (2005)103:1581-1586.
de Boer, M., van Deurzen, CHM., van Dijck, JAAM., Borm, GF., van Diest, PL., Adang, EMM., Nortier, JWR., Rutgers, EJT., Seynaeve, C., Menke-Pluymers, MRE., Bult, P., Tjan-Heijnen, VCG., Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer. N Engl J Med (2009); 361:653-663
Mulcahy, N. Sentinel Node eMicrometastases Need Additional Treatment in Breast Cancer of Clinical Oncology (ASCO) 45th Annual Meeting. ASCO 2009.
Alix-Panabières C, Müller V, Pantel K. Current status in human breast cancer micrometastasis. Curr Opin Oncol. (Nov.2007) 19(6):558-63.
Bartlett, J. M. S.; Stirling, D. A Short History of the Polymerase Chain Reaction.(2003) 226. pp. 3–6.
Min CJ, Tafra L, Verbanac KM. Identification of superior markers for polymerase chain reaction detection of breast cancer metastases in sentinel lymph nodes. Cancer Res. 1998;58:4581-4584.
Giuliano AE, Dale PS, Turner RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg. 1995;222:394-399.

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