Dr. Cody presents a very thorough review of the use of sentinel
lymphadenectomy in breast cancer. The article raises key issues
related to a procedure that is becoming more widespread and may
indeed replace axillary dissection for the staging of breast cancer.
The sentinel node concept is based on the assumption that if a tumor
spreads through the lymphatics, the lymph node that first drains the
primary tumor, ie, the sentinel lymph node, will be the node most
likely to harbor metastases. It follows that if the sentinel node is
free of metastases, there is a high likelihood that the rest of the
regional nodal basin will be negative.
The validity of this concept was first demonstrated in melanoma by
Morton and colleagues using intraoperative lymphatic mapping with
blue dye followed by sentinel lymph node dissection. This work
provided a model for the investigation of the sentinel node concept
in other cancers, particularly breast cancer. Many groups have now
published their series of sentinel lymphadenectomy in breast cancer,
using modified techniques and either dye, a radiopharmaceutical, or a
combination of both as the lymphagogue of choice.
The authors Table 1
summarizes the identification, sensitivity, false-negative, and
accuracy rates of the procedure cited in published series. The
authors of all of these series achieved excellent results with their
particular technique and validated these results by an immediate
complete axillary lymph node dissection. As Dr. Cody emphasizes, it
is apparent that, regardless of the agent used, the three different
approaches are quite comparable.
Issues Raised by Memorial Sloan-Kettering Pilot Study
Dr. Cody advocates the use of both radiopharmaceutical and blue dye,
and he describes a pilot study conducted at Memorial Sloan-Kettering
Cancer Center in which all patients underwent lymphoscintigraphy and
injection of blue dye followed by radioguided surgery with a handheld
gamma probe. We will discuss three issues raised by the results of
this pilot study.
First, while lymphoscintigraphy was positive in the axilla in only
75% of cases, the radioisotope allowed the detection of the sentinel
node alone in 88% of cases. As mentioned in this article, it is
interesting that a negative lymphoscintigram does not preclude
successful radiolocalization of the sentinel node at surgery.
Possible reasons for this phenomenon include the following: either
gamma camera imaging or positioning of the patient in nuclear
medicine was not optimal; image timing was miscalculated; or soft
tissue, skin, and air between the hot sentinel node and camera caused
excess scatter and loss of signal that became detectable only by the
handheld gamma probe. These are some of the reasons why the role of
preoperative lymphoscintigraphy as a routine procedure remains
unclear among those who advocate radioguided sentinel lymphadenectomy.
Second, it seems artificial to isolate the sentinel node
identification rate for each method when, in fact, no patient
received either agent alone. Perhaps lymphatic uptake of blue dye is
inhibited after the breast has been injected with a large volume of
saline and radiopharmaceutical.
Finally, we question the inclusion of intradermal injection of
radiopharmaceutical as a recommended option in the treatment
algorithm, given that Codys group did not validate this
technique with a complete axillary dissection in their initial study.
To date, there are few data supporting the intradermal injection of
radiopharmaceutical. This approach needs to be formally evaluated.
At the John Wayne Cancer Institute, we have been proponents of the
use of blue dye alone, while others profess the advantages of
radioisotope injection and localization with a handheld gamma probe,
either alone or together with dye. The debate will continue,
especially as newer agents emerge for detecting the sentinel node. If
a high level of accuracy is achieved with any number of different
techniques, the controversy will become moot.
The success and accuracy of the chosen technique require validation
within each contributing group of the multidisciplinary team. The
practicing surgeon also should be comfortable and familiar with the technique.
Selection of Patients
We agree entirely with Dr. Codys outline of cases selected for
sentinel lymphadenectomy. At the John Wayne Cancer Institute, we
currently include patients with high-grade or extensive ductal
carcinoma in situ (DCIS) in a separate experimental protocol.
It is likely that the detection of axillary metastases will increase
with the use of sentinel lymphadenectomy. Recent data show a 4.6%
incidence of axillary metastases in DCIS, which is much higher than
the historical incidence of roughly 1%. We can theorize that
scrutiny of a single sentinel node using immunohistochemistry may be
easier than searching the primary tumor for an area of microinvasion;
if metastases are identified, microinvasion may be assumed.
Internal Mammary Drainage Detected by Lymphoscintigraphy
Most of the specific clinical issues raised in the article can be
answered only by multicenter clinical trials, such as those presented
in the authors Table 5.
Internal mammary drainage detected by lymphoscintigraphy has
rekindled the debate on managing the internal mammary nodes in breast
cancer. Our practice is to obtain a lymphoscintigram in patients with
primary tumors in the medial hemisphere and then offer standard
axillary sentinel lymphadenectomy using blue dye. The majority of
lesions drain to the axilla, with an occasional lesion draining
solely to the internal mammary chain. In the latter case, the blue
sentinel node will still occasionally be found in the axilla, but, if
not identified, we would perform a complete axillary lymph node dissection.
We have attempted sentinel lymphadenectomy of internal mammary nodes
in a small number of patients but have not pursued the procedure to
any great degree. If this procedure could be refined, identification
of patients with internal mammary node positivity with minimal
surgery would help determine prognosis and adjuvant systemic
therapy.[4,5] Obviously, further investigation into the management of
internal mammary node drainage is warranted.
Importance of Adequate Training
Sentinel lymphadenectomy for breast cancer, by virtue of its less
invasive nature, will become commonplace and will be practiced by
surgeons who may or may not scientifically assess their results. We
stress that, presently, this remains an experimental procedure, and
that surgeons should complete an axillary lymph node dissection to
determine their success at their particular institution. Furthermore,
completion of the trials outlined by Dr. Cody must be supported.
In a recently completed multicenter trial using radioisotope alone,
surgeons were trained in the technique with five cases and then
entered patients into the study. The 11 surgeons who enrolled
patients in the study had a widely discrepant technical success rate
in identifying the hot spot. This result shows that a proper learning
phase is required by all surgeons who are interested in using
sentinel node lymphadenectomy, especially those who wish to
participate in the available trials. When completed, these trials
will hopefully provide answers to the questions posed by Dr. Cody
that all clinicians are struggling with in the management of patients
who have undergone sentinel lymphadenectomy for breast cancer.
1. Morton DL, Wen DR, Wong JH, et al: Technical details of
intraoperative lymphatic mapping for early stage melanoma. Arch Surg
2. O'Hea BJ, Hill AD, El-Shirbiny AM, et al: Sentinel lymph node
biopsy in breast cancer: Initial experience at Memorial
Sloan-Kettering Cancer Center. J Am Coll Surg 186(4):423-427, 1998.
3. Cox CE, Pendas S, Cox JM, et al: Guidelines for sentinel node
biopsy and lymphatic mapping of patients with breast cancer. Ann Surg
227(5):645-651; 651-653 [discussion], 1998.
4. Cody HS, Urban JA: Internal mammary node status: A major
prognosticator in axillary node-negative breast cancer. Ann Surg
Oncol 2(1):32-37, 1995.
5. Veronesi U, Cascinelli N, Greco M, et al: Prognosis of breast
cancer patients after mastectomy and dissection of internal mammary
nodes. Ann Surg 202(6):702-707, 1985.
6. Krag D, Weaver D, Ashikaga T, et al: The sentinel node in breast
cancera multicenter validation study. N Engl J Med