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Breast Cancer

Sentinel Lymph Node Biopsy in Male Patients with Early Breast Cancer

^aDepartment of Breast Surgery, ^bUniversity of Milan School of Medicine, ^cDepartment of Nuclear Medicine, ^dDepartment of Pathology and Laboratory Medicine, ^eBreast Imaging Unit, and ^fScientific Director; European Institute of Oncology, Milan, Italy

Key Words. Male breast cancer • Sentinel lymph node • Surgical treatment

Correspondence: Oreste Gentilini, M.D., Division of Breast Surgery, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy. Telephone: 39-02-57489376; Fax: 39-02-57489780; e-mail: oreste.gentilini{at}ieo.it

Received September 26, 2006; accepted for publication February 28, 2007.

	Learning Objectives

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After completing this course, the reader will be able to:

1. Evaluate the feasibility of sentinel lymph node biopsy in male breast cancer patients.
   
2. Determine which male breast cancer patients can be candidates for sentinel lymph node biopsy.
   
3. Identify the main biological features of male breast cancer and evaluate differences with respect to female breast cancer.
   

	ABSTRACT

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Mastectomy with axillary dissection is still the most commonly recommended procedure for male breast cancer. The aim of this study was to retrospectively evaluate our experience in 32 male patients with early breast cancer who underwent sentinel lymph node biopsy (SLNB) and axillary dissection only in cases of metastases in the sentinel lymph node (SLN). The median age was 58 years (range, 33–80). Lymphoscintigraphy was successful in all patients, with a mean number of visualized SLNs per patient of 1.3 (range, 1–2). At surgery, the identification rate of the SLN was 100%, with a mean number of removed SLNs per patient of 1.5 (range, 1–3). Twenty-six patients had negative SLNs, six patients had positive SLNs. Two patients with metastatic SLNs had additional positive nodes. After a median follow-up of 30 months (range, 1–63) no axillary reappearance of the disease occurred. As with women, we recommend SLNB in male patients with breast cancer and clinically negative axilla.

Disclosure of potential conflicts of interest is found at the end of this article.

	INTRODUCTION

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Male breast cancer is a rare disease, accounting for <1% of all breast cancers and <1% of all annual cancer deaths in men [1]. Because of the low number of affected patients, treatment for breast cancer in men has been extrapolated from treatment protocols for breast cancer in women. Men are more likely than women to have a delay between the onset of symptoms and a diagnosis of breast cancer, possibly because of the limited public awareness of breast cancer in men. This delay in diagnosis may contribute to men presenting at later stages than do women, and nodal involvement is present in up to 60% of male breast cancer patients [2].

Despite recent advances in the application of sentinel lymph node biopsy (SLNB) for axillary staging in female breast cancer patients, modified radical mastectomy remains the standard of care for male breast cancer patients in most institutions. After our previously published experience [3] at the European Institute of Oncology, Milan, Italy, we routinely offer SLNB to all male patients with breast cancer and clinically negative axillary nodes, according to our standard policy applied to women with breast cancer. In the present paper a larger series of male patients with longer follow-up is presented.

	PATIENTS AND METHODS

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Between April 1999 and January 2005, 75 men with breast cancer were treated at the European Institute of Oncology. This is a retrospective analysis of 32 patients with clinically negative axillary lymph nodes who had SLNB. All the other patients received complete axillary dissection because of the presence of clinically positive axillary nodes. Data were prospectively entered into our database and patients were discussed within a multidisciplinary meeting attended by surgeons, medical oncologists, radiation oncologists, and pathologists in order to give recommendations for adjuvant treatment. All patients signed written informed consent for both surgery and data collection in our database.

This paper represents an update of our previously published experience in which 18 patients were included [3]. Therefore, 14 additional patients are reported, with an updated and longer follow-up for the first 18 patients.

The preoperative diagnosis of cancer was documented by fine-needle aspiration cytological examination or core biopsy in 19 patients. The other 13 patients had previously undergone excision of the lump at other centers and were referred to our institute for completion of treatment. All patients underwent complete staging to rule out distant metastases.

According to the standard procedure adopted in our institute for female breast cancer patients [4], lymphoscintigraphy was performed in all patients the day before surgery by injecting colloid particles of human serum albumin labeled with freshly eluted 99mTc (12 MBq), in a volume of 0.2 ml. Radiopharmaceuticals (Nanocoll) were purchased from Nycomed-Amersham-Sorin (Saluggia, Vercelli, Italy). When an excisional biopsy had already been performed, the injection was performed subdermally close to the scar. Planar scintigraphic scans of the involved breast and axillary region in the anterior and anterior-oblique projections were performed.

All patients underwent total mastectomy. To perform the SLNB the s.c tissue of the axillary region was explored in the search for the SLN through the same incision as that made for the mastectomy or using a second axillary incision by employing a gamma detecting probe (Neo2000 GDS, Neoprobe Corp., Dublin, OH). All removed lymph nodes were evaluated intraoperatively according to our routine technique previously reported [4].

Briefly, the SLN was bisected along its major axis, embedded (cut surface up) in an optimal-cutting temperature compound (CellPath, Newton, U.K.), and frozen in isopentane cooled with liquid nitrogen. Lymph nodes <5 mm in diameter were embedded and frozen uncut.

If more than one SLN was obtained from a patient, all the nodes were examined in this way. For each node that was large enough to be cut, 15 pairs of frozen sections, each 4 µm thick, were cut at 50-µm intervals in each half of the node, amounting to about 60 sections per node. If residual tissue was left, additional pairs of sections were cut at 100-µm intervals until the lymph node had been completely sampled. One section in each pair of sections was stained with hematoxylin and eosin. If the result was ambiguous, the other section was intraoperatively stained for cytokeratins by means of a rapid method (EPOS Cytokeratin reagent with horseradish peroxidase; Dako, Copenhagen, Denmark) and stained for the monoclonal antibody MNF116. If metastases were found in the SLN, complete axillary dissection was performed immediately.

Patients were followed with physical examination every 6 months and diagnostic procedures according to their physician's recommendation. Those patients who had not been seen in the previous 6 months were called on the phone to update the follow-up. No patient was lost to follow-up.

	Results

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The median age of the patients was 58 years (range, 33–80). Characteristics of the patients and biological features of the tumors are depicted in Table 1. Lymphoscintigraphy and subsequent imaging successfully identified axillary hot spots in all patients with a mean number of 1.3 (range, 1–2). At surgery, the SLN was identified in all patients, with an identification rate of 100%, and a total of 48 SLNs were removed, all localized in the axillary region, with a mean number of 1.5 SLNs per patient (range, 1–3). Twenty-six patients had negative SLNs. Metastases in the SLN were found in four patients, and micrometastases were found in the remaining two patients. In four of these six patients, the SLN was the only positive node. One patient had one additional positive node, and one had another 15 positive nodes. Table 2 summarizes surgical treatment and adjuvant treatment received. After a median follow-up of 30 months (range, 1–63) one patient died of myocardial infarction and one patient developed prostate carcinoma. No events related to breast cancer or to overt axillary reappearance of the tumor occurred during this period.

	DISCUSSION

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Frequently, breast cancer is diagnosed in men at an advanced stage, making SLNB inappropriate, but still a considerable proportion of patients present with a clinically negative axilla, therefore making them candidates for a less invasive method of axillary staging. In our experience, 32 of 75 patients (42%) underwent SLNB, and 26 (34%) of these 75 patients had negative SLNs and were spared an unnecessary axillary dissection. Although a specific and detailed evaluation was not performed in this cohort of patients, we can state that we had no major complications and that patients widely accepted the procedure with a good quality of life after the operation, as previously demonstrated in their female counterparts [4]. In fact, according to a questionnaire administered to 200 women who entered our published prospective randomized trial, the women who underwent only SLNB had less pain, less numbness, less arm swelling, and better arm mobility than those who underwent axillary-node dissection.

In spite of the small number of patients, the findings of this series of male breast cancer patients compare favorably with data reported in the literature regarding SLNB in female breast cancer patients [4, 8]. In fact, lymphoscintigraphy and subsequent imaging identified one or two hot spots in all patients, and the surgical harvesting of the SLN occurred in all patients, proving that the technique is also simple and reproducible in men. Identification of SLNs also occurred in those patients who had undergone previous excisional biopsy of the tumors, similar to what has been reported in female patients [9]. It is interesting to note that among the six patients with positive SLNs, only two had additional involved axillary nodes, even though we still recommend complete axillary clearance whenever a positive SLN is found.

So far eight papers have been published on SLNB in men [2, 3, 10–15], with only a few patients reported. The detection rate was 100% in all the studies, supporting the idea that SLNB is a reproducible technique. No false negatives were reported in patients who received a backup axillary clearance, but it is impossible to draw conclusions regarding the false-negative rate of SLNB in male patients with breast cancer because of the very limited and inadequate sample of patients.

Because available data on this issue are limited, a randomized trial is needed in this specific setting. However, we acknowledge that this might be impractical because the rarity of the disease would probably make the accrual of patients too long, even within a multicentric study with a high number of participating centers. However, despite the lack of a randomized trial, we can make a number of speculations. First of all, axillary surgery is performed for staging purposes and not with curative intent. Furthermore, tumor biology, prognostic factors, and outcomes have been reported to be equivalent in male and female breast cancer patients, providing a basis for the extrapolation of treatment for men with breast cancer from treatment algorithms for women with this disease [7]. The staging power of the SLNB in women with breast cancer has already been validated [4], and in our experience only three patients of 953 with negative SLNs not submitted to axillary dissection developed axillary reappearance after a median follow-up of 38 months, showing a rate of overt axillary metastases that is lower than expected [16]. A panel of the American Society of Clinical Oncology stated that "although the data are limited,... it is unlikely that SLNB will be any less accurate in men than it is in women" [17]. Moreover, men are at no lower risk for the development of the morbidities associated with axillary dissection. The potential impact for men, though no more or less than for women, may be somewhat different. For men, because they frequently have vocations in which physical activity may be more pronounced, the impact may be more devastating. With all these considerations in mind, at our institute we routinely perform SLNB in selected male patients with early breast cancer and a clinically negative axilla.

	CONCLUSION

Top Learning Objectives Abstract Introduction Patients and Methods Results Discussion Conclusion Disclosure of Potential... References

 
SLNB in male patients with breast cancer is a simple and reliable method for staging the axilla and avoiding unnecessary axillary dissection, and in our opinion it should be considered the procedure of first choice in male patients with breast cancer and clinically negative axilla.

	DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST

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The authors indicate no potential conflicts of interest.

	REFERENCES

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