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EDITORIALS |
From the Department of Surgery, The University of Alabama, Birmingham, Alabama.
Correspondence: Address correspondence to: Kirby I. Bland, MD, University of Alabama at Birmingham, Department of Surgery, 1808 7th Ave. South, Room 502BB, Birmingham, AL 35233; Fax: 205-975-2199; E-mail: kirby.bland{at}ccc.uab.edu
Three articles that address the utility of sentinel lymph node biopsy and its application for accurate pathologic results and predictors of breast-conservation therapy (BCT) feasibility are included in this issue of Annals of Surgical Oncology. Axillary lymph node dissection (ALND) remains a vital procedure to the breast oncologist to properly stage the axilla in women with primary carcinoma of the breast.1 Women with locally advanced breast cancer (LABC) will, in general, require a modified radical mastectomy when technically eligible or breast conservation approaches after neoadjuvant chemotherapy.2 Further, for the woman contemplating breast conservation surgery with large tumors sans LABC, utilization of neoadjuvant therapy may achieve cytoreductive responses that allow breast conservation to be achieved.3,4
Contemporary practice in breast oncology demands the proper establishment of correct nodal histology (high predictive value; true positive; true negative) to allow the determination of the presence and number of lymph nodes involved with micrometastasis. These pathologic determinations after sentinel lymph node biopsy (SLNB) assist medical oncologists in the planning of proper adjuvant therapy and in the decision algorithm regarding postoperative therapy. Although our data have suggested a survival advantage after axillary node dissection in stage I and II disease,5 this survival advantage needs to be confirmed in prospective randomized trials. Unequivocally, ALND diminishes local-regional recurrence, and the ultimate consequence may be a decrease in distant recurrences. Thus ALND may enhance survival in this small cohort of patients who have retained micrometastasis in the untreated axilla. Further, a large number of positive lymph nodes portends a higher probability of developing systemic breast cancer recurrence.6 Thus accurate pathologic staging is the sine qua non for comprehensive therapy of the axilla to insure proper systemic therapy for confirmed micrometastasis in the high-risk patient. However, ALND is not without morbidity, although complications are rare for experienced surgeons who exercise consistent technical principles with dissection.7,8
Since its broad utilization by Morton et al.9 in 1992 for cutaneous melanoma, sentinel lymph node mapping (SLNM) with Lymphazurin blue dye has had an enlarging application. SLNM has been subsequently used with subcutaneous technetium 99m sulfur colloid (99mTc-sc) by Krag et al.10 in 1993 and by Albertini et al.11 in 1996 in combination with Lymphazurin dye. With the concern that residual lymphatics harboring breast cancer micrometastases may diminish survival, the Z-10 and Z-11 protocols of the American College of Surgeons Oncology Trials Group is evaluating the utility of SLNM in the staging and therapy of T1/T2 cancers with an N0 (clinically negative) axilla.
In many clinics, SLNM is replacing the standard elective ALND because of the minimal morbidity and high frequency of histological accuracy associated with the procedure.12–15 In many centers that use these staging principles, and where the proper technical employment of dye or sulfur colloid is possible, ALND has been abandoned for the sentinel lymph node histologically negative axilla. Unequivocally, when used by the experienced operative team in which step-wise serial sectioning and immunohistochemical evaluation is complete, SLNM is the most accurate detection tool used in breast cancer staging.
Although epidemiologically there is a decrease in the frequency of LABC in the educated cohort of patients who undergo serial mammographic screening, there is increasing use for neoadjuvant induction chemotherapy for LABC. The articles included as an aggregate in this issue of Annals of Surgical Oncology for our readers apply the principles of SLND in this subset of patients with LABC. Because many patients with LABC have typically been excluded from multi-institutional SLNM protocols, the overall accuracy and utility of the technique in these patients have not been fully studied. Early reports16 have suggested that SLND may not be as accurate in the subset of patients with LABC and should not be attempted because of the advanced nodal status and inherent technical problem expected to be generated with SLNM.
Miller et al.17 from the University of Texas at San Antonio attempted to evaluate patients who had received preoperative chemotherapy to determine whether they can undergo accurate SLNM using the combination staging technique with Lymphazurin and technetium 99mTc-sc. Of importance, the report of these San Antonio investigators confirmed that SLNM was successfully performed in more than 85% of these LABC patients who received neoadjuvant therapy. The success rate noted here is equivalent to those published reports involving patients who received no prior chemotherapy and is consistent with the recent series described for the Memorial Group by Cody et al.18 and Cohen et al.19 at the University of Texas M.D. Anderson Cancer Center. Moreover, the authors did not determine differences in the ease of identifying the sentinel node as a function of the type of therapy or number of chemotherapeutic cycles used in the induction process. In the group studied, for the patients who underwent successful mapping, the final pathologic status of the sentinel lymph node accurately reflected the status of the axillary contents for all patients in whom it was identified.
Stearns et al.20 from the Lombardi Cancer Center at Georgetown also assess the feasibility and predictive value of sentinel lymphadenectomy after neoadjuvant induction chemotherapy for LABC. The authors evaluated outcomes for T3 and T4 lesions with any nodal status and included 8 inflammatory and 26 noninflammatory cancers. Only vital blue dye was used for the sentinel lymph node identification, and all patients underwent levels I-II axillary dissections immediately after SLNM. In contrast to the article by Miller et al.,17 Stearns et al. identified a higher frequency of positive nodes in these LABC patients; however, the sentinel lymph node detection rate was identical to that reported by Miller et al. (85% vs. 86% accuracy). There was a 90% concordance between the sentinel lymph node histology and that of the ALND pathology. However, an increased frequency of false-negative sentinel nodes was evident with inflammatory breast cancer. Detection and concordance rates were 89% and 96%, respectively, in the noninflammatory variant (false-negative rate = 6%; negative predictive value = 88%).
The importance of the article by Stearns et al.20 lies in the prediction of accurate histology depending on the clinico-pathologic presentation of the breast cancer (inflammatory vs. noninflammatory histology). Sentinel lymphadenectomy after neoadjuvant therapy in the noninflammatory LABC appears reliable; its utility in inflammatory breast cancer is uncertain.
The article by Newman et al.21 from the M.D. Anderson Cancer Center is a prospective trial conducted for sequential therapy with preoperative paclitaxel- and doxorubicin-based combination therapy in patients with stage I (T>1 cm)/II/IIIA disease to evaluate the role and therapeutic impact for BCT eligibility. In this tumor size–variable mix of 100 consecutive subjects undergoing surgery, median tumor size at presentation was 2.4 cm, and 39% of the entire patient population were considered eligible for BCT. Induction was quite successful in reducing the median tumor size from 2.4 cm to 1.0 cm (P < 0.001); 59% of these breast cancer patients were therefore provided with the opportunity for consideration of BCT. The BCT conversion rate of 34% for eligibility criteria following neoadjuvant application in this BCT ineligible cohort was highly statistically significant. (P < 0.001)
Of additional importance is the fact that the authors confirm that pathology from mastectomy specimens originally deemed breast conservation ineligible would have been BCT eligible in an additional 27% as a consequence of neoadjuvant usage. This incorrect assumption of presumed multicentricity and/or diffuse calcifications is encouraging and will require additional study to identify those individuals who may be reconsidered for BCT after induction therapy. Thus the M.D. Anderson Group confirmed that induction chemotherapy enhances the probability or eligibility for BCT.
Additional questions have been raised and are appropriately addressed by the authors in stating that future efforts for improvement in breast imaging after chemotherapy is essential to enhance accurate prediction for conversion to breast conservation approaches. This appears to be of special concern in the patients presenting with diffuse calcifications or multicentricity, which in multivariant analysis commonly predicted that final pathology would indicate ineligibility for the conservation approach. Of interest, age, tumor size, and prior nodal status, were not predictors statistically of BCT eligibility. The additional finding of lobular histology and its multicentric implications did function as a predictor of the nonfeasibility of a conservative approach.
The implications of these three studies leaves the breast oncologist to ponder the issue of whether future considerations of induction neoadjuvant therapy are advantageous to the patient with LABC. First and foremost, the application of induction therapy may provide the surgeon the opportunity to achieve clear surgical margins with satisfactory cosmetic and functional outcomes that allow the patient to become eligible for breast conservation approaches. With our current imaging technical capabilities, the surgeon must realize that the full potential for adequacy of breast conservation has not yet been realized. Select patients will be committed to total mastectomy because of the inability of mammographers to assess, fully and accurately, the extent of disease before the completion of mastectomy.
In the article by Newman et al.,21 more than one quarter of the patient population in their study would have been eligible for breast conservation if accurate preoperative staging with reimaging had been possible. Further, as the applications of induction chemotherapy become more readily utilized internationally, the implications for accurate histologic staging with SLNM is obvious. Additionally, one may ask: will the estrogen receptor/progesterone receptor, HER2/neu status be altered with induction chemotherapy before SLNM? Prospective trials that address these questions as well as the influence on other pathologic, biochemical, cellular, and molecular markers, and their potential alteration by induction chemotherapy, will undoubtedly be required.
Received for publication January 22, 2002. Accepted for publication February 1, 2002.
REFERENCES
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