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Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer
The American Journal of Surgery 184 (2002) 307–309
Scientific paper
Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer Jovita U. N. Oruwari, M.D.a,b, Maureen A. Chung, M.D., Ph.D.a,b,*, Susan Koelliker, M.D.a,c, Margaret M. Steinhoff, M.D.a,d, Blake Cady, M.D.a,b a
The Breast Health Center, Women and Infants Hospital of Rhode Island, Providence, RI, USA b Department of Surgery, Brown University, 101 Dudley St, Providence, RI 02906, USA c Department of Radiology, Brown University, Providence, RI, USA d Department of Pathology, Brown University, Providence, RI, USA Manuscript received May 6, 2002; revised manuscript May 27, 2002
Presented at the Third Annual Meeting of the American Society of Breast Surgeons, Boston, Massachusetts, April 24 –28, 2002.
Abstract Background: Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. Methods: Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size ⬎1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. Results: From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. Conclusions: In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored. © 2002 Excerpta Medica, Inc. All rights reserved. Keywords: Axillary ultrasonography; Breast cancer; Neoadjuvant chemotherapy
Axillary lymph node metastasis and response to neoadjuvant therapy remain two of the most important prognostic indicators in women with locally advanced breast cancer (LABC). Neoadjuvant therapy utilizes preoperative chemotherapy to shrink the primary tumor and permits in vivo assessment of chemotherapeutic response. Approximately 20% of the time, there may be complete pathological response to the preoperative chemotherapy [1]; in these patients, it is important to have staged the axilla preoperatively. Preoperative modalities available for axillary evaluation * Corresponding author. Tel.: ⫹1-401-453-7540; fax: ⫹1-401-4537785. E-mail address: [email protected]
are clinical examination and ultrasonography. Few studies have reported on the use of axillary ultrasonography guided fine needle aspiration biopsy (US-FNAB) in breast cancer patients. The current study reports on the accuracy of USFNAB for preoperative axillary staging in patients with LABC who were candidates for neoadjuvant therapy.
Methods Patients with LABC treated at The Breast Health Center at Women and Infants’ Hospital between January 1998 and May 2001 were candidates for inclusion in this trial if they had undergone an axillary ultrasonography and US-FNAB.
0002-9610/02/$ – see front matter © 2002 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 2 ) 0 0 9 5 7 - 1
308
J.U.N. Oruwari et al. / The American Journal of Surgery 184 (2002) 307–309
LABC was defined as a primary tumor ⱖ3 cm or cytology positive axillary lymph node. Patients were examined clinically for axillary adenopathy and a core or incisional biopsy of the primary tumor performed to confirm the diagnosis. After clinical examination, sonographic evaluation of the axilla was performed. Lymph nodes were characterized as suspicious based on size ⬎1 cm, absence of a fatty hilum or decreased echogenecity. Lymph nodes suspicious for malignancy were selected for FNAB. If no lymph nodes were sonographically suspicious, the largest lymph node was biopsied. Three passes were made into each lymph node under sonographic guidance and cells aspirated using a 22-gauge needle. Aspirated cells were considered suspicious or positive for malignancy based on the microscopic appearance of clumped epithelial cells with prominent nucleoli and presence of nuclear abnormalities. Patients who met the criteria of LABC were offered neoadjuvant adriamycin-based chemotherapy; a minority of patients in this study chose to proceed directly to surgery. Definitive surgery consisted of breast conservation surgery or mastectomy; all patients had a level I and II axillary lymph node dissection. Patients received comprehensive whole breast or postmastectomy radiotherapy after surgery. Nodal status, as determined by clinical examination, preoperative ultrasonography and US-FNAB, was compared with axillary node dissection and the sensitivity and specificity of each test determined for the group. Subset evaluation was performed for patients who presented with clinically positive and clinically negative axillae.
Results Between January 1998 and May 2001, 26 women presented to the Breast Health Center with LABC. One patient had bilateral breast cancer (T4 lesion in the left breast with a clinically negative axilla and a T1 lesion on the right with a palpable axillary lymph node-cytology positive) for a total of 27 axillae evaluated. The median age of our study population was 48 years (range 31 to 80). The majority of patients had an invasive ductal carcinoma (23 of 27,85%); 1 patient presented with inflammatory breast cancer. Median preoperative tumor size was 4 cm (range 1 to 7 cm). Nineteen patients (70%) presented with palpable lymph nodes that were suspicious for metastatic involvement. Neoadjuvant therapy was initiated in 19 patients (74%) or 20 breasts; 7 women opted to proceed directly to surgery. In the patients who received neoadjuvant therapy, 55% (11 of 20) had breast conservation surgery as compared with 29% of the patients who proceeded directly to surgery. Clinical examination, sonographic axillary evaluation, and US-FNAB were compared with axillary node dissection. Seventy percent of patients had axillary adenopathy on initial evaluation; all of these patients had nodal metastasis confirmed at surgery. Three patients (15%) in the preoperative chemotherapy group had a complete clinical response,
Table 1 Accuracy of clinical examination, ultrasonography, and ultrasoundguided fine needle aspiration for determining axillary status in women with a locally advanced breast cancer
Sensitivity Specificity Accuracy
CE
US
US-FNAB
76 100 78%
91 100 92%
100 100 100%
CE ⫽ clinical examination; US ⫽ axillary ultrasonography; USFNAB ⫽ ultrasound-guided fine needle aspiration biopsy.
whereas 15 (75%) had partial response to chemotherapy. No patient had a complete pathologic response. Eight patients had a clinically negative axilla; 6 of 8 had axillary nodal involvement. The overall sensitivity and specificity of clinical examination was 76% and 100%, respectively (Table 1). Ultrasonographic examination of the axilla was more accurate than clinical examination in staging the axilla preoperatively. Most patients with a palpable lymph node had an abnormal lymph node identified sonographically. In the 8 patients who had a clinically negative examination, 5 had an abnormal lymph node on ultrasonographic examination. Accuracy of ultrasonography in assessing nodal status was 92%, with a sensitivity and specificity of 91% and 100%, respectively. US-FNAB, was the most accurate predictor of nodal metastasis with an accuracy of 100%. All patients who had nodal metastases on surgical dissection had cytology positive for malignant cells. Two patients with negative ultrasonography had positive FNAB. To determine if the absence of palpable lymph nodes altered the accuracy of our tests, the results obtained were compared depending on whether patients had presented with a clinically positive or negative axilla. All patients who had presented with a palpable lymph node had FNAB positive for malignancy. Eight of our patients presented with a clinically negative axilla. Six of these patients had a FNAB positive for malignant cells; these patients had axillary metastasis confirmed at surgery. FNAB was negative for malignancy in 2 patients; these patients had no lymph node metastasis after axillary dissection. These results suggest that US-FNAB is a useful test not only in patients who present with palpable lymph nodes, but also those who present with a clinically negative axillary examination.
Comments The introduction of neoadjuvant chemotherapy for patients with LABC has made it possible to assess in vivo tumor response to chemotherapy. In these patients, it is important to determine nodal status before neoadjuvant therapy since there may be no residual tumor cells in as many as 20% of patients [1]. Preoperative axillary nodal status is usually assessed by clinical examination of the axilla. However, axillary clinical examination is relatively
J.U.N. Oruwari et al. / The American Journal of Surgery 184 (2002) 307–309
inaccurate in patients undergoing neoadjuvant chemotherapy [2] and axillary lymph node dissection, and, to a lesser extent, sentinel node biopsy, remain the gold standard in breast cancer. These surgical modalities are limited by the accompanying morbidities and mortality of surgery and anesthesia. Furthermore, in patients undergoing neoadjuvant therapy, nodal status before therapy is important. If these nodes are surgically removed before neoadjuvant therapy, in vivo nodal chemosensitivity is lost. Noninvasive modalities for determining nodal status have been examined. Sonographic criteria for suspicious lymph nodes include size ⬎5 mm, loss of fatty hilum, cortical hypertrophy and inhomegeneity. Sensitivity and specificity have been reported as 36% to 92% and 69% to 100%, respectively [2– 8]. By using strict criteria of lymph nodes size ⬎1 cm, loss of a fatty hilum and a hypoechogenic parenchyma, the sensitivity and specificity in our study were 91% and 100%, respectively. The addition of fine needle aspiration biopsy to US was first published by Bonnena et al [8] who reported an accuracy rate of 88%. The accuracy of US-FNAB in our study population was 100%; this may be partly attributable to selection of patients with larger cancers or clinically positive axillae. However, even in patients with clinically negative axillae or sonographically benign lymph nodes, US-FNAB had a 100% accuracy rate. In conclusion, US-FNAB has a high sensitivity and specificity for staging the axilla in patients with LABC. It should be utilized in patients with large primary tumors who are
309
being considered for neoadjuvant chemotherapy. Studies are under way to evaluate the accuracy of US-FNAB in women presenting with smaller breast cancers. References [1] Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy of local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997;15:2483–93. [2] Pamilo M, Soiva M, Lavast E. Real time ultrasound, axillary mammography and clinical examination in detection of axillary lymph node metastases in breast cancer patients. J Ultrasound Med 1989;8:115–20. [3] Tate JJT, Lewis V, Archer T, et al. Ultrasound detection of axillary lymph node metastases in breast cancer. Eur J Surg Oncol 1989;15: 139 – 41. [4] de Freitas R, Costa MV, Schneider SV, et al. Accuracy of ultrasound and clinical examination in the diagnosis of axillary lymph node metastases in breast cancer. Eur J Surg Oncol 1991;17:240 – 4. [5] Vaidya JS, Vyas JJ, Thakur MH, et al. Role of ultrasonography to detect axillary node involvement in operable breast cancer. Eur J Surg Oncol 1996;22:140 –3. [6] Yang WT, Ahuja A, Tang A, et al. High resolution sonographic detection of axillary lymph node metastases in breast cancer. J Ultrasound Med 1996;15:241– 6. [7] Verbanck J, Vanderwiele I, Winter H, et al. Value of axillary ultrasonography and sonographically guided puncture of axillary nodes: a prospective study in 144 consecutive patients. J Clin Ultrasound 1997; 25:53– 6. [8] Bonnema J, van Geel AN, van Ooijen B, et al. Ultrasound guided aspiration biopsy for detection of nonpalpable axillary node metastasis in breast cancer patients: new diagnostic method. World J Surg 1997;21:270 – 4.
Scientific paper
Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer Jovita U. N. Oruwari, M.D.a,b, Maureen A. Chung, M.D., Ph.D.a,b,*, Susan Koelliker, M.D.a,c, Margaret M. Steinhoff, M.D.a,d, Blake Cady, M.D.a,b a
The Breast Health Center, Women and Infants Hospital of Rhode Island, Providence, RI, USA b Department of Surgery, Brown University, 101 Dudley St, Providence, RI 02906, USA c Department of Radiology, Brown University, Providence, RI, USA d Department of Pathology, Brown University, Providence, RI, USA Manuscript received May 6, 2002; revised manuscript May 27, 2002
Presented at the Third Annual Meeting of the American Society of Breast Surgeons, Boston, Massachusetts, April 24 –28, 2002.
Abstract Background: Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. Methods: Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size ⬎1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. Results: From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. Conclusions: In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored. © 2002 Excerpta Medica, Inc. All rights reserved. Keywords: Axillary ultrasonography; Breast cancer; Neoadjuvant chemotherapy
Axillary lymph node metastasis and response to neoadjuvant therapy remain two of the most important prognostic indicators in women with locally advanced breast cancer (LABC). Neoadjuvant therapy utilizes preoperative chemotherapy to shrink the primary tumor and permits in vivo assessment of chemotherapeutic response. Approximately 20% of the time, there may be complete pathological response to the preoperative chemotherapy [1]; in these patients, it is important to have staged the axilla preoperatively. Preoperative modalities available for axillary evaluation * Corresponding author. Tel.: ⫹1-401-453-7540; fax: ⫹1-401-4537785. E-mail address: [email protected]
are clinical examination and ultrasonography. Few studies have reported on the use of axillary ultrasonography guided fine needle aspiration biopsy (US-FNAB) in breast cancer patients. The current study reports on the accuracy of USFNAB for preoperative axillary staging in patients with LABC who were candidates for neoadjuvant therapy.
Methods Patients with LABC treated at The Breast Health Center at Women and Infants’ Hospital between January 1998 and May 2001 were candidates for inclusion in this trial if they had undergone an axillary ultrasonography and US-FNAB.
0002-9610/02/$ – see front matter © 2002 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 2 ) 0 0 9 5 7 - 1
308
J.U.N. Oruwari et al. / The American Journal of Surgery 184 (2002) 307–309
LABC was defined as a primary tumor ⱖ3 cm or cytology positive axillary lymph node. Patients were examined clinically for axillary adenopathy and a core or incisional biopsy of the primary tumor performed to confirm the diagnosis. After clinical examination, sonographic evaluation of the axilla was performed. Lymph nodes were characterized as suspicious based on size ⬎1 cm, absence of a fatty hilum or decreased echogenecity. Lymph nodes suspicious for malignancy were selected for FNAB. If no lymph nodes were sonographically suspicious, the largest lymph node was biopsied. Three passes were made into each lymph node under sonographic guidance and cells aspirated using a 22-gauge needle. Aspirated cells were considered suspicious or positive for malignancy based on the microscopic appearance of clumped epithelial cells with prominent nucleoli and presence of nuclear abnormalities. Patients who met the criteria of LABC were offered neoadjuvant adriamycin-based chemotherapy; a minority of patients in this study chose to proceed directly to surgery. Definitive surgery consisted of breast conservation surgery or mastectomy; all patients had a level I and II axillary lymph node dissection. Patients received comprehensive whole breast or postmastectomy radiotherapy after surgery. Nodal status, as determined by clinical examination, preoperative ultrasonography and US-FNAB, was compared with axillary node dissection and the sensitivity and specificity of each test determined for the group. Subset evaluation was performed for patients who presented with clinically positive and clinically negative axillae.
Results Between January 1998 and May 2001, 26 women presented to the Breast Health Center with LABC. One patient had bilateral breast cancer (T4 lesion in the left breast with a clinically negative axilla and a T1 lesion on the right with a palpable axillary lymph node-cytology positive) for a total of 27 axillae evaluated. The median age of our study population was 48 years (range 31 to 80). The majority of patients had an invasive ductal carcinoma (23 of 27,85%); 1 patient presented with inflammatory breast cancer. Median preoperative tumor size was 4 cm (range 1 to 7 cm). Nineteen patients (70%) presented with palpable lymph nodes that were suspicious for metastatic involvement. Neoadjuvant therapy was initiated in 19 patients (74%) or 20 breasts; 7 women opted to proceed directly to surgery. In the patients who received neoadjuvant therapy, 55% (11 of 20) had breast conservation surgery as compared with 29% of the patients who proceeded directly to surgery. Clinical examination, sonographic axillary evaluation, and US-FNAB were compared with axillary node dissection. Seventy percent of patients had axillary adenopathy on initial evaluation; all of these patients had nodal metastasis confirmed at surgery. Three patients (15%) in the preoperative chemotherapy group had a complete clinical response,
Table 1 Accuracy of clinical examination, ultrasonography, and ultrasoundguided fine needle aspiration for determining axillary status in women with a locally advanced breast cancer
Sensitivity Specificity Accuracy
CE
US
US-FNAB
76 100 78%
91 100 92%
100 100 100%
CE ⫽ clinical examination; US ⫽ axillary ultrasonography; USFNAB ⫽ ultrasound-guided fine needle aspiration biopsy.
whereas 15 (75%) had partial response to chemotherapy. No patient had a complete pathologic response. Eight patients had a clinically negative axilla; 6 of 8 had axillary nodal involvement. The overall sensitivity and specificity of clinical examination was 76% and 100%, respectively (Table 1). Ultrasonographic examination of the axilla was more accurate than clinical examination in staging the axilla preoperatively. Most patients with a palpable lymph node had an abnormal lymph node identified sonographically. In the 8 patients who had a clinically negative examination, 5 had an abnormal lymph node on ultrasonographic examination. Accuracy of ultrasonography in assessing nodal status was 92%, with a sensitivity and specificity of 91% and 100%, respectively. US-FNAB, was the most accurate predictor of nodal metastasis with an accuracy of 100%. All patients who had nodal metastases on surgical dissection had cytology positive for malignant cells. Two patients with negative ultrasonography had positive FNAB. To determine if the absence of palpable lymph nodes altered the accuracy of our tests, the results obtained were compared depending on whether patients had presented with a clinically positive or negative axilla. All patients who had presented with a palpable lymph node had FNAB positive for malignancy. Eight of our patients presented with a clinically negative axilla. Six of these patients had a FNAB positive for malignant cells; these patients had axillary metastasis confirmed at surgery. FNAB was negative for malignancy in 2 patients; these patients had no lymph node metastasis after axillary dissection. These results suggest that US-FNAB is a useful test not only in patients who present with palpable lymph nodes, but also those who present with a clinically negative axillary examination.
Comments The introduction of neoadjuvant chemotherapy for patients with LABC has made it possible to assess in vivo tumor response to chemotherapy. In these patients, it is important to determine nodal status before neoadjuvant therapy since there may be no residual tumor cells in as many as 20% of patients [1]. Preoperative axillary nodal status is usually assessed by clinical examination of the axilla. However, axillary clinical examination is relatively
J.U.N. Oruwari et al. / The American Journal of Surgery 184 (2002) 307–309
inaccurate in patients undergoing neoadjuvant chemotherapy [2] and axillary lymph node dissection, and, to a lesser extent, sentinel node biopsy, remain the gold standard in breast cancer. These surgical modalities are limited by the accompanying morbidities and mortality of surgery and anesthesia. Furthermore, in patients undergoing neoadjuvant therapy, nodal status before therapy is important. If these nodes are surgically removed before neoadjuvant therapy, in vivo nodal chemosensitivity is lost. Noninvasive modalities for determining nodal status have been examined. Sonographic criteria for suspicious lymph nodes include size ⬎5 mm, loss of fatty hilum, cortical hypertrophy and inhomegeneity. Sensitivity and specificity have been reported as 36% to 92% and 69% to 100%, respectively [2– 8]. By using strict criteria of lymph nodes size ⬎1 cm, loss of a fatty hilum and a hypoechogenic parenchyma, the sensitivity and specificity in our study were 91% and 100%, respectively. The addition of fine needle aspiration biopsy to US was first published by Bonnena et al [8] who reported an accuracy rate of 88%. The accuracy of US-FNAB in our study population was 100%; this may be partly attributable to selection of patients with larger cancers or clinically positive axillae. However, even in patients with clinically negative axillae or sonographically benign lymph nodes, US-FNAB had a 100% accuracy rate. In conclusion, US-FNAB has a high sensitivity and specificity for staging the axilla in patients with LABC. It should be utilized in patients with large primary tumors who are
309
being considered for neoadjuvant chemotherapy. Studies are under way to evaluate the accuracy of US-FNAB in women presenting with smaller breast cancers. References [1] Fisher B, Brown A, Mamounas E, et al. Effect of preoperative chemotherapy of local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 1997;15:2483–93. [2] Pamilo M, Soiva M, Lavast E. Real time ultrasound, axillary mammography and clinical examination in detection of axillary lymph node metastases in breast cancer patients. J Ultrasound Med 1989;8:115–20. [3] Tate JJT, Lewis V, Archer T, et al. Ultrasound detection of axillary lymph node metastases in breast cancer. Eur J Surg Oncol 1989;15: 139 – 41. [4] de Freitas R, Costa MV, Schneider SV, et al. Accuracy of ultrasound and clinical examination in the diagnosis of axillary lymph node metastases in breast cancer. Eur J Surg Oncol 1991;17:240 – 4. [5] Vaidya JS, Vyas JJ, Thakur MH, et al. Role of ultrasonography to detect axillary node involvement in operable breast cancer. Eur J Surg Oncol 1996;22:140 –3. [6] Yang WT, Ahuja A, Tang A, et al. High resolution sonographic detection of axillary lymph node metastases in breast cancer. J Ultrasound Med 1996;15:241– 6. [7] Verbanck J, Vanderwiele I, Winter H, et al. Value of axillary ultrasonography and sonographically guided puncture of axillary nodes: a prospective study in 144 consecutive patients. J Clin Ultrasound 1997; 25:53– 6. [8] Bonnema J, van Geel AN, van Ooijen B, et al. Ultrasound guided aspiration biopsy for detection of nonpalpable axillary node metastasis in breast cancer patients: new diagnostic method. World J Surg 1997;21:270 – 4.