LETTER TO THE EDITOR
Recurrence Rates in Breast Cancer Patients Who Had Sentinel Lymph Node Biopsy Alone Versus Completion Axillary Lymph Node Dissection: A 7-Year Clinical Follow-Up Study To the Editor: Lymph node status is known to be the most important prognostic factor in breast cancer. Sentinel lymph node (SLN) biopsy has been standard of care for clinically node negative (cN0) patients. In the past few years, a paradigm shift has occurred with the publication of American College of Surgeons Oncology Group (ACOSOG) Z0011 trial (1), which advocated for conservative management in even SLN positive patients. The Z0011 trial suggested completion axillary lymph node dissection (cALND) was not necessary in T1 and T2 breast carcinoma patients, since survival and recurrence rates did not appear to differ between those who had cALND versus those who had SLN biopsy alone (SLNB), up to two positive SLN, and adjuvant radiation therapy. We explored the validity and applicability of ACOSOG Z0011 trial to our own patient population. Our retrospective study identified a total of 302 patients with invasive breast cancer at our institution (2003– 2007), after obtaining institutional research board approval. Patients with invasive breast cancer without neo-adjuvant chemotherapy, those with complete pathology information, and clinical follow-up at a minimum of 24 months were included. Patients were excluded if they had cALND without SLNB or clinically multiple positive and/or matted axillary lymph nodes. Median clinical follow-up was 6.8 years (range 28– 115 months). From SLN negative group, mean age was 57.9 years (range 31–86); 71% postmenopausal and 28% premenopausal patients. Median tumor size was 1.5 cm. Pathologic tumor stages were 70% pT1, Address correspondence and reprint requests to: Sophia K. Apple, MD, 10833 Le Conte Ave CHS 1P-244, Los Angeles, CA 90098-1732, USA, e-mail: [email protected] DOI: 10.1111/tbj.12347 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 6, 2014 666–668
29% pT2, and 1% pT3 cases. From SLN positive group, mean age was 54.7 years (range 27–80); 58% postmenopausal and 41% premenopausal patients. Median tumor size was 2.3 cm. Pathologic tumor stages were 39% pT1, 50% pT2, 10% pT3, and 1% pT4 cases. SLN negative and positive patients comprised 69% and 31% of the cohort, respectively (See Fig. 1). Patients with SLN negative, ITC, micrometastasis, and macrometastasis undergoing cALND had nodal involvement as follows: 8% (2 of 24), 14% (one of seven ITC), 38% (five of 13 micrometastasis), 60% (30 of 50 macrometastasis), respectively. The risk of having positive non-SLNs in cALND was approximately 12 times higher in a patient with positive SLN than in a patient with negative SLN (Odds Ratio = 11.667; 95% CI 3.211 to 42.391, p < 0.0001). Local-regional recurrence and distant metastasis (LR/DM) were investigated. In SLN negative cases, LR/DM rates in cALND versus SLNB were 12.9% versus 6.7%, respectively (p = 0.266). In SLN positive cases, LR/DM in cALND versus SLNB were 14.2% versus 3.3%, respectively (p = 0.159). Within SLN negative cases only, LR/DM in cALND versus SLNB were 16.7% versus 6% (p = 0.082). Within SLN ITC group, LR/DM in cALND versus SLNB were 0% versus 16.7% (p = 0.508). Within SLN micrometastatic group who underwent cALND or SLNB, no patient experienced LR/DM. Lastly, in the SLN macrometastatic group with cALND versus SLNB, LR/DM were18% versus 4.5%, respectively (p = 0.161). None of the differences in LR/DM between cALND or SLNB were statistically significant. LR/DM and mortality rates between SLN negative and SLN positive patients were not significantly different, 8% versus 11%, respectively (p = 0.381). As SLNB has been shown to be noninferior to cALND in SLN negative patients (1,2), the role of
Letter to the Editor • 667
Total Patients (n = 302)
SLN Negative n = 209 (69%)
SLN Positive n = 93 (31%)
cALND n = 31/209 (15%)
SLN Biopsy only n = 178/209 (85%)
SLN Neg n = 24
SLN Neg (n =166) SLN ITC (n = 12)
SLN ITC n=7
ALN Neg (n = 22) ALN mac (n = 2)
ALN Neg (n = 6) ALN mac (n = 1)
cALND n = 63/93 (68%)
SLN mi n = 13
SLN Biopsy only n = 30/93 (32%)
SLN mac n = 50
ALN Neg (n = 8) ALN mi (n = 1) ALN mac (n = 4)
SLN mi (n =8) SLN mac (n = 22)
ALN Neg (n = 20) ALN mi (n= 1) ALN mac (n = 29)
Figure 1. Study flowchart detailing patients in each arm with regard to sentinel nodal status (SLN negative VS SLN positive), surgical management (cALND VS SLN Biopsy), and axillary lymph node status where applicable. (ALN = axillary lymph node; neg = negative; ITC = isolated tumor cells; mi = micrometastasis; mac = macrometastasis.)
cALND is being further explored in SLN positive patients. Our results confirm that presence of metastatic tumor in SLN strongly predicts positive nonSLNs, with 12 times higher risk in those with positive versus negative SLNs. However, LR/DM did not differ significantly between patients with cALND and those with SLNB alone, even in our cohort with a median clinical follow-up of 6.8 years. The natural question then becomes: does cALND reduce recurrence rates in sentinel node positive disease? Bilimoria et al. observed 97,314 patients, who underwent SLNB (23% and 55% of micrometastatic and macrometastatic tumor, respectively) (3) and found that recurrence and survival rates were comparable to those who had cALND. Subsequently, landmark trials have supported foregoing cALND in early stage breast cancer (1,4,5). These strongly argued for a limited group of SLN positive patients to forego cALND and to prevent subsequent morbidity. One of the strengths in our study is that observations were recorded despite differences in surgical, medical, and radiation management approaches, and recurrence rates still appeared comparable between cALND and SLNB alone groups. Another positive feature was longer clinical follow-up and strict minimum follow-up of 24 months. Furthermore, availability of detailed pathologic characterization of primary tumor and sentinel and axillary nodal tumor burden allowed us to specifically address the question of nodal status
and recurrence rates. Limitations of this retrospective study include the relatively small number of patients and disease-related events. The growing body of literature advocates for SLNB alone as adequate intervention in many patients and proposes that the argument for cALND is diminishing. Our study supports this paradigm shift; however, an even longer clinical follow-up will be needed to confirm these observations. Until then, the medical community must continue to engage in the discussion and provide evidence-based insights for the maximal benefit of each of our patients. Disclosure No conflicts of interest or financial disclosures. Maria E. Vergara-Lluri, MD* Raquel Prati, MD† Jeffrey Petersen, MD‡ Yasaman Omidvar, MD§ Sophia K. Apple, MD‡ *Department of Pathology, USC, Los Angeles, California; † Department of Surgery, UCLA, Los Angeles, California; ‡ Department of Pathology, UCLA, Los Angeles, California; and §Department of Internal Medicine, UCLA, Los Angeles, California
668 • letter to the editor
REFERENCES 1. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010; 252:426–32; discussion 32-3. 2. Kell MR, Burke JP, Barry M, Morrow M. Outcome of axillary staging in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2010;120:441–7. 3. Bilimoria KY, Bentrem DJ, Hansen NM, et al. Comparison of sentinel lymph node biopsy alone and completion axillary lymph
node dissection for node-positive breast cancer. J Clin Oncol 2009;27:2946–53. 4. Yi M, Giordano SH, Meric-Bernstam F, et al. Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone versus SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database. Ann Surg Oncol 2010;17(Suppl 3):343–51. 5. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA: J American Medi Assoc 2011;305:569–75.
Recurrence Rates in Breast Cancer Patients Who Had Sentinel Lymph Node Biopsy Alone Versus Completion Axillary Lymph Node Dissection: A 7-Year Clinical Follow-Up Study To the Editor: Lymph node status is known to be the most important prognostic factor in breast cancer. Sentinel lymph node (SLN) biopsy has been standard of care for clinically node negative (cN0) patients. In the past few years, a paradigm shift has occurred with the publication of American College of Surgeons Oncology Group (ACOSOG) Z0011 trial (1), which advocated for conservative management in even SLN positive patients. The Z0011 trial suggested completion axillary lymph node dissection (cALND) was not necessary in T1 and T2 breast carcinoma patients, since survival and recurrence rates did not appear to differ between those who had cALND versus those who had SLN biopsy alone (SLNB), up to two positive SLN, and adjuvant radiation therapy. We explored the validity and applicability of ACOSOG Z0011 trial to our own patient population. Our retrospective study identified a total of 302 patients with invasive breast cancer at our institution (2003– 2007), after obtaining institutional research board approval. Patients with invasive breast cancer without neo-adjuvant chemotherapy, those with complete pathology information, and clinical follow-up at a minimum of 24 months were included. Patients were excluded if they had cALND without SLNB or clinically multiple positive and/or matted axillary lymph nodes. Median clinical follow-up was 6.8 years (range 28– 115 months). From SLN negative group, mean age was 57.9 years (range 31–86); 71% postmenopausal and 28% premenopausal patients. Median tumor size was 1.5 cm. Pathologic tumor stages were 70% pT1, Address correspondence and reprint requests to: Sophia K. Apple, MD, 10833 Le Conte Ave CHS 1P-244, Los Angeles, CA 90098-1732, USA, e-mail: [email protected] DOI: 10.1111/tbj.12347 © 2014 Wiley Periodicals, Inc., 1075-122X/14 The Breast Journal, Volume 20 Number 6, 2014 666–668
29% pT2, and 1% pT3 cases. From SLN positive group, mean age was 54.7 years (range 27–80); 58% postmenopausal and 41% premenopausal patients. Median tumor size was 2.3 cm. Pathologic tumor stages were 39% pT1, 50% pT2, 10% pT3, and 1% pT4 cases. SLN negative and positive patients comprised 69% and 31% of the cohort, respectively (See Fig. 1). Patients with SLN negative, ITC, micrometastasis, and macrometastasis undergoing cALND had nodal involvement as follows: 8% (2 of 24), 14% (one of seven ITC), 38% (five of 13 micrometastasis), 60% (30 of 50 macrometastasis), respectively. The risk of having positive non-SLNs in cALND was approximately 12 times higher in a patient with positive SLN than in a patient with negative SLN (Odds Ratio = 11.667; 95% CI 3.211 to 42.391, p < 0.0001). Local-regional recurrence and distant metastasis (LR/DM) were investigated. In SLN negative cases, LR/DM rates in cALND versus SLNB were 12.9% versus 6.7%, respectively (p = 0.266). In SLN positive cases, LR/DM in cALND versus SLNB were 14.2% versus 3.3%, respectively (p = 0.159). Within SLN negative cases only, LR/DM in cALND versus SLNB were 16.7% versus 6% (p = 0.082). Within SLN ITC group, LR/DM in cALND versus SLNB were 0% versus 16.7% (p = 0.508). Within SLN micrometastatic group who underwent cALND or SLNB, no patient experienced LR/DM. Lastly, in the SLN macrometastatic group with cALND versus SLNB, LR/DM were18% versus 4.5%, respectively (p = 0.161). None of the differences in LR/DM between cALND or SLNB were statistically significant. LR/DM and mortality rates between SLN negative and SLN positive patients were not significantly different, 8% versus 11%, respectively (p = 0.381). As SLNB has been shown to be noninferior to cALND in SLN negative patients (1,2), the role of
Letter to the Editor • 667
Total Patients (n = 302)
SLN Negative n = 209 (69%)
SLN Positive n = 93 (31%)
cALND n = 31/209 (15%)
SLN Biopsy only n = 178/209 (85%)
SLN Neg n = 24
SLN Neg (n =166) SLN ITC (n = 12)
SLN ITC n=7
ALN Neg (n = 22) ALN mac (n = 2)
ALN Neg (n = 6) ALN mac (n = 1)
cALND n = 63/93 (68%)
SLN mi n = 13
SLN Biopsy only n = 30/93 (32%)
SLN mac n = 50
ALN Neg (n = 8) ALN mi (n = 1) ALN mac (n = 4)
SLN mi (n =8) SLN mac (n = 22)
ALN Neg (n = 20) ALN mi (n= 1) ALN mac (n = 29)
Figure 1. Study flowchart detailing patients in each arm with regard to sentinel nodal status (SLN negative VS SLN positive), surgical management (cALND VS SLN Biopsy), and axillary lymph node status where applicable. (ALN = axillary lymph node; neg = negative; ITC = isolated tumor cells; mi = micrometastasis; mac = macrometastasis.)
cALND is being further explored in SLN positive patients. Our results confirm that presence of metastatic tumor in SLN strongly predicts positive nonSLNs, with 12 times higher risk in those with positive versus negative SLNs. However, LR/DM did not differ significantly between patients with cALND and those with SLNB alone, even in our cohort with a median clinical follow-up of 6.8 years. The natural question then becomes: does cALND reduce recurrence rates in sentinel node positive disease? Bilimoria et al. observed 97,314 patients, who underwent SLNB (23% and 55% of micrometastatic and macrometastatic tumor, respectively) (3) and found that recurrence and survival rates were comparable to those who had cALND. Subsequently, landmark trials have supported foregoing cALND in early stage breast cancer (1,4,5). These strongly argued for a limited group of SLN positive patients to forego cALND and to prevent subsequent morbidity. One of the strengths in our study is that observations were recorded despite differences in surgical, medical, and radiation management approaches, and recurrence rates still appeared comparable between cALND and SLNB alone groups. Another positive feature was longer clinical follow-up and strict minimum follow-up of 24 months. Furthermore, availability of detailed pathologic characterization of primary tumor and sentinel and axillary nodal tumor burden allowed us to specifically address the question of nodal status
and recurrence rates. Limitations of this retrospective study include the relatively small number of patients and disease-related events. The growing body of literature advocates for SLNB alone as adequate intervention in many patients and proposes that the argument for cALND is diminishing. Our study supports this paradigm shift; however, an even longer clinical follow-up will be needed to confirm these observations. Until then, the medical community must continue to engage in the discussion and provide evidence-based insights for the maximal benefit of each of our patients. Disclosure No conflicts of interest or financial disclosures. Maria E. Vergara-Lluri, MD* Raquel Prati, MD† Jeffrey Petersen, MD‡ Yasaman Omidvar, MD§ Sophia K. Apple, MD‡ *Department of Pathology, USC, Los Angeles, California; † Department of Surgery, UCLA, Los Angeles, California; ‡ Department of Pathology, UCLA, Los Angeles, California; and §Department of Internal Medicine, UCLA, Los Angeles, California
668 • letter to the editor
REFERENCES 1. Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010; 252:426–32; discussion 32-3. 2. Kell MR, Burke JP, Barry M, Morrow M. Outcome of axillary staging in early breast cancer: a meta-analysis. Breast Cancer Res Treat 2010;120:441–7. 3. Bilimoria KY, Bentrem DJ, Hansen NM, et al. Comparison of sentinel lymph node biopsy alone and completion axillary lymph
node dissection for node-positive breast cancer. J Clin Oncol 2009;27:2946–53. 4. Yi M, Giordano SH, Meric-Bernstam F, et al. Trends in and outcomes from sentinel lymph node biopsy (SLNB) alone versus SLNB with axillary lymph node dissection for node-positive breast cancer patients: experience from the SEER database. Ann Surg Oncol 2010;17(Suppl 3):343–51. 5. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA: J American Medi Assoc 2011;305:569–75.
