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Is Completion Axillary Dissection Necessary For This Patient?

Article  in  Journal of Breast Health · July 2014

DOI: 10.5152/tjbh.2014.0001

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 Case Discussion J Breast Health 2014; 10: 184-185
DOI: 10.5152/tjbh.2014.0001

Is Completion Axillary Dissection Necessary For

This Patient?
Sadullah Girgin1, Atilla Soran2, Nilüfer Güler3, Maktav Dinçer4, Gökhan Demir5
1
Department of General Surgery, Dicle University Faculty of Medicine, Diyarbakır, Turkey
2
Magee-Womens Hospital, Pittsburgh University, Pittsburgh, USA
3
Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
4
Department of Radiation Oncology, İstanbul University Çapa Faculty of Medicine, İstanbul, Turkey
5
Department of Internal Medicine, Acıbadem Hospital, İstanbul, Turkey

Case Discussion
A 70-year-old female patient presents to the breast clinic for annual screening. She has no family history of breast cancer. Her physical
examination is normal, however an area of 0.5cm in size located in the lower inner quadrant of the right breast has microcalcifications
and the adjacent area of approximately 2cm shows structural distortion on mammography (BIRADS 5). The core biopsy reveales
high grade, solid ductal carcinoma in situ that contains areas of comedo necrosis and invasive ductal carcinoma in one border. The
estrogen receptor (ER) (+), progesterone receptor (PR) (-), Her 2 (-) and Ki-67 is reported as 12% . The patient undergoes segmental
mastectomy with wire guide and sentinel lymph node biopsy (SLNB). A 1% isosulfane blue and gamma probe is used for the detec-
tion of SLN. One SLN that was not macroscopically suspicious is sent to the pathology department peroperatively, without a request
for frozen section evaluation. The paraffin section examination shows a grade 3, ER (+), PR (-) and HER- neu2n (-) invazive tumor
with a 2 cm integrity diameter. Lymphovascular invasion (LVI) is positive, and comedo necrosis that surrounds the invasive tumor
and forms 15% of the tumor volume are determined, as well as a nuclear grade 3 ductal carcinoma in situ containing microcalcifica-
tions. The nearest margins to DCIS are 0.3cm at the medial and 0.2cm at the lateral borders, with negative surgical margins. The
pathologic evaluation of the aferomentioned single lymph node shows an 8mm metastasis with 0.2 X 0.2 cm extracapsular extension
by hematoxylin and eosin (H&E).

Is Completion Axillary Dissection Necessary For This Patient?

Surgery: Sadullah Girgin; Dicle University Department of General Surgery
Axillary lymph node dissection (ALND) has been recognized as the most important factor in local recurrence and survival of breast
cancer for many years. Although more conservative approaches for excision of the primary tumor in the breast has been suggested since
the second half of the twentieth century, until recently there had been no change in ALND (1, 2). The aim of surgical intervention to
the axilla in breast cancer is; to provide local control, to reduce the local-regional recurrence and thus contribute to overall survival,
to stage the disease, and to direct adjuvant therapy. However, the technique’s not being so innocent and the fact that significant sur-
vival advantage is not achieved in the majority of patients with breast cancer by axillary treatment has brought ALND into question,
especially in early stage breast cancer (3). Therefore, in the last decade, SLNB technique was introduced instead of ALND in patients
with invasive breast cancer who are clinically negative in the axillary region. The current standard approach in SLNB positive patients
is completion axillary dissection. However, in 40-70% of patients with positive SLN lymph node, no other node is affected. In other
words, in 40-70% of SLN -positive patients, an unnecessary complementary ALND is being performed (3, 4). Predictors of metastatic
non-SLN are characteristics of the primary tumor and those of the metastatic SLN’s. The most powerful independent predictive factors
for non-SLN metastases are; the diameters of the primary tumor and the SLN metastasis. The non-SLN metastasis risk is higher in
patients with tumor diameter >2 cm than in patients with tumor size <2 cm. The number and size of metastatic SLN are also important
predictive factors for positive non-SLN. If the SLN metastasis diameter is <1 mm, the incidence of non-SLN metastases is 0-27%. If
the SLN metastasis diameter is >2 mm, the incidence of the non-SLN metastases is 75%. In addition, the presence of lymphovascular
invasion in the primary tumor is an important factor that increases the rate of non-SLN metastasis. If lymphovascular invasion is not
present in the primary tumor the incidence of non-SLN metastasis is 12-43%, while in the presence of lymphovascular invasion the

Address for Correspondence:

Sadullah Girgin, Dicle Üniversitesi Tıp Fakültesi, Genel Cerrah Anabilim Dalı, Diyarbakır, Türkiye Received: 21.02.2013
184 Phone: +90 532 637 87 38 e-mail: [email protected] Accepted: 21.03.2013
 Girgin et al. Case Discussion

incidence of non-SLN metastasis is 30-60% (5, 13). Travaglini and after sentinel lymph node dissection with or without axillary dissection
colleagues (14) reported that the presence of lymphovascular inva- in patients with sentinel lymph node metastases. The American Colleg-
sion in the primary tumor was the only significant predictive factor eof Surgeons Oncology Group Z0011 randomized trial. Ann Surg 2010;
among studied parameters. Until very recently, completion axillary 252:426-433. (PMID: 20739842)
lymph node dissection (CALND) was recommended all SLN -posi- 4. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. Twen-
ty-five-year follow up of a randomized trila comparing radical mastec-
tive patients except the presence of micrometastases and isolated tu-
tomy, total mastectomy and total mastectomy followed by irradiation. N
mor cells. However, the ACOSOG Z0011 study offers important
Eng J Med 2002; 347:567-575. (PMID: 12192016)
suggestions in this regard. This study is a randomized study that eval-
5. Greco M, Agresti R, Cascinelli N, Casalini P, Giovanazzi R, Maucione A,
uates the effectiveness of axillary lymph node dissection in clinical Tomasic G, Ferraris C, Ammatuna M, Pilotti S, Menard S. Breast cancer
T1 -2 N0 M0 breast cancer patients with SLN-positivity, eho were patients treated without axillary surgery: clinical implications and biologi-
treated with breast -conserving surgery followed by radiotherapy and cal analysis. Ann Surg 2000; 232:1-7. (PMID: 10862188)
adjuvant systemic therapy. It was concluded that axillary dissection 6. Veronesi U, Paganelli G, Viale G, Luini A, Zurrida S, Galimberti V, In-
in such patients does not contribute to local recurrence and survival tra M, Veronesi P, Robertson C, Maisonneuve P, Renne G, De Cicco C,
(3, 15). While there are controversial aspects of this study, it is one De Lucia F, Gennari R. A randomized comparison of sentinel–node bi-
of the highly reliable studies on this subject. Although it is a very opsy with routine axillary dissection in breast cancer. N Eng J Med 2003;
important study that will help in clinical practice, it fails to adress 349:546-553. (PMID: 12904519)
the implementation of CALND in patients with clinically positive 7. Mansel RE, Fallowfield L, Kissin M, Goyal A, Newcombe RG, Dixon JM,
axillary lymph nodes and locally advanced disease who received neo- Yiangou C, Horgan K, Bundred N, Monypenny I, England D, Sibbering
adjuvant chemotherapy and underwent mastectomy. According to M, Abdullah TI, Barr L, Chetty U, Sinnett DH, Fleissig A, Clarke D, Ell
PJ. Randomized multicenter trial of sentinel node biopsy versus standard
the ACOSOG Z0011 study, if the patient is SLNB (+) and will not
axillary treatment in operabl breast cancer: The ALMANAC trial. J Natl
receive either partial breast irradiation, mastectomy, or neoadjuvant
Cancer Inst 2006; 98:599-609. (PMID: 16670385)
chemotherapy, ALND may be omitted, and radiotherapy and sys-
8. Giuliano AE, Haigh PI, Brennan MB, Hansen NM, Kelley MC, Ye W,
temic chemotherapy may be implemented. The formulations and Glass EC, Turner RR. Prospective observational study of sentinel lymph-
scoring systems that aid in determining the likelihood of metastasis adenectomy without further axillary dissection in patients with sentinel
in other nodes in the axilla, in patients with positive SLN, is called node-negative breast cancer. J ClinOncol 2000; 18:2553-2559. (PMID:
the nomogram. The success rate of existing nomograms in estimat- 10893286)
ing non-sentinel lymph node metastasis (NSLNM) varies in differ- 9. Sachdev U, Murphy K, Derzie A, Jaffer S, Bleiweiss IJ, Brower S. Predic-
ent patient groups. In this patient, the probability of NSLNM is tors of nonsentinel lymph node metastasis in breast cancer patients. Am J
81% according to the world’s most proven nomogram developed at Surg 2002; 183: 213-217.
Memorial Sloan- Kettering Cancer Center, and is 53 % by the Turk- 10. Unal B, Gur AS, Kayiran O, Johnson R, Ahrendt G, Bonaventura M,
ish model developed for our country (MF08 -01 model). According Soran A. Models for predicting non-sentinel lymph node positivity in
to both of these results from nomogram models, CALND should sentinel node positive breast cancer: the importance of scoring system. Int
be done in this patient. The presence of one positive lymph node J Clin Pract 2008; 62:1785-1791. (PMID: 19143863)
11. Wong SL, Edwards MJ, Chao C, Tuttle TM, Noyes RD, Woo C, Cer-
in SLNB may suggest that additional assessment of the axilla is re-
rito PB, McMasters KM; University of Louisville Breast Cancer Sentinel
quired. Although approximately 27% of patients in the ACOSOG
Lymph Node Study Group. Predicting the status of the nonsentinel axil-
study had NSLNM, it had no effect on either local recurrence or
lary nodes: a multicenter study. Arch Surg 2001; 136:563-568. (PMID:
survival. Another subject that should be considered in the discussed 11343548)
patient is the presence of extracapsular extension of the SLN me- 12. Rahusen FD, Torrenga H, van Diest PJ, Pijpers R, van der Wall E, Licht
tastases, however this issue has not been addressed in the study. J, Meijer S. Predictive factors for metastatic involvement of nonsentinel
Many studies showed that extracapsular extension is predictive for nodes in patients with breast cancer. Arch Surg 2001; 136:1059-1063.
NSLNM. CALND is not required in the patient according to the (PMID: 11529831)
American College of Surgeons Oncology Group study. However, it 13. Reynolds C, Mick R, Donohue JH, Grant CS, Farley DR, Callans LS,
should be kept in mind that the general approach to SLN -positive Orel SG, Keeney GL, Lawton TJ, Czerniecki BJ. Sentinel lymph node
patients in current guidelines including the NCNN guideline, ex- biopsy with metastasis: can axillary dissection be avoided in some patients
cept for patients with good prognostic features, is implementation in breast cancer? J ClinOncol 1999; 17:1720-1726. (PMID: 10561208)
of CALND. The high nomogram values of ​​ this patient and extra- 14. Travagli JP, Atallah D, Mathieu MC, Rochard F, Camatte S, Lumbroso
capsular extension of the SLN suggest that CALND should be done J, Garbay JR, Rouzier R. Sentinel lymphadenectomy without systematic
axillary dissection in breast cancer patients: predictors of non-sentinel
(16). However, taking tumor size and patient age to consideration, it
lymph node metastasis. Eur J Surg Oncol 2003; 29:403-406. (PMID:
should also be discussed whether axillary radiotherapy can be used
12711299)
instead of CALND?
15. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blu-
mencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary
References
dissection vs no axillary dissection in women with invasive breast cancer
1. Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphad- and sentinel node metastasis: a randomized clinical trial. JAMA 2011;
enectomy in breast cancer. J Clin Oncol 1997; 15:2345-2350. (PMID: 305:569-575. (PMID: 21304082)
9196149) 16. Gur AS, Unal B, Ozbek U, Ozmen V, Aydogan F, Gokgoz S, Gulluoglu
2. Engel J, Lebeau A, Sauer H, Hölzel D. Are we wasting our time with the BM, Aksaz E, Ozbas S, Baskan S, Koyuncu A, Soran A; Turkish Fed-
sentinel technique? Fifteen reasons to stop axilla dissection. Breast 2006; eration of Breast Disease Associations Protocol MF08-01 investigators.
15:451-454. (PMID: 16054813) Validation of breast cancer nomograms for predicting the non-sentinel
3. Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch lymph node metastases after a positive sentinel lymph node biopsy in a
AM, Saha S, Hunt KK, Morrow M, Ballman K. Locoregional recurrence multi-center study. Eur J Surg Oncol 2010; 36:30-35. 185
 J Breast Health 2014; 10: 184-185

Medical Oncology: Nilüfer Güler; Department of systemic therapy and RT application had a positive impact on both
Medical Oncology, Hacettepe University OS and DFS.

Our patient is 70 years old; lumpectomy and SLNB is applied upon The implementation of completion axillary dissection in our patient,
detection of a tumor in the right breast lower outer quadrant at screen- and detection of lymph node metastases as a result of this dissection
ing mammography. Pathological diagnosis: Invasive ductal carcinoma, would change the expected 10-year OS and DFS rather than the
grade 3, ER-positive (percentage rate is not clear); PR negative and choice of treatment. When our patient’s information is entered in to
HER2 negative. Ki-67 is 12% and lymphovascular invasion (LVI) the Adjuvant online 8.0 version as a patient with no additional health
is positive. Tumor diameter is 2 cm; high-grade ductal carcinoma in problems (HER2 and PR, Ki-67 is entered) 10 years, the risk of relapse
situ (DCIS) is present in 15% around the tumor. Surgical margins are at 10 years is calculated as 43% and the risk of death as 24% (6). With
negative, and the closest surgical margin is 2 mm away from the focus adjuvant 3rd generation chemotherapy regimens and adjuvant aroma-
of DCIS. Axillary lymph nodes are not palpable on physical examina- tase inhibitor, the risk of relapse is decreased by 58% and mortality risk
tion, however gross metastasis and extracapsular spread is determined is reduced by 55%. In case of detection of more lymph node metastasis
in the single SLN. We have no information on the status of our pa- by ALND, the benefits of combined therapy do not change. Prog-
tients’ overall health status. We do not know whether she has addi- nostic information regarding recurrence and death varies; the 10-year
tional medical problems. recurrence and mortality rates are calculated as 65% and 45% if 4-9
ALNs are positive for metastasis and as 85% and 68% if >9 ALNs are
Is Completion Axillary Dissection Necessary For This positive, respectively. If the patient has significant co-morbidites, the
Patient? benefit of adjuvant systemic therapy decreases accordingly. Hormonal
therapy alone may be recommended in such patients.
According to the given data, our patient has T1 N1 M0 (assuming that
metastasis screening had been done and found negative) breast can- Another point to be considered in our patient is the localization of
cer. The aim of axillary dissection is to improve local regional control, the tumor in the inner quadrant. The likelihood of internal mammary
and to identify the correct staging and prognosis of the disease. The lymph node metastasis increases in tumors of the inner quadrant; this
importance of molecular sub-grouping is increasing in the selection rate is 2% in tumors localized at the outer quadrant whereas it may
of adjuvant systemic therapy and the significance of axillary lymph raise upto 17-20% in tumors localized at the inner quadrant (7). Lo-
nodes is decreasing. Our patient has a luminal type B breast cancer. calization does not affect the choice of systemic treatment. It will be
The tumor’s being Grade 3 and LVI positivity are adverse prognostic important in planning adjuvant radiotherapy (RT).
factors that show the necessity of chemotherapy (CT) (1). The number
As a result, ALND does not change the selection of adjuvant systemic
of positive ALN does not alter the choice of treatment (2). There is a
therapy in our patient. According to the results of two studies, it does
mismatch between Ki-67 and grade in the pathology report. In such
not affect the OS or DFS (3-5). However, the special information of
cases, a second pathology consultation may be required if treatment
our patient is that extracapsular spread is detected in lymph nodes. In
selection would be altered.
these two studies, information is not available on this topic.
The ACOSOG Z0011 study (1900 patients with T1 and T2 tumors,
who received breast conserving surgery, had metastasis in 1 or 2 SLNs,
References
without gross extracapsular extension in the SLN were randomized to 1. Curigliano G, Criscitiello C, Andrè F, Colleoni M, Di Leo A. Highlights
tangential RT and systemic therapy, and ALND groups) and Amarosa from the 13th St Gallen International Breast Cancer Conference 2013.
study (1425 patients with T1 and T2 tumors, with clinical N0 disease Access to innovation for patients with breast cancer: how to speed it up?
but SLN positive were randomized to ALND and axillary RT (ART) Ecancermedicalscience 2013; 7:299. (PMID: 23589728)
2. Breast Cancer; NCCN Clinical Practice Guidelines in Oncology v.3
arms) have been published in the last 5 years (3-5). In the ACOZOG
2013. Avaliable from: URL: www.NCCN.com
Z0011 study, after a median foloow-up of 6.3 years, the 5-year overall
3. Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blu-
survival (OS) and disease-free survival (DFS) was 91.8%, and 82.2 mencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary
% in the ALND arm and 92.5% and 83.9% in the SLND arm, re- dissection vs no axillary dissection in women with ınvasive breast cancer
spectively, and no significant difference was found between arms. and sentinel node metastasis: a randomized clinical trial. JAMA 2011;
Similarly, there was no difference in terms of local regional recurrence 305:569-575. (PMID: 21304082)
between arms. Lymphedema, paresthesia, seroma, and wound healing 4. Straver ME, Meijnen P, van Tienhoven G, van de Velde CJ, Mansel RE,
Bogaerts J, Demonty G, Duez N, Cataliotti L, Klinkenbijl J, Westenberg
problems were significantly more frequent in the ALND group than
HA, van der Mijle H, Hurkmans C, Rutgers EJ. Role of axillary clearance
the other group (p<0.001). In this study, an average of two SLNs was after a tumor-positive sentinel node in the administration of adjuvant
removed. The effect of presence of extracapsular extension in the SLN therapy in early breast cancer. J Clin Oncol 2010; 28:731-737. (PMID:
is unknown. The median 6.1 -year follow- up results of the AMAROS 20038733)
study have been reported in 2013 ASCO (American Society of Clini- 5. Rutgers JE, Donker M, Straver ME, Meijnen P, van De Velde CJH, Man-
cal Oncology) (5). The axillary recurrence rate, 5-year OS and DFS sel RE, et al. Radiotherapy or surgery of the axilla after a positive sentinel
were 0.54% and 1.03%; 86.9% and 82.6%; and 93.3% and 92.5% in node in breast cancer patients: Final analysis of the EORTC AMAROS
trial (10981/22023). J Clin Oncol 31, 2013 (suppl; abstr LBA1001)
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6. Adjuvant online for breast cancer version 8.0. Avaliable from: URL: www.
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higher in the ALND arm (40% and 28% at 1 year, 22% and 14% at 7. Urban JA, Marjani MA. Significance of internal mammary lymph node
5 years, p<0.0001). In this study, information regarding presence of metastases in breast cancer. Am J Roentgenol Radium Ther Nucl Med
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 Girgin et al. Case Discussion

Radiation Oncology: Maktav Dinçer; Department of study criteria, the patient may be assessed for systemic therapy and
Radiation Oncology, İstanbul University only breast irradiation without considering risk ratios by nomograms
and without any local treatment directed to the axilla (axillary lymph
The number of axillary metastatic ganglia is considered both sci- node dissection and/or axilla radiotherapy). On the other hand, if
entifically and traditionally when determining radiation therapy the benefit of adding peripheral lymphatic irradiation in the pres-
indication for treatment of breast cancer (1). The decision to use ence of even one ganglion metastasis is proven in the newly closed
peripheral lymphatic irradiation area in addition to breast or chest randomized trials, addition of lymphatic radiotherapy from a specific
wall irradiation is also made according to the number of ganglia with area may again become popular in SLN positive patients (12, 13).
metastasis (2, 3). Leading authors suggest, not relying on published
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of control (6, 7). We would recommend radiotherapy of the breast ty-five year follow up of a randomized trial comparing radical mastec-
and axilla/supraclavicular areas to this patient because she partially tomy, total mastectomy and total mastectomy followed by irradiation. N
Engl J Med 2002; 347:567-575. (PMID: 12192016)
does not fit the Z0011 criteria and the risk of more than four metas-
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la increase in the direction of being more conservative (act like in ara JL, Mège JP, Caillet P, Pigneur F, Dao TH, Salmon R, Calitchi E, Bosc
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tive consequences of this approach is detected, the Z0011 approach optimal coverage and dose distribution in axillary levels I-II and sentinel
node area. Ann Oncol 2013; 24:2023-2028.
will gain widely acceptance. While adopting Z0011 results, it should
10. Gralow JR1, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von
be remembered that axillary surgery/radiotherapy is not performed
Minckwitz G, Buzdar AU, Smith IE, Symmans WF, Singh B, Winer EP.
only if all patient characteristics (histopathologic findings of the tu- Preoperative therapy in invasive breast cancer: pathologic assessment and
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local method treating the axilla is not tangential breast irradiation (8,
13. Matzinger O, Heimsoth I, Poortmans P, Collette L, Struikmans H, Van
9). The breast radiation area used in Z0011 does not cover the axilla
Den Bogaert W, Fourquet A, Bartelink H, Ataman F, Gulyban A, Pierart
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in conditions where axillary surgery or radiotherapy are not used. Groups. Toxicity at three years with and without irradiation of the inter-
The axilla may have been controlled by systemic treatment or the nal mammary and medial supraclavicular lymph node chain in stage I to
patient’s immune system (10, 11). Therefore, in the coming years, if III breast cancer (EORTC trial 22922/10925). Acta Oncol 2010; 49:24-
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 J Breast Health 2014; 10: 184-185

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without axillary dissection. In principle, chemotherapy is recom-
mended to node-positive patients, nevertheless its benefits are more 9:1871-1881. (PMID: 24295417)
limited in patients over the age of 70 years and the decision should 2. Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B, Erlander
be made by considering individual properties (1). The use of Onco- MG, Dunbier A, Sidhu K, Lopez-Knowles E, Goss PE, Dowsett M. Predic-
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Adjuvant therapy with aromatase inhibitors is an option in patients
who are older than 70 years and are receptor positive, considering assay, 21-gene recurrence score, and IHC4 in the TransATAC study popula-
other comorbid factors (2). tion. Lancet Oncol 2013; 14:1067-1076. (PMID: 24035531)

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