1. Sentinel Lymph Node Dissection (SND)
Elshami M Elamin, MD
Medical Oncologist
Central Care Cancer Center
Wichita, KS - USA

2. INTRODUCTION
LN mets are the most significant prognostic indicator for breast cancer
SLN biopsy can be used as an initial evaluation of the axilla in patients with clinically negative axillary nodes.

3. No ALND Negative Positive Yes ALND Stage I-II *SLN candidate SN not
mapping
Positive
Yes
ALND
SN not
identified
*SLN involvement identified by H&E.
*IHC for equivocal cases only
*SLN +ve by routine IHC is not recommended in clinical decision making

4. Contribution of local therapy
We all agree:
ALND reliably identifies nodal mets
ALND maintains regional control
Agree  Disagree
Contribution of local therapy
to breast ca survival

5. ROLE OF LN DISSECTION Diagnostic and/or Therapeutic? LN –ve: LN+ve:
70-90% 5YS
10% chance of death in 10Y
LN+ve:
50-70% risk of relapse
35% chance of death in 10Y
1-3 LN+ve: % 5YS
>4 LN+ve: % 5YS

6. ALND remain the standard of care for breast cancer pts that have + SLN
A meta-analysis of breast cancer pts showing that locally controlling breast cancer via ALND improve disease patient survival
ALND remain the standard of care for breast cancer pts that have + SLN

7. ALND
In the absence of definitive data showing superior survival from ALND.
ALND should be considered optional in pts:
Favorable tumors
Unlike change of adj therapy
Elderly
Co-morbidities

8. ALND SLND ALND risks: Restricted range of motion Pain discomfort
Lymphedema
Infection
Seroma
SLND

9. Sentinel L. Node Dissection
Candidates:
Clinically -ve nodes
Solitary T1 or T2
?? High grade/extensive DCIS
No large hematoma or seroma
No neoadjuvant chemo
SLN can’t be identified or +ve:
Formal axillary dissection

10. SLND Lymphatic mapping: Blue dye = 83% success rate
Lymphoscintigraphy = 94%
Combined = 97%
False –ve: 0-11%

11. SLND
Minimally invasive way to determine whether the axilla is involved
Decision to eliminate nodal dissection in face of a negative SLN is being examined by large clinical trial.
If SLN +ve proceed with complete nodal dissection

12. SLN micrometastsis N0(i+) or N1mi
Definition: SLN metastases between 0.2mm and 2.0mm in size. It is considered negative by standard H&E, but positive by CK-IHC staining
Clinical significance remains unknown
ALND: Yes or No????
Treat as N0 or N1????

13. Clinical Dilemma Hansen et al JCO 27:4679–4684:
pts with isolated tumor cells (ITCs) and pN0[i+] and pN1mi do not have worse 8-year DFS or OS compared with pN0 pts.
Pts with SLN mes >2 mm (pN1) have significantly reduced survival.
de Boer et al. NEJM 361:653–663:
Pts with ITCs and pN1mi have reduced 5-year DFS

14. NCCN: *SLN involvement identified by H&E.
*IHC for equivocal cases only
*SLN +ve by routine IHC is not recommended in clinical decision making

15. *Prognostic
Advantage
*? DFS
ALND
risks

16. When SLN positive !!! NO Study conclusively demonstrated:
Survival benefit or
Detriment for omitting ALND

17. SLND
SLND accurately identifies nodal metastasis of early breast cancer
But it is not clear whether further nodal dissection affects survival

18. The Current Standard SLND alone: ALND: If SLN is free of cancer
If SLN contains cancer

19. A: --------------------
Q: Whether ALND affects overall survival in breast cancer with SNL metastasis or whether SNLD alone is sufficient?
A: 

20. Axillary Dissection vs No Axillary Dissection in Women With Invasive Breast Cancer and Sentinel Node Metastasis. Z0011 trial
Originally presented at the 2010 ASCO Annual Meeting
Published on February 9, 2011, JAMA

21. Study Design Randomized, multi-center, Phase III non-inferiority trial
Conducted at 115 sites (May 1999 to Dec 2004)
I or IIA (891 pts)
No palpable LN
Randomized 1:1
SLND  ALND or SLND alone
Both groups had a lumpectomy and adjuvant systemic treatment

22. Not eligible SLN by IHC > 3 positive SLNs Matted LNs
Gross extra nodal disease
Neoadjuvant therapy

23. Setting, and Patients
Age, stage of cancer, and tumor size did not vary significantly between the two groups
The median number of LN removed in the ALND group was 17 compared with 2 in the SLND group
The adjuvant systemic therapies received by both groups were comparable:
96% and 97% of the ALND and SLND patients
The majority of pts received whole-breast RT

24. Objective of the study
To determine the effects of complete ALND on survival of patients with SLN metastasis of breast cancer

25. RESULTS

26. Main Outcome Measures
OS was the primary end point, with a noninferiority margin of a 1-sided hazard ratio of less than 1.3 indicating that SLND alone is noninferior to ALND.
DFS was a secondary end point.

27. 5 year OS
0.7% absolute difference
Favoring SLND

28. significantly more frequent in the ALND group
RESULTS
SLND compared to ALND was not statistically inferior in terms of OS (P=0.008)
The 5 YOS rates:
92.5% and 91.8% in the SLND-alone compared to the ALND
DFS did not vary between the groups
Morbidity:
Wound infections
Axillary seromas
Lymphedema
significantly more frequent in the ALND group

29. Total Locoregional recurrence rate at 5 years
2.5% in SLND
3.6% in ALND
Further F/U unlikely would result enough additional recurrences to generate aclinically meaningful
survival difference

30. DISCUSSION

31. Study Implications
The trial results suggest that women may be exposed to morbidity due to ALND with no meaningful improvement in overall survival, including women classified as high-risk (ER/PR -ve)

32. limitations of the study
Failure to achieve a target accrual of 1900 pts
Potential randomization imbalance that favored the SLND-only cohort
Follow-up was approximately 6 yrs and a longer-term follow-up would be beneficial, as early-stage breast cancer can reoccur at 10 to 15 years after diagnosis

33. ASCO Sentinel Lymph Node Biopsy Guideline Panel pointed out:-
This data will likely change physician practice for early stage disease
Caution:
That the study results do not apply to early-stage pts with high risk for reoccurrence:
Three or more positive SLN
Larger tumors
Those who received preoperative chemotherapy

34. ASCO members pointed out:
The results currently apply only to early stage breast cancer
Tumors < 5 cm
No clinically evident nodal involvement
Lumpectomy/RT
No MRM pts included in the study
>95% received adj systemic therapy
1-2 positive SLN
No extracapsular extension
We have concerns about routinely omitting axillary dissection in younger women (under age 50), and cancers with particularly aggressive features, including those considered high grade
In some cases, additional information about possible remaining lymph node involvement will be necessary to make decisions about chemotherapy or radiation, and further surgery may still be warranted

35. According to Z0011
The only additional information gained from ALND is the number of involved LN
Unlikely to change systemic therapy decison
Z0011 results indicate that women with a positive SLN and clinical T1-2 undergoing L/RT  systemic therapy do not benefit from ALND in terms of:
Local control
DFS OS

36. Z0011 vs NSABP B04 Z0011 NSABP B04 6 yrs f/u: No survival difference
N+ve: 100%
5YS: > 90%
First axillary failure in SLND: Only 0.9%
Conclusion:
High rate of locoregional control even without ALND
NSABP B04
25 yrs f/u No survival difference
N+ve: 40%
5YS: only 60%
First axillary failure: 19%
NSABP B04: N-ve pts: rad mastectomy vs total mastectomy + Nodal RT or Delayed Nodal RT for node recurrence

37. Z0011 vs NSABP B04
Changes of breast cancer management during the interval between the 2 studies
Improved imaging
Detailed pathologic evaluation
Improved planning of surgical and radiation approaches
More effective systemic therapy

38. The International Breast Cancer Study Group Trial of ALND vs Observation
> 50% of pts did not receive breast or axillary RT
Women >60 on adj Tamoxifen and No axillary treatment:
Axillary recurrence was only 3%
OS was 73% (median F/U of 6.6Y)

39. Is ALND really neccessory ?

40. For which pts is the ALND remains the standard of care?
Pts with positive SLN and:
Mastectomy
Lumpectomy without RT
Partial breast RT
Neoadjuvant therapy
Whole breast RT in the prone position (low axilla is not treated)

41. Last Words
These findings should encourage new and continuing dialogue between physicians and breast cancer patients and their families regarding the most appropriate treatment options available

42. THANKS