SENTINEL LYMPH NODE DISSECTION
(SND)
Elshami M Elamin, MDMedical Oncologist
Central Care Cancer Centerwww.ccancer.comWichita, KS - USA
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.
Stage I-II
*SLN candidate
SLNmapping
Negative
Positive
SN notidentified
No ALND
YesALND
*SLN involvement identified by H&E.*IHC for equivocal cases only*SLN +ve by routine IHC is not recommended in clinical decision making
We all agree: ALND reliably identifies nodal mets ALND maintains regional control
Agree Disagree
Contribution of local therapy to breast ca survival
ROLE OF LN DISSECTION Diagnostic and/or Therapeutic?
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: 60-80% 5YS >4 LN+ve: 30-50% 5YS
5
ALND
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
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
ALND
ALND risks: Restricted range of motion Pain discomfort Lymphedema Infection Seroma
SLND
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
9
SLND
Lymphatic mapping: Blue dye = 83% success rate Lymphoscintigraphy = 94% Combined = 97% False –ve: 0-11%
10
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
11
SLN micrometastsisN0(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????
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
NCCN:
*SLN involvement identified by H&E.*IHC for equivocal cases only*SLN +ve by routine IHC is not recommended in clinical decision making
ALND risks
*Prognostic Advantage*? DFS
• NO Study conclusively demonstrated:
• Survival benefit or
• Detriment for omitting ALND
When SLN positive !!!
SLND
SLND accurately identifies nodal metastasis of early breast cancer
But it is not clear whether further nodal dissection affects survival
The Current Standard
• SLND alone:• If SLN is free of cancer
• ALND:• If SLN contains cancer
Q: Whether ALND affects overall survival in breast cancer with SNL metastasis or whether SNLD alone is sufficient?
A: --------------------
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
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
Not eligible SLN by IHC > 3 positive SLNs Matted LNs Gross extra nodal disease Neoadjuvant therapy
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
Objective of the study
To determine the effects of complete ALND on survival of patients with SLN metastasis of breast cancer
RESULTS
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.
5 year OS
0.7% absolute difference Favoring SLND
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
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
DISCUSSION
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)
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
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
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
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
Z0011 vs NSABP B04 Z0011
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
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
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)
For which pts is the ALND remains the standard of care?
Pts with positive SLN and:1. Mastectomy2. Lumpectomy without RT3. Partial breast RT4. Neoadjuvant therapy5. Whole breast RT in the prone position (low axilla
is not treated)
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
THANKS