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