This document discusses surgical management of the axilla after neoadjuvant chemotherapy for breast cancer. It provides background on how axillary lymph node dissection was previously the standard approach but is now being reevaluated. Sentinel lymph node biopsy after neoadjuvant chemotherapy may accurately stage the axilla and spare some patients from axillary lymph node dissection if the sentinel nodes are negative, though identification rates are slightly lower than without chemotherapy. The document concludes that current evidence suggests an algorithm involving axillary ultrasound before and sentinel lymph node biopsy after neoadjuvant chemotherapy to guide need for further axillary lymph node dissection.

1. MANAGEMENT OF THE
AXILLA AFTER
NEOADJUVANT
CHEMOTHERAPY FOR
BREAST CANCER
DR. HAYTHAM M. FAYED (MD)
LECTURER OF SURGICAL ONCOLOGY
ALEXANDRIA FACULTY OF MEDICINE

2. Surgical management of the axilla in patients presented by operable
breast cancer has evolved significantly over the past 30 years.
Axillary lymph node status is a significant prognostic pathologic
variable in patients with operable primary breast cancer, and it remains
the most powerful predictor of recurrence and survival. The number of
lymph nodes with metastasis also has prognostic importance.

3. Axillary lymph node dissection (ALND) was established as the
undisputed standard of care at the end of the nineteenth
century as part of the Halsted radical mastectomy and
remained so near the end of the twentieth century.
The therapeutic role of ALND was challenged by a
randomized clinical trial (National Surgical Adjuvant Breast
and Bowel Project [NSABP] B-04)

4. That trial showed that elective ALND or axillary radiotherapy
did not improve long-term outcomes for patients with
clinically negative axilla.
However, even following publication of the results of the B-04
trial in the late 1970s, the procedure still remained the
standard of care for axillary staging because of the need to
obtain the prognostic information of pathologic nodal status
and the need to identify candidates for adjuvant
chemotherapy.

5. In addition, ALND in patients with pathologically positive
axillary nodes provided excellent control of the disease in the
axilla.
The need to avoid the morbidity of ALND in histologically
node-negative patients without losing prognostic information
led to the development of lymphatic mapping and sentinel
lymph node biopsy (SLNB).

6. Developments in the field have been facilitated thanks
to therapeutic adjuncts such as radiation,
chemotherapy, hormonal agents, and other targeted
therapies.

7. Indications for chemotherapy in a neoadjuvant setting in
invasive breast cancer include large or locally aggressive
tumors in an attempt to downsize the tumor and in some
cases facilitate breast-conserving techniques.
Furthermore, the use of NAC in breast cancer allows in vivo
evaluation of tumor response and cancer sensitivity to
chemotherapeutic agents and provides important prognostic
information.

8. It has been well reported that the subtypes of breast cancer,
as determined by their molecular profiles, behave
differentially in response to chemotherapy, with luminal A
subtypes having the least favorable responses compared with
luminal B, triple-negative, or HER2-overexpressing tumors.
Moreover, the survival advantage provided by a pathologic
complete response in these 3 subtypes is not conferred in the
same manner in luminal A tumors showing pathologic
complete response.

9. Thresholds for using NAC have decreased, with use in
early breast cancer increasing to facilitate breast
conservation, particularly in cancers positive for the
HER2/neu receptor with high predicted partial, or
indeed complete, pathologic response.

10. As a result, an axillary pathologic complete response (pCR) is
observed in 20 to 42% of the clinically node-positive patients.
In HER2-positive disease it is even more pronounced, with an
axillary pCR in as much as 74% of patients.

11. In patients with clinically node positive breast cancer,
an axillary pCR is associated with a more favourable
survival.

12. It seems rational to assume that aggressive surgical treatment
of the axilla with an ALND might be omitted in patients in
whom an axillary pCR is achieved, since the axilla has already
been cleared of tumour deposits by systemic treatment.
This could spare patients from treatment-related morbidity,
such as upper limb oedema and shoulder dysfunction.

13. How to assess axillary pathologic
response after NAC?

14. In patients who are considered for NC, absence of
information on pathologic axillary nodal status at
presentation is often of concern.
Thus, assessing axillary nodal status with
noninvasive/minimally invasive techniques is essential.

15. Several recent and on-going trials have been initiated to
evaluate imaging modalities to identify patients with an
axillary pCR in whom ALND might be omitted.
The use of imaging techniques only, however, has not shown
to predict an axillary pCR accurately; MRI has not been
extensively studied and PET-CT has a reported accuracy of
72%.

16. Axillary ultrasonography with fine-needle aspiration (FNA) or
core needle biopsy of abnormal lymph nodes is a simple,
minimally invasive study that can help establish axillary lymph
node involvement and provide direct evidence of
chemosensitivity of axillary metastases to NC.

17. SLNB is another option for assessing axillary nodal status
before NC and its feasibility and accuracy in typical
candidates for NC has previously been shown in small series
and as part of multicenter and randomized trials.
However, the use of SLNB before NC is controversial.

18. Sentinel lymph node biopsy in patients treated
with neoadjuvant chemotherapy

19. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
NC is able to downstage the number of involved axillary
lymph nodes as an important parameter in the definition of
the pathological complete response (pCR).
Clinical observations suggest a lower LNY after NC, which
might be due to chemotherapy dependent parameters
influencing detection rates.

20. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
NC downstages involved axillary lymph nodes in a
considerable proportion of patients.
With SLNB becoming the standard of care for staging the
axilla in early-stage breast cancer, patients who present with
either overt or subclinical involvement of the axilla could
potentially be spared from ALND if, following NC, the SLN is
found to be negative.

21. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
This approach is naturally predicated on the
demonstration of the feasibility and accuracy of SLNB
after NC, which has been assessed in single-institution
series, multicenter series, and meta-analyses.

22. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
Single Institution Experience
Limited early experience with SNB after NC
Initial small studies have shown variability in:
• Rates of SN identification (72-100%)
• Rates of false negative SN (0%-33%)

23. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy

24. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy

25. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
Multi-Center Studies: NSABP B-27 (n=428)
Identification Rate: 85%
•With blue dye: 78%
•With isotope + blue dye: 88-89%
False Negative Rate: 11%
•With blue dye: 14%
•With isotope + blue dye: 8.4%
Mamounas EP: J Clin Oncol, 2005

26. Sentinel lymph node biopsy in patients treated with neoadjuvant chemotherapy
SNB After NC
Meta-Analysis of Single-Institution
and Multi-Center Studies
Mamounas EP: J Clin Oncol, 2005
Conclusion:
SNB is a reliable
tool for
planning treatment
after NC

27. Evaluating the accuracy of SLNB in patients with
negative axillary nodes is not a true test of its
sensitivity, since any node removed at SLNB will
be tumor-free and will accurately reflect axillary
status.

28. Recent publications, including several meta-
analyses as well as a large series from MD
Anderson Cancer Center have shown that SLNB
is an accurate means of staging the axilla after
completion of NAC in patients who are clinically
node negative at presentation.

29. Most studies however, show that identification rates are
worse after NAC than before or without it.
Rates of downstaging after NAC have been quoted to be
between 20 %– 40 %.
Therefore, concerns exist regarding to the reliability and
sensitivity of SLNB after NAC for patients who may be node-
positive prior to treatment.

30. Not surprisingly, patients with residual nodal disease after
completion of neoadjuvant chemotherapy are known to have
a worse prognosis than those with a complete pathologic
response.
For these patients loco-regional control is achieved by ALND
and nodal radiation.

31. Take home messages
 Data suggest neoadjuvant chemotherapy (NAC) can
downstage the axilla in up to 40% of breast cancers, yet
there is no consensus regarding timing and extent of
axillary surgery post NAC.
 Sentinel lymph node biopsy (SLNB) after NAC is also
debated.

32. Take home messages
 After literature review an algorithm may be suggested for
management of the axilla after NAC:
 Any patient with clinically involved nodes pre-NAC
undergoes ALND post-NAC.
 All patients have pre-NAC axillary ultrasound (USS). If node
negative pre-NAC, perform SLNB post-NAC.

33. Take home messages
 After literature review an algorithm may be suggested for
management of the axilla after NAC:
 If SLNB positive, for axillary lymph node dissection (ALND).
 If US shows positive node but there is complete clinical
response (CCR) and complete radiological response (CRR)
post-NAC, for SLNB. If SLNB positive then ALND, if SLNB
negative consider radiotherapy without ALND.