Download locally advanced breast cancer after neoadjuvant treatment

LOCALLY ADVANCED BREAST
CANCER AFTER NEOADJUVANT
TREATMENT AND DOWN STAGING:
MODIFIED RADICAL MASTECTOMY
Fiorita Poulakaki
MD, PhD, FEBS(on Breast Surgery)
Breast Surgeon,
Head of Department, Metropolitan Hospital
Athens, GREECE
QUESTIONS : Evidence based
answers
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What is locally advanced ? DEFINITION /STAGING
How about Neoadjuvant treatment ? Improves outcomes in most of the
cases!!!
Target of Neoadjuvant treatment ? Breast Conservation , Improved
Overall Survival or both?
Pitfalls ? Oncoplastic issues. Can we offer a good cosmetic result?
PATTERNS of response after neoadjuvant treatment? Can we EVER be
safe about the margins??
How about the axilla ?Sentinel Node Biopsy or Axillary Clearence ?
What is locally advanced Breast Cancer?
What is locally advanced Breast Cancer?
Locally Advanced Breast Cancer:
Both options after Neoadj.
Treatment
How can we choose : Selective
criteria for BC surgery after
neoadjuvant chemotherapy :
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-Complete resolution of skin edema;
-Residual tumor size <5 cm;
-No evidence of multicentric lesion;
-Absence of extensive intramammary lymphatic invasion/
extensive microcalcification.
If any of the above is still present :
Go for MASTECTOMY
CANCER June 2, 1992, Volume 69, No. 11, Breast-Conserving Surgery for
Advanced CA/Singletary et al.
Effect of Neoadjuvant Systemic therapy in Locally
advanced breast Cancer: Downstaging and overall
survival improvement is usually achieved.
Neoadjuvant treatment : Which
patients have the greatest benefit
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Known biologic factors can help determine which patients are most
likely to be downstaged after neoadjuvant chemotherapy
: High-grade breast tumors
ER negative and/or
HER2 positive
have a higher likelihood of pathologic complete response (pCR) to
neoadjuvant chemotherapy.
-Rouzier et al found that patients with ER-positive, HER2-negative
luminal tumors had only a 6% pCR rate with paclitaxel, fluorouracil,
doxorubicin, and cyclophosphamide neoadjuvant chemotherapy, d
compared with 45% for HER2-positive or basal-like tumors.
-Neoadjuvant chemotherapy can downstage node-positive axilla
as well as tumors in the breast, with pCR seen in as many as 40%
of patients who were initially node-positive but became nodenegative with chemotherapy.
- Furthermore, in patients with HER2-positive tumors, the
addition of anti-HER2 agents (trastuzumab and pertuzumab)
has further improved axillary pCR. ( NeoSphere Trial)
Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S14702045(11)70336-9. Epub 2011 Dec 6.
Gianni L et al.
NeoSphere Trial
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The NeoSphere trial investigated the single and combination use of
pertuzumab and/or trastuzumab with or without docetaxel in HER2positive breast cancer. Of the 417 patients randomly assigned to the
different arms :
45.8% of patients receiving both pertuzumab and trastuzumab plus
docetaxel had a pCR, compared with
29% of those treated with trastuzumab plus docetaxel,
24% of those who received pertuzumab and docetaxel, and
16.8% of those who received only trastuzumab and pertuzumab (P =
.0141)
Lancet Oncol. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.
Gianni L et al.
Oncoplastic issues
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Can we actually always offer a good cosmetic
result?
In our decision, the ratio between size of the
tumor and the size of the breast is important
because the surgeon, will plan to remove the tumor
with adequate margin and good cosmetic result.
Even with complicated oncoplastic techniques, the
cosmetic result sometimes ( especially with locally
advanced tumors) will not be superior from
Mastectomy+reconstruction !!!!
BUT...
Patterns of response !!!!!!!
3 types of patterns of response after receiving NST
(Neoadjuvant Systemic Therapy) :
1) Pathologic complete response (gross tumor has totally disappeared).
2) Concentric shrinkage (tumor has shrunk to a small volume and there is
no residual nodule in the peripheral area).
3) Mosaic pattern (multifocal residual, tumor has shrunk to small volume
like the concentric pattern but it has still many small nodules in the edge
of the tumor).
The third pattern of response, the mosaic pattern (multifocal
residual).
(A) This is the real negative margin after removing tumor in mosaic
pattern.
(B) There are still many small nodules outside the edge of skin
incision after finishing the operation but the surgeon cannot
identify these nodules and the pathological result shows
negative margin.
- The mosaic pattern response can be evaluated by physical
examination, mammogram, breast ultrasound and magnetic
resonance imaging (MRI) which is the most accurate one.
- MRI can improve the assessment of neoadjuvant
chemotherapy response with sensitivity ranging from 70%
to 100% and 50-100% specificity when the tumors respond
to chemotherapy.
-However, MRI cannot detect the absence
of residual tumors foci and underestimate the residual
noninvasive lesion in the breast following neoadjuvant
chemotherapy.
Yuan Y, Chen XS, Liu SY, Shen KW. Accuracy of MRI in prediction of pathologic complete
remission in breast cancer after preoperative therapy: a meta-analysis. AJR Am J Roentgenol 2010;
195:260.
Margin status after neoadjuvant
chemotherapy
- Surgical excision doesn’t attempt to remove the
whole volume of lesion before neoadjuvant
treatment, because the goal of wide excision is to
remove any residual lesion with clear margins.
- If the lesion after responding to neoadjuvant
chemotherapy can be observed in mammography
such as microcalcification or spiculated lesion,
specimen mammography should be sent to confirm
that the whole lesion is removed
AXILLA and NEOADJUVANT
- Node evaluation is based on the clinical exam of the axilla:
a) Clinically suspicious axillary exam — For patients with palpable
axillary nodes, we perform an ultrasound-guided fine needle aspiration
(FNA) and/or core needle biopsy of one or more suspicious nodes prior
to neoadjuvant treatment to determine if the axillary nodes are
pathologically involved
●If the FNA is negative, we suggest a sentinel lymph node biopsy (SLNB)
to stage the axilla prior to treatment.
●If the FNA is positive, no further evaluation is required. Data suggest that
sentinel node detection rate is low and associated with a high falsenegative rate (FNR)
Kuehn T, Bauerfeind I, Fehm T, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy
(SENTINA): a prospective, multicentre cohort study. Lancet Oncol 2013; 14:609. –
Boughey JC, Simon VJ, Mittendorf EA, et al. The role of sentinel lymph node surgery in patients presenting with node positive breast cancer
(T0-T4, N1-2) who receive neoadjuvant chemotherapy- results from the ACOSOG Z1071 trial. Cancer Res 2012; 72:94s.
AXILLA and NEOADJUVANT
b) Clinically benign axillary exam — SLNB should be performed prior to
initiation of neoadjuvant therapy.
- Results of this procedure may more accurately reflect the status of the
axillary nodes if performed before initiation of neoadjuvant therapy as
compared with following completion of that treatment, although the
status of the lymph nodes after neoadjuvant therapy may have greater
prognostic significance.
●If the SLNB is negative, no further evaluation is necessary.
●If the SLNB is positive, further treatment will depend on the outcome
following neoadjuvant chemotherapy.
SLNB is positive (pN+) before
Neoadjuvant treatment
- Subsequent management can be stratified based on pathological findings.
- Patients with evidence of up to 2 pathologically involved sentinel nodes
after SLNB should be either offered radiation therapy (RT) that covers
the axilla or undergo an axillary lymph node dissection (ALND).
- However, for patients in whom pathologically involved axillary nodes were
identified by a post-NACT SLNB, some experts would favor a
completion ALND.
- Patients with >3positive sentinel nodes should undergo an ALND.
- Patients incidentally found to have a positive non-sentinel node during the
SLNB should undergo an ALND.
Take home axilla message
- While SLNB has replaced ALND for sentinel lymph node–negative patients
and some patients with limited axillary metastases, optimal management
of the axilla after neoadjuvant chemotherapy is not clear.
- Avoiding the morbidity of ALND is preferred in any patient who will not
derive additional benefit from the procedure.
-Difficult to accurately identify who these patients are after neoadjuvant
chemotherapy.
-Patients who are clinically node-positive prior to neoadjuvant
chemotherapy should undergo ALND, since SLNB may not accurately
identify residual axillary disease even if the patient is clinically nodenegative after neoadjuvant chemotherapy.
- Currently this is the only way to ensure that appropriate locoregional
control is obtained.
- No study has adequately evaluated outcomes in patients in whom ALND is
omitted after neoadjuvant chemotherapy, and further studies are
necessary to help determine optimal axillary management.
Don’t miss the target !!!
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One of the primary objectives of neoadjuvant
therapy is to improve surgical outcomes for
patients with newly diagnosed breast cancer
The goal of surgery is to obtain the maximal
locoregional control with minimal disfigurement
and provide accurate staging to determine
prognosis and subsequent adjuvant treatment.
Thank you for your attention
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