LOCALLY ADVANCED BREAST CANCER AFTER NEOADJUVANT TREATMENT AND DOWN STAGING: MODIFIED RADICAL MASTECTOMY

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1 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

2 QUESTIONS : Evidence based answers 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?

3 What is locally advanced Breast Cancer?

4 What is locally advanced Breast Cancer?

5 Locally Advanced Breast Cancer: Both options after Neoadj. Treatment

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7 How can we choose : Selective criteria for BC surgery after neoadjuvant chemotherapy : -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.

8 Effect of Neoadjuvant Systemic therapy in Locally advanced breast Cancer: Downstaging and overall survival improvement is usually achieved.

9 Neoadjuvant treatment : Which patients have the greatest benefit 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.

10 -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 Jan;13(1): doi: /S (11) Epub 2011 Dec 6. Gianni L et al.

11 NeoSphere Trial The NeoSphere trial investigated the single and combination use of pertuzumab and/or trastuzumab with or without docetaxel in HER2- positive breast cancer. Of the 417 patients randomly assigned to the different arms : % 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 % of those who received only trastuzumab and pertuzumab (P =.0141) Lancet Oncol Jan;13(1): doi: /S (11) Epub 2011 Dec 6. Gianni L et al.

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14 Oncoplastic issues 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!!!!

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16 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).

17 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.

18 - 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 % 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.

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24 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

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26 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.

27 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.

28 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.

29 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.

30 Don t miss the target!!! 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.

31 Thank you for your attention شكرا