الفهرس 
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Abstract
In Egypt; Breast cancer is a phenomenal public health problem accounting for approximately 29% of newly diagnosed cancers. Sixteen percent of all cancer deaths among women are attributed to breast cancer, making it the second leading cause of cancer related death. Locally Advanced Breast Cancer (LABC) accounts for 12-29% of all breast cancer of which about 5% of inflammatory type. These patients are at risk of local and systemic recurrence rates inspite of aggressive treatment.
The multi-disciplinary approach, including surgery, chemotherapy, endocrine therapy and radiation therapy, has become the standard treatment for primary breast cancer patients. Neoadjuvant or primary chemotherapy in large primary breast cancer has been used with the purpose of reducing tumor volume and promoting less aggressive surgery. The disease’s downstaging promotes higher conservative breast surgery rates and in patients with objective clinical and pathological response, an increase in disease free and overall survival rates has been observed. However, about 10% – 35% of the patients do not benefit from this clinical approach. The identification of this group of patients could avoid the chemotherapy side effects and point them toward other therapeutic alternatives. Recent studies have been focused on the role of HER-2\neu as a predictive factor of response to neoadjuvant chemotherapy. The HER-2\neu proto-oncogene encodes a transmembrane tyrosine growth factor receptor that is overexpressed in approximately 25–30% of breast cancers.
The aim of this work was to evaluate the feasibility of conservative breast surgery (CBS) in operable locally advanced breast cancer (LABC) after downstaging with neoadjuvant chemotherapy. Also we evaluated the expression of HER-2\neu proteins as a prognostic factor (i.e., associated with survival) and as a predictive factor (i.e., associated with disease response to chemotherapy) in patients with LABC who were treated with neoadjuvant anthracycline chemotherapy.
Forty patients with operable locally advanced breast cancer were selected according to TNM classification admitted to the hospital of Medical Research Institute, University of Alexandria; The patients were divided as twenty patients proved to be HER-2\neu positive cases (Group A) while the other twenty patients proved to be HER-2\neu negative (Group B) with exclusion of patients with distant metastasis and patients who received previous anticancer treatment. Consent was taken from every patient to be included in this study.
All patients included in this study were subjected to complete history taking, full clinical examination including general examination and breast examination. Laboratory investigations (CBC, liver and renal functions, Serum calcium and alkaline phosphatase and tumor markers (CEA, CA 15.3)) were done for every patient also, radiological investigations including Ultrasound (U\S) abdomen and pelvis, Plain X-ray chest and CT if needed, Breast imaging by U\S Mammography both breasts and Plain X-ray spine Bone scan if needed. Core tissue biopsy was taken from the breast mass by Tru-cut needle for immunohistochemical staining for assessment of HER-2\neu expression. The response to neoadjuvant chemotherapy was evaluated after four cycles of anthracycline-based regimen (5-fluorouracil, adriamycin or epirubicin and cyclophosphamide) (FAC or FEC) both clinically and radiologically. Patients were stratified according to their response into four categories: Complete responders, Partial responders, Non-responders and Progressive disease. The responder group including the complete responders and the partial responders were submitted to CBS or modified radical mastectomy (MRM) according to the degree of response while the non-responder group including the non-responders and progressive disease were submitted to (MRM). Following surgery, all patients received four additional cycles of FAC or FEC chemotherapy. Locoregional radiotherapy were initiated within 6 weeks of completion of adjuvant chemotherapy. Pathological examination of the surgical specimen for diagnosis, typing, grading and number of involved LN out of excised axillary LN. All studied patients were followed up for at least 24 months after surgery (monthly during the first year then every 2 months during the second year) for assessment of disease recurrence ( site, time after initial surgery) and overall survival. Data were analyzed using the Statistical Package for Social Sciences (SPSS ver.20 Chicago, IL, USA).
There was no statstically significant difference between the two groups regarding the age, tumor characteristics before receiving the neoadjuvant chemotherapy (TNM classification, tumor largest diameter, clinical staging) and neoadjuvant chemotherapy regimen received. (P= 0.196, 1.000, 0.247, 1.000, 1.000 respectively).
There was statstically significant difference between the two groups regarding the response, tumor characteristics after receiving the neoadjuvant chemotherapy (TNM classification, tumor largest diameter, clinical staging) and the primary surgery submitted. (P= 0.003, 0.000, 0.000, 0.000, 0.002 respectively) in favor of HER-2\neu negative cases (Group B) which showed better response to neoadjuvant chemotherapy, more downstaging and more feasibility to conservative breast surgery (CBS) than HER-2\neu positive cases (Group A). Also better axillary LNs status was noted in HER-2\neu negative cases (Group B) than HER-2\neu positive cases (Group A) (P= 0.000). The local recurrence after primary surgery in HER-2\neu positive cases was more observed than HER-2\neu negative cases (P= 0.004) and the duration from the time of primary surgery to the time of the incidence of local recurrence was shorter in HER-2\neu positive cases than HER-2\neu negative cases (P= 0.003) which was reflected as longer DFS in Her-2/neu negative group (P= 0.003). All cases included in this study in both groups complete the period of follow up (24 months) and all of them attended all visits predetermined in the study protocol. No mortality between the studied patients has been registered in the period of follow up (survival (OS) =100% in both groups).
from the results of this study, we can conclude that: Conservative breast surgery (CBS) for locally advanced breast cancer (LABC) is feasible after four cycles of neoadjuvant chemotherapy (FAC or FEC regimen) in HER-2/ neu negative patients. HER-2/neu is a good predictor for response to neoadjuvant chemotherapy (FAC or FEC regimen) as HER-2/ neu negative tumors are more responsive to neoadjuvant chemotherapy (FAC or FEC regimen) than HER-2/ neu positive tumors. Also, neoadjuvant chemotherapy can downstage axilla and reduce the number of positive axillary lymph nodes which can be reflected upon the prognosis. Also HER-2/ neu is a good prognostic factor regarding local recurrence in breast cancer after primary surgery as HER-2/ neu positive tumors are more liable to get local recurrence than HER-2/ neu negative tumors. HER-2/ neu is a good prognostic factor regarding disease free survival (DFS) in breast cancer after primary surgery as patients who have HER-2/ neu positive tumors having less DFS than those who have HER-2/ neu negative tumors.