Ans. is 'a' i.e., MRM o Here let's first see the TNM staging of this tumor. This patient is having Stage III disease (T4, NI or N2, MO) according the TNM table given below.TNM Classification of Breast Cancer (Accord to AJCC - 6/e. ofAJCC Cancer Staging Manual)T0-No clinical evidence of primary'tumorTis-Carcinoma in situT1-Tumor 2 cm or less in greatest dimensionT2-Tumor more than 2 cm but not more than 5 cm in greatest dimension.T3-Tumor more than 5 cm in greatest dimensionT4-Tumor of any size with direct extension to a) chest wall or b) skin or c) bothT4a-Extension to chest wall (excluding the pectoralis)T4b-Edema (including Peaud1 Orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast.T4c-Both T4a& T4b.T4d-Inflammatory' CarcinomaN0-No regional lymphnode metastasisN1-Metastasis to ipsilateral axillary' lymph nodes, mobileN,2 N2a-Metastasis to ipsilateral axillary' lymph nodes, fixed or mattedN2b-Metastasis to ipsilateral internal mammary' nodes in the absence of clinically evident axillary' lymphN3: N3a-Metastasis to ipsilateral infraclavicular lymph nodeN3b-Metastasis to ipsilateral internal mammary lymph node and ipsilateral axillary' lymph nodeN3c-Metastasis to ipsilateral supraclavicular lymph nodesM0-No distant metastasisM1-Distant metastasis Staging according to TNM ClassificationStage 0-TisN0 M0Stage I-T1N0 M0Stage II-T0N1 M0 T1T2T3N1N0/N1N0M0M0M0Stage IIIT3Any T4Any N2, N3N1MoStage IVAny M1 Stage III or Advanced Local-Regional Breast Cancer is managed by: Neoadjuvant chemotherapy + MRM + adjuvant radiation therapy + chemotherapy + antiestrogen therapyLets see the management of all the stages of breast cancer:Stage 1 & H breast cancers f Earh invasive breast cancers) are managed byPrimary therapy for local management &Adjuvant therapyo Primary therapy consists of:Mastectomy with assessment of axillary lymph node status (or modified radical mastectomy) or# Breast conservation (lumpectomy, wide local excision or quadrantectomy) with assessment of axillary lymph node status + radiotherapy.o Various trials have found both these methods to be equally effective. Breast conservation is the preferred form of treatment because of cosmetic advantages. However there are certain contraindications for conservative surgery (described in subsequent question)o Management of axillarylymph nodesEarlier dissection of axillary lymph nodes (level I and II) was performed to assess the lymph node status (i.e. presence or absence of occult metastasis)Now Sentinel lymph node biopsy is considered the standard for evaluation of the axillary lymph nodes for metastasis in women who have clinically negative lymph nodes, (the sentinel lymph node is the first regional lymph node to receive tumor cells that metastasize along the lymphatic pathway from the primary breast cancer)Axillary Lymph node dissection is performed for clinically palpable axillary lymphnodes or metastatic disease detected in sentinel lymph node biopsy.o Adjuvant chemotherapy is given toAll node-positive cancersNode negative cancers if> 1 cm in sizeNode negative cancer > 0.5 cm in size with adverse prognostic factors such asBlood vessel or lymph vessel invasionHigh nuclear gradeHigh histological gradeHER 2/neu overexpressionNegative hormone receptor statuso Adjuvant hormone therapy (tamoxifen) is added to all those with estrogen receptor positive tumors.o HER-2/neu expression is determined for all patients with newly diagnosed breast cancer and may be used to provide prognostic information in patients with node-negative breast cancer and predict the relative efficacy of various chemotherapy regimens. Trastuzumab is the HER-2/neu-targeted agent that is added to the adjuvant therapy if the tumor shows overexpression of HER-2/neu receptors.Advanced Local-Regional Breast Cancer (Stage HI)(Neoadjuvant chemotherapy + MRM + adjuvant radiation therapy + chemotherapy + antiestrogen therapy)o Here the disease is advanced on the chest wall or in regional lymph nodes (or both), with no evidence of metastasis to distant sites. Such patients are recognized to be at significant risk for the development of subsequent metastases, and treatment addresses the risk for both local and systemic relapse,o In an effort to provide optimal local-regional disease-free survival as well as distant disease-free survival for these women, surgeiy is integrated with radiation therapy and chemotherapy,o Neoadjuvant chemotherapy (administration of therapeutic agents prior to the main treatment) should be considered in the initial management of all patients with locally advanced stage III breast cancer,o Surgical therapy for women with stage III disease is usually a modified radical mastectomy, followed by adjuvant radiation therapy and chemotherapy. Antiestrogen therapy (tamoxifen) is added for hormone receptor positive tumors.Chemotherapy is used to maximize distant disease-free survival, whereas radiation therapy is used to maximize local- regional disease-free survival.o In selected patients with stage III A cancer, neoadjuvant (preoperative) chemotherapy can reduce the size of the primary cancer and permit breast-conserving surgery.Distant Metastases fStage IV)(mainly palliative treatment)o Treatment for stage IV breast cancer is not curative but may prolong survival and enhance a woman's quality of life,o Hormonal therapies that are associated with minimal toxicity are preferred to cytotoxic chemotherapy. Appropriate candidates for initial hormonal therapy include women with hormone receptor-positive cancers; women with bone or soft tissue metastases only; and women with limited and asymptomatic visceral metastases.o Systemic chemotherapy is indicated for women with hormone receptor-negative cancers, symptomatic visceral metastases, and hormone-refractory metastases.o Bisphosphonates, which may be given in addition to chemotherapy or hormone therapy, should be considered in women with bone metastases.