Stage I & II breast cancers (Early invasive breast cancers ) are managed by 1. Primary therapy for local management  2. Adjuvant therapy Primary therapy consists of: Mastectomy with an assessment of axillary lymph node status (or modified radical mastectomy) or Breast conservation (lumpectomy, wide local excision or quadrantectomy) with an assessment of axillary lymph node status + radiotherapy. 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) Management of axillary lymph nodes Earlier 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 thirst 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 lymph nodes or metastatic disease detected in sentinel lymph node biopsy. Adjuvant chemotherapy is given to all node-positive cancers node-negative cancers if > 1 cm in size.Node-negative cancer > .5 cm in size with adverse prognostic factors such as blood vessel or lymph vessel invasion high nuclear grade high histological grade HER 2/neuoverexpression negative hormone receptor status Adjuvant hormone therapy (tamoxifen) is added to all those with estrogen receptor positive tumors. 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 is the tumor shows overexpression of HER-2/neu receptors. Advanced Local-Regional Breast Cancer (Stage III ) (Neoadjuvant chemotherapy + MRM + adjuvant radiation therapy + chemotherapy + antiestrogen therapy)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. In an effort to provide optimal local-regional disease-free survival as well as distant disease-free survival for these women, surgery is integrated with radiation therapy and chemotherapy. 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. 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. In selected patients with stage IIIA cancer, neoadjuvant (preoperative) chemotherapy can reduce the size of primary cancer and permit breast-conserving surgery. Distant Metastases (Stage IV ) (mainly palliative treatment) Treatment for stage IV breast cancer is not curative but may prolong survival and enhance a woman’s quality of life. 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. Systemic chemotherapy is indicated for women with hormone receptor-negative cancers, symptomatic visceral metastases, and hormone-refractory metastases. Bisphosphonates, which may be given in addition to chemotherapy or hormone therapy, should be considered in women with bone metastases. About Adjuvant Therapy, Adjuvant therapy is the use of systemic therapy (chemotherapy or/and hormone therapy) in patients who have received local therapy but are at risk of relapse. The objective is to eliminate the occult metastasis responsible for late recurrences while they are microscopic and theoretically most vulnerable to anticancer agents. Adjuvant chemotherapy is given to all node-positive cancers node-negative cancers if > 1 cm in size node-negative cancer > .5 cm in size with adverse prognostic factors such as blood vessel or lymph vessel invasion high nuclear grade high histological grade HER 2/neuover expression negative hormone receptor status Adjuvant hormone therapy (tamoxifen) is added to all those with estrogen receptor positive.The use of chemotherapy in postmenopausal women is controversial. In postmenopausal women, chemotherapy is frequently used upto age 70 yrs, if she can tolerate it. In older women, chemotherapy is performed less frequently.In estrogen-positive tumors, in postmenopausal women, antiestrogen (tamoxifen / aromatase inhibitors) Therapy is the preferred form of adjuvant systemic treatment. Neoadjuvant chemotherapy it involves the administration of adjuvant therapy before primary therapy (surgery & radiation therapy) it has shown to down-stage the tumor. Previously CMF (cyclophosphamide, methotrexate & 5 - fluorouracil) was the chemotherapeutic regimen of choice. “CMF is no longer considered adequate adjuvant chemotherapy and modem regimens include an anthracycline (doxorubicin or epirubicin) and the newer agents such as the taxanes (paclitaxel and docetaxel)”- Bailey and Love 25/e p844 Anti-HER-2/neu antibody therapy. (Trastuzumab) HER-2/neu expression for all newly diagnosed patients with breast cancer is now recommended. Trastuzumab is added to the chemotherapy for tumors overexpressing HER-2/neu receptors (Trastuzumab is added along with taxanes).