59 Breast cancer 1
It is a malignancy originating from breast tissue including both early stages which are potentially curable, and metastatic breast cancer (MBC) which is usually incurable. Most breast carcinomas are adenocarcinomas and are classified as ductal or lobular. The development of malignancy is a multistep process with pre invasive (or noninvasive) and invasive phases. The goal of treatment for noninvasive carcinomas is to prevent the development of invasive disease. 2
Risk factors of breast cancer Both personal and family histories influence a women risk of developing breast cancer. 1- female gender 2- age (the incidence of breast cancer increases with increasing age). 3- Endocrine factors A- Early menarche but (early natural menopause and bilateral oophorectomy before age 35 years decrease risk of breast cancer). B- Nulliparity C- Late age at first birth ( 30) D- Postmenopausal estrogen replacement E- Oral contraceptive use. 4- Benign breast disease ( proliferation only, atypical hyperplasia) 3
5- Genetic factors Mutations occur in tumor suppresser genes [BRCA1 and BRCA2]), 6- Environmental and lifestyle factors A- Obesity B- Radiation C- reserpine and other drugs causes increase prolactin levels. 4
Clinical presentation of breast tissue The initial sign in more than 90% of women with breast cancer is a painless lump that is typically, unilateral, solid, hard, irregular, and non mobile. In approximately 10% of cases, stabing or aching pain. Less commonly, nipple changes. In more advanced cases prominent skin edema, redness, warmth, and induration of the underlying tissue may be observed. 5
Breast cancer cells spread by lymph channels, and through the blood to distance sites. When breast cancer cells can be detected clinically or radiologically in sites distant from the breast, the disease is referred to as advanced or metastatic breast cancer. Tissue involved with metastases are lymph nodes, skin, bone, liver, lungs and brain. Symptoms of bone pain, difficulty breathing, abdominal enlargement, jaundice, and mental status changes may signal the clinical presentation of metastatic breast cancer. 6
Diagnosis Initial workup for a woman presenting with a lesion or suggestive symptoms should include a careful history, physical examination of the breast, three-dimensional mammography, and possibly other breast imaging techniques such as ultrasound. Breast biopsy is indicated for a mammographic abnormality that suggests malignancy or a mass that is palpable on physical examination. 7
Staging and prognosis Stage is based on The size of the primary tumor (T1 4). Presence and extent of lymph node involvement (N1 3). Presence or absence of distant metastases (M0 1). Early Breast Cancer Stage 0: Carcinoma in situ or disease that has not invaded the basement membrane. Stage I: Small primary tumor without lymph node involvement. Stage II: Involvement of regional lymph nodes. Locally Advanced Breast Cancer Stage III: Usually a large tumor with extensive nodal involvement in which node or tumor is fixed to the chest wall. Advanced or Metastatic Breast Cancer Stage IV: Metastases in organs distant from the primary tumor. 8
Early breast cancer therapy Local-Regional Therapy Treatment Surgery alone can cure most patients with in situ cancers and approximately one-half of those with stage II cancers. Breast-conserving therapy (BCT) is appropriate primary therapy for most women with stage I and II disease; it is preferable to modified radical mastectomy because it produces equivalent survival rates with cosmetically superior results. BCT consists of lumpectomy (i.e., excision of the primary tumor and adjacent breast tissue) followed by radiation therapy (RT) to prevent local recurrence. 9
RT is administered to the entire breast to eradicate residual disease after BCT. Reddening and erythema of the breast tissue with subsequent shrinkage of total breast mass are minor complications associated with RT. Simple or total mastectomy involves removal of the entire breast without dissection of underlying muscle or axillary nodes. This procedure is used for carcinoma in situ where the incidence of axillary node involvement is only 1% or with local recurrence following breast conservation therapy. Axillary lymph nodes should be sampled for staging and prognostic information. 10
Systemic adjuvant therapy Systemic adjuvant therapy is defined as the administration of systemic therapy following local therapy ( surgery, radiation, or a combination of these) when there is no evidence of metastatic disease, but high likelihood of disease recurrence. 11
Neoadjuvant or primary systemic therapy The use of preoperative systemic therapy is using in both early- stage and locally advanced breast cancers. The advantages of preoperative systemic therapy include 1- Decrease in the size of the tumor to minimize surgery. 2- to determine response to chemotherapy/ hormone therapy in vivo therapy. 12
Adjuvant Chemotherapy Early administration of effective combination chemotherapy at a time when a tumor burden is low should increase the likelihood of cure and minimize emergence of drug-resistant. Combination regimens more effective than single agent chemotherapy. Anthracycline-containing regimens (e.g., doxorubicin & epirubicin) significantly reduce the rate of recurrence and improve overall survival 5 and 10 years after treatment as compared with regimens that contain cyclophosphamide, methotrexate, and fluorouracil. 13
Both node-negative and node- positive patients benefit from anthracycline-containing regimens. The addition of Taxanes, docetaxel and paclitaxel, a newer class of agents, to adjuvant regimens resulted in significantly improved disease-free survival and overall survival in node-positive breast cancer patients. 14
Chemotherapy should be initiated within 3 weeks of surgical removal of the primary tumor. The optimal duration of treatment is about 12 to 24 weeks. Trastuzumab in combination with adjuvant chemotherapy is indicated in patients with early stage, HER2-positive breast cancer (human epidermal growth factor receptor 2) is one such gene that can play a role in the development of breast cancer. 15
Adjuvant endocrine therapy Hormonal therapies that have been studied in the treatment of primary or early breast cancer include tamoxifin, oophorectomy, ovarian irradiation, LHRH agonist, anastrozole, letrozole, and exemestane. Tamoxifen is the gold standard for adjuvant endocrine therapy. It has both estrogenic and antiestrogenic properties. Tamoxifen 20 mg daily, beginning soon after completing chemotherapy and continuing for 5 years, reduces the risk of recurrence and mortality. 16
Premenopausal women benefit from ovarian ablation with luteinizing hormone-releasing hormone (LHRH) agonists (e.g., goserelin) in the adjuvant setting, either with or without concurrent tamoxifen. (Anastrozole, letrozole, or exemestane) options for adjuvant hormonal therapy in postmenopausal women.they are used either in place of or after tamoxifen. 17
Locally advanced breast cancer (stage III) Neo adjuvant or primary chemotherapy is the initial treatment of choice. Primary chemotherapy with either an Anthracycline (e.g., doxorubicin & epirubicin) or taxane (docetaxel and paclitaxel ) -containing regimen is recommended. Surgery followed by chemotherapy and adjuvant RT should be administered to minimize local recurrence. 18
Metastatic breast cancer ( stage IV) The choice of therapy for MBC is based on the site of disease involvement and presence or absence of certain characteristics, as follow. Endocrine Therapy Endocrine therapy is the treatment of choice for patients who have hormone receptor-positive metastases in soft tissue, bone, pleura, or, if asymptomatic, viscera. Compared with chemotherapy, endocrine therapy has an equal probability of response and a better safety profile. 19
Patients are sequentially treated with endocrine therapy until their tumors cease to respond, at which time chemotherapy can be given. Treatment breast metastases cancer in postmenopausal women: Aromatase inhibitors (Anastrozole, letrozole, and exemestane) are approved for first-line therapy for advanced breast cancer in postmenopausal women. 20
Tamoxifen is the antiestrogen of choice in both premenopausal and postmenopausal with metastatic breast cancer who have tumors that are hormonereceptor positive. Toremifene has similar efficacy and tolerability as tamoxifen and is an alternative to tamoxifen in postmenopausal patients. 21
Fulvestrant is a second-line therapy of postmenopausal metastatic breast cancer patients who have tumors that are hormone receptor positive with disease progression following anti-estrogen therapy in patients on tamoxifen. It have similar efficacy and safety when compared to anastrozole. Megestrol acetate are generally reserved for third-line therapy. They cause weight gain, fluid retention, and thromboembolic events. 22
Treatment breast metastases cancer in premenopausal women: Ovarian ablation (oophorectomy) is considered by some to be the endocrine therapy of choice in premenopausal women and produces similar overall response rates as tamoxifen. An LHRH analog, goserelin, leuprolide, or triptorelin, is a reversible alternative to surgery. 23
Cytotoxic therapy Chemotherapy is preferred to endocrine therapy for women with hormone receptor-negative tumors; rapidly progressive lung, liver, or bone marrow involvement; or failure of endocrine therapy. Anthracyclines (e.g., doxorubicin & epirubicin) & taxane (docetaxel and paclitaxel ) produce response rates of 50% to 60% when used as first-line therapy for MBC. Single agent capecitabine, vinorelbine, or gemcitabine have response rates of 20% to 25% when used after an anthracycline and a taxane. 24
Ixabepilone, is indicated as monotherapy or in combination with capecitabine in MBC patients who have previously received an anthracycline and a taxane. Response rates and time to progression were increased with combination therapy as compared with capecitabine alone. 25
Biologic Therapy Trastuzumab, a monoclonal antibody that binds to HER2, produces response rates of 15% to 20% when used as a single agent and increases response rates, time to progression, when combined with chemotherapy. Lapatinib, a tyrosine kinase inhibitor that targets HER2, improved response rates and time to progression in combination with capecitabine, as compared to capecitabine alone, in patients previously treated with an anthracycline, taxane, and trastuzumab. 26
Radiation Therapy Radiation is commonly used to treat painful bone metastases or other localized sites of disease including brain and spinal cord lesions. Pain relief is seen in approximately 90% of patients who receive RT. 27