Locally advanced breast cancer

Combined Modality of Locally Advanced Breast Cancer Locally Advanced Breast Cancer ... 

Docetaxel acts by disrupting cells microtubular network, which is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. Docetaxel is indicated in locally advanced or metastatic breast cancer locally advanced or metastatic non-small-cell lung cancer. The first compound of this series, paclitaxel (Taxol), was isolated from the bark of the Western yew tree in 1971. Paclitaxel and its congenic, the semisynthetic docetaxel (Taxotere), exhibit unique pharmacological actions as... 

Determine the treatment goals for early-stage, locally advanced, and metastatic breast cancer. 

Neoadjuvant chemotherapy is appropriate for patients with locally advanced or inflammatory breast cancer, followed by local therapy and further adjuvant systemic therapy. 

Most breast cancers diagnosed are small tumors (less than or equal to 2 cm), and disease is localized in all racial and ethnic groups. However, blacks and other minority women have proportionally more cases of disease diagnosed at more advanced stages compared with white women. This is thought to reflect access to and use of screening mammography and timely treatment. 

In most instances, external-beam radiation therapy used in conjunction with breast-conserving procedures involves 4 to 6 weeks of radiation therapy directed to the breast tissue to eradicate residual disease. Complications associated with radiation therapy to the breast are minor and include reddening and erythema of the breast tissue and subsequent shrinkage of total breast mass beyond that predicted on the basis of breast tissue removal. Some clinical situations also require postmastectomy radiation therapy as well (see section on locally advanced breast cancer). 

The use of preoperative systemic therapy is gaining favor in both early-stage and locally advanced breast cancers. This approach to therapy, referred to as neoadjuvant or primary systemic therapy, most often consists of chemotherapy but in special circumstances also may include hormonal therapy (e.g., in inoperable patients with significant comorbidities). The advantages of preoperative systemic therapy include... 

TREATMENT LOCALLY ADVANCED BREAST CANCER (STAGE III)... 

Locally advanced cancer breast cancer generally refers to breast carcinomas with significant primary tumor and nodal disease but in which distant metastases cannot be documented. A wide variety of clinical scenarios can be seen within this group of patients, including neglected tumors that have spread locally and inflammatory breast cancers that are a unique clinical entity. Many locally advanced breast cancers are diagnosed in patients who have had symptoms for months to years and have neglected to seek medical attention. Patients with inflammatory breast cancer often are treated inappropriately for cellulitis with antibiotics for several weeks to months. 

The goal of therapy with early and locally advanced breast cancer is to cure the disease. Breast cancer is currently incurable after it has advanced beyond local-regional disease. The goal of treatment of metastatic breast cancer is to improve symptoms, maintain quality of life, and extend survival. Thus it is important to choose therapy with good activity while minimizing toxicities. Treatment of metastatic breast cancer with either cytotoxic or endocrine therapy often results in regression of disease and improvements in quality of life. 

Locally advanced breast cancer often is treated with neoadjuvant therapy to make the tumor surgically respectable. During neoadjuvant chemotherapy, laboratory values to monitor chemotherapy toxicity are obtained prior to each cycle of chemotherapy, and a physical examination and ultrasound exams to detect size of tumor are performed after the cycles of neoadjuvant therapy are completed. After a complete surgical resection, monitoring proceeds as described earlier for early breast cancer. 

The goal of therapy with early and locally advanced breast cancer is cure. The goals of therapy with MBC are to improve symptoms, improve quality of life, and prolong survival. 

The goal of neoadjuvant chemotherapy in locally advanced breast cancer is cure. Complete pathologic response, determined at the time of surgery, is the desired end point. 

Buzdar A, O Shaughnessy JA, Booser DJ, Pippen JE Jr, Jones SE, Munster PN, et al. (2003) Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer. J Clin Oncol 21 1007-1014... 

Kafka, A., Sauer, G., Jaeger, C., et al. (2003) Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer. Int. J. Oncol. 22, 1117-1121. 

Currently, anastrozole and letrozole are efficacious in early-stage, locally advanced, and mefasfafic disease and fhus they present with the most complete data set for the different stages of breast cancer. Although it seems rather unlikely that one will be able to detect differences with respect to clinical effects at the tumour level, the indirect comparison of different AIs suggests a stronger evidence for the use of exemestane compared with other AIs for breast cancer therapy [90]. 

Skinner KA, Silberman H, Florentine B, et al. Preoperative paclitaxel and radiotherapy for locally advanced breast cancer surgical aspects. Ann Surg Oncol 2000 7(2) 145-149. 

The management of locally advanced breast cancer requires the integration of surgery, chemotherapy, and radiation therapy. This chapter summarizes the existing experience and addresses some of the remaining issues in combined modality therapy of locally advanced and inflammatory breast cancer. 

LOCALLY ADVANCED BREAST CANCER SEQUENTIAL THERAPIES... 

LOCALLY ADVANCED BREAST CANCER CONCURRENT CHEMORADIATION... 

Encouraged by the promising results achieved in other tumor types (4-6), in the early 1990s we hypothesized that locally advanced breast cancer could also be treated by primary concurrent chemoradiation (chemo-RT). Moreover, LABC could be a clinical setting to conduct interesting translational research. A series of observations justified this position ... 

The management of locally advanced breast cancer and inflammatory breast cancer has evolved over the past twenty years. In general, surgery has maintained a role in the combined management of this disease but most studies have tested strategies to increase the extent of pathological response, especially in view of its prognostic implications. 

Schaake-Koning C, van der Linden EH, Hart G, Engelsman E. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer a randomized clinical study. Int J Radiat Oncol Biol Phys 1985 11 1759-1763. 

Rubens RD, Bartelink H, Engelsman E, et al. Locally advanced breast cancer the contribution of cytotoxic and endocrine treatment to radiotherapy. An EORTC Breast Cancer Co-operative Group Trial (10792). EurJ Cancer Clin Oncol 1989 25 667-678. 

FormentiSC, Uziely B, DunningtonG, etal. Continuous infusion (ci) 5-fluorouracil (FU) with radiation in locally advanced breast cancer clinicopathological and biological correlates (Meeting abstract). 

Formenti SC, Dunnington G, Uzieli B, et al. Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy. Int J Radiat Oncol, Biol, Physics 1997 39 1059-1068. 

Merajver SD, Weber BL, Cody R, et al. Breast conservation and prolonged chemotherapy for locally advanced breast cancer the University of Michigan experience. J Clin Oncol 1997 15 2873-2881. 

Morrell LE, Lee YJ, Hurley J, et al. A Phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma. Cancer 1998 82 503-511. 

Karlsson YA, Malmstrom PO, Hatschek T, et al. Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide prognostic and therapeutic implications. Cancer 1998 83 936-947. 

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