Stage IV Breast Cancer

Overview

Patients diagnosed with Stage IV or metastatic breast cancers have disease that has spread from the affected breast to one or more distant sites in the body. Historically, metastatic breast cancer has been considered incurable; the goal of treatment has been to provide relief from symptoms and prolong the duration and quality of life. However, there have been some important advances resulting in the addition of many more treatment options for managing this disease. These include the now widespread use of taxane chemotherapy, the development of targeted therapies, and the development of more active hormonal therapy drugs.

The following is a general overview of the diagnosis and treatment of stage IV breast cancer. Recent advances in treatment have resulted in new treatment options that reduce symptoms and improve survival. Each person with stage IV breast cancer is different, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.

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The topics covered in this section include:

Chemotherapy Treatment of Metastatic Breast Cancer

Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Patients with breast cancer that does not have estrogen/progesterone receptors, those not responding to hormonal treatment, and individuals requiring symptomatic relief from progressive breast cancer may benefit from treatment with chemotherapy. There are currently several standard treatment regimens available, and approximately 25% of patients who undergo chemotherapy will experience a complete remission of their cancer.

The type of chemotherapy that is selected depends on the goal of treatment. If the goal of treatment is to reduce symptoms and improve quality of life, it may be more desirable to select a chemotherapy treatment with minimal side effects. On the other hand, if the goal of treatment is to attempt to cure the cancer, treatment with more aggressive chemotherapy regimens or participation in clinical studies evaluating new treatment strategies may be more appropriate.

It is important to carefully consider the goals of treatment. One reason for this is that initial treatment of Stage IV breast cancer is typically more effective than retreating cancer that has recurred. This is because cancer cells may become resistant to therapy. Patients who are interested in aggressive treatment and whose goal is cure may want to consider aggressive therapy or participation in a clinical study as their first or initial treatment.

Taxanes

In recent years, a class of chemotherapy drugs called the taxanes has been widely used in the treatment of breast cancer. Taxotere® (docetaxel) and Taxol® (paclitaxel) are both taxanes that, when used in combination or sequentially with other chemotherapy drugs, appear to have more anti-cancer activity than previous non-taxane chemotherapy for the treatment of metastatic breast cancer. The best schedule for administering taxanes is still being evaluated. Some research indicates that more frequent administration may be better than the standard schedule of every three weeks.[1] 

Results from a large clinical trial indicate that Taxotere produces higher anti-cancer response rates, progression-free survival, and overall survival compared to Taxol (see table 1).[2] 

Table 1: Taxotere versus Taxol in the treatment of breast cancer

  Taxotere Taxol
Anti-cancer response 32% 25%
Progression-free survival 5.7 months 3.6 months
Overall survival 15.4 months 12.7 months

Abraxane™ (nanoparticle albumin-bound paclitaxel): A new technique for delivering anti-cancer drugs has been recently developed, called nanoparticle albumin-bound (nab) technology. Abraxane™ is a treatment that delivers the anti-cancer drug paclitaxel using nab technology. This technique utilizes albumin, the most abundant protein in the body, to deliver the paclitaxel directly to cancer cells.

Abraxane offers several advantages over the conventional formulation of paclitaxel, which is known as the drug Taxol and is comprised of a toxic, chemical solvent in addition to the active drug. With Abraxane 50% more drug can be administered, more active drug is transported into the cancer cells, and patients experience fewer side effects.

In a clinical trial that directly compared of Abraxane to Taxol in the treatment of 454 patients with metastatic breast cancer, Abraxane doubled anti-cancer response rates and significantly prolonged time to disease progression with fewer side effects compared to Taxol.[3] [4] (see table 2).

Table 2: Abraxane improves outcomes compared to Taxol

  Abraxane Taxol
Response rate 33% 19%
Time to cancer progression 23.0 weeks 16.9 weeks
Overall survival 65 weeks 55.7 weeks
Grade 4 neutropenia
(low white blood cell count)
9% 22%

 

Combination Chemotherapy Regimens

Combinations of two or more chemotherapy drugs are referred to as regimens. Regimens have been shown to kill more cancer cells than single chemotherapy drugs. This is because each type of drug interrupts cells from replicating at different points in their lifecycle. Since all cancer cells are not at the same phase of development at the same time, chemotherapy regimens have the ability to interrupt and kill more cancer cells.

The optimal schedule for administering regimens is still being evaluated. Administering chemotherapy drugs in sequence (one following another), rather than together as a combination, has shown promise.

Regimens that Include a Taxane

Current research indicates that the following taxane-containing regimens improve outcomes over either a single drug or a conventional regimen:

Doxorubicin and paclitaxel (AT): Two clinical trials, published in 2001 and 2003, have shown that patients who receive AT live longer, are cancer-free longer, or experience a longer period of time before their cancer progresses than those who receive the common chemotherapy treatment consisting of fluorouracil, doxorubicin, and cyclophosphamide (FAC)[5] [6] (see table 3).

Table 3: AT versus FAC in the treatment of metastatic breast cancer

  AT FAC
Time to cancer recurrence (2001) 8.3 months 6.2 months
Average survival (2001) 23.3 months 18.3 months
Time to cancer progression (2003) 8.1 months 6.6 months

TAC (Taxotere, doxorubicin, and cyclophosphamide): In an attempt to further improve treatment, a third drug has been added to the AT regimen and evaluated as initial treatment for patients with metastatic breast cancer. Partial or complete disappearance of cancer following treatment with TAC occurred in 77% of patients. Two years following treatment, nearly 60% of patients were still alive.[7] 

Gemzar® (gemcitabine) and Taxol (GT): Results of a clinical trial reported in 2004 indicate that Gemzar and Taxol improves survival over Taxol alone in the treatment of patients with metastatic breast cancer who have stopped responding to anthracycline treatment (see table 4).[8] 

Table 4: Survival benefit of Gemzar and Taxol over Taxol alone

  Gemzar and Taxol Taxol alone
1-year survival 70.0% 60.9%
Overall survival 18.5 months 15.8 months

 

In May of 2004, the FDA approved GT for initial treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing chemotherapy, unless anthracyclines were clinically contraindicated.

Hormonal Therapy
Chemotherapy
Targeted Therapy
Strategies to Improve Treatment

CancerConnect Breast Cancer Community & Discussions

CC.com_tb3You are not alone—The CancerConnect Breast Cancer Community is the leading Social Media Application for Breast Cancer patients and caregivers seeking information, inspiration, and support in the wake of a cancer diagnosis. With over 50,000 members the network offers patients and caregivers a thriving community to support the many ongoing needs from diagnosis to survivorship. Login or register here.

References


[1] Seidman D, Berry C, Cirrincione C, et al. CALGB 9840: Phase III study of weekly (W) paclitaxel (P) via 1-hour (h) infusion versus standard (s) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology. New Orleans LA. 2004; Abstract #512. 

[2] Jones SE, Overmoyer EB, Budd GT, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. Journal of Clinical Oncology. 2005;23:5542-5551. 

[3] O’Shaughnessy J, Tjulandin S, Davidson N, et al. ABI-007 (Abraxane®), a nanoparticle albumin-bound paclittaxel demonstrates superior efficacy vs. taxol in MBC: a phase III trial (Abstract #44). Proceedings from the 26th annual San Antonio Breast Cancer Symposium ( 12/3/03 ), Abstract #44.  

[4] New Antitubulin Agents. Proceedings from the 22nd annual Miami Breast Cancer Conference. Presented by Dr. Perez. Friday February 25, 2005. 2:45 pm. Miami, Florida. 

[5] Jassem J, Pienkowski T, Pluzanska A, et al. Doxorubicin and Paclitaxel Versus Fluorouracil, Doxorubicin, and Cyclophosphamide as First-Line Therapy for Women With Metastatic Breast Cancer: Final Results of a Randomized Phase III Multicenter Trial. Journal of Clinical Oncology. 2001;19(6):1707-1715. 

[6] Bontenbal M, Braun JJ, Creemers GJ, de Boer AC, et al. Phase III study comparing AT (Adriamycin, Docetaxel) to FAC (Fluorouracil, Adriamycin, Cyclophosphamide) as first-line chemotherapy (CT) in patients with metastatic breast cancer (MBC). Proceedings from the 12th European Conference on Clinical Oncology, 2003; Copenhagen , Denmark.

[7] Nabholtz JM, Mackey JR, Smylie M, et al. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Journal of Clinical Oncology. 2001;19:314-321.

[8] Albain KS , Nag S, Calderillo-Ruiz G, Jordaan JP, et al. Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall survival. Proceedings from the 40th annual meeting of the American Society of Clinical Oncology held in New Orleans LA , June 4-8, 2004, Abstract #510.

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