Breast metastase

Most centres perform contrast-enhanced studies at 3-month intervals in patients with colorectal metastases. The follow-up interval should be tailored to the underlying primary tumour and the biological behaviour, i.e. most of our patients with breast metastases have followup scans at 4- 6-month intervals and most patients with more indolent neuro-endocrine metastases have scans at 6- to 12-month intervals. 

MTX is part of curative therapeutic schedules for acute lymphoblastic leukemias (ALL), Burkitt s lymphoma, and choriocarcinoma. It was also used in adjuvant therapy of breast cancer. High dose MTX with leucovorin rescue can induce about 30% remissions in patients with metastatic osteogenic sarcoma. MTX is one of the few antineoplastic drugs that can be safely administered intrathecally for the treatment of meningeal metastases and leukemic infiltrations (routine prophylaxis in ALL). In addition, MTX can be used as an immunosuppressive agent for the treatment of severe rheumatoid arthritis and psoriasis. 

Warning associated with the administration of estrogen include an increased risk of endometrial cancer, gallbladder disease, hypertension, hepatic adenoma (a benign tumor of the liver), cardiovascular disease, increased risk of thromboembolic disease and hypercalcemia in those with breast cancer and bone metastases. 

Intraarterial infusion of microspheres containing adriamycin was used for the local treatment of breast cancer and recurrent breast cancer with liver metastases (123). A reduction in tumor size was noted when the microspheres were injected into the internal and lateral thoracic arteries for treatment of the primary tumor. However, hepatic artery injection for liver metastases resulted in improvement in only one of three patients treated. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

The usual metastatic sites for solid tumors are the brain, the bone, the lung, and the liver. It is important to realize and educate patients that breast cancer cells may metastasize to the brain, so the individual doesn t have brain and breast cancer but breast cancer metastases to the brain. 

An NIH Consensus Development Conference Statement22 advises that adjuvant hormonal therapy should be recommended to women whose tumors contain hormone-receptor protein regardless of age, menopausal status, involvement of axillary lymph nodes, or tumor size. They also support a benefit of adjuvant chemotherapy for most women with lymph node metastases or with primary breast cancers larger than 1 cm in diameter (both node-negative and node-positive).22... 

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. 

Tamoxifen can be used in both premenopausal and postmenopausal women with metastatic breast cancer who have tumors that are hormone-receptor-positive. The toxicities of tamoxifen are described in the section on adjuvant endocrine therapy. The only additional toxicity that one might expect to find in the setting of metastatic breast cancer (specifically bone metastases) is a tumor flare or hypercalcemia, which occurs in approximately 5% of patients following the initiation of any SERM therapy and is not an indication to discontinue SERM therapy. It is generally accepted that this is a positive indication that the patient will respond to endocrine therapy. 

Cytotoxic chemotherapy is eventually required in most patients with metastatic breast cancer. Patients with hormone-receptor-negative tumors require chemotherapy as initial therapy of symptomatic metastases. Patients who respond initially to hormonal manipulations eventually cease to respond and go on to require chemotherapy. The median duration of response is 5 to 12 months, but some patients will have an excellent response to an initial course of chemotherapy and may live 5 to 10 years or longer without evidence of disease. In general, median survival of patients after treatment with commonly used drug combinations for metastatic breast cancer is 14 to 33 months. The median time to response has ranged from 2 to 3 months in most studies, but this period depends in large part on the site of measurable disease. The median time to appearance of response is between 3 and 6 weeks in patients whose disease is primarily in the skin and lymph nodes, 6 to 9 weeks in patients with metastatic lung involvement, 15 weeks in patients with hepatic involvement, and nearly 18 weeks in patients with bone involvement. Thus it is often the case that an immediate response to therapy is not... 

For women whose breast cancer has metastasized to bone, bisphosphonates are recommended, in addition to chemotherapy or endocrine therapy, to reduce bone pain and fractures.28,64 Pamidronate (90 mg) and zoledronate (4 mg) can be given intravenously once each month. These bisphosphonates are given in combination with calcium and vitamin D. 

Around 20,000 cancer patients experience spinal cord compression in the United States every year, most of which involves the thoracic spine (approximately 70%). Cancers that inherently metastasize to bone (e.g., breast, prostate, and lung) are the most frequent etiologies identified. Most spinal cord compression occurs in patients with a known malignancy however, 8% to 34% occurs as the initial presentation of cancer, especially in patients with non-Hodgkins lymphoma, multiple myeloma, and lung cancer.17... 

Brain metastasis is the most common neurologic complication seen in patients with cancer. Approximately 170,000 patients develop brain metastases in the United States each year.20 Many malignancies are frequently associated with brain metastases (Table 96-7). While melanoma is the tumor type most likely to metastasize to the brain, brain metastases owing to lung and breast cancers are seen more often because they are among the most common cancers. In addition, brain metastasis may be diagnosed at the same time as the primary malignancy in around 20% of cases.22 Around 80% of brain metastases occur in the cerebral hemispheres, 15% in the cerebellum, and 5% in the brain stem. 

Thus, expression of CXCR4 on tumor cells, which is common to many breast cancers as well as other cancer types, may contribute to malignant behavior in several ways. CXCR4 expression by tumor cells may interact with CXCL12 to facilitate tumor cell growth and escape from oxygen starvation-induced apoptosis and as a mechanism to home (metastasize) to secondary sites. 

A 50- year-old female had a radical mastectomy three years ago for hormone-dependent breast adenocarcinoma. She is now complaining of shortness of breath, and chest X-ray shows diffuse lung metastases. As part of her therapeutic regimen, she is given intramuscular hormone replacement therapy (1IRT). 

The answer is d. (Hardman, pp 1275-1276J Tamoxifen is an estrogen antagonist used in the treatment of breast cancer. Postmenopausal women with metastases to soft tissue and whose tumors contain an estrogen receptor are more likely to respond to this agent Little benefit is derived from tamoxifen if the tumor does not have estrogen receptors. 

Toremifen is a SERM considered a tamoxifen analog characterized by one chlorine atom and is approved for first-line treatment of metastasic breast cancer in postmenopausal women who have tumors that are either ER(+) or of unknown status. In a 3-year face-to-face study with tamoxifen, there were no significant differences between both drugs. The number and profile of adverse events are also similar. Experience with toremifen is limited and far from that accumulated with tamoxifen. 

Ingle JN, Krook JE, Green SJ et al. (1986) Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastasic breast cancer. J Clin Oncol 4 178-185... 

Metastatic bone disease (MBD) is characterized by very high levels of bone turnover in regions proximal to the tumour [33]. Bone resorption inhibitors such as bisphosphonates represent the current standard of care for the treatment of bone metastases primarily due to breast or prostate cancer and multiple myeloma. It has been proposed that other strong anti-resorptives such as a Cat K inhibitor could be useful in the treatment of bone metastases. Evidence for this has been presented in the form of a preclinical MBD model in which human breast cancer cells are implanted into nude mice. Treatment with a Cat K inhibitor gave a significantly lower area of breast cancer-mediated osteolytic lesions in the tibia [34]. In a separate study, the efficacy of a Cat K inhibitor in the reduction in tumour-induced osteolysis was found to be enhanced in the presence of the bisphosphonate zolendronic acid [35,36]. When prostate cancer cells were injected into the tibia of SCID mice, treatment with a Cat K inhibitor both prevented and diminished the progression of cancer growth in bone [37]. 

Then, last year, I discovered I had a fibrous growth in my breast about four or five inches long. And it grew very rapidly. I didn t want to have it removed, but I finally agreed to. I thought that was the end of it, but when a biopsy was done there were cancer cells found inside it. It was a cancer that rarely will metastasize, and when it does it goes to the chest, so it s contained it is not genetically linked. As far as cancers go, this is not a bad one to have. But it does not respond to chemotherapy or radiation. 

The presence or absence of metastases in local lymph nodes is widely used as a prognostic marker. Generally, patients with metastasis in these lymph nodes have a significantly poorer outcome than those patients without metastases. However, at least in the case of breast cancer, about 25-30% of node-negative patients die from their disease within 10 years. As mentioned earlier, there is a particular urgent need for new markers to identify those high-risk, axillary node-negative breast cancer patients. 

Symon Z, Peyser A, Tzemach D, et al. Selective delivery of doxorubicin to patients with breast carcinoma metastases by Stealth liposomes. Cancer 1999 86 72-78. 

The phase-three results were unblinded in March 2003 and overall, for all types of metastatic brain cancer, were reported as nonpositive, showing the drug to have efficacy but not at the statistical level set at the beginning of the trial by Alios Therapeutics Inc. for a successful phase-three trial. The subset analysis for the different types of metastatic cancer to brain, however, showed that breast cancer patients had a 100% increase in survival. The 500 plus patient trial also demonstrated RSR 13 to be extremely safe, confirming our early design feature of using a known antilipidemic drug, clofibrate, as a substructure. An NDA for RSR 13 with trade name efaproxaril was reviewed by the PDA on a fast track review for use in treatment of metastases of breast cancer to brain. 

On June 2, 2004, the PDA gave an approvable letter to market efaproxaril if the ongoing phase-three trial, called ENRICH (Enhancing Whole Brain Radiation Therapy in Patients with Breast Cancer and Hypoxic Brain Metastases), designed specifically for the use of efaproxaril to treat metastatic breast cancer to brain, is successful. The ENRICH phase three trial will seek to enroll approximately 360 patients at up to 50 cancer centers across North/South America and Europe. In the letter, the PDA stated, if the study shows effectiveness in this population (increased survival) using the prespecified analysis, and the study is otherwise satisfactory, we believe it would, together with the subset result in RT-009, support approval (http //biz.yahoo.eom/prnews/040602/law025 l.html). 

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