Management and prognosis of breast cancer

As therapies for breast cancer continue to emerge, the issues of how to best monitor success and gauge prognosis remain important questions.
The following abstracts have been presented at the CTRC-AACR Annual San Antonio Breast Cancer Symposium.

Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of Trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial

Researchers, led by Edith Perez, at the Mayo Clinic in Jacksonville, found a 25 percent reduction in the risk of breast cancer recurrence when Trastuzumab ( Herceptin ) was administered concurrently, rather than following chemotherapy.
All patients enrolled in this phase III trial were receiving standard chemotherapy of Doxorubicin and Cyclophosphamide followed by Paclitaxel.
The researchers conducted two separate comparisons.
The first included 2,448 patients randomly assigned to chemotherapy alone or chemotherapy followed by Trastuzumab. After 5.5 years, the researchers observed 386 events. After adjustment for possible confounding variables, they found that event-free survival increased from 72 percent with chemotherapy alone to 80 percent with chemotherapy followed by Trastuzumab.
The second comparison included 1,903 women. The researchers compared those who received Trastuzumab after chemotherapy with those who received it concurrently with Paclitaxel. At five years, disease-free survival increased from 80 percent to 84 percent.

Circulating tumor cells and epithelial mesenchymal transition in breast cancer: describing the heterogeneity of microscopic disease

Circulating tumor cells ( CTCs ) are an important predictor of survival in metastatic breast cancer patients. When CTCs undergo epithelial-mesenchymal transition ( EMT ), resulting in a loss of epithelial markers, they may escape conventional detection.
The presence of an increased number of CTCs is associated with poor prognosis in breast cancer patients. Cells with this EMT phenotype are probably involved in tumor dissemination and represent tumor initiating cells. Identification of therapeutic targets on these cells could lead to eradication of micrometastatic disease in breast cancer, as well as in other epithelial tumors.
When epithelial cells undergo EMT, they lose their epithelial receptors. As a result, they are no longer detected by current detection assays. In addition, these cancer cells become resistant to chemotherapy or radiation therapy.
In this prospective study, Mego and colleagues ( University of Texas MD Anderson Cancer Center ) used approximately 5 mL of peripheral blood from patients with varying stages of breast cancer and isolated the CTCs using magnetic beads coated with monoclonal antibodies. Using a polymerase chain reaction, they then isolated RNA to detect genes that are involved in EMT.
Patients who had triple-negative breast cancer more commonly overexpressed EMT genes compared to non-triple-negative patients.

Mucinous breast carcinoma: occult multifocality/multicentricity in a favorable disease

A large sample of patients with pure mucinous breast cancer demonstrated a favorable prognosis. However, Researchers also found an association with significant occult multicentricity/multifocality.
Mucinous carcinoma is a rare form of cancer, diagnosed in about 2 percent of patients with breast cancer. Cancer cells within the breast produce mucous, forming a jelly-like tumor. Previous research has shown that the disease has a favorable prognosis; therefore, Researchers have recommended treating patients with the minimal effective therapy versus the maximum tolerated treatment.
Perkins and colleagues ( University of Texas MD Anderson Cancer Center ) reviewed charts for 264 patients diagnosed with a pure mucinous carcinoma from 1965 to 2005.
At five years, overall survival was 95 percent; the 10- and 15-year rate was 97 percent. Rates for distant metastases-free survival were similar: 88 percent at five years; 95 percent at 10 years; and 94 percent at 15 years. The five-year local regional control rate was 83 percent; at 10 years it was 92 percent; and at 15 years it was 85 percent.
Initially, 10 percent of the patients had a multicentric/multifocal presentation; however, a detailed pathology review revealed a 38 percent rate of multicentric/multifocal disease after resection.

Tumor Ki67 proliferation index within 4 weeks of initiating neoadjuvant endocrine therapy for early identification of non-responders

As a prognostic tool, the preoperative endocrine prognostic index ( PEPI ) has been developed as a way to identify estrogen-receptor positive ( ER+ ) breast cancers that have a poor long-term outcome because of a failure to respond to Tamoxifen ( Nolvadex ) or an aromatase inhibitor after three to four months of pre-surgical treatment.
The PEPI is based on pathological tumor size, nodal stage, ER status and a protein marker for proliferation, Ki67. A team at Washington University School of Medicine has now developed a faster way to identify patients with poor outcome disease by measuring tumor Ki67 early, just two to four weeks after starting neoadjuvant endocrine therapy. By assessing tumor response to endocrine therapy sooner, non-responding tumors can be triaged to neoadjuvant chemotherapy. This approach is currently undergoing prospective evaluation in the American College of Surgeons Z1031 trial.
Researchers measured Ki67 levels in tumors of 158 postmenopausal women in two independent trials with confirmed ER+ stage II and III breast cancers two to four weeks into endocrine therapy.
Tumor Ki67 measuring more than 10 percent accurately predicted higher rates of relapse, and the absence of a group of patients with such a low score suggested adjuvant chemotherapy is not likely to be of benefit.

Source: American Association for Cancer Research, 2009



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