Tumor Cells In Axillary Nodes Research Articles

Abstract P1-12-04: Long Term Follow-Up of a Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer

Abstract Introduction: Overexpression of vascular endothelial growth factor (VEGF) in breast cancer tumors has been associated with resistance to anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods: Patients were treated with a neoadjuvant regimen of letrozole, 2.5 mg/day (PO) and bevacizumab 15 mg/kg every 3 weeks (IV) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at three week intervals and tumor assessment (physical exam and tumor ultrasound) at six week intervals. Results: Twenty-five evaluable patients were treated. The regimen was well tolerated except for two patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The four patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. Two of the 17 responding patients were lost to follow-up; with a median follow-up of 50 months, no relapses have been seen in the 15 responsive patients, including 10 patients who received no adjuvant chemotherapy. Two patients with progressive disease at 9 and 16 weeks received neoadjuvant chemotherapy, surgery and radiation. One of these patients relapsed at 35 months and the other is NED at 44 months. Four patients had stable disease and all received adjuvant chemotherapy; one patient relapsed at 25 months, and the reminder are NED at 44-52 months. Overall, 2 out of 21 patients with adequate follow-up had disease reoccurrence (9.5%) at a median follow-up of 45 months. Conclusion: Combination neoadjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in impressive clinical and pathologic responses. Data suggest that patients having an objective response to neoadjuvant therapy had excellent 4 year disease-free survival (100%) while relapsed occurred in 2 out of 6 patients who failed to have an objective response despite additional neoadjuvant or adjuvant chemotherapy. The Breast Cancer Translational Research Consortium has an ongoing randomized phase II trial of letrozole ± bevacizumab in this patient population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-04.

A Pilot Trial of Pre-Operative (Neoadjuvant) Letrozole in Combination with Bevacizumab in Post-Menopausal Women with Newly Diagnosed Estrogen and/or Progesterone Receptor Positive Breast Cancer.

Abstract Purpose Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods Patients were treated with a neo-adjuvant regimen of letrozole, 2.5mg/day (P.O.) and bevacizumab 15mg/kg Q3 weeks (I.V.) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at 3 week intervals and tumor assessment (physical exam and tumor ultrasound) at 6 week intervals. PET scans were carried out prior to therapy and 6 weeks after initiation of therapy. Surgery was done 4 weeks after the last dose of bevacizumab. Results Twenty five evaluable patients were treated. The regimen was well tolerated except for 2 patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The 4 patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. 8/25 patients (32%) attained stage 0 or 1 status. PET scan response at 6 weeks correlated with clinical CR and breast pathologic CR at 24 weeks (p < 0.0036). Conclusion Combination neo-adjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in impressive clinical and pathologic responses. The Breast Cancer Translational Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1088.

Experimental observations on the significance of cell burden in tumor control

Experiments using a transplanted murine lymphosarcoma in syngeneic mice show that an initial inoculum of at least 106 tumor cells is needed to generate an immune response adequate to repel subsequent challenge from similar cells. The relationship among cell burden, dose of x radiation, and tumor control was studied. The experiments demonstrated that the number of tumor cells rejected as the result of an immunizing inoculation is approximately equivalent to the number of cells needed to initiate immunity. A correlation was established between the size of the initial injection and the probability of tumor invasion of regional lymph nodes. In addition, the existence was shown of a progressive increase in the number of tumor cells in axillary lymph nodes in mice in which the primary tumor recurs following irradiation, while in those mice in which the primary tumor is controlled, tumor cells in the axillary nodes disappear shortly after the local treatment. Several trials indicated that in this particular tumor system, the host's immunologic response will prevent the growth of 104−105 cell inocula but that larger numbers of cells overwhelm the natural defenses and grow unabated. Our evidence supports the clinical observation that moderate doses of irradiation will control subclinical tumor cell populations. In addition, it is suggested that the immune response of the host may enhance the effects of radiation not only by increasing local cell kill but also by preventing the proliferation of disseminated cells outside the irradiated volume.