Social support and its implications in older, early-stage breast cancer patients in CALGB 49907 (Alliance A171301).

BACKGROUND: Studies point to a direct association between social support and better cancer outcomes. This study examined whether baseline social support is associated with better survival and fewer chemotherapy-related adverse events in older, early-stage breast cancer patients. METHODS: This study is a pre-planned secondary analysis of CALGB 49907/Alliance A171301, a randomized trial that compared standard adjuvant chemotherapy versus capecitabine in breast cancer patients 65 years of age or older. A subset reported on the extent of their social support with questionnaires that were completed 6 times over 2 years. RESULTS: The median age of this 331-patient cohort was 72 years (range: 65, 90); 179 (55%) were married, and 210 (65%) lived with someone. One hundred forty-five patients (46%) described a social network of 0-10 people; 110 (35%) of 11-25; and 58 (19%) of 26 or more. The Medical Outcomes Study (MOS) social support survey revealed that the median scores (range) for emotional/informational, tangible, positive social interaction, and affectionate social support were 94 (3, 100), 94 (0, 100), 96 (0, 100), and 100 (8, 100), respectively. Social support scores appeared stable over 2 years and higher (more support) than in other cancer settings. No statistically significant associations were observed between social support and survival and adverse events in multivariate analyses. However, married patients had smaller tumors, and those with arthritis reported less social support. CONCLUSION: Although social support did not predict survival and adverse events, the exploratory but plausible inverse associations with larger tumors and arthritis suggest that social support merits further study.

Regional immunity in melanoma: immunosuppressive changes precede nodal metastasis.

In order to characterize the degree of immunosuppression in regional immunity in patients with melanoma, we used immunohistochemistry to analyze markers of T-cell subtype and polarity, costimulation, dendritic cell maturation, monocytes, lymphatic vasculature, and angiogenesis. Specifically, we analyzed expression of CD4, CD8, CD14, CD40, CD86, CD123, HLA-DR, IL-10, LYVE, VEGFR3, and VEGF-C in lymph nodes. We compared sentinel lymph nodes with and without metastasis from patients with melanoma with both infection inflamed (reactive) and dormant human lymph nodes. There were no differences demonstrated between sentinel lymph nodes with or without metastasis from patients with melanoma in any of the markers that were tested. Both groups of sentinel lymph nodes had fewer CD8(+) T cells than either set of control nodes. Whereas the infection inflamed lymph nodes demonstrated Th2 polarity, the dormant lymph nodes demonstrated Th1 polarity. In conclusion, changes in regional immunity appeared to precede metastasis in melanoma. Whether there was tumor present in sentinel lymph nodes or not, these nodes demonstrated a marked decrease in cytotoxic T cells compared with both sets of controls. Furthermore, the control lymph nodes used for comparison can significantly impact interpretation, as the dormant and reactive lymph nodes markedly varied in their immune profiles. These immunologic changes may explain the successful metastasis of melanoma in the midst of the immune environment of the sentinel lymph node, and lend insights into the mechanisms of lymphatic metastases in other solid malignancies.

Cytokeratin-19 and mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group trials, N0234/336/436/437.

PURPOSE: To investigate the associations between baseline and posttreatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four North Central Cancer Treatment Group metastatic breast cancer (MBC) trials in which specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic, Rochester, MN). EXPERIMENTAL DESIGN: Blood was collected at treating sites from MBC patients before (baseline), during, and at the end of treatment with erlotinib + gemcitabine (N0234), sorafenib (N0336), irinotecan + cetuximab (N0436), or paclitaxel-poliglumex + capecitabine (N0437). CTCs from 10 mL of EDTA blood were enriched with CD45 depletion, 24 to 30 hours postblood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized to ß(2)-microglobulin and calibrated to healthy blood using the 2(-ΔΔCq) algorithm; positivity was defined as 2 or more. RESULTS: CK19+mRNA cells were detected in 56% to 75% and MGB1+mRNA cells in 23% to 38% of 86 patients at baseline. CK19+mRNA cells were detected in 30% to 67% and MGB1+mRNA cells in 14% to 64% of 110 postbaseline serial samples. The presence of baseline CK19+mRNA cells (P = 0.01) but not MGB1+mRNA cells (P = 0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) seemed to be associated with clinical response (P = 0.05). CONCLUSIONS: CTC gene expression analysis conducted by a reference laboratory is feasible when blood is collected from treating sites and processed 24 to 30 hours postcollection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.