The chemokine monocyte chemoattractant protein (MCP)-1 is thought to be involved in breast carcinogenesis. We evaluated MCP-1 serum levels in patients with breast cancer (n = 135), ductal carcinoma in situ (DCIS) I–III (n = 30), benign breast lesions (n = 143) and in healthy women (n = 27). We determined the value of MCP-1 serum levels as a differentiation marker between malignant, preinvasive and benign breast diseases and as a predictive marker for the biological phenotype of breast carcinoma. Median (range) MCP-1 serum levels in patients with breast cancer, DCIS I–III, benign breast lesions and healthy women were 200 (57–692) pg/ml, 194 (58–525) pg/ml, 174 (39–529) pg/ml and 175 (67–425) pg/ml, respectively. No differences were ascertained between the patient groups. In patients with breast cancer, increased MCP-1 serum levels were correlated with advanced tumor stage (p = 0.04) and lymph node involvement (p = 0.04). We were not able to establish MCP-1 as a differentiation marker between malignant and benign breast diseases. Our data might indicate that MCP-1 influences breast carcinogenesis by facilitating tumor growth and metastatic spread, thus altering the biological phenotype of the disease.

BACKGROUNDGenes encoding enzymes involved in estrogen metabolism are held to be candidate genes for associations with breast disease. In these candidate genes, no critical combination of single‐nucleotide polymorphisms (SNPs) for assessing breast carcinoma risk has been reported to date.METHODSIn a large case–control study, the authors investigated 10 estrogen‐metabolizing SNPs in 396 patients with breast carcinoma, 154 patients with fibroadenoma, and 1936 healthy control patients without breast carcinoma in their personal history. The following 10 SNPs were analyzed using sequencing‐on‐chip technology via a solid‐phase polymerase chain reaction assay performed on oligonucleotide microarrays: catechol‐O‐methyltransferase Val158Met G→A, 17‐beta‐hydroxysteroid dehydrogenase type 1 vIV A→C, cytochrome P‐450 (CYP) family 17 A2 allele T→C, CYP1A1‐1 MspI restriction fragment length polymorphism (RFLP) T→C, CYP1A1‐2 Ile462Val A→G, CYP19‐1 Trp39Arg T→C, CYP19‐2 Arg264Cys C→T, CYP19‐3 Cys1558Thr C→T, steroid‐5‐alpha reductase type 2 Val89Leu G→C, and vitamin D receptor BsmI RFLP. A total of 21,350 genotypes were evaluated. Associations and two‐way interaction models were calculated using stepwise logistic regression.RESULTSIn a multiple model, CYP1A1‐1 (P = 0.004) and CYP1A1‐2 (P = 0.03) were found to be associated with significantly decreased and increased risks of breast carcinoma, respectively. When two‐way interactions involving investigated SNPs were ascertained, no significant interactions among polymorphisms were noted. Comparison of patients with fibroadenoma with control patients revealed significantly increased and decreased risks of fibroadenoma when the mutant alleles of CYP17 (P = 0.02) and CYP1A1‐1 (P = 0.04), respectively, were present.CONCLUSIONSThe authors obtained the first SNP data indicating that CYP17 and CYP1A1‐1 play a role in the pathogenesis of fibroadenoma. Although the authors were not able to develop interaction models involving SNPs, they did provide evidence that CYP1A1 is a low‐penetrance susceptibility gene with respect to breast carcinoma in a large series of Caucasian women. Cancer 2004. © 2004 American Cancer Society.

The time course of microvascular changes in the environment of irradiated tumors was studied in a standardized human protocol. Eighty skin biopsies from 40 patients with previously treated primary breast cancer were taken from irradiated skin and corresponding contralateral unirradiated control areas 2 to 8 weeks, 11 to 14 months, or 17+ months after radiotherapy (skin equivalent dose 30 to 40 Gy). Twenty-two biopsies of 11 melanoma patients who had undergone lymph node dissection were used for unirradiated control. We found an increase of total podoplanin(+) lymphatic microvessel density resulting mainly from a duplication of the density of smallest lymphatic vessels (diameter <10 microm) in the samples taken 1 year after radiation. Our findings implicate radiogenic lymphangiogenesis during the 1st year after therapy. The numbers of CD68(+) and vascular endothelial growth factor-C(+) cells were highly elevated in irradiated skin in the samples taken 2 to 8 weeks after radiotherapy. Thus, our results indicate that vascular endothelial growth factor-C expression by invading macrophages could be a pathogenetic route of induction of radiogenic lymphangiogenesis.

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