Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.

It was evident that study design exclusion and inclusion criteria rendered the majority of the study population ineligible. Among African Americans, comorbidity is a major issue that warrants considerable attention.

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This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

BACKGROUND. Several cancer surveys have shown that African-American women (AAW) develop highly aggressive breast tumors and experience about three times higher mortality rates compared with other populations. Generally, breast tumors in AAW are poorly differentiated or undifferentiated and exhibit increased frequency of nuclear atypia, higher mitotic activity, higher S-phase fraction, and tumor necrosis. The molecular factors responsible for these tumor characteristics are mostly unknown. METHODS. To explore whether the aggressive tumor biology observed in AAW is related to distinct alterations in estrogen receptor (ER) isoforms, the relative expression levels of four functionally active ER isoform mRNAs, ER␣ wild type, ER␤ wild type, ER␣ exon 3⌬, and ER␣ exon 5⌬, were measured by reverse transcriptasepolymerase chain reaction analysis in 18 immunohistochemically ER␣ positive tumors and in 6 ER␣ negative tumors and their matched normal tissues. RESULTS. In the tumors of AAW, the protective ER␤ isoform was decreased significantly compared with matched normal tissues (paired t test; n ϭ 24 patients; P ϭ 0.0018). In addition, both the constitutively active ER␣ exon 5⌬ and the dominant negative ER␣ exon 3⌬ mRNA levels were elevated in tumor tissues compared with matched normal tissues (paired t tests; n ϭ 24 patients; P ϭ 0.0002 and P ϭ 0.024, respectively). CONCLUSIONS. The data presented here show for the first time that functionally active ER isoform profiles in the breast tumors of AAW are different from those in Caucasian women. The tumors in AAW are characterized by decreased levels of the protective ER␤ isoform and elevated levels of the constitutively active ER␣ exon 5⌬ isoform. Variations in estrogen-mediated signaling because of the alterations in these two ER isoforms may account in part for differences in tumor biology between AAW and Caucasian women. Cancer 2002;94:615-23.