Tumor heterogeneity breast cancer

Tumor heterogeneity refers to the existence of distinct subpopulations of tumor cells with specific characteristics within a single neoplasm. Breast cancer is a classic example of a heterogeneous disease. First, the term breast cancer does not itself refer to a single disease. Breast cancers include many different diseases including (but not limited to) adenomas, papillomas, invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS) (6). 

Many cancers are heterogeneous, and do not consistently express tumor markers. It is clear that no single tumor marker will detect aU cancers. Therefore the detection of multiple antigens should increase the sensitivity of detection. This is also the pase with autoantibody detection. Using a single auto antibody the detection of primary breast cancer was between 35% and 47% however using four autoantibodies (p53, MUCl, c-rayc, and c-erbB-2) the sensitivity can be increased to 82%. ... 

Shipitsin, M., Campbell, L. L., Argani, P., et al. (2007) Molecular definition of breast tumor heterogeneity. Cancer Cell 11, 259-273. 

The majority of patients with disseminated ERP+ breast cancer will respond to hormonal manipulation. With subsequent relapses many of these patients respond to additional hormonal therapy. It is postulated that breast cancer is a heterogenous disease composed of hormone-sensitive and hormone-resistant clones, and that measurement of the estrogen receptor protein identifies the dominant cell population. Megestrol acetate (MEG) treatment of advanced breast cancer has achieved tumor regression in sensitive patients (M9). 

Target Validation. Several approaches, including those that involve the use of arrays, can be taken to validate short-listed therapeutic candidates. Genes whose transcript profiles suggest additional analysis can be profiled using TMAs in tens to hundreds of tissues by immunohistochemistry [142]. TMAs can be used to identify heterogeneities between primary tumors and their metastases, as demonstrated in the analyses of erbB2 in primary and metastatic breast cancers... 

The precise mechanism of SERM action is not well understood, but clearly, the ER is a primary target, as a signal transduction pathway, to modulate drug action in different tissues. Different concentrations of ER are present in breast cancers, which can be explained by heterogeneity in the tumor cell population. The more cells in the tumor that contain ERs, the higher the overall ER content, and the more likely the tumor will respond to antiestrogen therapy. Approximately 60% of ER-positive (receptor-rich) tumors are responsive to any form of additive or ablative endocrine therapy, whereas only 10% of ER-negative (receptor-poor) tumors respond to endocrine therapy (123). The current standard of care is to determine the ER status of the tumor in all patients with breast cancer. 

As was the case with primary tumors, the oxygenation of metastatic lesions is generally heterogeneous and lower than that of normal tissues at the site of metastatic growth. Metastatic lesions of breast cancers tended to have a poorer oxygenation status than the primaries. Local recurrences of breast cancers also seem to have a higher hypoxic fraction than the primary tumors, although this information is based on only one communication (FUller et al. 1994). 

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