Breast Cancer Subtypes

At a Glance

While most of us think of breast cancer as a single disease, evidence suggests there are multiple subtypes of breast cancer that occur at different rates in different groups, respond to different kinds of treatment, grow and spread at different rates, and have varied long-term survival rates. In addition, risk factors may vary for each different subtype of breast cancer.

Breast Cancer Groupings

Breast cancer is not a single disease, and diagnostic and prognostic descriptions of subtypes of breast cancer have become increasingly sophisticated over the past decades. Different cancer subtypes may be associated with different traditional risk factors.

Breast cancers are grouped according to:

The Tumor , Nodes, Metastasis (TNM) system of staging breast cancer

  • Where the tumor first occurs (ductal or lobular cancer)
  • Whether the tumor is in situ (contained within the walls of the ducts or lobes) or invasive (extending beyond the walls).
  • If the tumor is invasive, the number and location of lymph nodes that might be affected is recorded, as is information about whether or not the cancer has metastasized beyond the mammary and lymph systems.

The reproductive status (pre-menopausal or post-menopausal) of the woman in whom the cancer has been found. Often age 50 is used as a proxy for post-menopausal status.

Biological markers (proteins found in cells that have been associated with mechanisms underlying breast cancer).[1], [2], [3]

  • Luminal A—these tumors are estrogen receptor positive (ER+) that are often low grade with slow tumor growth. These tumors have the best prognosis.
  • Luminal B—these tumors are also ER+ andlow grade, but with quicker tumor growth than Luminal A.
  • Her-2 Over-expression—these tumors overexpress human epidermal growth factor receptor-2 (Her-2) and tend to grow quickly but are responsive to targeted therapy with treatments  such as Herceptin.
  • Triple Negative (also called basal-type)—these tumors are estrogen receptor negative (ER-), progestin receptor negative (PR-), and HER-2 negative. Although the basal subtype is only found in about 15 percent of breast cancer diagnoses, it has been shown to be aggressive, unresponsive to treatment and, ultimately, indicative of a poor prognosis.[4], [5]

As the field of genomics has expanded, researchers have conducted rapid screening assays that have examined variations in gene (DNA) sequences and their protein products that might be associated with subtypes of breast cancers.[6] One study analyzed almost 2,000 breast tumor samples and determined that 10 separate subtypes of breast cancer could be identified, based on clusters of genes that were either expressed or not, in particular patterns.[7] Many of these gene clusters also mapped onto the four main biological markers above.

Interactions of Breast Cancer Subtypes and Risk Factors

Different cancer subtypes may be associated with different traditional risk factors. For example, one study indicated that incidence of luminal B breast cancer may be increased in women who gain substantial weight after age 18.[8]

Menopausal status may also interact with other factors in altering risk for developing particular subtypes of breast cancer.  For example, more than five years of Hormone Replacement Therapy (HRT) is associated with higher incidence of HER-2 overexpressing cancers in postmenopausal women.  On the other hand, for premenopausal women, being significantly overweight or obese increased risk for more aggressive triple negative breast cancer, while decreasing the risk for luminal cancers.[9] Triple negative breast cancer is diagnosed more often in African American women than in European-American women in the United States.[10]

 

[1] Perou, C.M., Sørlie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Rees, C.A., Pollack, J.R., Ross, D.T., Johnsen, H., Akslen, L.A. and Fluge, Ø., 2000. Molecular portraits of human breast tumours. Nature, 406(6797), pp.747-752.

[2] Sørlie, T., Tibshirani, R., Parker, J., Hastie, T., Marron, J., Nobel, A., … Botstein, D. (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Nat Acad Sci, 100, 8418–8423.

[3] Alizart, M., Saunus, J., Cummings, M. and Lakhani, S.R., 2012. Molecular classification of breast carcinoma. Diagnostic Histopathology, 18(3), pp.97-103.

[4] Perou, C.M., Sørlie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Rees, C.A., Pollack, J.R., Ross, D.T., Johnsen, H., Akslen, L.A. and Fluge, Ø., 2000. Molecular portraits of human breast tumours. Nature, 406(6797), pp.747-752.

[5] Rakha, E.A., Reis-Filho, J.S. and Ellis, I.O., 2008. Basal-like breast cancer: a critical review. Journal of Clinical Oncology, 26(15), pp.2568-2581.

[6] Sims, A.H., 2009. Bioinformatics and breast cancer: what can high-throughput genomic approaches actually tell us?. Journal of clinical pathology, 62(10), pp.879-885.

[7] Curtis, C., Shah, S.P., Chin, S.F., Turashvili, G., Rueda, O.M., Dunning, M.J., Speed, D., Lynch, A.G., Samarajiwa, S., Yuan, Y. and Gräf, S., 2012. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 486(7403), pp.346-352.

[8] Tamimi, R.M., Colditz, G.A., Hazra, A., Baer, H.J., Hankinson, S.E., Rosner, B., Marotti, J., Connolly, J.L., Schnitt, S.J. and Collins, L.C., 2012. Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast cancer research and treatment, 131(1), pp.159-167.

[9] Turkoz, F.P., Solak, M., Petekkaya, I., Keskin, O., Kertmen, N., Sarici, F., Arik, Z., Babacan, T., Ozisik, Y. and Altundag, K., 2013. Association between common risk factors and molecular subtypes in breast cancer patients. The Breast, 22(3), pp.344-350.

[10] Amend, K., Hicks, D. and Ambrosone, C.B., 2006. Breast cancer in African-American women: differences in tumor biology from European-American women. Cancer Research, 66(17), pp.8327-8330.

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