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TCGA's Study of Breast Lobular Carcinoma

What is breast cancer?

This cancer starts in the tissues of the breast. Breast cancer is the most frequently diagnosed cancer and the second cause of cancer deaths in women. In 2010, 207,090 women were estimated to have been diagnosed with invasive breast cancer in the United States and approximately 40,000 women were estimated to have died of their disease.1 

Men can also have breast cancer, although male breast cancer is rare. In 2010, 1,970 American men were estimated to have been diagnosed and 390 were estimated to have died of breast cancer.1 Due to early detection through use of mammograms and improvements in treatment, breast cancer deaths have steadily decreased since the 1990s. Additional information on breast cancer.

TCGA focused mainly on two types of invasive breast cancer: ductal carcinoma and lobular carcinoma. Invasive ductal carcinoma is the most common type of breast cancer. It comprises about 65–85% of all breast cancer and develops in the milk ducts of the breast. About 10% of all cases of advanced breast cancer2 are invasive lobular breast carcinoma. This cancer develops in the breast milk-producing lobules or glands.

What have TCGA researchers learned about lobular carcinoma?

  • Genomic characteristics of lobular carcinoma distinguish it from the more common ductal carcinoma, providing unique opportunities for targeted therapy:
    • All lobular carcinoma tumors were defined by loss of cell-to-cell adhesion protein E-cadherin through varied routes of genomic disruption.
    • Lobular carcinomas demonstrated frequent mutations in different genes involved in estrogen receptor signaling compared to ductal carcinoma, suggesting that these tumor types may rely on different mechanisms to activate estrogen receptor-mediated gene expression.
    • Lobular carcinomas contained a greater degree of Akt signaling pathway activation than ductal carcinomas, indicating that lobular carcinoma may have increased sensitivity to Akt pathway inhibitors.
  • Three subtypes of lobular carcinoma: reactive-like, immune-related, and proliferative, show distinct clinical outcomes.
    • The reactive-like subtype was associated with the best outcomes and the proliferative was associated with the poorest.
  • Tumors that could not be identified as lobular or ductal based on histology were a mixed subtype, as they could be grouped with either lobular or ductal types based on their molecular features.

TCGA's original breast cancer study and expanded study with focus on ductal versus lobular subtypes

TCGA Research Network publications

Find NCI-supported breast cancer clinical trials


Selected References

1American Cancer Society. Cancer Facts and Figures 2010. Atlanta: American Cancer Society, Inc. 2010.

2Wood WC, Muss HB, Solin LJ, Olopade OL: Malignant Tumors of the Breast. In: DeVita VT Jr, Hellman S, Rosenberg SA ed. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005: 1420.

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