The Four Major Molecular Subtypes of Breast Cancer

The Four Major Molecular Subtypes of Breast Cancer
National Cancer Institute

The Four Major Molecular Subtypes of Breast Cancer – NCI Press Release 

The four major molecular subtypes of breast cancer have been determined for the first time by researchers that have used national data to determine the incidence of the  by age, race/ethnicity, poverty level, and several other factors. These four subtypes respond differently to treatment and have different survival rates. The new data will help researchers more accurately stratify breast cancer by clinically relevant degrees of risk and potentially have an impact on breast cancer treatment. Moreover, armed with this information, women will be able to better understand the implications for their health based on their breast cancer subtype.

These findings, along with statistical analyses of the most common types of cancer, were reported today in JNCI. “The Annual Report to the Nation on the Status of Cancer, 1975-2011” showed continuing declines in cancer deaths for both men and women, for children, and for nearly all major cancer sites. The report was co-authored by experts from the North American Association of Central Cancer Registries (NAACCR), the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), and the National Cancer Institute (NCI) at the National Institutes of Health.

Breast cancer subtypes have major implications for determining treatment and may hold important clues to the origins of breast cancer. There are four molecular subtypes, which can be approximated by their hormone receptor (HR) status and expression of the HER2 gene: Luminal A (HR+/HER2-), Luminal B (HR+/HER2+), HER2-enriched (HR-/HER2+), and triple negative (HR-/HER2-). These subtypes are now being recorded by cancer registries across the nation, giving statisticians the ability for the first time to comprehensively examine breast cancer rates based on clinically meaningful subtypes.

The new report suggests that some of the differences in rates of breast cancer incidence and mortality across racial and ethnic groups are related to differences in the incidence of different subtypes. Geographic variation in rates that the authors observed were based on multiple factors, including underlying demographic patterns, regional cultures and associated behaviors, as well as access to care.

The researchers found unique racial/ethnic group-specific patterns by age, poverty level, geography, and by specific tumor characteristics. Rates of HR+/HER2- breast cancer, the least aggressive subtype, were highest among non-Hispanic whites, aligning with previously reported findings. Rates of HR+/HER2- breast cancer decreased with increasing levels of poverty for every racial and ethnic group. Also consistent with prior studies, non-Hispanic blacks had higher incidence rates of the most aggressive breast cancer subtype, triple negative, than other racial/ethnic groups.

Non-Hispanic blacks also had the highest rates of late-stage disease and of poorly/undifferentiated pathology among all the subtypes. All of these factors are associated with lower survival and correspond with blacks having the highest rates of breast cancer deaths.

“In addition to confirming the largely encouraging trends in cancer mortality rates for men, women, and children, this year’s report assesses breast cancer as four molecularly defined subtypes, not as a single disease. This is a welcome step, depending on medically important information that already guides therapeutic strategies for these subtypes,” said NCI Director Harold Varmus, M.D. “Further, it is a harbinger of the more rigorous classification of cancers based on their molecular features that is now being aggressively pursued under the President’s Precision Medicine Initiative. The new diagnostic categories now being defined will increasingly support our ability to prevent and treat breast and many other kinds of cancer, as well as monitor their incidence and outcomes more rigorously over time.”


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