New analysis of breast cancer subtypes could lead to better risk stratification

Annual Report to the Nation shows that mortality and incidence for most cancers continue to decline

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For the first time, researchers have used national data to determine the incidence of the four major molecular subtypes of breast cancer 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.”

The report also details trends in incidence and death rates of many major cancers and all cancers combined. Overall cancer incidence — new cases of cancer — continued to decrease in men, remained stable in women, and increased in children. The authors also found that there has been a relatively consistent decline in overall cancer mortality rates since the early 1990s, withrates from 2002 to 2011decreasing by about 1.8 percent per year among males and by 1.4 percent per year among females. Among children up to 19 years old, mortality rates have continued to decrease since 1975, with the exception of the period between 1998 and 2003.

“The continued decline in cancer death rates among men, women, and children is encouraging, and it reflects progress we are making in cancer prevention, early detection, and treatment,” said CDC Director Tom Frieden, M.D. “However, the continuing high burden of preventable cancer, and disparities in death rates among races and ethnicities, show that we still have a long way to go.”

For the most recent reporting period, the rate of decline in lung cancer incidence and mortality has accelerated in both men and women, most likely reflecting sustained public health efforts to decrease smoking rates. Colorectal cancer incidence and mortality among both men and women, and prostate cancer incidence and mortality in men, continue the downward trends seen in previous years.

“The drop in incidence in lung and colorectal cancers shows the lifesaving impact of prevention,” said John R Seffrin, Ph.D., American Cancer Society Chief Executive Officer. “But we have a long way to go, not only in these two cancers but in the many other cancers where the trend has not been so positive.”

Overall cancer incidence rates decreased by 0.5 percent per year from 2002 to 2011. Among men, incidence rates decreased an average of 1.8 percent per year from 2007 to 2011; incidence rates were stable in women from 1998 to 2011. Among children up to 19 years of age, incidence rates have increased by 0.8 percent per year over the past decade, continuing a trend dating from 1992 whose cause remains uncertain.

The report also noted some trends that require greater evaluation:

Incidence rates of thyroid and kidney cancers are increasing among both men and women. Increases in rates for new cases of thyroid and kidney cancers may be due to several factors, but no increase in mortality has been noted for these diseases. Incidence and mortality rates of liver cancer are increasing among both men and women. These increases may reflect, in part, increasing rates of hepatitis C and/or behavioral risk factors, such as alcohol abuse, for which there are opportunities for intervention Unlike the declines in incidence of other tobacco-related cancers, incidence rates are increasing for oral/oropharyngeal cancers overall among white men. This may be associated with increased HPV-associated oropharyngeal cancers, despite a decline in those oral cancers that are more closely associated with tobacco use. Incidence and mortality rates are increasing for uterine cancer among white, black, and Asian Pacific Islander women, with the largest increase seen in black women. The cause of these increases is unknown.