Early menstrual cycle could play role in development of ER-negative breast cancer among African-American women

Early age at menarche, or first menstrual cycle, could play a role in the disproportionate incidence of estrogen receptor (ER)-negative breast cancers diagnosed among African-American women, according to a study published in the Journal of the National Cancer Institute.

The study is a result of a multicenter collaborative research effort that formed the African American Breast Cancer Epidemiology and Risk Consortium (AMBER), which includes Christine Ambrosone, PhD, Professor and Chair of the Department of Cancer Prevention and Control at Roswell Park Cancer Institute (RPCI), Andrew Olshan, PhD, Professor and Associate Director for Population Sciences at the University of North Carolina Lineberger Comprehensive Cancer Center, and Julie Palmer, ScD, Professor of Epidemiology at the Slone Epidemiology Center at Boston University.

AMBER researchers investigated the epidemiologic and genetic causes for more aggressive breast cancer in African-American women. They combined four epidemiologic studies with large numbers of African-American participants: The Black Women's Health Study (BWHS), the Multiethnic Cohort Study (MEC), the Carolina Breast Cancer Study (CBCS), and the Women's Circle of Health Study (WCHS).

The goal was to examine whether relationships between age at menarche and breast cancer are the same for tumors that are ER-positive or ER-negative, particularly among African-American women. ER-negative breast cancer is generally more aggressive and known to be associated with a poorer prognosis than ER-positive disease.

Analysis of data from 4,426 African-American women diagnosed with breast cancer and more than 17,000 women without the disease showed that the pathways to ER-negative and ER-positive breast cancer appear to be different.

"It is known that exposures such as ionizing radiation have a great impact on the risk of women who are later diagnosed with breast cancer if the exposure occurs during puberty, a time when breast cells appear to be extremely sensitive.
Indications are that the resulting cancers tend to be ER-negative. African-American girls tend to have earlier menarche than European-Americans, and that age is getting younger over time. It is possible that early age at menarche could play a role in the disproportionate number of ER-negative breast cancers diagnosed in African-American women," says Dr. Ambrosone, who is lead author of the study.

Reduced risk of ER-positive breast cancer with later age at menarche was primarily observed among women who had previously had children, with the greatest increased risk for those with longer spans between menarche and childbirth. However, for ER-negative breast cancer, childbirth status had no impact on the protective effects of later age at menarche.

The researchers conclude that age at menarche may be critical even in the development of ER-negative breast cancer, regardless of having children, and that the origins of ER-negative vs. ER-positive breast cancer at the cellular and molecular level may be different.

"These analyses are from the largest study of breast cancer in African-American women, to date. The AMBER consortium used rich epidemiological data and information about breast cancer subgroups, and included women from across the United States. We believe the findings from the study are generalizable to most African-American women," says Dr. Palmer, a co-author of the study.

"Our findings add further evidence to the growing knowledge that there are distinct etiologic pathways for ER-negative and ER-positive breast cancer. This study underscores that these differences likely begin at a very early age," adds Dr. Olshan.